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Valle J.W.,University of Manchester | Faivre S.,University Paris Diderot | Hubner R.A.,The Christie NHS Foundation Trust | Grande E.,Ramon y Cajal University Hospital | Raymond E.,University Paris Diderot
Cancer Treatment Reviews | Year: 2014

Pancreatic neuroendocrine tumors (pNETs) are infrequent malignancies which manifest in both functional (hormone-secreting) and more commonly non-functional (non-secreting) forms. The oral multitargeted tyrosine kinase inhibitor sunitinib and mammalian target of rapamycin (mTOR) inhibitor everolimus are approved as targeted therapies for patients with well-differentiated, non-resectable disease and evidence of disease progression. The recent approval of sunitinib for the management of advanced pNET is based on a continuous daily dosing (CDD) schedule that differs from the intermittent 4. weeks on/2. weeks off (4/2) schedule approved for sunitinib in advanced renal cell carcinoma (RCC) and imatinib-resistant gastrointestinal stromal tumor (GIST). Therefore, although clinicians may be familiar with therapy management approaches for sunitinib in advanced RCC and GIST, there is less available experience for the management of patients with a CDD schedule. Here, we discuss the similarities and differences in the treatment of pNET with sunitinib compared with advanced RCC and GIST. In particular, we focus on the occurrence and management of sunitinib-related toxicity in patients with pNET by drawing on experience in these other malignancies. We aim to provide a relevant and useful guide for clinicians treating patients with pNET covering the management of events such as fatigue, mucositis, hand-foot syndrome, and hypertension. © 2014 The Authors.

Levin B.R.,Emory University | Baquero F.,Ramon y Cajal University Hospital | Johnsen P.J.,University of Tromso
Current Opinion in Microbiology | Year: 2014

A simple epidemiological model is used as a framework to explore the potential efficacy of measures to control antibiotic resistance in community-based self-limiting human infections. The analysis of the properties of this model predict that resistance can be maintained at manageable levels if: first, the rates at which specific antibiotics are used declines with the frequency of resistance to these drugs; second, resistance rarely emerges during therapy; and third, external sources rarely contribute to the entry of resistant bacteria into the community. We discuss the feasibility and limitations of these measures to control the rates of antibiotic resistance and the potential of advances in diagnostic procedures to facilitate this endeavor. © 2014 Elsevier Ltd.

Noval S.,Hospital Universitario La Paz | Visa J.,University of Barcelona | Contreras I.,Ramon y Cajal University Hospital
Graefe's Archive for Clinical and Experimental Ophthalmology | Year: 2013

Background: Optic nerve head drusen (ONHD) are deposits due to abnormalities in axonal metabolism and degeneration. Studies so far have focused on adults. Our aim was to study the effect of ONHD on visual function as well as optic nerve head structure using optical coherence tomography (OCT) in children. Methods: Subjects younger than 18 years of age with ONHD and who had a reliable visual field defect in at least one eye due to ONHD were considered for inclusion. All subjects underwent an extensive ophthalmic examination including best-corrected visual acuity (BCVA), funduscopy, and SITA 24-2 standard automated perimetry. OCT scanning was performed using Cirrus-HD Model 4000. Retinal nerve fiber layer (RNFL) thickness data were compared with a group of age-matched healthy children. Results: Fifteen children were included, with a mean age of 13 years (range 7 to 17 years). BCVA was 1.0 in all eyes, except in a child with concomitant esotropia. ONHD were bilateral in 13 children. Among the 28 eyes with ONHD, 12 (43 %) were classified as type 1 (buried), eight (29 %) as type 2 (ringed) and eight (29 %) as type 3 (superficial). All children had a visual field defect in at least one eye, according to the inclusion criteria; however, two eyes (7 %) had no defect in spite of the presence of ONHD. Five eyes showed an isolated enlarged blind spot (18 %), 15 cases showed a nasal defect (54 %), and six eyes showed a constricted visual field (21 %). RNFL thickness was higher in type 1 and 2 ONHD than in the control group, although these differences were only significant for the average, superior, and inferior quadrant thicknesses in type 1 and the inferior quadrant in type 2. RNFL thickness was lower in type 3 ONHD than in the control group, although these differences were only significant for the average, superior, and nasal quadrant thicknesses. Conclusions: ONHD may lead to the development of visual field defects, even in children. In initial stages, ONHD produce an increase in RNFL thickness as measured with OCT. As drusen develop and become superficial, the RNFL thickness decreases. The temporal quadrant is often undamaged, probably reflecting the preservation of central visual acuity. © 2013 Springer-Verlag Berlin Heidelberg.

