bluuebunny/crossref_metadata_2025 huggingface dataset:
Myelodysplastic Syndromes – Unexpected Insights Stimulate the Biological Landscape
Authors: Raza Azra , Galili Naomi ,   Professor of Medicine, and Director, Myelodysplastic Syndrome Center, St Vincent’s Comprehensive Cancer Center,   Associate Professor of Medicine, New York Medical College, and Director, Bone Marrow Translational Laboratory, St Vincent’s Comprehensive Cancer Center
Published: October 2015

The biology of myelodysplastic syndromes (MDS) is characterised by excessive proliferation followed by intramedullary apoptosis of haematopoietic cells. Clonal expansion would at first seem to be incompatible with excessive apoptosis; however, a dual action of pro-inflammatory cytokines that stimulate the progenitor cells while inducing apoptosis in their maturing progeny could explain this paradox. Until recently, these were the only biological characteristics common to all subtypes of MDS. Novel insights emerging from the studies of micro RNAs (miRNAs), gene expression profiling and single nucleotide polymorphism (SNP) arrays are providing additional molecular and genetic features linking the heterogeneous phenotypes. Expression arrays have indicated that genes involved with ribosomal biogenesis and the translational processes controlled by the ribosomal proteins are deregulated in multiple MDS subtypes. Specifically, RPS14, which lies in the commonly deleted region (CDR) of patients with 5q- syndrome, was shown to be causative for that specific phenotype. Certain congenital anaemias also have abnormalities in ribosomal proteins, thus linking acquired and inherited diseases. In addition to excessive apoptosis and proliferation, deregulated ribosomal biogenesis appears to be another unifying mechanism between the syndromes of myelodysplasia. Finally, DNA microarray studies and SNP arrays are yielding novel data in terms of prediction of response to drugs and identification of patients at high risk of developing MDS. These biological insights, some quite unexpected, are opening the doors to entirely novel areas of research and will hopefully lead to better outcomes for patients through translational research.
Iron Overload, Oxidative Damage and Ineffective Erythropoiesis in Myelodysplastic Syndromes
Authors: Invernizzi Rosangela ,   Associate Professor of Internal Medicine, and Chief, Haematological Cytology Laboratory, University of Pavia
Published: October 2015

A high level of apoptosis may be responsible for the ineffective haematopoiesis in myelodysplastic syndromes (MDS). Recently, it has been demonstrated that the erythroid apoptosis of low-risk MDS is initiated at a very early stage in stem cells and is associated with mitochondrial dysfunction. However, the underlying pathogenetic mechanisms causing malfunctioning of mitochondria and initiation of the intrinsic apoptotic cascade are not completely clear. Recent studies suggest a close relationship between impaired iron metabolism and pathogenesis of myelodysplasia. In fact, iron overload, which is apparent in refractory anaemia with and without ring sideroblasts, may lead to the generation of intracellular free radicals, thereby causing oxidative damage and inducing apoptosis in haematopoietic progenitors. This review summarises current knowledge supporting the role of iron-related oxidative damage in the pathogenesis of MDS. The relationship between mitochondrial iron homeostasis impairment and ineffective erythropoiesis in refractory anaemia with ring sideroblasts as well as the various functions of the cytosolic and mitochondrial ferritins are also discussed.
Health Technology Assessment of Multiplex Reverse Transcriptase Polymerase Chain Reaction Screening for Translocations at Diagnosis in Acute Myeloid Leukaemia
Authors: Johnsen Hans E , Hoffmann Marianne H , Klausen Tobias W , Davidsen Ulla H , Bergmann Olav J , Boegsted Martin , Nyegaard Mette , Bukh Anne , Dybkaer Karen ,   Department of Haematology, Aalborg Hospital, Aarhus University Hospital,   Herlev Hospital, University of Copenhagen,   Herlev Hospital, University of Copenhagen,   Herlev Hospital, University of Copenhagen,   Herlev Hospital, University of Copenhagen,   Herlev Hospital, University of Copenhagen,   Department of Haematology, Aalborg Hospital, Aarhus University Hospital,   Department of Haematology, Aalborg Hospital, Aarhus University Hospital,   Department of Haematology, Aalborg Hospital, Aarhus University Hospital,   Department of Haematology, Aalborg Hospital, Aarhus University Hospital
Published: October 2015

It is predicted that gene diagnostics will become fundamental for future individualised treatment strategies in cancer patients following initial technological investigations and a step-by-step clinical validation. This report is a health technology assessment (HTA) of the use of a novel gene diagnostic assay in acute myeloid leukaemia (AML) with a focus on the technology, the patient, the organisation and economic aspects. In 202 patients with AML, a diagnostic bone marrow or a peripheral blood sample was available for gene analysis, identifying favourable risk translocations by a commercial (HemaVision®) multiplex reverse transcription polymerase chain reaction (RT-PCR) screening assay covering 28 fusion transcripts. The multiplex RT-PCR technology identified five fusion transcripts in five samples not identified by conventional cytogenetics and increased the number of patients identified as having a favourable prognosis from 16 to 21; one translocation identified by cytogenetics was not found by RT-PCR analysis. Using a prospective questionnaire analysis, a convincing 95% (19/20) patient acceptance was documented for the diagnostic genetic analyses and the outcomes. However, patient understanding requires individual time and dialogue, in accordance with patient rights and modern individualised treatment strategies. The implementation of this strategy may benefit from already existing research laboratories forming a homogenous organisation using standardised technologies, which will make Denmark a high-quality partner in international clinical trials of new therapeutic strategies. The average economic cost per patient analysed using this technique is €600, which represents a modest <1% increase in the total average cost of €75,000 for AML treatment. In conclusion, this HTA documented that the technology complements classic fluorescencein situhybridisation (FISH) and provides additional information that can be used in response evaluation via already existing laboratories, but not without an increase in expense for health authorities. However, the increase in cost is limited compared with the costs of therapy and new drugs.
Clinical Management of Relapsed/Refractory Acute Myeloid Leukaemia
Authors: Parikh Sameer A , Faderl Stefan ,   Fellow,   Associate Professor of Medicine, Department of Leukemia, University of Texas MD Anderson Cancer Center
Published: October 2015

