A phase Ib/II study of galunisertib in combination with nivolumab in solid tumors and non-small cell lung cancer.

BACKGROUND: In this phase Ib/II open-label study, tumor immune suppression was targeted in patients with advanced refractory solid tumors and patients with recurrent/refractory non-small cell lung cancer (NSCLC) using galunisertib with nivolumab. METHODS: Eligible patients were ≥ 18 years old, had an Eastern Cooperative Oncology Group performance status ≤ 1, and were treatment-naive for anti-programmed cell death-1, its ligand, or transforming growth factor ß receptor 1 kinase inhibitors. Phase Ib was an open-label, dose-escalation assessment of the safety and tolerability of galunisertib with nivolumab in patients with advanced refractory solid tumors. Phase II evaluated the safety of galunisertib with nivolumab in NSCLC patients who had received prior platinum-based treatment but were immuno-oncology agent-naive. RESULTS: This trial was conducted between October 2015 and August 2020. No dose-limiting toxicities were observed in phase I. In the phase II NSCLC cohort (n = 25), patients received 150 mg twice daily galunisertib (14 days on/14 days off dosing schedule for all phases) plus nivolumab at 3 mg/kg (intravenously every 2 weeks). In this phase, the most frequent treatment-related adverse events (AEs) were pruritus (n = 9, 36%), fatigue (n = 8, 32%), and decreased appetite (n = 7, 28%). No grade 4 or 5 treatment-related AEs were observed. Six (24%) patients had confirmed partial response (PR) and 4 (16%) had stable disease; 1 additional patient had confirmed PR after initial pseudo-progression. The median duration of response was 7.43 months (95% confidence interval [CI]: 3.75, NR). Among the 7 responders, including the delayed responder, 1 had high PD-L1 expression (≥ 50%). The median progression-free survival was 5.26 months (95% CI: 1.77, 9.20) and the median overall survival was 11.99 months (95% CI: 8.15, NR). Interferon gamma response genes were induced post-treatment and cell adhesion genes were repressed, although the association of these observations with tumor response and clinical outcomes was not statistically powered due to limited samples available. CONCLUSIONS: The study met its primary endpoint as galunisertib combined with nivolumab was well tolerated. Preliminary efficacy was observed in a subset of patients in the Phase 2 NSCLC cohort. TRIAL REGISTRATION: Trial registered with ClinicalTrials.gov (NCT02423343; 22.04.2015).

Cross-sectional associations of persistent organic pollutants measured in adipose tissue and metabolic syndrome in clinically diagnosed middle-aged adults.

INTRODUCTION: Although often overlooked in clinical settings, accumulation of persistent organic pollutants (POPs) in visceral adipose tissue (VAT) is thought to be a relevant risk factor for metabolic syndrome (MetS). METHODS: One hundred and seventeen patients undergoing non-oncological surgery were randomly recruited and classified as MetS + if presented 3 out of the 5 MetS components: waist circumference (WC), systolic and diastolic blood pressure (SBP and DBP, respectively), serum glucose, insulin, triglycerides (TG) and high-density lipoprotein (HDL) cholesterol levels, according International Diabetes Federation (IDF) criteria. Seventeen organochlorine pesticides (OCPs) and polychlorinated biphenyls (PCBs) were measured in adipose tissue samples. Linear, logistic and weighted quantile sum (WQS) regression models, adjusted for age and sex, were performed. RESULTS: One third of the participants were males (36.8%) with a median age of 44 years, showing clinical evidences of MetS (35.0%). Adjusted linear regression models showed that WC correlated positively with all OCP concentrations. Higher fasting serum glucose levels were related to higher HCB and γ-HCH concentrations. The remaining OCPs and PCBs were not associated with this MetS component. HCB was inversely associated with HDL cholesterol levels, while PCB-180 was positively associated. HCB and γ-HCH concentrations were also positively correlated with DBP and SBP levels. PCB-138 was also positively associated with SBP. Adjusted logistic models revealed that exposure to HCB and γ-HCH were associated with increased odds of MetS [ORs (95%CI) 1.53 (1.22-1.92) and 1.39 (1.10-1.76) respectively; p < 0.01]. No associations were observed for the remaining POPs. WQS models showed a positive and significant mixture effect of POPs on the odds of MetS (exp [beta] = 2.34; p < 0.001), with γ-HCH (52.9%), o,p'-DDT (26.9%) and HCB (19.7%) driving the association. CONCLUSIONS: Our findings support that POPs accumulated in VAT, specifically HCB and (gamma)-HCH, are associated with both isolated components and clinically diagnosed SMT.

Effect of aflibercept plus FOLFIRI and potential efficacy biomarkers in patients with metastatic colorectal cancer: the POLAF trial.

