bluuebunny/crossref_metadata_2025 huggingface dataset:
Dry Eye and Clinical Disease of Tear Film, Diagnosis and Management
Authors: Achtsidis Vasilis , Kozanidou Eleftheria , Bournas Panos , Tentolouris Nicholas , Theodossiadis Panos G ,   Consultant Ophthalmologist,   Consultant Ophthalmologist, Department of Ophthalmology, Worthing Hospital, West Sussex, UK,   Senior SpR in Internal Medicine,   Consultant Ophthalmologist and Clinical Lead, Department of Ophthalmology, “St Panteleimon” General Hospital of Nikaia, Piraeus, Greece,   Associate Professor in Internal Medicine and Clinial Lead, 1st Department of Propaedeutic Medicine, Athens University Medical School, Laiko General Hospital, Athens, Greece,   Associate Professor in Ophthalmology and Clinical Lead, 2nd Department of Ophthalmology, Attikon University Hospital, University of Athens, Greece
Published: October 2015

Dry eye disease (DED) is a clinically significant multifactorial disorder of the ocular surface and tear film as it results in ocular discomfort and visual impairment and predisposes the cornea to infections. It is important for the quality of life and tends to be a chronic disease. It is also common, as the prevalence is estimated between 5 % to 30 % and this increases with age. Therefore, it is recognised as a growing public health problem that requires correct diagnosis and appropriate treatment. There are two main categories of DED: the deficiency of tear production (hyposecretive), which includes Sjögren syndrome, idiopathic or secondary to connective tissue diseases (e.g. rheumatoid arthritis), and non-Sjögren syndrome (e.g. age-related); and the tear evaporation category, where tears evaporate from the ocular surface too rapidly due to intrinsic causes (e.g. meibomian gland disease or eyelid aperture disorders) or extrinsic causes (e.g. vitamin A deficiency, contact lenses wear, ocular allergies). Management of the disease aims to enhance the corneal healing and reduce patients discomfort. This is based on improving the balance of tear production and evaporation by increasing the tear film volume (lubrication drops) and improving quality of tear film (ex omega-3 supplements, lid hygiene, tetracyclines), reducing the tear film evaporation (paraffin ointments, therapeutic contact lenses), reducing tears drainage (punctal plugs, cautery) and finally by settling down the ocular surface inflammation (steroids, cyclosporine, autologous serous), as appropriate. In this article we will review the clinical presentation, differential diagnosis and treatment options for DED.
Managing Insufficiently Responsive DMO Patients Post-NICE Guidance
Authors: Chakravarthy Usha , Downey Louise , Kuppermann Baruch D , Bourne Rupert , Hamilton Robin , Cudrnak Tomas ,   Centre for Experimental Medicine, School of Medicine, Dentistry and Biomedical Sciences, Queens University, Northern Ireland, UK,   Hull and East Yorkshire Eye Hospital, UK,   Gavin Herbert Eye Institute, University of California, Irvine, US,   Hinchingbrooke, Moorfields and Addenbrookes and Vision & Eye Research Unit, Anglia Ruskin University, Cambridge, UK,   Moorfields Eye Hospital, London, UK,   Bradford Teaching Hospital, Bradford, UK
Published: October 2015

A satellite symposium, chaired by Usha Chakravarthy, was held at the Royal College of Ophthalmologists Annual Congress in Birmingham, entitled Managing Insufficiently Responsive DMO Patients Post-NICE Guidance. While therapies targeting vascular endothelial growth factor (VEGF), such as ranibizumab, have proven benefit in the treatment of diabetic macular oedema (DMO), patients with disease of longer duration may not respond as well to these therapies, a result of the more complex pathophysiology of chronic DMO, involving retinal inflammation. Corticosteroids offer a multi-factorial treatment approach, acting on numerous biochemical and anatomical pathways, unlike ranibizumab and bevacizumab, which inhibit VEGF and consequently confer their benefits through the modification of a single pathway. The ILUVIEN® intravitreal implant, contains 190 μg of fluocinolone acetonide (FAc), with an average release rate of 0.2 μg/ day for up to 36 months. Its benefits are most pronounced in patients with chronic DMO. ILUVIEN is indicated for the treatment of vision impairment associated with chronic DMO, considered insufficiently responsive to available therapies. The effectiveness of ILUVIEN was demonstrated in phase III clinical trials, and these benefits are being replicated in routine clinical practice. In this symposium, the speakers described clinical scenarios that demonstrated the utility of ILUVIEN in patients with DMO that are insufficiently responsive to currently available first-line therapies.
Bleb-less Surgery and Phaco – the iStent Saga
Authors: Feijoo J Garcia ,   Professor and Chairman, Department of Ophthalmology, Hospital Clínico San Carlos, Universidad Complutense de Madrid, Madrid, Spain; 2. Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Madrid, Spain; 3. Cooperative Research Network on Age-Related Ocular Pathology, Visual and Life Quality, Instituto de Salud Carlos III, Madrid, Spain
Published: October 2015

In the past years there is been a rapid evolution of cataract surgery; however, in glaucoma filtration surgery is still the gold standard. New techniques and devices have been developed and may change the surgical algorithm. Minimally invasive glaucoma surgery (MIGS) is safe, can be performed abinternothrough sub-1.8 mm corneal incisions and a postop intraocular pressure in mid-teens can be obtained.
Recent Progress in Magnetically Actuated Microrobotics for Ophthalmic Therapies
Authors: Ullrich Franziska , Fusco Stefano , Chatzipirpiridis, George , Pané Salvador , Nelson Bradley J ,   Researcher,   Researcher,   Researcher,   Senior Research Scientist,   Professor, Institute of Robotics and Intelligent Systems, ETH Zurich, Switzerland
Published: October 2015

