bluuebunny/crossref_metadata_2025 huggingface dataset:
Experimental Therapies and Clinical Trials in Bone Sarcoma
Authors: Chugh Rashmi
Published: April 2017

Sarcomas originating in the bone represent a challenge for physicians and patients. Because they constitute only 0.2% of all adult malignancies and 6% of pediatric malignancies, resources for studying this disease are often limited.1,2 Nonetheless, significant advancements have been made in the treatment of this disease, and there are ongoing efforts toward improvement. This article discusses recently completed and currently enrolling clinical trials for the 3 most common bone sarcomas: osteosarcoma, Ewing's sarcoma family tumors, and chondrosarcoma.
Pelvic Bone Sarcomas: Controversies and Treatment Options
Authors: Morris Carol D.
Published: April 2017

Treatment of pelvic bone sarcomas remains one of the most challenging areas of orthopedic oncology for all members of the disease management team. Although considerable advances have been made in all aspects of sarcoma treatment, the prognosis for patients with primary sarcomas of the pelvis continues to be guarded, and therefore, much controversy exists regarding optimal surgical management, radiation therapy, and systemic therapy. This article summarizes the current treatment paradigms for the 3 most common bone sarcomas (osteosarcoma, Ewing's sarcoma, and chondrosarcoma), highlighting the unresolved issues in their management as they pertain to the pelvis.
Malignant Biliary Tract Obstruction: Evaluation and Therapy
Authors: Chu David , Adler Douglas G.
Published: April 2017

Malignant biliary tract obstruction is a common clinical entity. Patients with tumors causing biliary tract obstruction are often asymptomatic until disease is significantly advanced. Symptoms of obstructive jaundice can significantly impair quality-of-life unless intervention to decompress the biliary tract, either curative or palliative, is performed. This article reviews the evaluation and management of patients with malignant biliary tract obstruction, including the available imaging and treatment modalities (endoscopic, percutaneous, and surgical approach) for relieving malignant biliary tract obstruction.
Vertebral Augmentation for Compression Fractures Caused by Malignant Disease
Authors: Rastogi Rahul , Patel Trusharth , Swarm Robert A.
Published: April 2017

Vertebral compression fractures are common in malignant disease and frequently cause severe back pain. However, management of that pain with conventional medical, radiotherapy, or surgical modalities is often inadequate. Vertebral augmentation techniques, such as vertebroplasty and kyphoplasty, are minimally invasive techniques in which methylmethacrylate bone cement is percutaneously injected into compressed vertebral bodies. Vertebral augmentation often improves mechanical stability of compressed vertebrae, provides pain relief, and may prevent progression of vertebral collapse. Kyphoplasty may provide increased chance for vertebral body height restoration, but the clinical importance of slight change in vertebral body height is unclear. Vertebral augmentation can be used in conjunction with other treatment modalities, and associated pain relief may improve patient tolerance of needed antitumor therapies, such as radiation therapy. Vertebral augmentation is generally very well tolerated, and complications associated with bone cement extravasation beyond the vertebral body have rarely been reported. Because it often provides good to excellent relief of otherwise intractable pain and is generally well tolerated, vertebral augmentation is becoming a first-line agent for management of painful vertebral compression fractures, especially in the setting of malignant disease.
Complications of Radioactive Iodine Treatment of Thyroid Carcinoma
Authors: Lee Stephanie L.
Published: April 2017

Radioactive iodine (RAI) in the form of 131I has been used to treat thyroid cancer since 1946. RAI is used after thyroidectomy to ablate the residual normal thyroid remnant, as adjuvant therapy, and to treat thyroid cancer metastases. Although the benefits of using RAI in low-risk patients with thyroid cancer are debated, it is frequently used in most patients with thyroid cancer and is clearly associated with acute and long-term risks and side effects. Acute risks associated with RAI therapy include nausea and vomiting, ageusia (loss of taste), salivary gland swelling, and pain. Longer-term complications include recurrent sialoadenitis associated with xerostomia, mouth pain, dental caries, pulmonary fibrosis, nasolacrimal outflow obstruction, and second primary malignancies. This article summarizes the common complications of RAI and methods to prevent and manage these complications.
Reassessing the Standard of Care in Indolent Lymphoma: A Clinical Update to Improve Clinical Practice
Authors: Rummel Mathias
Published: April 2017

Non-Hodgkin's lymphoma (NHL) represents a diverse group of hematologic malignancies originating in B or T lymphocytes. Approximately 85% of NHLs are of B-cell origin, with the remainder mostly of T-cell origin. The most common NHL types are diffuse large B-cell lymphoma (31%) and follicular lymphoma (22%). More than 65,000 new cases of NHL develop each year, and approximately 20,000 people with NHL died of the disease 2009. NHL is the seventh most common cancer in the United States, contributes to approximately 4% to 5% of all cancer cases in the United States, and causes approximately 3% of all cancer-related deaths. Currently, nearly 500,000 people are living with the disease or are in remission. Several new and encouraging advances have been made in the treatment of indolent NHL. Although the watch and wait approach still has a role, combined immunochemotherapy remains the standard of care for both first-line and relapsed/refractory disease. As front-line treatment, bendamustine plus rituximab may become a new standard of care, especially for older patients. In contrast, rituximab in combination with chemotherapy followed by rituximab maintenance seems to be the optimal option in patients with relapsed disease.
Managed Care & Medical Oncology: The Focus is on Value
Authors: Danielson Elizabeth , DeMartino Jessica , Mullen Jill A.
Published: April 2017