Conventional chemotherapy for patients with relapsed/refractory acute myeloid leukaemia (AML) remains unsatisfactory, with median survival ranging from 18 weeks following first relapse to six weeks in those with a second or higher relapse. The only potentially curative therapy is stem cell transplantation. Duration of first complete remission (CR) is the best predictor of response to salvage therapy. Novel therapies directed against a number of molecular aberrations associated with AML are being developed, including anti-CD33 monoclonal antibodies, FMS-like tyrosine kinase (FLT3) inhibitors, nucleoside analogues, hypomethylating agents and histone deacetylatase inhibitors, among others. Clinical trials combining novel agents with conventional chemotherapy are of particular interest, and definition of dose, schedule and combination partners remains an area of intense research.
Deacetylase Inhibition in Haematological Malignancies – Advanced T-cell Lymphoma, Hodgkin’s Lymphoma, Multiple Myeloma, Acute Myelogenous Leukaemia and Myelodysplastic Syndrome
Authors: Ocio Enrique M , Maiso Patricia , Mateos María-Victoria ,   Consultant Physician, Haematology Department, University Hospital of Salamanca,   Researcher, Dana-Farber Cancer Institute, Harvard University,   Consultant Physician, Haematology Department, University Hospital of Salamanca
Published: October 2015

One of the groups of novel targeted drugs that has been most extensively studied in the last few years are histone deacetylase inhibitors (HDACis). These compounds inhibit the deacetylation induced by deacetylase (DACs) in both histone and non-histone proteins, resulting in an antitumour effect. The first HDACi to obtain approval by the US Food and Drug Administration (FDA) for an oncological indication was vorinostat for the treatment of cutaneous T-cell lymphoma (CTCL). Other HDACis have also shown activity in this disease. The activity of these agents in monotherapy in highly refractory Hodgkin’s lymphoma (HL) patients also shows clear therapeutic potential. Regarding acute myeloid leukaemia (AML), myelodysplastic syndrome (MDS) and multiple myeloma (MM), the antitumour activity in monotherapy, despite showing hints of activity, has been limited; however, based on pre-clinical studies, some combinations with other novel or well-established agents, such as anthracyclins or 5-azacytidine in the case of AML/MDS or with bortezomib or lenalidomide for MM, are ongoing, with promising signs of activity. Therefore, the use of these agents alone or in combination with other treatments seems to be an attractive approach for patients with haematological malignancies.
Philadelphia-negative Chronic Myeloproliferative Disorders in Children
Authors: Randi Maria Luigia , Putti Maria Caterina ,   Professor of Haematology and Internal Medicine, Department of Medical and Surgical Science,   Physician, Department of Paediatric Haematology-Oncology Clinic, Department of Paediatrics, Padua University Medical School
Published: October 2015

Philadelphia-negative chronic myeloproliferative disorders (Ph-MPDs) are clonal haematopoietic disorders typically found in medianadvanced age. The recently discovered acquiredJAK2V617F mutation and other somatic mutations inJAK2,TPO,MPLandEPO-Rin the myeloid cells of these patients are now considered specific biological markers, and their presence is considered a main diagnostic criterion of these diseases. Ph-MPD are extremely rare in children and need to be distinguished from other more common causes of thrombocytosis and erythrocytosis. Essential thrombocythaemia (ET) is the less rare Ph-MPD, while polycythaemia vera (PV) and primary myelofibrosis (PMF) are occasional findings in paediatrics. In this group of patients the incidence of haemorrhagic and thrombotic complications, as well as transformation into MF and acute leukaemia, seem to be rarer than in adults. Moreover, the biological markers found in adults with Ph-MPDs are not as common in paediatric cases, and familial forms are relatively frequent. Therefore, the tests used in adults are not exhaustive for most children. Because gene mutations are detectable in a minority of paediatric cases, new markers are needed to better understand such cases. Therapy is devoted to reducing symptoms, not improving collateral drug effects. New drugs targeting the JAK2 molecule are under development and open new possibilities in the treatment of these rare diseases.
Diagnosis and Treatment of Erythrocytosis
Authors: McMullin Mary Frances ,   Professor of Clinical Haematology, Queens University, Belfast
Published: October 2015