Age-related visual loss and ageing demographics account for a large impact on societal health costs on a global scale. Efficient ocular surgery must be precise, safe and cost effective. Current research focuses on robotic systems to assist in ophthalmic surgery. Furthermore, several platforms for drug delivery in the posterior segment of the eye have been introduced. Moreover, magnetic manipulation of tethered and untethered structures has been suggested to assist in teleoperated ophthalmic surgery and targeted drug delivery in the posterior eye due to its many advantages. Magnetic manipulation systems generate magnetic fields and gradients to guide magnetic objects with high precision and force feedback. A hybrid actuation system for guiding a flexible catheter with a sharp edge magnetic tip has been introduced for capsulorhexis  a major step in cataract surgery. Research has demonstrated the potential of wireless magnetic microrobots for targeted drug delivery and simple mechanical operations in the posterior eye segment inex vivoandin vivoexperiments.
Early Detection of Fabry Disease – The Important Role of Ophthalmology
Authors: Willoughby Colin ,   Professor of Molecular Ophthalmology, Department of Eye and Vision Science, Institute of Ageing and Chronic Disease, Faculty of Health & Life Sciences, University of Liverpool, UK
Published: October 2015

The diagnosis of Fabry disease (FD; MIM #301500), a rare genetic disorder, is often missed or delayed as the systemic symptoms of FD show similarities to several other common medical conditions. Delayed diagnosis has significant clinical implications for the patient as FD can result in end-stage renal disease and life-threatening cardiovascular or cerebrovascular complications. Early diagnosis is preferable in achieving the best clinical outcomes for patients. FD demonstrates several classic ocular features, which are asymptomatic and observable through a routine eye examination. These features usually present early in the course of the disease and the identification of the ocular signs of FD offer a vital opportunity to diagnose FD, maximising the chance to improve patient outcomes.
Choroidal Imaging with Swept Source Optical Coherence Tomography – A Review
Authors: Piasecka Katarzyna , Michalewska Zofia ,   Third Municipal Hospital K Jonscher, Lodz, Poland,   Third Municipal Hospital K Jonscher, Lodz, Poland,   Ophthalmic Clinic Jasne Blonia, Lodz, Poland
Published: October 2015

The choroid provides up to 70 % of blood and oxygen to the eye. Pathological changes of this vascular tissue may lead to malnutrition of the retina and therefore be involved in the pathogenesis of numerous retinal disorders. Swept source optical coherence tomography (SS-OCT) is a new development of a non-invasive imaging technique that uses a tunable laser source with a higher wavelength light than conventional spectral domain OCT (SD-OCT). This enables visualisation of tissues below the retinal pigment epithelium. Thanks to SS-OCTs ultrahigh speed and ultrahigh resolution it is possible to assess choroidal layers as well as to automatically create 3D maps of its thickness and volume. This review is to discuss how SS-OCT has improved our understanding of choroidal anatomy and function in various retinal and chorioretinal diseases. In future, detailed evaluation of choroid may play a crucial role in the diagnosis and management of various retinal diseases.
Aflibercept – Setting its Sights on Diabetic Macular Oedema
Authors: Korobelnik Jean-François , Schlingemann Reinier , Pearce Ian ,   Centre Hospitalier Universitaire, Bordeaux, France,   Department of Ophthalmology, University of Amsterdam, The Netherlands,   Royal Liverpool University Hospital, UK
Published: October 2015

A satellite symposium entitled Aflibercept*  Setting Its Sights On Diabetic Macular Oedema (DMO) was chaired by Jean-François Korobelnik and was convened at the 2014 European Association for Vision and Eye Research (EVER) Congress. The symposium discussed the science behind DMO, in particular, the role of vascular endothelial growth factor (VEGF) and associated inflammatory mechanisms that alter fluid transport from capillaries into retinal tissues leading to focal leakage, fluid accumulation, macular damage and eventual blindness. This discussion of the pathophysiology emphasised the importance of VEGF as a target for DMO treatments. Management of diabetes and prevention of progression of diabetic retinopathy leading to DMO requires strict control of glycated haemoglobin (HbA1c), blood pressure and lipid levels. Once DMO has developed and vision is impaired, the anti-VEGF agents have emerged as vital components of disease management and are becoming the first-line standard of care. Aflibercept (EYLEA®) and ranibizumab (Lucentis®) are approved agents for DMO and have shown significant efficacy in clinical trials in terms of visual acuity gains, decreased retinal thickness and have good safety profiles. The symposium finally focused on the use of aflibercept in DMO. In large-scale trials (VIVID and VISTA), this treatment has been compared head-to-head with laser treatment and during 1 year of treatment, showed substantial efficacy benefits, no new safety signals and the potential for lower frequency intravitreal dosing at 8- rather than 4-week intervals for monitoring andpro re natadosing.
Severe Dry Eye Disease – Facing the Treatment Challenges
Authors: Setten Gysbert van , Labetoulle Marc , Aragona Pasquale , Leonardi Andrea ,   Associate Professor of Clinical Ophthalmology, St Eriks Eye Hospital, Karolinska Institutet, Stockholm, Sweden,   Professor of Ophthalmology, Ophthalmology Department, Bicêtre Hospital, Assistance Publique - Hôpitaux de Paris, South Paris University, France,   Professor of Ophthalmology, Head of the National Health System Referral Center for Ocular Surface Disease, University of Messina, Messina, Italy,   Assistant Professor of Clinical Ophthalmology, Department of Neuroscience, Ophthalmology Unit, University of Padua, Italy
Published: October 2015