A previous NCCN Oncology Insights Report™ described the factors making cancer care a priority for managed care organizations (MCOs) and emerging trends in managing costs of cancer care. To better understand the concerns of MCOs and how they are addressing cancer costs and quality, NCCN interviewed senior physician executives from the 3 largest payors in the United States. The interviews provided insights into how these companies managed oncology care, with an emphasis on drugs and biologics. As a follow-up to the previous report, NCCN conducted additional interviews with medical executives from 10 MCOs between February and April 2010. The organizations represented in these interviews were Aetna, BlueCross BlueShield of Minnesota, BlueShield of Michigan, CareFirst BlueCross BlueShield, Empire BlueCross BlueShield, HealthNow, Humana, Independence BlueCross, Priority Health, and UnitedHealthcare. Although this group is diverse, it does not constitute a representative cross-section of MCOs across the United States. NCCN interviewed these executives about the priority of cancer care management for their organizations and the strategies being used to address cost and quality of cancer care. The information garnered from these interviews was qualitative in nature. A separate quantitative analysis of trends in oncology managed care has already been published, and throughout this report, data from the 2009–2010 Genentech Oncology Trend Report are referenced to supplement findings from the NCCN interviews.
NCCN Oncology Risk Evaluation and Mitigation Strategies White Paper: Recommendations for Stakeholders
Authors: Johnson Philip E. , Dahlman George , Eng Kirby , Garg Rekha , Gottlieb Scott , Hoffman James M. , Howell Peyton , Jahanzeb Mohammad , Johnson Shirley , Mackler Emily , Rubino Mark , Sarokhan Brenda , Marc Stewart F. , Tyler Tim , Vose Julie M. , Weinstein Sharon , Li Edward C. , DeMartino Jessica
Published: April 2017

REMS are a particularly important issue for oncology and the National Comprehensive Cancer Network (NCCN). A disproportionate number of drugs with complex REMS are used in patients with cancer or hematologic disorders. REMS policies and processes within oncology may act as a model for other clinical areas. A breadth of experience and access to a wide knowledge base exists within oncology that will ensure appropriate development and consideration of the practical implications of REMS. NCCN is uniquely positioned to assume a leadership role in this process given its status as the arbiter of high-quality cancer care based on its world-leading institutions and clinicians. Notwithstanding the potential benefits, the successful design, implementation, and analysis of the FDA's recent requirement for REMS for some high-risk drugs and biologics will present significant challenges for stakeholders, including patients, providers, cancer centers, manufacturers, payors, health information technology vendors, and regulatory agencies. To provide guidance to these stakeholders regarding REMS challenges, the NCCN assembled a work group comprised of thought leaders from NCCN Member Institutions and other outside experts. The Work Group identified challenges across the REMS spectrum, including the areas of standardization, development and assessment of REMS programs, medication guides, provider knowledge and impact on prescribing, provider burden and compensation, and incorporation of REMS into clinical practice.
Is There a Need for Axillary Dissection in Breast Cancer?
Authors: Wilson Jason P. , Mattson David , Edge Stephen B.
Published: April 2017

The involvement of axillary nodes remains a significant prognostic factor in breast cancer. However, management has changed from complete surgical staging to sentinel lymph node biopsies. Although little controversy exists regarding patients with negative sentinel lymph node biopsies, some remains regarding what to do with patients with small volume of axillary disease. This article focuses on the examination of recent evidence in management of the axilla. It focuses on both the prognostic and therapeutic information gleaned from isolated tumor cells and micrometastatic disease and on the use of completion axillary lymph node dissections or axillary radiation in preventing regional recurrence.
Inflammatory Breast Cancer
Authors: Dushkin Holly , Cristofanilli Massimo
Published: April 2017

Inflammatory breast cancer (IBC) represents the most virulent form of breast cancer, characterized by involvement of the skin and rapid progression of the disease. Management involves careful coordination of multidisciplinary modalities, including imaging, systemic chemotherapy, surgery, and radiation therapy. The use of neoadjuvant chemotherapy has contributed significantly to improvement in overall survival since the first descriptions of this entity, and has made the role of locoregional therapy, including surgery and radiation, critical to continued improvements in this disease. This article examines the unique epidemiology and pathology of IBC, and reviews the various treatment modalities, noting the significance of a multimodality approach and delineating each of the specific components. Moreover, the current research in IBC is briefly described, which experts hope will further improve systemic therapies.
Role of Adjuvant and Posttreatment Exercise Programs in Breast Health
Authors: Ligibel Jennifer A.
Published: April 2017