An erythrocytosis arises when the red cell mass is increased. This can be due to a primary intrinsic defect in the erythroid progenitor cells or secondary to erythropoietin production from some source. Primary and secondary causes can be congenital or acquired. Rare, primary congenital defects are due to mutations leading to truncation of the erythropoietin receptor. The main acquired, primary erythrocytosis is polycythaemia vera. Among the congenital secondary causes, a number of defects in the genes in the oxygen-sensing pathway have recently been described, which lead to a secondary erythrocytosis. An extensive list of acquired secondary causes needs to be considered. A number of patients do not have an identifiable cause of erythrocytosis and are therefore described as having idiopathic erythrocytosis. Investigation should commence with careful clinical evaluation. Determination of the erythropoietin level is then a first step to guide the further direction of investigation. In those with congenital defects, a number of serious thromboembolic events have been described, but there is little information available about outcomes in these individuals and, therefore, no evidence to guide management. In this group, consideration should be given to the use of venesection to attain an achievable haematocrit level, and also low-dose aspirin therapy.
Imatinib Blood Level Testing – Current Perspectives and Key Questions
Authors: Mahon François-Xavier , Molimard Mathieu , Foryciarz Kajetana , Davies Andrea , Fava Carmen , Friedecky David , Schleyer Eberhard , Schuld Peter , Guilhot François ,   Professor of Haematology and Medical Biology, University Hospital of Bordeaux,   Professor, Department of Pharmacology, University of Bordeaux,   Staff Member, Haematology Department, Jagiellonian University,   Member, Chronic Myeloid Leukaemia Research Group, Department of Haematology, University of Liverpool,   Research Fellow, University of Turin,   Member, Laboratory for Inherited Metabolic Disorders, Department of Clinical Biochemistry, University Hospital and Palacky University Olomouc,   Medical Director, Department II for Internal Medicine, Carl von Basedow Hospital, Saalkreis,   Medical Director of Haematology, Novartis Oncology Region Europe Business Unit,   Head, Department of Oncology Haematology and Cell Therapy, University Hospital Centre of Poitiers
Published: October 2015

Imatinib is the gold standard for the treatment of chronic myeloid leukaemia. Several recent studies have revealed a correlation between imatinib trough plasma levels and clinical response, suggesting that measurement of plasma levels can be a useful tool for optimising imatinib dose. However, a number of important questions on the use of imatinib blood level testing (BLT) remain unanswered. These questions were discussed at a European expert meeting held in Bordeaux, France, under the auspices of the European Treatment and Outcome Study (EUTOS) for chronic myeloid leukaemia. The key views were that: imatinib blood level measured between days seven and 29 of treatment could be a prognostic indicator and an important baseline for evaluating subsequent measurements; an imatinib trough plasma threshold for optimal response of 1,000ng/ml has been proposed but needs further validation; there is insufficient evidence to define any relationship between imatinib plasma levels and adverse events; and, although it is not yet possible to define and validate a comprehensive algorithm for the application of BLT in clinical practice, a working model has been developed. Pan-European collaboration, data pooling and initiation of a prospective clinical trial would be important steps in addressing current uncertainties.
Progress in the Front-line Treatment of Multiple Myeloma
Authors: Knop Stefan , Kortüm Klaus Martin , Einsele Hermann ,   Consultant,   Staff Physician,   Full Professor of Internal Medicine, and Director, Department of Internal Medicine II, Division of Haematology and Medical Oncology, University Hospital Würzburg
Published: October 2015

Multiple myeloma (MM) is a clonal plasma cell tumour that requires systemic treatment once disease-related symptoms arise. Symptomatic MM is defined by at least one of the following: hypercalcaemia, renal failure, anaemia and/or bone lesions. Several therapeutic milestones have been achieved during the last few decades, resulting in improved prognosis for affected subjects. The alkylator melphalan has been a backbone of MM treatment since its introduction in the 1960s. The compound is currently used at high doses followed by autologous stem cell transplantation (ASCT) in patients ≤65–70 years of age in conventional doses in conjunction with prednisone and either thalidomide (MPT) or the proteasome inhibitor bortezomib (VMP). Both regimens have proved superior to MP alone in randomised clinical trials. In patients eligible for ASCT, initial cytoreduction should be performed using one of the ‘novel’ compounds (thalidomide, bortezomib, lenalidomide) in combination with dexamethasone because of enhanced response both before and after ASCT compared with standard anthracycline/dexamethasone. However, it has not yet been determined which combination should best be used in a given patient. Whether up-front allogeneic transplantation may contribute to improved outcomes in younger patients depends on results from clinical trials that have been fully recruited, but longer follow-up is awaited in the near future.
The Treatment of Diffuse Large B-cell Lymphoma with Poor Prognosis in the Rituximab Era – State of the Art and Future Perspectives
Authors: Vitolo Umberto , Chiappella Annalisa , Frairia Chiara , Botto Barbara ,   Director,   Clinical Research Fellow,   Haematology Fellow,   Permanent Staff Member, Department of Haematology 2, San Giovanni Battista Hospital and University of Turin
Published: October 2015

Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin’s lymphoma. The International Prognostic Index, gene profiling and early positron-emission tomography (PET) evaluation are important prognostic factors, each with a different role in predicting outcome. The addition of rituximab to standard chemotherapy – cyclophosphamide, doxorubicine, vincristine and prednisone (CHOP) – improved the outcome in elderly newly diagnosed DLBCL patients and in young patients with favourable prognostic profiles. The best treatment of young poorprognosis patients affected by DLBCL is controversial. Several phase II trials have demonstrated that the addition of rituximab to dose-dense chemotherapy CHOP14 or the addition of rituximab to high-dose chemotherapy (HDC) with peripheral stem cell transplantation were feasible and effective. The question of whether rituximab–HDC may be more effective compared with rituximab–dose-dense chemotherapy is under investigation in randomised phase III trials by major international groups. Novel therapeutic options should be investigated to increase the outcome in poor-prognosis DLBCL patients, both as single agents and in combination with standard therapy. Radioimmunotherapy, immunomodulating agents (IMiDs), dacetuzumab (SGN-40), mammalian target of rapamycin (mTOR) inihibitors, proteasome inhibitors, histone deacetylase inhibitors and anti-angiogenetic agents (anti-vascular endothelial growth factor [VEGF]) are under evaluation in clinical trials. The results will provide new insights into the treatment of DLBCL following poor prognosis.
Increased Efficacy of Anaemia Treatment in Cancer
Authors: Clifford Ruth , Littlewood Tim J ,   Specialist Registrar,   Consultant Haematologist, Department of Haematology, Cancer and Haematology Centre, Churchill Hospital, Oxford Radcliffe Hospitals NHS Trust
Published: October 2015

Approximately 75% of patients receiving chemotherapy for cancer will become anaemic during the course of their treatment. Many of these patients will be symptomatic. Correction of the anaemia with erythropoiesis-stimulating agents (ESAs) improves the haemoglobin concentration in more than half of these patients. Several recent trials have suggested that the rate and speed of haemoglobin response can be improved if intravenous (IV) iron is given in combination with the ESA, and also that the IV iron preparations are safe.
The Cancer Stem Cell Concept in Multiple Myeloma – From Phenomenology to Characterisation
Authors: Fogd Kirsten , Hansen Steen Møller , Madsen Louise Hvilshøj , Kjeldsen Malene Krag , Johnsen Hans E ,   Post-doctral Researcher,   Research Assistant,   Research Laboratory Technician,   PhD Student,   Professor of Clinical Haematology, Department of Haematology, Aalborg Hospital, Aarhus University Hospital
Published: October 2015

Although there have been great developments in the treatment regimes offered to patients with multiple myeloma (MM), it is still an incurable disease. An emerging idea in MM research is the concept of the cancer stem cell, which has been identified in other cancer types in an attempt to explain incurability. The cancer stem cell is defined in the same manner as regular tissue stem cells. They are thought to be infrequent among the tumour cells, quiescent and able to maintain their population by self-renewal. Although ‘the cancer stem cell’ has not yet been identified, substantial evidence has been gathered over the past few years suggesting that a tumour-initiating cell population may be present in MM. Further characterisation of B-lineage subsets in bone marrow and blood, including memory B cells and plasmablasts, is necessary to support the concept that the cancer stem cell is one of the central players in the pathogenesis of this disease.
Partial Breast Irradiation as an Alternative to Whole Breast Radiation
Authors: Valachis Antonis , Mauri Davide ,   PhD Student, Department of Medical Oncology, University Hospital of Heraklion,   Head, Department of Medical Oncology, General Hospital of Lamia
Published: October 2015

Accelerated partial breast irradiation (APBI) is a novel method of post-operative radiotherapy that consists of irradiation of a limited volume of mammary gland immediately surrounding the tumour bed over a shorter time than whole breast irradiation. Several modalities are currently being explored as a means to deliver APBI, including multicatheter interstitial brachytherapy, the MammoSite breast brachytherapy catheter (Cytyc Corporation, Marlborough, MA), intraoperative radiation therapy and 3D conformal external-beam radiation therapy. To date, although still limited, randomised evidence is encouraging about the future role of APBI since it does not seem to jeopardise overall survival in patients with early breast cancer. Additional phase III studies are under way to determine the subgroups of patients who will really benefit from APBI.
Diagnosis of Lung Cancer — Improving Survival Rates
Authors: Athey Victoria L , Tod Angela M , Suckling Rupert , Rogers Trevor K ,   Clinical Research Fellow, Department of Respiratory Medicine, University of Sheffield,   Principal Research Fellow, Centre for Health and Social Care Research, Sheffield Hallam University,   Deputy Director of Public Health, NHS Doncaster,   Consultant Respiratory Physician and Director, Research and Development, Doncaster and Bassetlaw NHS Foundation Trust
Published: October 2015

Lung cancer is a major global health burden with high incidence rates but poor long-term survival. Currently, the majority of cases are diagnosed at an advanced stage when surgical resection is not feasible. Screening for lung cancer has been a major focus of research for the last 40 years. Despite this, there is still a lack of evidence to promote its use outside clinical trials. More recently, interest has focused on promoting earlier recognition of symptomatic disease among both the general public and primary care physicians in order to encourage more timely investigation and referral to secondary care. The hope is that this approach may increase the proportion of disease identified in the early stages, allowing more surgical resections and improved five-year survival rates. This article provides an overview of the current evidence base in terms of early diagnosis of lung cancer and provides some examples of innovations to promote this.
Colorectal Carcinoma in the Post-liver-transplant Setting — A Short Overview
Authors: Nicolaas Jerome Sint , Kuipers Ernst J , van Leerdam Monique E ,   PhD Researcher,   Professor of Medicine and Chair, Departments of Internal Medicine and Gastroenterology and Hepatology,   Gastroenterologist and Clinical Epidemiologist, Department of Gastroenterology and Hepatology, Erasmus MC University Medical Centre
Published: October 2015