Dry eye disease (DED) is a multifactorial disease of the tears and ocular surface that results in symptoms of discomfort, visual disturbance and tear instability with potential damage to the ocular surface. It is often accompanied by hyperosmolarity of the tear film and inflammation of the ocular surface. The symposium Severe Dry Eye Disease  Facing the Treatment Challenges held at the International Symposium on Ocular Pharmacology and Therapeutics (ISOPT) included four presentations from ophthalmological experts. The first presented a clinicalbased approach to facilitate the evaluation of DED in clinical practice and to provide ophthalmologists with straightforward tools to address objective signs of the disease and to alleviate subjective patients symptoms. This was followed by a description of a stepwise approach to anti-inflammatory treatment of severe DED, highlighting the usefulness of topical ciclosporin for treating inflammatory conditions of the ocular surface such as severe DED. This was illustrated by the third speaker who presented the results of a clinical study (SICCANOVE) showing that, compared with vehicle, treatment with ciclosporin 0.1% yielded reduced corneal damage in patients with severe DED that appeared to be enhanced in patients with more severe keratitis. Last, a diagnostic algorithm of severe DED provided by a group of European experts (ODISSEY) was presented to facilitate important decision-making in advanced stages of the disease. The need for a consensus in diagnosis, terminology and therapy at a European and international level was emphasised. Aside from the intention to make diagnosis less complicated and technically advanced, the aspects of immunomodulatory treatment were addressed as an area for future research. Other future objectives in the treatment of DED include detection of possible precursor stages to offer the possibility of preventative care. Social economic effects are also important and increased international collaboration will be needed to address global inconsistencies in treatment.
The LENSAR® Laser System–fs 3D for Femtosecond Cataract Surgery
Authors: Packer Mark , Klyce Stephen D , Smith Craig ,   Clinical Associate Professor, Oregon Health and Science University, Oregon, US,   Adjunct Professor of Ophthalmology, Mount Sinai School of Medicine, NY, US,   Principal Systems Engineer, LENSAR® Inc., Orlando, Florida, US
Published: October 2015

The LENSAR® Laser Systems ergonomic design permits flexible functionality in any operating environment. Its low-pressure liquid interface eliminates corneal compression and facilitates accurate and complete capsulotomy construction. The Augmented Reality imaging system utilises a variable super luminescent diode for scanning structured illumination to provide high-contrast, high-definition targets, which guide the laser. Real-time imaging adjustments compensate for minute degrees of tissue displacement, permitting unrivalled precision in corneal incision architecture. Precise laser spot application allows fragmentation of all grades of cataract, without the need for unnecessarily large safety margins. Iris registration compensates for cyclotorsion in the construction of arcuate incisions by aligning preoperative corneal biometry to intraoperative imaging. The ability to define the cataract grade intraoperatively facilitates efficient phacofragmentation by permitting surgeon-specified preset patterns for the full range of nuclear densities. The LENSAR Laser System represents the state of the art in femtosecond cataract surgery.
Thin-flap LASIK with a High-frequency, Low-energy, Small Spot Femtosecond Laser – Effectiveness and Safety
Authors: Vryghem Jérôme C , Heireman Steven , Devogelaere Thibaut ,   Ophthalmologist and Eye Surgeon, Brussels Eye Doctors, Brussels, Belgium,   Ophthalmologist and Eye Surgeon, Brussels Eye Doctors, Brussels, Belgium,   Ophthalmologist and Eye Surgeon, Brussels Eye Doctors, Brussels, Belgium
Published: October 2015

Objective:To evaluate clinical results of a high-frequency, low-energy, small spot femtosecond laser for the creation of thin corneal flaps in laserin situkeratomileusis (LASIK) used in a comparative case series at a private practice in Brussels, Belgium.Methods:A series of 75 patients selected for LASIK refractive surgery were enrolled for treatment with the Ziemer FEMTO LDV femtosecond laser and received a corneal flap of either 90 μm (59 patients, 103 eyes) or 80 μm (16 patients, 27 eyes) nominal thickness. Prospective evaluation included flap dimensions, intra- and post-operative complications and visual outcomes.Results:Mean flap thickness was 89.03 (standard deviation [SD]: ± 8.26 μm) in the 90 μm group and 81.91 (SD ± 6.80 μm) in the 80 μm group. Mean uncorrected visual was 1.19 ± 0.26 in the 90 μm group and 1.10 ± 0.25 in the 80 μm group. Mean manifest refractive spherical equivalent was –0.12 ± 0.26 D in the 90 μm group and –0.07 ± 0.31 D in the 80 μm group. There was no significant visual loss (≥2 lines loss of best corrected visual acuity) in either group. One flap tear occurred in the 90 μm group (0.97 %) and two pseudo-buttonholes occurred in the 80 μm group (7.41 %). No other clinically relevant complications occurred intra- or post-operatively.Conclusions:The Ziemer LDV femtosecond laser offers a high degree of precision in the creation of 90 and 80 μm flaps for LASIK. Using this device for creating 90 μm flaps can be considered a safe and effective procedure. A higher rate of complications were shown in 80 μm flaps.
Whatever Happened to the Contact Lens as a Therapeutic Modality in Keratoconus?
Authors: Toker Ebru ,   Professor of Ophthalmology and Chair, Marmara University Medical School, Department of Ophthalmology, Istanbul, Turkey
Published: October 2015