Growing evidence suggests that physical activity may be an important part of survivorship care for women with a history of breast cancer. Observational evidence suggests that women who are physically active after breast cancer diagnosis have a 30% to 50% lower risk of breast cancer recurrence, breast cancer death, and overall death compared with sedentary individuals. Although randomized controlled trials have not been performed to test the ability of exercise to improve outcomes in women with early-stage breast cancer, many small intervention studies have shown the safety and potential benefits of exercise in the adjuvant and posttreatment settings. These studies have shown that physical activity can be performed safely both during and after adjuvant treatment for breast cancer, and that women who increase physical activity in these settings experience improvements in fitness, strength, quality of life, and other end points. Although more research is needed to fully define the role of exercise in breast cancer survivors, the many proven benefits of physical activity have led the American Cancer Society and American College of Sports Medicine to encourage regular participation in moderate-intensity recreational activity for most breast cancer survivors. This article reviews the growing evidence that exercise could be an important part of breast cancer survivorship, and describes current exercise guidelines for breast cancer survivors.
Why, When, and How to Prevent Hepatitis B Virus Reactivation in Cancer Patients Undergoing Chemotherapy
Authors: Keam Bhumsuk , Lee Jeong-Hoon , Im Seock-Ah , Yoon Jung-Hwan
Published: April 2017

Hepatitis B virus (HBV) reactivation is a serious clinical problem in HBV carriers undergoing chemotherapy. The clinical course of HBV reactivation can be separated into 2 phases: 1) an increase in HBV replication and 2) hepatic injury. Patients with resolved HBV infections (negative for hepatitis B surface antigen [HBsAg], and positive for both hepatitis B core antibody [anti-HBc] and/or hepatitis B surface antibody) can experience HBV reactivation, and Western guidelines recommend that not only HBsAg but also anti-HBc be screened before initiation of chemotherapy or immunosuppressive therapy. Several meta-analyses have repeatedly confirmed the prophylactic role of lamivudine in preventing HBV reactivation. In conclusion, screening for HBV is required before chemotherapy, and prophylactic antiviral therapy can reduce not only the incidence of HBV reactivation but also HBV-related morbidity and mortality.
Optimization of Postremission Therapy in Follicular Lymphoma: Efficacy of Rituximab Maintenance
Authors: Roy Rupali , Gordon Leo I.
Published: April 2017

Rituximab has been proven to be an important part of the treatment of newly diagnosed and relapsed or refractory follicular lymphoma both alone and in combination with chemotherapy. Given its tolerability, rituximab has now been investigated in the maintenance setting in an effort to further improve progression-free and overall survival in patients with follicular lymphoma.
Role of Routine Imaging in Lymphoma
Authors: Wagner-Johnston Nina D. , Bartlett Nancy L.
Published: April 2017

Patients with lymphoma commonly undergo routine imaging studies after treatment completion, yet the appropriate interval, duration, and modality of follow-up, and the overall efficacy of various approaches is unclear. Existing guidelines are vague and not evidence-based, and consequently, practice patterns are varied. Most surveillance approaches in lymphoma have focused on early detection of recurrence, with the hope of prolonged survival and potential cure. Concerns regarding the prognostic value of frequent scanning, cost-effectiveness, and long-term risks associated with prolonged radiation exposure have led many to question the role of routine imaging in this setting. Given the multiple lymphoma subtypes and the clinical heterogeneity of these entities, a single approach to follow-up may not be reasonable. Much of the available literature focuses on Hodgkin lymphoma, and may not be generalizable. Retrospective series show that most relapses are detected by signs and symptoms regardless of the imaging schedule. In summary, clinicians are still left with “expert opinion” to guide them. This article examines the available data outlining the role of surveillance imaging in lymphoma.
Risk Stratification for Acute Pulmonary Embolism
Authors: Kline Jeffrey A. , Miller David W.
Published: April 2017

This article discusses state-of-the-art techniques for predicting risk of death after acute pulmonary embolism (PE), with special attention to how underlying malignancy adversely affects survival after an episode. Current methods of risk stratification generally categorize patients with PE as low-, moderate-, and high-risk for in-hospital adverse outcomes of respiratory failure, circulatory shock, and death. Published risk stratification studies find that patients with PE and an underlying malignancy have a worse prognosis, but no validated risk stratification criteria have been published specifically for these patients. Standard treatment is full-dose heparin followed by oral anticoagulation. The term escalated treatment refers to the use of systemic or intrapulmonary fibrinolytic agents, catheter-based treatment, or surgical embolectomy. Most patients with low-risk PE (normal vital signs and normal serum troponin, brain natriuretic peptide, and normal echocardiography) are treated successfully with standard anticoagulation, and many can be treated as outpatients. In contrast, patients with high-risk PE (systolic blood pressure < 90 mm Hg and no contraindications) often benefit from escalated treatment. Treatment decisions for patients with moderate-risk PE (normotension with evidence of right ventricular damage or dysfunction) are most controversial. Most patients in this category of risk recover with standard therapy, but some benefit from escalated treatment. Patients with cancer with an incidentally discovered PE should be risk stratified the same as those who have clinically suspected PE.
Role of Surgery for Locally Advanced and Metastatic Renal Cell Carcinoma
Authors: Torrey Robert , Spiess Philippe E. , Pal Sumanta K. , Josephson David
Published: April 2017