Colorectal cancer (CRC) is a major health problem in the Western world. Certain high-risk groups are recommended for more vigilant CRC screening and shorter surveillance intervals. There is no consensus as to whether liver transplant (LT) recipients should be classified as a high-risk group for developing CRC during the post-transplant follow-up. LT recipients do have an increased risk for certainde novomalignancies including skin malignancy and post-transplant lymphoproliferative disorder (PTLD), but it remains controversial as to whether this also pertains to CRC. Several aspects should be taken into account when evaluating this aspect in post-LT patients. This article aims to provide the most updated evidence concerning CRC in the post-LT period. It focuses on defining high-risk groups for CRC after LT, and provides an overview of the incidence of CRC post-LT, the role for pre-LT screening colonoscopy and the results from post-LT surveillance.
Liver Resection of Colorectal Metastases in Elderly Patients
Authors: Bhangui Prashant , Adam Rene ,   Clinical and Research Fellow, Hepatobiliary Centre, Paul Brousse Hospital,   Professor of Surgery, Faculty of Medicine, Paris South University, and President, Medical Board and Head, Onco-surgical Unit, Hepatobiliary Centre, Paul Brousse Hospital
Published: October 2015

The ageing population, the specific epidemiology of colorectal cancer (CRC) and the high incidence of colorectal liver metastases (CRLM) have all led to a significant increase in elderly patients with CRLM seeking surgical management. Due to physiological and functional changes with advancing age (which may decrease the ability of the elderly to sustain aggressive treatment) and the lack of validated guidelines, surgeons still hesitate to plan surgical resection of CRLM in the elderly. Recently, a few studies have suggested that resection of CRLM in the elderly is feasible and yields good short- and long-term outcomes in the context of an intention-to-treat strategy. This article discusses the relevant literature and tries to put forth possible recommendations for the surgical management of elderly patients with CRLM. No chronological upper age limit should contraindicate curative treatment and well-selected elderly patients with advanced CRC can be offered a similar chance of long-term survival with the use of an optimal onco-surgical strategy.
Treatment Strategies in Metastatic Renal Cell Carcinoma
Authors: Ravaud Alain , Bernhard Jean Christophe , Gross-Goupil Marine ,   Professor and Head, Department of Medical Oncology,   Fellow in Urology, Department of Urology,   Medical Oncologist, Department of Oncology, University Hospital of Bordeaux
Published: October 2015

Metastatic renal cell carcinoma (mRCC) is associated with a poor clinical outcome. Until recently, treatment recommendations were limited to immunotherapy and nephrectomy; however, an increased understanding of the molecular biology of RCC has led to the advent of targeted therapies directed against vascular endothelial growth factor/receptor (VEGF/VEGFR) or the mammalian target of rapamycin (mTOR) pathways, both major mediators of tumour growth and progression. These targeted agents have significantly improved outcomes in patients with mRCC, revolutionising treatment. These treatments have overlaps and important distinctions in terms of clinical effects, toxicity and patient populations in which they have been investigated. Concerns in terms of the appropriate sequencing of these agents, their combined use and their role in the context of nephrectomy have emerged as clinically relevant and are being actively investigated.
Squamous Cell Vulval Carcinoma and Pregnancy — A Review
Authors: Palmer Julia , Vatish Manu , Tidy John ,   Lead, Colposcopy Services and Specialist Consultant, Gynaecological Cancer Surgery, Royal Hallamshire Services,   Senior Lecturer, Consultant and Clinical Director, Obstetrics and Gynaecology, University Hospitals Coventry and Warwickshire,   Consultant Gynaecologist, Colposcopist and Specialist, Gynaecological Cancer Surgery, Royal Hallamshire Services
Published: October 2015

Maternal vulval carcinoma and pregnancy following vulval cancer are rare. However, vulval carcinoma in younger women is increasing, thus we are progressively more likely to encounter patients with either vulval carcinoma in pregnancy, or pregnancy following treatment for vulval cancer. Given the paucity of available information we performed a literature review considering the strategies employed in the management of these women. A computerised search (MEDLINE®/embase®) was performed to identify all registered articles pertaining to squamous cell vulval carcinoma diagnosed or treated in pregnancy, and all cases of pregnancy following treatment for vulval cancer. In addition, cross-references of all selected articles were checked. Twenty-four reports were identified in the literature. In total, 21 cases of vulval carcinoma in pregnancy and 13 cases of pregnancy following vulval cancer were considered. Reports in the literature of vulval cancer associated with pregnancy span a time period of over 65 years making the production of definitive guidelines problematic as significant changes in the management of vulval cancer and changes in obstetrical and neonatal care need to be accounted for. Longer-term maternal and neonatal outcomes are also difficult to substantiate. Centralised data collection would be beneficial in these rare tumours, and in other malignant tumours diagnosed and treated during pregnancy.
Current First-line and Salvage Treatment Strategies in Patients with Advanced-stage Follicular Lymphoma
Authors: Heinzelmann Frank , Bamberg Michael , Weinmann Martin ,   Radiation Oncology Specialist,   Medical Director,   Vice Director and Leading Senior Physician, Department of Radiation Oncology, University of Tübingen
Published: October 2015