Over the past decade the management of keratoconus has changed from the traditional model limited only to rigid gas permeable lenses or penetrating keratoplasty to an array of newer medical and surgical treatment modalities that focus on both prevention of disease progression and improvement of functional visual acuity. New design contact lenses such as keratoconus design rigid gas permeable lenses, soft lenses, hybrid and scleral lenses offer the advantage of better comfort together with improved vision. Fitting of these contemporary contact lenses may postpone or avoid the need for keratoplasty in most of the patients with keratoconus.
Low-energy Stereotactic Radiotherapy for Treatment of Exudative Age-related Macular Degeneration Adjunctive to Anti-VEGF Therapy
Authors: Hatz Katja , Zimmermann Frank , Kardamakis Dimitrios , Lazaridis Emmanouil , Binder Jörg , Papachristofilou Alexandros , Pruente Christian ,   Vista Klinik Binningen, Binningen, Switzerland,   Department of Ophthalmology, Kantonsspital Liestal, Liestal, Switzerland,   University of Basel, Basel, Switzerland,   Department of Radiation Oncology, University Clinic Basel, Switzerland,   Department of Radiation Oncology, Medical School, Patras, Greece,   EyeRAD SWISS Medical Center, Switzerland,   EyeRAD SWISS Medical Center, Switzerland,   EyeRAD SWISS Medical Center, Switzerland,   Department of Radiation Oncology, University Clinic Basel, Switzerland,   Vista Klinik Binningen, Binningen, Switzerland,   Department of Ophthalmology, Kantonsspital Liestal, Liestal, Switzerland,   University of Basel, Basel, Switzerland
Published: October 2015

The number of cases of patients with exudative age-related macular degeneration (wet AMD) is increasing, partly due to an ageing population and lifestyle risk factors, such as smoking. The treatment of wet AMD has been revolutionised by the advent of anti-vascular endothelial growth factor (anti-VEGF) agents, though it is an important aim to reduce the treatment burden for patients with the need for highly frequent treatment. Previously, combinations of anti-VEGF with Verteporfin PhotoDynamic Therapy and radiation therapy were used to achieve this aim. More recently, stereotactic radiotherapy (SRT) has been shown in the IRay Plus Anti-VEGF Treatment For Patients With Wet AMD (INTREPID) study to preserve vision while sparing injections of anti-VEGF. Using a highly collimated, narrow X-ray beam, the dose of radiation is delivered in three closely spaced applications within a single session through different entry points in the inferior pars plana of the affected eye. The total application time is usually less than 60 minutes. Centred on the fovea, the sequential beams converge on the retina to deliver a 16 Gy dose to an area of 4 mm in diameter. In this opinion-based article, the practical application of SRT adjunctive to anti-VEGF therapy is discussed and illustrated with a series of case studies.
Intravitreal Ranibizumab for Diabetic Macular Oedema
Authors: Bandello Francesco , Cicinelli Maria Vittoria , Parodi Maurizio Battaglia ,   Department of Ophthalmology, University Vita-Salute, Ospedale San Raffaele, Milan, Italy,   Department of Ophthalmology, University Vita-Salute, Ospedale San Raffaele, Milan, Italy,   Department of Ophthalmology, University Vita-Salute, Ospedale San Raffaele, Milan, Italy
Published: October 2015

Diabetic macular oedema (DMO) is the most frequent cause of vision loss in patients affected by diabetes mellitus, and has a remarkable effect on public health. The treatment with focal/grid laser photocoagulation was considered in the past decades as the standard of care, but the recent advent of new pharmacological approaches, based on the use of intravitreal anti-vascular endothelial growth factor (anti-VEGF), has completely revolutionised the management of DMO. The most important molecule of this class of drugs is represented by ranibizumab, which has been clinically supported by several randomised clinical trials. The present review aims at providing a comprehensive summary of the most important investigations regarding the ranibizumab treatment of DMO.
Micro-incision Vitrectomy Surgery – Past, Present and Future
Authors: Nagpal Manish , Verma Amrita , Goswami Sangeeta ,   Consultant Vitreoretinal Surgeon,   Fellow in Retina and Vitreous,   Fellow, Retina Foundation, Ahmedabad, India
Published: October 2015

The advent of micro-incision vitrectomy surgery (MIVS) changed the approach, indications and complications of vitreoretinal surgeries forever. Since its introduction in 2002, MIVS has been gaining popularity amongst retinal surgeons for managing a wide variety of vitreoretinal disorders. MIVS allows for more efficient surgery, faster recovery time and better visual outcomes than 20G vitrectomy. The use of instrumentation having small diameters reduced trauma from conjunctival and scleral manipulation as well as post-operative inflammation and corneal astigmatism. Further refinement of techniques with the introduction of 27G for routine procedures increases the comfort for the patient and minimises the recovery time. In this review, we briefly summarise the journey of MIVS to its present status and discuss the various advances that have taken place to achieve better efficiency and results.
Case Report Of Solitary Eccrine Spiradenoma Of Eyelid
Authors: Singh Sudhir , Saraf Subodh , Goswami Divyesh , Singh Sumit ,   Senior Consultant and Head Of Department, Department of Ophthalmology, JW Global Hospital & Research Centre, Mount Abu, Rajasthan, India,   Ophthalmology Registrar, Global Hospital Institute of Ophthalmology, Sirohi, Rajasthan, India,   Consultant Pathologist, JW Global Hospital & Research Centre, Mount Abu, Rajasthan,   Consultant Ophthalmologist, Mathura, Uttar Pradesh, India
Published: October 2015