Both locally advanced and metastatic renal cell carcinoma (RCC) present a challenge in terms of their optimal management. This article reviews the literature and evaluates the role of surgery in the treatment of advanced RCC. Surgery is the optimal treatment for locally advanced RCC and minimal, resectable, metastatic disease. Patients with metastatic disease, and some forms of locally advanced disease, may also benefit from multimodal management with local surgical therapy and systemic treatment using either immunotherapy or targeted therapy. Regardless of the disease stage, patients with locally advanced or metastatic RCC represent heterogenous patient populations with different disease characteristics and risk factors. Individualization of care in the setting of a sound oncologic framework may optimize the risk/benefit ratio within individual patient cohorts.
Role of Immunotherapy for Renal Cell Cancer in 2011
Authors: George Saby , Pili Roberto , Carducci Michael A. , Kim Jenny J.
Published: April 2017

High-dose interleukin-2 (IL-2) and interferon were the most commonly administered therapies before the recent introduction of targeted agents, including vascular endothelial growth factor and mammalian target of rapamycin pathway inhibitors. Although the new agents result in a progression-free survival benefit, high-dose IL-2 remains the only agent with proven efficacy in producing durable complete and partial responses in patients with metastatic renal cell carcinoma (RCC). Furthermore, although the use of single-agent interferon has decreased significantly since the introduction of targeted therapy, it remains in the frontline setting in combination with bevacizumab as a result of 2 large phase III trials. Lastly, improved understanding of immune regulation has led to the advancement of targeted immunotherapy using immune checkpoint inhibitors that have shown promising activity and are moving forward in clinical development. This article focuses on the current status of immunotherapy in the management of metastatic RCC.
The Impact of Genomics on the Management of Myeloma
Authors: Corre Jill , Avet-Loiseau Hervé
Published: April 2017

Myeloma is a complex disease, characterized by a wide heterogeneity in clinical presentation, evolution, and molecular portraits. The successive use of cytogenetics, molecular cytogenetics, expression genomics, copy number genomics, and, more recently, deep sequencing, has shown that this heterogeneity can be used to identify markers usable for not only prognostication but also therapeutic choice and, ultimately, discovery of druggable targets. The use of some of these techniques is now mandatory for the management of patients. Although risk-adapted therapy is not yet a routine practice in myeloma, these molecular changes are essential for the definition of the prognosis.
Gene Expression Analysis and Immunohistochemistry in Evaluation of Cancer of Unknown Primary: Time for a Patient-Centered Approach
Authors: Handorf Charles R.
Published: April 2017

Molecular medicine is rapidly changing the diagnosis and management of cancer of unknown primary. The science, business, and economics of the genomic revolution have moved at such a pace that coordinating practical application of all available tools, such as gene expression analysis and immunohistochemistry, often seems to clash. In fact, very little work has been done to actively coordinate use of these techniques, each of which can be very resource-intensive. The Institute of Medicine proposed the STEEEP principles, a basic set of guidelines that maintain that the best patient care is safe, timely, effective, efficient, equitable, and patient-centered. Application of these principles will help lead to a better understanding of the most appropriate use of modern diagnostic modalities.
Multidisciplinary Management of Early-Stage Rectal Cancer
Authors: Phillips John G. , Hong Theodore S. , Ryan David P.
Published: April 2017

Because patients with locally advanced rectal cancer are at high risk for both recurrence and distant disease, they require adjuvant therapy. In the United States, the current standard of care is neoadjuvant chemoradiation followed by surgery and adjuvant chemotherapy. Neoadjuvant chemoradiation has been shown to improve local recurrence rates and decrease toxicity. However in the era of total mesorectal excision surgery, no study has shown a survival benefit to either chemoradiation or postoperative chemotherapy. Newer biologic therapies, although promising in initial early trials, have yet to show a significant benefit in adjuvant therapy for rectal cancer.
Continuous Low-Irradiance Photodynamic Therapy: A New Therapeutic Paradigm
Authors: Rogers Gary S.
Published: April 2017

A principal factor in determining the biologic consequences of photodynamic therapy (PDT) is the light fluence rate. Preclinical and, more recently, clinical studies have focused on low-irradiance schemes, suggesting that prolonged light exposure, better known as CLIPT (continuous low-irradiance PDT), may improve tumor control while reducing morbidity. After a brief look at the origin of light therapy and photosensitizers, this article turns to the promising animal research supporting the use of low- and ultra-low fluence rate PDT, which serves as the basis of the ongoing CLIPT dosimetry trials for patients with chest wall progression of breast cancer. The future of CLIPT seems to be a home-based therapy using a portable, self-contained energy delivery system.
Using Cellular Mechanisms to Develop Effective Combinations of Photodynamic Therapy and Targeted Therapies
Authors: Hasan Tayyaba
Published: April 2017

The bond between the research laboratory and the clinic is especially strong in the field of photomedicine. Much is learned in preclinical animal models, which is translated to the clinic for investigation, and then refinements in theory and technique are explored back in the laboratory. With many cancers becoming resistant to treatment, photodynamic therapy (PDT) offers a mechanistically distinct alternative. Studies have shown that PDT not only mitigates chemoresistance but also synergizes with chemotherapy and molecularly targeted therapies. From the world of biochemistry comes this unique look at 2 approaches to maximize the photodynamic effect through PDT combinations with targeted therapies: 1) using the molecular response after PDT to guide the selection of targeted agents and 2) preconditioning cancer cells to modulate nuclear molecular targets before PDT.
High-Grade Glioma/Glioblastoma Multiforme: Is There a Role for Photodynamic Therapy?
Authors: Whelan Harry T.
Published: April 2017