In patients with advanced-stage follicular lymphoma (FL) there are many treatment options available. Besides watchful waiting in asymptomatic patients, current first-line treatment strategies include rituximab ± single-agent chemotherapy, chemoimmunotherapy and radioimmunotherapy. In case of relapse, the use of chemoimmunotherapy, radioimmunotherapy and autologous haematopoietic stem cell transplantation (HSCT) results in enhanced response rates, progression-free survival (PFS) and overall survival (OS) compared with chemotherapy alone. However, long-term results are marred by high relapse rates and the risk of secondary malignancies after autologous HSCT. To date, in patients with relapsed/chemoresistant disease, myeloablative/reduced intensity conditioning protocols in combination with allogeneic HSCT presumably constitute the only curative approach but are associated with high treatment-related mortality. Although advances in supportive care have resulted in improved outcomes, reliable strategies for adequate patient selection are mandatory. In the palliative setting, low-dose involved-field irradiation constitutes an effective treatment option in order to control local symptoms with potential long-lasting response.
Magnetic-resonance-guided Focused Ultrasound Surgery in the Treatment of Oncology Patients — Fundamentals and Review of Early Clinical Applications
Authors: Valero Pedro , Gomez-Gonzalez Emilio , Sabino Araceli , Valero Maria , Suárez-Ramos Jerónimo ,   Director of Oncology, Hospital Infanta Luisa, Seville,   Director, Group of Interdisciplinary Physics, Department of Applied Physics III, School of Engineering, University of Seville,   Researcher and Medical Oncologist,   Researcher and Medical Oncologist,   Director of Radiology, Instituto Cartuja
Published: October 2015

Magnetic-resonance-guided focused ultrasound surgery (MRgFUS) is a novel non-invasive surgical procedure in the field of image-guided interventions. Thermal ablation is achieved using focused ultrasound beams controlled by magnetic resonance. Energy delivered to focal (sonication) spots allows for a very precise and controlled increase in temperature, resulting in coagulative necrosis of target tissue. 3D visualisation and temperature monitoring allow for realtime feedback and control. Post-treatment evaluation is performed in the same session. Since there is no dose limit, the procedure can be repeated as needed. An expanding number of applications are currently being developed in oncology. This article reviews the fundamentals and initial clinical data, including palliative treatment of pain in bone metastases, breast cancer, diseases of the central nervous system, prostate cancer, hepatocellular carcinoma and targeted drug delivery.
Video-endoscopic Inguinal Lymphadenectomy
Authors: Correa Walter F , Tobias-Machado Marcos ,   Fellow, Urological Oncology and Laparoscopy,   Head, Urological Oncology Section, Department of Urology, ABC Medical School and Brazilian Institute of Cancer Control
Published: October 2015

Penile carcinoma is a rare malignant disease with a significantly higher incidence in some areas of underdeveloped countries. Inguinal nodal involvement is found in 2040% of cases at diagnosis and nodal metastasis is an important predictive factor for survival. Although recent data demonstrated a survival benefit with immediate resection of clinically occult lymph-node metastases, surgical morbidity is still high. Videoendoscopic inguinal lymphadenectomy (VEIL) was described in the clinical arena six years ago to duplicate the open template, reducing morbidity without compromising oncological control. All technical variations described for open surgery were safe and feasible using the endoscopic approach. In terms of reproducibility, preliminary results of a worldwide survey identified that 11 centres were already performing VEIL. Reduced morbidity and good midterm oncological results are important arguments for growing acceptance of this new minimally invasive option to manage inguinal lymph nodes in high-risk penile cancer patients.
Men’s Health — Time to Change Our Approach
Authors: Meryn Siegfried ,   General Secretary, International Society of Mens Health, and Chairman, Department of Medical Education, Medical University of Vienna
Published: October 2015

Significant gender disparities exist in life expectancy (the average life expectancy of men is 5.07.2 years less than that of women) and major disease morbidity. There is an urgent need to understand the major issues related to mens health that contribute to these significant disparities. Men have a higher death rate from 14 of the 15 leading causes of death (all except Alzheimers disease). They have a nearly threefold higher rate of death from bladder cancer and twice as high a rate of death from kidney cancer than women. For all cancers except non-melanoma skin cancer, breast cancer and the sex-specific cancers, men also have a higher rate of incidence and death when considering all ages. The International Society of Mens Health (ISMH) believes that raising awareness of prostate health  prostate disease as well as testosterone and hypogonadism  will empower and motivate men to consult their physician. It will also be a promoter and catalyst for detecting many other existing or underlying conditions and comorbidities. The most important goals are to empower men to manage their own health and to talk about worries regarding their health.
Survivin-directed Anticancer Therapies – A Review of Pre-clinical Data and Early-phase Clinical Trials
Authors: Doolittle Helen , Morel Armand , Talbot Denis ,   Researcher, North West Thames Academic Foundation Programme, Hammersmith Hospital, Imperial College, London,   Clinical Research Assistant, Oxford Lung Cancer Group, Churchill Hospital, University of Oxford,   Consultant Medical Oncologist, and Reader, Oxford Cancer Centre, University of Oxford
Published: October 2015