Eccrine spiradenoma, a sweat gland tumor, is rarely found in the eyelid. We encountered a 73-year-old man with a nodular growth in his left upper eyelid, which had developed over the last 12 years. He had developed mild pain in the past. Excision was carried out under local anesthesia in a pentagon fashion with clear margins. The histopathology was suggestive for a benign eccrine spiradenoma.
Asthma Exacerbations – The Focus For Treatment Of Severe Asthma?
Authors: Bidder Therese M , Robinson Douglas S ,   Clinical Nurse Specialist,   Lead Consultant, Severe Asthma Service, Respiratory Medicine, UCLH NHS Foundation Trust, London, UK
Published: October 2015

Asthma exacerbations (worsening of symptoms requiring oral corticosteroid treatment) impair quality of life, interfere with normal activities and can lead to hospital admission or even death. Predicting and preventing exacerbations is therefore an important focus in asthma management. Good patient education and adherence with appropriate treatment are important, as is detection of when this is not achieved. Increasingly it is recognised that uncontrolled airway inflammation in a risk factor for exacerbation, and detection and control of untreated inflammation can reduce exacerbation rates. As specific biologics are available for asthma treatment it will be important to use biomarkers to select those subgroups that will benefit from each type of treatment.
Bone Metastases in Advanced Prostate Cancer
Authors: Saad Fred ,   Centre Hospitalier de l’Université de Montréal,Hôpital Notre-Dame,Montreal,Canada
Published: October 2015

Men with advanced prostate cancer are at high risk for development of bone metastases,resulting in clinically significant skeletal morbidity and severe bone pain. Studies of early-generation bisphosphonates,clodronate, and pamidronate,demonstrated transient palliative effects on bone pain in patients with bone metastases, but failed to demonstrate long-term clinical benefit.A small,open-label study of ibandronate demonstrated significant reductions in pain,but these results have not been confirmed in a larger,randomized,controlled trial. Currently,zoledronic acid is the only bisphosphonate that has demonstrated statistically significant reductions in skeletal morbidity – including durable pain reduction– in this patient population in a randomized placebocontrolled trial.Therefore,zoledronic acid therapy should be considered to prevent skeletal morbidity and improve the quality of life of prostate cancer patients with bone metastases.
Multimodality Approaches to Improving Post-operative Pain and Outcomes
Authors: Chamberlain Ronald S , Blackshear Robert H ,   Chairman and Surgeon in Chief, Department of Surgery, Saint Barnabas Medical Center, and Professor, Department of Surgery, University of Medicine and Dentistry of New Jersey,   Chairman, Department of Anesthesiology, Skaggs Regional Medical Center
Published: October 2015

Pain is an inevitable complication of surgery. It not only impedes healing and recovery in the surgical patient, but also imposes a great deal of strain on healthcare resources. Post-operative ileus (POI), a frequent complication following surgery (especially of the abdomen), is intimately related to modes of pain control. Important aspects of effective pain control measures include improvement in quality of life and patient satisfaction as well as the prevention or limitation of post-operative complications, particularly POI. A comprehensive review of numerous peri-operative management methods reveals only limited benefit, if any, when employed individually. Strategies incorporating various preventive–therapeutic approaches devised to manage surgical patients in a ‘fast-track’ manner peri-operatively may provide better outcomes.
Benefits of Vorinostat in Treating Advanced Cutaneous T-cell Lymphoma
Authors: Zhang Chunlei , Duvic Madeleine ,   Assistant Professor,   Professor of Internal Medicine and Dermatology, and Deputy Chairman, Department of Dermatology, University of Texas MD Anderson Cancer Center
Published: October 2015

Vorinostat (suberoylanilide hydroxamic acid) is the first US Food and Drug Administration (FDA)-approved histone deacetylase (HDAC) inhibitor for the treatment of cutaneous manifestations in patients with cutaneous T-cell lymphomas (CTCLs) who have progressive, persistent, or recurrent disease on or following two systemic therapies. In two phase II trials, vorinostat was safe and effective at an oral dose of 400mg/day, with an overall response rate of 24–30% in refractory advanced patients with CTCL including large cell transformation and Sézary syndrome. Most patients with CTCL also experience significant itching relief with vorinostat therapy. The most frequent side effects of vorinostat include gastrointestinal symptoms, fatigue, and thrombocytopenia. These side effects are dose-related and reversible upon cessation of therapy. Translational studies have shown that vorinostat hasin vitroandin vivoantitumor activities against CTCL, including selective induction of tumor T-cells, inhibition of angiogenesis, suppression of STATs, and upregulation of proapoptotic proteins. Constitutive activation of STATs may predict vorinostat resistance in CTCL, and inhibitors of JAK/STAT combined with vorinostat may help to overcome resistance and improve the clinical response of vorinostat. Further identification of predictive biomarkers of vorinostat will help to select patients most likely to benefit from treatment and to develop better combination therapies for patients with CTCL.
Advances in the Prognosis and Treatment of Medullary or Anaplastic Thyroid Cancer
Authors: Voigt Wieland , Jordan Karin , Schmoll Hans-Joachim ,   Department of Hematology/Oncology, Martin Luther University of Halle-Wittenberg,   Department of Hematology/Oncology, Martin Luther University of Halle-Wittenberg,   Department of Hematology/Oncology, Martin Luther University of Halle-Wittenberg
Published: October 2015