In the United States, the 5-year survival rate for patients of all ages with all types of brain tumors is approximately 20%, with the scale skewed toward even poorer survival in patients with gliomas. Although surgery and radiotherapy are primary treatment options, surgery is rarely curative and radiotherapy has had little impact on overall survival. Predominantly studied in adults with advanced high-grade gliomas, photodynamic therapy (PDT) represents a paradigmatic shift in the treatment of brain tumors. With no clear standard of care for brain tumors, PDT may emerge as a potential alternative, although challenges regarding its clinical use remain and studies confirming its promise are necessary.
Photodynamic Therapy in Cholangiocarcinoma
Authors: Kahaleh Michel
Published: April 2017

Most patients with hilar cholangiocarcinoma have unresectable disease and require palliation with biliary stenting to alleviate symptoms. Although chemotherapy and radiotherapy have been ineffective, many studies have suggested that the use of photodynamic therapy (PDT) may improve quality of life and perhaps survival in these patients. The ability of PDT to transmit through bile makes it a unique platform for intervention in the biliary tree. This article addresses the clinical implications of endoscopic biliary drainage, explores past and present study findings with PDT for cholangiocarcinoma, and offers an introduction to the novel techniques for direct visualization.
Photodynamic Therapy for Head and Neck Lesions in the Subtropics
Authors: Civantos Francisco
Published: April 2017

Surgery, radiotherapy, and chemotherapy remain standard treatment options for patients with head and neck carcinomas, but because they are often associated with complications, there is room for improvement. Although not widely practiced and still off-label, photodynamic therapy (PDT) is a promising alternative for superficial malignant or premalignant lesions of the upper aerodigestive tract. It also may be useful for those with recurrent surface disease after surgery or radiotherapy. After an historic look at the data on PDT for head and neck tumors, this article offers a current perspective from a fairly selective PDT program that has achieved dramatic lasting responses. Where PDT may fit in the treatment spectrum for head and neck cancers is one of the unanswered questions requiring further study.
Advances in the Treatment of Non-Small Cell Lung Cancer
Authors: Horn Leora
Published: April 2017

Clinical trial data continue to emerge on treatments in advanced non-small cell lung cancer (NSCLC), supporting the strategy that histology and molecular driver mutations should guide treatment selection. During her presentation at the NCCN 19th Annual Conference, Dr. Leora Horn highlighted 3 specific areas in which the 2014 NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for NSCLC focus attention: updates on the assortment of chemotherapy options, targeted therapies and how acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors appears to have become the catalyst of the development of newer-generations of agents, and the revisited role of newer immunotherapeutic options.
Point/Counterpoint: Early Detection of Prostate Cancer: Do the Benefits Outweigh the Consequences?
Authors: Carroll Peter R. , Vickers Andrew J.
Published: April 2017

Few clinical issues have polarized the oncology community as much as screening for prostate cancer, with advocates of prostate-specific antigen (PSA) testing vocal on one side and skeptics just as vocal on the other. At the NCCN 19th Annual Conference, Dr. Peter R. Carroll and Dr. Andrew J. Vickers tackled the controversy surrounding early detection of prostate cancer, focusing attention on the randomized trial results at the heart of the matter; over-detection (the Achilles’ heel of screening); and the rationale behind the new, streamlined 2014 NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Prostate Cancer Early Detection, which emphasize selective early detection and treatment and are tightly aligned with the NCCN Guidelines for Prostate Cancer.
Optimizing Surveillance and Balancing Evidence With Patient Expectations
Authors: Denlinger Crystal , Langbaum Terry S.
Published: April 2017

For most cancers, intensive posttreatment surveillance does not improve survival, but can induce anxiety in patients and may lead to unnecessary testing due to false-positive results. For colorectal cancer, more intensive surveillance, especially during the first few survivorship years, is warranted. For breast cancer, surveillance for second primary cancers with annual mammography is warranted. This may also be the case for non-small cell lung cancer. For other tumors, less routine surveillance testing can be recommended.
Common Controversies in the Management of Gallbladder Cancer
Authors: Are Chandrakanth
Published: April 2017

Gallbladder cancer is a rare and lethal malignancy. Most patients are best served at high-volume centers of excellence, where they are likely to receive evidence-based care derived from a multidisciplinary approach. Surgical resection is recommended for early-stage disease, whereas if the disease is unresectable, the treatment options include biliary drainage, gemcitabine-based combination chemotherapy, fluoropyrimidine chemoradiation, clinical trial enrollment, or best supportive care. While treatment by T-stage is straightforward in many cases, the debate regarding simple versus radical cholecystectomy is still active for patients with T1b disease. Other controversies exist over the necessity of resecting the bile duct and port sites, the extent of lymph node dissection and hepatic resections, and the value of resection for patients with jaundice.
International Adaptation and Use of NCCN Guidelines
Authors: Bazarbachi Ali , Zelenetz Andrew D.
Published: April 2017