BACKGROUND: Patients with transitional cell carcinoma of the urothelial tract (TCCU) who fail initial platinum-based chemotherapy for advanced disease represent a challenge in daily clinical practice. Vinflunine is approved by the European Medicine Agency (EMA) but, up to now, limited experience has been reported outside clinical trials.METHODS: We assessed the efficacy and safety of vinflunine in an unselected group of 102 consecutive patients with metastatic TCCU.RESULTS: The median age was 67 years (range 45-83). Among the most common comorbidities that patients presented at baseline were hypertension (50.5%) and diabetes (20.7%).Distant metastases were present in retroperitoneal nodes (58%), lung (29.3%), and bone (20.2%). The ECOG 0, 1 and 2 performance status at the start of vinflunine were 31.3%, 60.6% and 8.1%, respectively. The most commonly reported adverse events of any grade were constipation 70.6% (5.9% grade 3-4), vomiting 49.1% (2% grade 3-4), neutropenia 48.1% (12.8% grade 3-4) and abdominal pain 34.3% (4.9% grade 3-4). A median of 4 cycles of vinflunine was administered per patient (range 1-18). Median progression free and overall survival for all patients (N = 102) were 3.9 months (2.3-5.5) and 10 months (7.3-12.8), respectively. Time to tumor progression was 4.3 months (2.6-5.9). Two patients (2%) achieved CR, 23 (22.5%) patients had PR, and 42 (41.2%) presented SD as best response. The clinical benefit rate with vinflunine was 65.7%.CONCLUSIONS: Our results show that the behavior of vinflunine in routine clinical practice resembles that of the pivotal phase III randomized study.

Pascual J.M.,University of Leon | Prieto R.,University of San Carlos | Carrasco R.,Ramon y Cajal University Hospital
Acta Neurochirurgica | Year: 2011

Purpose: This study investigates retrospectively the clinical, neuroradiological, pathological and surgical evidence verifying the infundibulo-tuberal topography for craniopharyngiomas (CPs). Infundibulo-tuberal CPs represent a surgical challenge due to their close anatomical relationships with the hypothalamus. An accurate definition of this topographical category is essential in order to prevent any undue injury to vital diencephalic centres. Methods: A systematic review of all scientific reports involving pathological, neuroradiological or surgical descriptions of either well-described individual cases or large series of CPs published in official journals and text books from 1892 to 2011 was carried out. A total of 1,232 documents providing pathological, surgical and/or neuroradiological evidence for the infundibulo-tuberal or hypothalamic location of CPs were finally analysed in this study. Findings: For a total of 3,571 CPs included in 67 pathological, surgical or neuroradiological series, 1,494 CPs (42%) were classified as infundibulo-tuberal lesions. This topography was proved in the autopsy of 122 non-operated cases. The crucial morphological finding characterizing the tubero-infundibular topography was the replacement of the third ventricle floor by a lesion with a predominant intraventricular growth. This type of CP usually presents a circumferential band of tight adherence to the third ventricle floor remnants, formed by a functionless layer of rective gliosis of a variable thickness. After complete surgical removal of an infundibulo-tuberal CP, a wide defect or breach at the floor of the third ventricle is regularly observed both in the surgical field and on postoperative magnetic resonance imaging studies. Conclusions: Infundibulo-tuberal CPs represent a major topographical category of lesions with a primary subpial development at the floor of the third ventricle. These lesions expand within the hypothalamus itself and subsequently occupy the third ventricle; consequently, they can be classified as not strictly intraventricular CPs. A tight attachment to the hypothalamus and remnants of the third ventricle floor is the pathological landmark of infundibulo-tuberal CPs. © 2011 Springer-Verlag.

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