Despite being the most common endocrine malignancy, thyroid cancer accounts for approximately only 1% of all reported malignancies. Anaplastic thyroid cancer (ATC) is one of the most aggressive forms and accounts for 2–5% of cases of all thyroid cancers, while medullary thryroid cancer (MTC) accounts for 3–5%. As a result of their distinct clinical and molecular characteristics, it is necessary to pursue different multimodal strategies. Significant progress in decoding the molecular biology of thyroid cancer has been made; however, the outcomes of ATC are still dismal. Although aggressive multimodal locoregional treatment reduces the rate of relapse, patients continue to die of metastatic disease owing to the lack of active systematic treatment regimes. Therapy for MTC took an optimistic turn with the discovery of the RET protooncogene, which led to the introduction of targeted agents in the treatment concept. Although these emerging therapies have raised hopes, their impact on clinical outcome needs to be clarified by future randomised trials.
Respiratory Homeostasis and Exploitation of the Immune System for Lung Cancer Vaccines
Authors: Yagui-Beltrán Adam , Coussens Lisa M , Jablons David M ,   Post-doctoral Fellow,   Professor of Pathology,   Ada Distinguished Professor of Thoracic Oncology and Chief of General Thoracic Surgery, Helen Diller Family Comprehensive Cancer Center, University of California San Francisco
Published: October 2015

Lung cancer is the leading cause of all cancer deaths in the US. The international scientific and clinical community has made significant advances toward understanding specific molecular mechanisms underlying lung carcinogenesis; however, despite these insights and advances in surgery and chemoradiotherapy, the prognosis for non-small-cell lung cancer (NSCLC) remains poor. Nonetheless, significant effort is being focused on advancing translational research evaluating the efficacy of novel targeted therapeutic strategies for lung cancer. Illustrative examples of this include antagonists of the epidermal growth factor receptor (EGFR), tyrosine kinase inhibitors (TKIs) such as gefitinib and erlotinib, and a diverse assortment of anti-angiogenic compounds targeting growth factors and/or their receptors that regulate tumorassociated angiogenic programs. In addition, with the increased awareness of the significant role chronically activated leukocytes play as potentiators of solid-tumor development, the role of innate and adaptive immune cells as regulators of lung carcinogenesis is being examined. While some of these studies are examining how novel therapeutic strategies may enhance the efficacy of lung cancer vaccines, others are evaluating the intrinsic characteristics of the immune response to lung cancer in order to identify rate-limiting molecular and/or cellular programs to target with novel anticancer therapeutics. In this article, we explore important aspects of the immune system and its role in regulating normal respiratory homeostasis compared with the immune response accompanying development of lung cancer. These hallmarks are then discussed in the context of recent efforts to develop lung cancer vaccines, where we have highlighted important concepts that must be taken into consideration for future development of novel therapeutic strategies and clinical trials assessing their efficacy.
The Efficacy of Imatinib in Unresectable/Metastatic Gastrointestinal Stromal Tumors
Authors: Patel Shreyaskumar R , Wong Patrick ,   Professor of Medicine, University of Texas MD Anderson Cancer Center,   Technical Editor, Touch Briefings
Published: October 2015

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal malignancy in the gastrointestinal tract. Their pathogenesis is largely based on gain-of-function mutations in the c-kitproto-oncogene, resulting in constitutive activation of the KIT receptor tyrosine kinase. Historically, there were limited options for the medical management of GIST, with tumor recurrence frequently observed following complete surgical resection of primary localized GIST and a grim prognosis for patients with unresectable or metastatic disease. However, the introduction of the tyrosine kinase inhibitor (TKI) imatinib mesylate has had a major impact on treatment outcomes for these patients with GIST. Imatinib is currently approved for the treatment of patients with KIT/CD117-positive unresectable and/or metastatic malignant GISTs. Initial therapy with the conventional 400mg/day dose is highly recommended in these patients, while a higher dose (800mg/day) has shown promise in patients who have KIT exon 9-mutant GIST and those who experience disease progression on the conventional dose. Neoadjuvant therapy has also been shown to be safe and beneficial as a palliative treatment.
Advances in the Treatment Options for Kidney Cancer— Is There an Optimal Regimen?
Authors: Ratnayake Gihan , Larkin James , Pickering Lisa ,   Medical Oncology Registrar,   Consultant Medical Oncologist,   Consultant Medical Oncologist, Royal Marsden Hospital, London
Published: October 2015