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) describe a continuum of cancer care in the United States, from initial diagnosis through treatment and referral to hospice beyond treatment. However, in many other countries, there are no regional or national clinical practice guidelines. In 2008, the NCCN-MENA (Middle East and North Africa) project was launched to adapt the NCCN Guidelines to this part of the world. During their joint presentation at the NCCN 19th Annual Conference, Dr. Ali Bazarbachi and Dr. Andrew D. Zelenetz explored the modification process of NCCN Guidelines for MENA and shared examples of how it improved the care of patients with adult T-cell leukemia or lymphoma and younger patients with diffuse large B-cell lymphoma—regardless of where they live.
Growth and nutritional status of adolescents of public education system
Authors: Silva Janine Pereira da , Silva Valmin Ramos da , Almeida Patrícia Casagrande Dias de , Pinasco Gustavo Carreiro , Bernardes Tiago Pina , Sasso João Guilherme Ribeiro Jordão , Spalenza Natanna Siqueira , Leone Claudio , Lamounier Joel Alves
Published: April 2017

Introduction: The prevalence of obesity in children and adults has increased worldwide exponentially over the past two decades, becoming an important issue of global public health. Objective: To describe the growth and nutritional status of adolescents of  public schools. Method: Epidemiological, cross-sectional study, a representative sample of students aged 10 to 14 years of the public schools of the Metropolitan Region of Grande Vitória (MRGV), State of Espírito Santo, Brazil. Data on gender, age, skin colour/race, pubertal stage, socioeconomic class, weight and height were obtained. In the nutritional evaluation, the Height/Age (H/A) and Body Mass Index/Age (BMI/A) indexes, in z-score, of the WHO reference (2007) were considered. For statistical analysis, we used the Qui-square test and Student's t test (Mann-Whitney test for non-normal distribution), and significance level of p <0.05. Study approved by the Institutional Research Ethics Committee. Results: There were assessed 818 adolescents, with average age of 12.8 ± 1.1 years, female predominance (58.3%), mixed skin colour/race (41.7%), post-pubertal stage (53, 4%) and socioeconomic class C (59.5%). It was identified very low stature in 0.4% and low stature in 1.8% of adolescents. Overweight was diagnosed in 227 (27.7%) students, represented by overweight (18.7%), obesity (8.4%) and severe obesity (0.6%); While 0.2% presented severe thinness and 2.7% thinness.  The mean z-score of girls' height (p = 0.024) was higher than the WHO reference, as well as the BMI z-score of girls (p = 0.0001) and boys (p = 0.0002). Conclusion: Adolescents of public schools of MRGV achieve adequate growth, even higher, on average, proposed by WHO (2007). However, they also present a high prevalence of overweight, indicating that the region is at an advanced stage of nutritional transition.
Evolutionary changes in transcription factor coding sequence quantitatively alter sensory organ development and function
Authors: Weinberger Simon , Topping Matthew P , Yan Jiekun , Claeys Annelies , Geest Natalie De , Ozbay Duru , Hassan Talah , He Xiaoli , Albert Joerg T , Hassan Bassem A , Ramaekers Ariane
Published: April 2017

Animals are characterized by a set of highly conserved developmental regulators. Changes in the cis-regulatory elements of these regulators are thought to constitute the major driver of morphological evolution. However, the role of coding sequence evolution remains unresolved. To address this question, we used the Atonal family of proneural transcription factors as a model. Drosophila atonal coding sequence was endogenously replaced with that of atonal homologues (ATHs) at key phylogenetic positions, non-ATH proneural genes, and the closest homologue to ancestral proneural genes. ATHs and the ancestral-like coding sequences rescued sensory organ fate in atonal mutants, in contrast to non-ATHs. Surprisingly, different ATH factors displayed different levels of proneural activity as reflected by the number and functionality of sense organs. This proneural potency gradient correlated directly with ATH protein stability, including in response to Notch signaling, independently of mRNA levels or codon usage. This establishes a distinct and ancient function for ATHs and demonstrates that coding sequence evolution can underlie quantitative variation in sensory development and function.
Metformin ameliorates insulitis in STZ-induced diabetic mice
Authors: Jiang Guo-Jun , Han Xue , Tao Yu-Long , Deng Ya-Ping , Yu Jia-Wen , Cai Jian , Ren Guo-Fei , Sun Yuan-Nan
Published: April 2017

Background & Aims

Metformin is currently the most widely used first-line hypoglycemic agent for diabetes mellitus. Besides glucose-lowering action, there is increasingly interest in the potential anti-inflammatory action of this drug. In the present study, we investigated the actions of metformin on experimental insulitis using STZ-induced diabetic mice.

Methods

Mice with acute diabetes induced by STZ were administered metformin by gavage. Changes of blood glucose and body weight, and the daily amount of food and water intake were measured. Pancreatic tissues were collected for histologic analyses. Pathological assessment and immunohistochemistry analysis were used to determine the effect of metformin on insulitis. Inflammatory cytokines in the pancreas and insulin levels were measured through ELISA analysis.

Results

Metformin significantly reduced blood glucose levels and improved aberrant water intake behavior in experimental diabetic mice. No significant differences were observed in terms of body weight and food intake behavior in metformin-treated animals. In the STZ-induced model of diabetes, we found the appearance of pronounced insulitis. However, metformin administration reduced the severity of insulitis assessed by blind pathological scoring. In addition, metformin treatment improved insulin levels in experimental diabetic mice. ELISA assay revealed decreased levels of inflammatory response marker IL-1βand TNF-αin the pancreatic tissues following metformin treatment.