Survivin, the smallest member of the inhibitor-of-apoptosis family, is a promising target for anticancer therapies. It plays key roles in apoptosis and the cell cycle, and has been shown to be upregulated in many cancer types while being minimally expressed in normal adult tissue. A number of survivin-directed anticancer therapies are currently in development, including transcriptional repressors, antisense oligonucleotides, hammerhead ribozymes, small interfering RNAs (siRNAs), dominant-negative mutants, small molecular inhibitors, cyclin-dependent kinase (CDK) inhibitors and immunotherapies. This article reviews the roles of survivin in mitosis and apoptosis, its regulation and the pre-clinical and clinical data on the emerging survivin-directed therapies.
The Neurogenic Component of Cutaneous Toxicities Induced by Chemotherapy – New Solutions
Authors: Chanez Jean-François ,   Head, Scientific Department, Evolife Laboratoires
Published: October 2015

Most chemotherapies cause cutaneous side effects. Docetaxel entered the therapeutic arsenal in the 1990s; while undeniably a sign of progress, it can also cause cutaneous side effects. Other chemotherapeutic drugs can induce secondary cutaneous effects, such as acneiform rash, hand–foot syndrome or mucositis. Hair loss, reversible or not, and nail disorders are also well-known deleterious effects encountered with several drugs used in oncology. Furthermore, the development of new targeted therapies is contributing to an increased frequency of these undesirable effects. New products that take into account the neurogenic phenomena implicated in the local inflammatory response to chemotherapy are required to offer new alternative care for various cutaneous and mucocutaneous side effects.
Fertility Preservation Options for Patients with Cancer
Authors: Hulvat Melissa C , Jeruss Jacqueline S ,   Breast-surgical Oncologist, and Co-Director, Bass Breast Center, Northwest Healthcare,   Assistant Professor, and Course Director, Surgical Ethics, Department of Surgery, Robert H Lurie Comprehensive Cancer Center and Lynn Sage Comprehensive Breast Center, Northwestern University Feinberg School of Medicine
Published: October 2015

Improving survival for many cancers that affect children and young adults, together with advances in fertility preservation, make a cancer-free future that includes a family a realistic possibility for patients who desire this option. Although it is difficult for many clinicians and patients to reconcile fears surrounding a life-threatening diagnosis with hope for long-term survival and even a future family, addressing this vital survivorship issue early in the course of diagnosis and treatment is imperative if the fullest range of fertility-preserving options is to be offered. Oncological therapies, including chemotherapy, radiation and surgery, pose various threats to fertility. Children, adolescents and young men and women with cancer have different options for maintaining their ability to have biological children. The current state of the science for fertility preservation in each of these demographic groups is discussed in this article. A multidisciplinary approach to the care of young cancer patients, a timely assessment of threats to fertility and opportunities for intervention provide young cancer patients with the best chance for a healthy future that includes biological offspring.
Targeted Therapy in Combination with Chemotherapy in Recurrent and/or Metastatic Head and Neck Cancer
Authors: Specenier Pol , Vermorken Jan B ,   Medical Oncologist,   Professor of Oncology, and Head, Department of Medical Oncology, Antwerp University Hospital
Published: October 2015

Two epidermal growth factor receptor (EGFR)-targeting strategies are used in recurrent and/or metastatic squamous cell cancer of the head and neck (SCCHN): monoclonal antibodies and small-molecule tyrosine kinase inhibitors. Thus far, the monoclonal antibody cetuximab has been studied in most detail. Based on the results of two randomised phase III trials, cetuximab in combination with platinum-based chemotherapy should be considered the new standard first-line regimen for patients with recurrent and/or metastatic disease for whom a platinum-based regimen regimen is considered the best treatment option. Other EGFR-directed monoclonal antibodies are under investigation. The role of EGFR tyrosine kinase inhibitors (TKIs) in SCCHN is less well established and early data on other targeted agents have also been disappointing thus far. Dual pathway inhibition may overcome resistance to single pathway inhibition.
Potential of a New Blood Test for Colorectal Cancer Screening –The Septin 9 Gene Biomarker
Authors: Weiss Gunter , Rösch Thomas ,   Vice President, Product Development, Epigenomics AG,   Director, Department of Interdisciplinary Endoscopy, University Hospital Hamburg-Eppendorf
Published: October 2015

Despite clear evidence for a better prognosis when detected early, in most countries colorectal cancer (CRC) has a low compliance rate in terms of screening. There are several methods of CRC screening ranging from a variety of stool tests, e.g. faecal occult blood test (FOBT), to endoscopy (sigmoidoscopy, colonoscopy). A blood test for CRC detection is a new alternative, at least for patients not willing to accept screening colonoscopy or to undergo FOBT. The septin 9 biomarker is a potential candidate to fulfil this purpose. It has been validated in several case–control studies, showing a strong association of plasma-containing methylated DNA within the septin 9 gene (mSEPT9) with the presence of CRC. If sensitive methylated-DNA-detection technologies are used formSEPT9 detection in blood plasma samples, sensitivities of about 50% for stage I, 70–80% for stages II and III and 90–100% for stage IV at a specificity of ≥90% have been reported in these studies. Screening experts assume that such a blood-based test will increase compliance to CRC screening. Further studies are ongoing or have just been completed, including a large prospective screening trial involving 8,000 individuals in the US and Germany. The main objectives of this clinical investigation, called Prospective Evaluation of Septin 9 Performance for Colorectal Cancer Screening (PRESEPT), are to determine the performance of the septin 9 test for identification of CRC in a screening population and to demonstrate the health economic benefit of septin 9 in this setting. Results are expected in April 2010. This article presents an update on current analytical and clinical data onmSEPT9.
BRAF V600E as a Therapeutic Target in Colorectal Cancer
Authors: Tie Jeanne , Desai Jayesh ,   Medical Oncology Research Fellow, Ludwig Colon Cancer Initiative Biomarker Laboratory, Ludwig Institute for Cancer Research, Melbourne,   Medical Oncologist, Department of Medical Oncology, Royal Melbourne Hospital and Peter MacCallum Cancer Institute, Melbourne
Published: October 2015