Treatment of renal cell carcinoma had long been hindered by poor responses to standard chemotherapeutic agents. Immunological modulators have some activity in metastatic disease but with considerable treatment-associated morbidity. Recent years have resulted in a shift in the treatment of advanced renal cell carcinoma towards novel targeted agents. Pivotal phase III trials involving bevacizumab, sorafenib, sunitinib, and temsirolimus have demonstrated improved disease control over the previous standards of first-line cytokine therapy and second-line palliative care. These trials have led to a change in routine practice in metastatic disease and the development of internationally accepted treatment algorithms. However, an optimal treatment paradigm has not yet been established: the role of combination therapy and the sequential use of these agents, and new investigational agents, remains the subject of ongoing investigation. In addition, these novel agents are being evaluated in the adjuvant and neoadjuvant settings.
Exercise and Cancer-related Fatigue
Authors: Mustian Karen M , Peppone Luke J , Palesh Oxana G , Janelsins Michelle C , Mohile Supriya G , Purnell Jason Q , Darling Tom V ,   Assistant Professors, James P Wilmot Cancer Center, University of Rochester School of Medicine and Dentistry,   Assistant Professors, James P Wilmot Cancer Center, University of Rochester School of Medicine and Dentistry,   Assistant Professors, James P Wilmot Cancer Center, University of Rochester School of Medicine and Dentistry,   Assistant Professors, James P Wilmot Cancer Center, University of Rochester School of Medicine and Dentistry,   Assistant Professors, James P Wilmot Cancer Center, University of Rochester School of Medicine and Dentistry,   Assistant Professors, James P Wilmot Cancer Center, University of Rochester School of Medicine and Dentistry,   Assistant Professors, James P Wilmot Cancer Center, University of Rochester School of Medicine and Dentistry
Published: October 2015

Cancer-related fatigue is the most common side effect reported by cancer patients during and after treatment. Cancer-related fatigue significantly interferes with a patient’s ability to perform activities of daily living and maintain functional independence and quality of life. Cancer-related fatigue can also interfere with a patient’s ability to complete treatments. The purpose of this article is to provide an overview of cancer-related fatigue, its pathopsychophysiology, and the role of exercise in the management of this side effect.
Role of Epidermal Growth Factor Receptor Mutational Testing in Personalizing the Treatment of Non-small-cell Lung Cancer
Authors: Ginsburg Philip J ,   Chief Medical Officer, Iris International, Inc
Published: October 2015

Better methods of combating non-small-cell lung cancer (NSCLC) are constantly being sought. The recent movement towards the implementation of a personalized approach to treatment in oncology is a positive step in this direction. Epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) drugs such as gefitinib (Iressa®) and erlotinib (Tarceva®) are approved for the treatment of certain types and stages of non-small-cell lung cancer (NSCLC). It is now possible to determine the likelihood of response of a given patient’s tumor to treatment with this type of cancer drug using molecular diagnostic methods that detect the presence or absence of specific EGFR mutations. These diagnostic and therapeutic advances offer the potential to improve patient care and bring new hope to cancer patients.
Buckle Up for Breast Cancer—Deaths from Breast Cancer Can Be Analyzed in the Same Way as Deaths in Automobile Accidents
Authors: Webb Matthew L , Cady Blake , Michaelson James S ,   Research Assistant, Department of Surgical Oncology, and Research Coordinator, Endocrine Unit, Massachusetts General Hospital,   Emeritus Professor of Surgery, Brown Medical School, and Director, Breast Health Center, Woman and Infants Hospital of Rhode Island,   Assistant Professor of Pathology, Departments of Pathology and Surgery, Massachusetts General Hospital, and Department of Pathology, Harvard Medical School
Published: October 2015

Background:Randomized population mammographic screening trials demonstrated a statistically significant mortality reduction in screened women. Studies in Sweden and The Netherlands show that screening is the main reason that the death rate has decreased in the general population, but ony limited data are available to assess this in the US. In a previous report, 75% of breast cancer deaths occurred in the small proportion of unscreened women. This conclusion needs confirmation.Methods:In a large hospital consortium, 6,997 invasive breast cancer diagnoses occurred between 1990 and 1999. Among all subsequent deaths through 2007, breast cancer deaths in Massachusetts women were documented by review of hospital and outpatient records. Regular screening was defined as two or more screening mammograms at intervals of two years or less in asymptomatic women.Results:After 12.5 (range: eight to 17) years of median follow-up, 461 deaths from breast cancer were confirmed. Seventy-two deaths (15.6%) resulted from non-palpable screen-detected cancers, 44 deaths (9.6%) resulted from palpable interval cancers, and a total of 116 deaths (25.2%) occurred in regularly screened women. Three hundred and twenty-two deaths (69.9%) occurred in women who had never had screening mammography, and 23 deaths (5%) occurred after one or more previous mammograms, none within two years of diagnosis. Thus, 345 breast cancer deaths (74.8%) occurred in women who were not regularly screened.Conclusion:The most effective method of avoiding death from breast cancer is for women to participate in regular screening mammography.
Denosumab in the Treatment of Giant Cell Tumor of Bone
Authors: Thomas David ,   Associate Professor, University of Melbourne, and Victorian Cancer Agency Research Fellow, Ian Potter Foundation Centre for Cancer Genomics and Predictive Medicine, Peter MacCallum Cancer Centre
Published: October 2015

Giant cell tumor of bone (GCT) is a rare, benign tumor characterized by localized bone destruction. GCT is thought to be biphenotypic, comprising a neoplastic stromal cell population and an osteoclast-like giant cell population. Recent studies have established that receptor activator of NF κβ ligand (RANKL) plays an important role in GCT. Although its actions are not fully understood, RANKL acts as an obligate signal for normal osteoclast formation and function. The development of an antagonist to RANKL, denosumab, has led to clinical trials in osteoporosis, bone metastases in cancer, and GCT. Generally well-tolerated, denosumab is an extremely effective inhibitor of osteoclast differentiation and function in humans. A preliminary study of the use of denosumab in patients with advanced or unresectable GCT has suggested considerable activity and clinical benefit. The eventual role of denosumab in GCT is currently the subject of an ongoing clinical trial.
Pancreatic Adenocarcinoma in the Older Adult
Authors: Gayle Arlene A , LoConte Noelle K ,   Hematology-oncology Fellow,   Assistant Professor, University of Wisconsin Carbone Cancer Center, University of Wisconsin Hospital and Clinics
Published: October 2015