Conclusion

Metformin attenuated insulitis in the STZ-induced mice model of diabetes. This islet-protective effect might be partly correlated with the anti-inflammatory action of metformin.
An inhibitory RNA aptamer against the lambda cI repressor shows transcriptional activator activity in vivo
Authors: Ohuchi Shoji , Suess Beatrix
Published: April 2017

RNA aptamers are one of the promising components for constructing artificial genetic circuits. In this study, we developed a transcriptional activator based on an RNA aptamer against one of the most frequently applied repressor proteins, lambda phage cI. In vitro selection (Systematic Evolution of Ligands by EXponential enrichment) and following in vivo screening identified an RNA aptamer with the intended transcriptional activator activity from an RNA pool containing a 40‐nucleotide long random region. Quantitative analysis showed a 35‐fold elevation of reporter expression upon aptamer expression. These results suggest that the diversity of artificial transcriptional activators can be extended by employing RNA aptamers against repressor proteins to broaden the parts for constructing genetic circuits.
Characterizing frontal eddies along the East Australian Current from HF radar observations
Authors: Schaeffer Amandine , Gramoulle A. , Roughan M. , Mantovanelli A.
Published: April 2017

The East Australian Current (EAC) dominates the ocean circulation along south‐eastern Australia, however, little is known about the submesoscale frontal instabilities associated with this western boundary current. One year of surface current measurements from HF radars, in conjunction with mooring and satellite observations, highlight the occurrence and propagation of meanders and frontal eddies along the inshore edge of the EAC. Eddies were systematically identified using the geometry of the high spatial resolution (∼1.5 km) surface currents, and tracked every hour. Cyclonic eddies were observed irregularly, on average every 7 days, with inshore radius ∼10 km. Among various forms of structures, frontal eddies associated with EAC meanders were characterized by poleward advection speeds of ∼0.3–0.4 m/s, migrating as far as 500 km south, based on satellite imagery. Flow field kinematics show that cyclonic eddies have high Rossby numbers (0.6–1.9) and enhance particle dispersion. Patches of intensified surface divergence at the leading edge of the structures are expected to generate vertical uplift. This is confirmed by subsurface measurements showing temperature uplift of up to 55 m over 24 h and rough estimates of vertical velocities of 10s of meters per day. While frontal eddies propagate through the radar domain independently of local wind stress, upfront wind can influence their stalling and growth, and can also generate large cold core eddies through intense shear. Such coherent structures are a major mechanism for the transport and entrainment of nutrient rich coastal or deep waters, influencing physical and biological dynamics, and connectivity over large distances.
Fjord light regime: Bio‐optical variability, absorption budget, and hyperspectral light availability in Sognefjord and Trondheimsfjord, Norway
Authors: Mascarenhas V. J. , Voß D. , Wollschlaeger J. , Zielinski O.
Published: April 2017

Optically active constituents (OACs) in addition to water molecules attenuate light via processes of absorption and scattering and thereby determine underwater light availability. An analysis of their optical properties helps in determining the contribution of each of these to light attenuation. With an aim to study the bio‐optical variability, absorption budget and 1% spectral light availability, hydrographical (temperature and salinity), and hyperspectral optical (downwelling irradiance and upwelling radiance) profiles were measured along fjord transects in Sognefjord and Trondheimsfjord, Norway. Optical water quality observations were also performed using Secchi disc and Forel‐Ule scale. In concurrence, water samples were collected and analyzed via visible spectrophotometry, fluorometry, and gravimetry to quantify and derive inherent optical properties of the water constituents. An absorption model (R2 = 0.91, n = 36, p < 0.05) as a function of OACs is developed for Sognefjord using multiple regression analysis. Influenced by glacial meltwater, Sognefjord had higher concentration of inorganic suspended matter, while Trondheimsfjord had higher concentrations of CDOM. Increase in turbidity caused increased attenuation of light upstream, as a result of which the euphotic depth decreased from outer to inner fjord sections. Triangular representation of absorption budget revealed dominant absorption by CDOM at 443–555 nm, while that by phytoplankton at 665 nm. Sognefjord however exhibited much greater optical complexity. A significantly strong correlation between salinity and acdom440 is used to develop an algorithm to estimate acdom440 using salinity in Trondheimsfjord.
Indian Ocean sources of Agulhas leakage
Authors: Durgadoo Jonathan V. , Rühs Siren , Biastoch Arne , Böning Claus W. B.
Published: April 2017