Colorectal cancer is a major cause of cancer death in developed countries. Increasing knowledge of the underlying signalling pathways and molecular defects involved in carcinogenesis has led to the development of a multitude of novel target-based therapeutics. The Ras/Raf/MEK/ERK mitogen-activated protein kinase (MAPK) signalling pathway plays a critical role in colorectal cancer progression. Therefore, targeting components of this pathway has been the subject of intense therapeutic effort. BRAF, a principal effector of Ras in this signalling cascade, was found to be mutated in a variety of cancers, including a small percentage of colorectal cancers. This article summarises the rationale for targeting BRAFV600Ein colorectal cancer, a potential strategy to enrich the colorectal cancer population for the BRAFV600Emutation, and the prognostic and predictive role of BRAFV600Emutations in metastatic colorectal cancer.
Immune Self-tuning in Renal Cell Carcinoma
Authors: Busse Antonia , Keilholz Ulrich ,   Post-doctoral Research Fellow, Ludwig Institute for Cancer Research,   Professor of Medicine, and Vice Chair, Department of Haematology, Oncology and Transfusion Medicine, University Hospital Benjamin Franklin, Free University Berlin
Published: October 2015

Although renal cell carcinoma (RCC) is an immunogenic tumour, and although there is evidence that in a small proportion of cases antitumour immune responses may mediate tumour regression or at least disease stabilisation, patients with progressive disease have no effective antitumour immune response. Besides preventing recognition of the tumour by immune effector cells, RCC escapes the immune system by induction of tolerance through manipulating the function and proliferation of immune effector cells. This tuning of the immune response can occur by active suppression of immune effector cells through inhibitory molecules expressed on the tumour surface and through various tumour-secreted soluble factors, or it can be mediated indirectly by induction of immunosuppressive cells. This review provides an overview of the most common mechanisms that mediate immune tolerance in RCC and discusses the therapeutic perspectives of immunoregulatory strategies in the era of targeted therapies.
Comparative Efficacy of Reduced or Standard Doses of Lenograstim for Peripheral Blood Stem Cell Mobilisation and Transplantation – A Review
Authors: öztürk Mustafa , Arpaci Fikret ,   Assistant Professor,   Chief, Department of Medical Oncology, Gulhane Military Medical Academy
Published: October 2015

Recombinant human granulocyte colony-stimulating factors (G-CSFs) are used for mobilisation of peripheral blood stem cells (PBSCs) and their subsequent infusion. Lenograstim is the glycosylated recombinant form of human G-CSF. Compared with filgrastim, lenograstim has a greater capacity to stimulate the colony growthin vitroof both purified CD34 and unmanipulated PBSCs. Due to the increased potency of lenograstim, several clinical studies were carried out to show the comparative efficacy of reduced or standard doses of lenograstim for PBSC mobilisation and transplantation.In vivoprospective randomised studies indicate that lenograstim is more potent than filgrastim. Shortcourse low-dose lenograstim was found to be as effective as the standard dose in reducing neutrophil engraftment time following high-dose chemotherapy and PBSC recovery. Lenograstim at a 25% lower dose does not negatively affect the number of CD34+ stem cells harvested or the engraftment results.
Anti-natural Killer Inhibitory Receptors in Elderly Patients with Acute Myeloid Leukaemia
Authors: Vey Norbert , Olive Daniel ,   Haematologist, and Head, Leukaemia and Myelodysplastic Syndrome, Department of Haematology,   Immunologist, and Head, Immunology Department, Paoli-Calmettes Institute, Marseille
Published: October 2015

Treatment with anti-killer-cell immunoglobulin-like receptor (KIR) monoclonal antibody (mAb) is a new approach aimed at harnessing the antileukaemic potential of natural killer (NK) cells for the treatment of acute myeloid leukaemia (AML). NK cell antitumour activity is regulated by a balance between activating and inhibitory receptors (KIR). 1-7F9/IPH2101 is a fully human immunoglobulin G4 (IgG4) mAb that binds to inhibitory KIR and blocks binding with its ligand (human leukocyte antigen C [HLA-C] molecule) on leukaemic cells.In vitro,and in a surrogatein vivomodel in mice, treatment with 1-7F9/IPH2101 was able to induce NK cell activation and cytotoxicity against leukaemic cells. Patients with AML often display abnormal NK cell function, while evidence of an impact of NK cell status on AML outcome has been reported in allogeneic transplantation. 1-7F9/IPH2101 is currently under clinical investigation in patients with AML. This article reviews the mechanisms of NK cell antileukaemic activity and its role and defects in AML. Currently available data on the pre-clinical and clinical development of 1-7F9/IPH2101 are presented, and the rationale for its future use as a single agent or in combination is discussed.