Pancreatic adenocarcinoma is common among older adults, who may be more frail or have comorbid medical conditions that make treatment more challenging. Pancreatic adenocarcinoma is a lethal malignancy with relatively few effective treatment options. To date, most clinical research has not enrolled large numbers of older adults, despite this being the demographic predominantly affected by this illness. In this article, etiology and treatments for pancreatic adenocarcinoma are reviewed with a particular emphasis on studies that have examined matters relating to treating older adults; future directions for research are also explored.
Feasibility of New-generation Infrared Imaging Screening for Breast Cancer in Rural Communities
Authors: Gutierrez-Delgado Francisco , Vázquez-Luna José Guadalupe ,   Director, Center for the Study and Prevention of Cancer (CEPREC), Juchitan, and Professor of Oncology and Medicine, Medical Sciences PhD Program, National Autonomous University of Mexico,   Professor, Department of Physics and Mathematics, Autonomous University of Puebla
Published: October 2015

Breast cancer is a major public health problem worldwide. Important advances have improved survival, but early detection remains the main clinical challenge in reducing mortality. Currently, mammography is the ‘gold standard’ tool for breast cancer screening. However, the search for an early breast cancer detection method is the subject of extensive research. Although infrared imaging or breast thermography for early breast cancer detection has been evaluated since the late 1950s, the negative results reported in 1979 by the Breast Cancer Detection and Demonstration Project decreased interest in this imaging modality. Advances in infrared imaging and reduced equipment costs have, however, renewed interest in breast thermography. Breast cancer in developing countries requires new strategies to increase early detection and access to care. In this article, we highlight the principles and advances of infrared imaging technology and describe our experience with new-generation infrared imaging for early breast cancer detection in rural communities in southern Mexico.
Management of Cancer-related Cognitive Dysfunction—Conceptualization Challenges and Implications for Clinical Research and Practice
Authors: Jean-Pierre Pascal ,   Assistant Professor of Pediatrics, and Member, Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, and Adjunct Assistant Professor of Radiation Oncology, James P Wilmot Cancer Center, University of Rochester Medical Center
Published: October 2015

Cancer-related cognitive dysfunction (CRCD)—especially impairments in attention and memory—constitutes a significant problem for cancer patients and survivors. Incidence rates of CRCD range from 17 to 75%. Cognitive impairment experienced by cancer patients can be severe and long-lasting. Strategies to ameliorate this condition have been hindered by difficulties in understanding the precise etiology of CRCD and a lack of consensus on appropriate and reliable assessment approaches. This article provides an overview of the magnitude of the problem and discusses pathophysiology, current theories, clinical presentation, assessment concerns, and management of CRCD.
Multidrug Combinations for First-line Therapy of Advanced Non-small-cell Lung Cancer
Authors: Tran Ha N , Ramalingam Suresh S ,   Fellow, Hematology and Oncology,   Associate Professor, Chief of Thoracic Oncology, and Director of Medical Oncology, Winship Cancer Institute of Emory University
Published: October 2015

Lung cancer is a common disease with a high mortality rate. Non-small-cell lung cancer (NSCLC), which accounts for almost 85% of all cases of lung cancer, is often diagnosed at an advanced stage. Platinum-based two-drug combination regimens have become the standard of care and should be considered in patients with a good performance status (Eastern Cooperative Oncology Group performance status scale 0–1). The addition of a third chemotherapy agent is not recommended, since there is additional toxicity without a definite survival benefit. In recent years, histology has emerged as an important factor in treatment selection. In patients with non-squamous NSCLC, the cisplatin–pemetrexed regimen has demonstrated superiority over cisplatin–gemcitabine and has emerged as a preferred regimen for this subset of patients. The addition of targeted agents such as bevacizumab or cetuximab to platinum doublets has also demonstrated modest improvements in overall survival for firstline therapy of advanced NSCLC. The identification of patient-selection methods for the use of these agents remains a major challenge. Recently, the use of maintenance therapy has emerged as an option for patients who complete the recommended four to six cycles of chemotherapy. This article reviews the various first-line therapy options for advanced NSCLC.
Accelerated Partial Breast Irradiation and Hypofractionated Whole Breast Radiation
Authors: Rowe Bryan P , Moran Meena S ,   Resident,   Associate Professor, Department of Therapeutic Radiology, Yale University School of Medicine
Published: October 2015

Breast conservation therapy (BCT), consisting of local excision of the breast tumor to achieve negative margins followed by whole breast irradiation, is standard treatment for early-stage breast cancer. The conventional radiotherapy course treats the entire breast, typically followed by a boost to the tumor bed over six to seven weeks. While the efficacy and cosmetic outcomes of conventionally fractionated whole breast radiation are well-established, two strategies are being investigated to address the lengthy treatment time associated with adjuvant radiotherapy for early-stage breast cancer. Accelerated partial breast irradiation (APBI) involves treatment to the tumor bed plus a small margin, allowing completion of therapy in five days or less. A variety of techniques, each with unique advantages and disadvantages, is currently under investigation for delivering APBI. Hypofractionated whole breast radiation (hWBRT) involves treating the entire breast with larger daily doses of radiation over three to four weeks. This article reviews the principles behind APBI and hWBRT, the indications for each technique, and relevant data supporting their use.