We examine the mean pathways, transit timescales, and transformation of waters flowing from the Pacific and the marginal seas through the Indian Ocean (IO) on their way toward the South Atlantic within a high‐resolution ocean/sea‐ice model. The model fields are analyzed from a Lagrangian perspective where water volumes are tracked as they enter the IO. The IO contributes 12.6 Sv to Agulhas leakage, which within the model is 14.1 ± 2.2 Sv, the rest originates from the South Atlantic. The Indonesian Through‐flow constitutes about half of the IO contribution, is surface bound, cools and salinificates as it leaves the basin within 10–30 years. Waters entering the IO south of Australia are at intermediate depths and maintain their temperature‐salinity properties as they exit the basin within 15–35 years. Of these waters, the contribution from Tasman leakage is 1.4 Sv. The rest stem from recirculation from the frontal regions of the Southern Ocean. The marginal seas export 1.0 Sv into the Atlantic within 15–40 years, and the waters cool and freshen on‐route. However, the model's simulation of waters from the Gulfs of Aden and Oman are too light and hence overly influenced by upper ocean circulations. In the Cape Basin, Agulhas leakage is well mixed. On‐route, temperature‐salinity transformations occur predominantly in the Arabian Sea and within the greater Agulhas Current region. Overall, the IO exports at least 7.9 Sv from the Pacific to the Atlantic, thereby quantifying the strength of the upper cell of the global conveyor belt.
Parameterization of aerosol scavenging due to atmospheric ionization under varying relative humidity
Authors: Zhang Liang , Tinsley Brian A.
Published: April 2017

Simulations and parameterizations of the modulation of aerosol scavenging by electric charges on particles and droplets for different relative humidities have been made for 3 μm radii droplets and a wide range of particle radii. For droplets and particles with opposite‐sign charges, the attractive Coulomb force increases the collision rate coefficients above values due to other forces. With same‐sign charges, the repulsive Coulomb force decreases the rate coefficients, and the short‐range attractive image forces become important. The phoretic forces are attractive for relative humidity less than 100% and repulsive for relative humidity greater than 100% and have increasing overall effect for particle radii up to about 1 μm. There is an analytic solution for rate coefficients if only inverse square forces are present, but due to the presence of image forces, and for larger particles the intercept, weight, and the flow around the particle affecting the droplet trajectory, the simulated results usually depart far from the analytic solution. We give simple empirical parameterization formulas for some cases and more complex parameterizations for more exact fits to the simulated results. The results can be used in cloud models with growing droplets, as in updrafts, as well as with evaporating droplets in downdrafts. There is considered to be little scavenging of uncharged ice‐forming nuclei in updrafts, but with charged ice‐forming nuclei it is possible for scavenging in updrafts in cold clouds to produce contact ice nucleation. Scavenging in updrafts below the freezing level produces immersion nuclei that promote enhanced freezing as droplets rise above it.
Microseepage of methane to the atmosphere from the Dawanqi oil‐gas field, Tarim Basin, China
Authors: Tang Junhong , Xu Yue , Wang Guojian , Etiope Giuseppe , Han Wei , Yao Zhitong , Huang Jingang
Published: April 2017

The microseepage of natural gas from subsurface hydrocarbon reservoirs is a widespread process in petroleum basins. On a global scale, microseepage represents an important natural source of atmospheric methane (CH4). To date, microseepage CH4 flux data have been obtained from ~20 petroleum systems in North America, Europe, and Asia. While the seasonal variations of gas flux due to soil methanotrophic activity are known, the role of geological factors in controlling gas fluxes has been poorly investigated. Here we present new microseepage data from the Dawanqi oil‐gas field located within the Tarim Basin (China), a petroleum system characterized by intense faulting and shallow (<700 m) reservoirs. We measured CH4 fluxes from the ground at 51 sites along three transects by using a closed‐chamber connected to a portable gas sensor using off‐axis integrated cavity output spectroscopy. Our results indicate that the highest CH4 fluxes occur over faults and/or shallow reservoirs, especially those that were not developed and that have higher fluid pressures. Microseeping CH4 is thermogenic, like that occurring within the Dawanqi reservoirs, as demonstrated by 13C enrichment (δ13C from −46.3‰ to −30.7‰) in the chamber. Mean and range microseepage values (17 mg m−2d−1; from −1.4 to 330 mg m−2d−1) are similar to those reported for other petroleum fields with active tectonics. Our results confirm that dry soil over petroleum fields can be a net source of atmospheric CH4 and its flux is primarily controlled by faulting, and reservoir depth and pressure. These factors shall be considered in global bottom‐up seepage emission estimates.
Seagrass blade motion under waves and its impact on wave decay
Authors: Luhar M. , Infantes E. , Nepf H.
Published: April 2017

The hydrodynamic drag generated by seagrass meadows can dissipate wave‐energy, causing wave decay. It is well known that this drag depends on the relative motion between the water and the seagrass blades, yet the impact of blade motion on drag and wave‐energy dissipation remains to be fully characterized. In this experimental study, we examined the impact of blade motion on wave decay by concurrently recording blade posture during a wave cycle and measuring wave decay over a model seagrass meadow. We also identified a scaling law that predicts wave decay over the model meadow for a range of seagrass blade density, wave period, wave height, and water depth scaled from typical field conditions. Blade flexibility led to significantly lower drag and wave decay relative to theoretical predictions for rigid, upright blades. To quantify the impact of blade motion on wave decay, we employed an effective blade length, le, defined as the rigid blade length that leads to equivalent wave‐energy dissipation. We estimated le directly from images of blade motion. Consistent with previous studies, these estimates showed that the effective blade length depends on the dimensionless Cauchy number, which describes the relative magnitude of the wave hydrodynamic drag and the restoring force due to blade rigidity. As the hydrodynamic forcing increases, the blades exhibit greater motion. Greater blade motion leads to smaller relative velocities, reducing drag, and wave‐energy dissipation (i.e., smaller le).