BACKGROUND: Aflibercept is an antiangiogenic drug against metastatic colorectal cancer (mCRC) combined with 5-fluorouracil/leucovorin/irinotecan (FOLFIRI); however, no antiangiogenic biomarker has yet been validated. We assessed aflibercept plus FOLFIRI, investigating the biomarker role of baseline vascular endothelial growth factor A (VEGF-A) and angiotensin-converting enzyme (ACE). METHODS: Phase II trial in oxaliplatin-treated mCRC patients who received aflibercept plus FOLFIRI. The reported 135 ng/mL ACE cut-off was used and ROC analysis was performed to assess the optimal VEGF-A cut-off for progression-free survival (PFS). Overall survival (OS), time to progression (TTP), time to treatment failure (TTF), overall response rate (ORR) and disease control rate (DCR) were also assessed. RESULTS: In total, 101 patients were followed for a median of 12 (6-17) months. The 1941 pg/mL VEGF-A was an optimal cut-off, with a longer median PFS when VEGF-A was <1941 versus ≥1941 pg/mL (9 versus 4 months). Patients with VEGF-A < 1941 pg/mL showed longer median OS (19 versus 8 months), TTP (9 versus 4 months) and TTF (8 versus 4 months), along with higher ORR (26% versus 9%) and DCR (81% versus 55%). No differences were identified according to ACE levels. CONCLUSIONS: This study supports aflibercept plus FOLFIRI benefits, suggesting VEGF-A as a potential biomarker to predict better outcomes.

Effects of Padel Competition on Brain Health-Related Myokines.

Padel is becoming one of the most widespread racket sports that may have potential health benefits. Considering that several myokines mediate the cross-talk between skeletal muscles and the brain, exerting positive effects on brain health status, this study was designed to evaluate the responses of brain-derived neurotrophic factor (BDNF), leukemia inhibitory factor (LIF), and irisin (IR) to padel competition in trained players and to determine whether these responses were sex-dependent. Twenty-four trained padel players (14 women and 10 men with a mean age of 27.8 ± 6.3 years) participated voluntarily in this study. Circulating levels of BDNF, LIF, and IR were assessed before and after simulated padel competition (real playing time, 27.8 ± 8.49 min; relative intensity, 75.2 ± 7.9% maximum heart rate). Except for BDNF responses observed in female players (increasing from 1531.12 ± 269.09 to 1768.56 ± 410.75 ng/mL), no significant changes in LIF and IR concentrations were reported after padel competition. In addition, no sex-related differences were found. Moreover, significant associations between IR and BDNF were established at both pre- and post-competition. Our results suggest that while competitive padel practice stimulates BDNF response in female players, padel competition failed to boost the release of LIF and IR. Future studies are needed to further explore the role of these exercise-induced myokines in the regulation of brain functions and to identify the field sports that can contribute to myokine-mediated muscle-brain crosstalk.

Virtual Reality Treatment for Public Speaking Anxiety in Students. Advancements and Results in Personalized Medicine.

Public speaking anxiety (PSA) is a common phobia in the student population. Traditionally, exposure therapy has been used as a treatment. However, the use of virtual reality (VR) is increasingly common to treat PSA. The purpose of this paper was to analyze the published scientific literature on VR as a treatment for PSA in students. The articles indexed in two databases (Web of Science and Scopus) were analyzed, with a time period from the beginning of the first publications until 2019 included. The systematic literature review was based on fixed inclusion and exclusion criteria. A total of 13 studies were identified which included 481 students. The results collected indicate that the duration of treatments to have positive effects was at least one week, where the number of sessions was between one and twelve. Furthermore, most VR treatments reported positive effects. Finally, this study showed evidence that VR treatment for PSA is effective while being less invasive than in vivo exposure.

Análisis cientimétrico de las publicaciones indexadas en journal citation reports sobre educación física / Análise cientométrica de publicações indexadas no journal citation reports sobre educação física / Scientometric analysis of publications indexed in journal citation reports on physical education

En los últimos años, la Educación Física se ha consolidado como una disciplina de estudio que acapara gran interés. Como consecuencia, la producción científica ha ido en aumento, reflejándose en la cantidad de artículos que se publican sobre el tema. El objetivo de este trabajo ha sido analizar la producción científica sobre Educación Física, indexada en Web of Science, desde sus inicios hasta el año 2017. Para ello, se ha realizado un estudio bibliométrico, recogiendo los indicadores de producción, dispersión e impacto de la producción científica en la Educación Física. Entre los resultados, se constata que la literatura se encuentra en una etapa de crecimiento exponencial. Además, desde los inicios de la producción científica, en 1902, sobre este tópico se han configurado determinadas revistas, instituciones, países y autores como referentes en la temática. Finalmente, el estudio ofrece una visión general del avance de las publicaciones de impacto sobre Educación Física

Nos últimos anos, a Educação Física se estabeleceu como um campo de estudo de grande interesse. Como consequência, a produção científica tem vindo a aumentar, o que se reflete na quantidade de artigos publicados sobre o assunto. O objetivo deste trabalho foi analisar a produção científica em Educação Física, indexada em Web of Science, desde o seu início até 2017. Para isso, foi realizado um estudo bibliométrico, reunindo os indicadores de produção, dispersão e impacto da produção científica na Educação Física. Dentre os resultados, observa-se que a literatura está em fase de crescimento exponencial. Além disso, desde o início da produção científica sobre esse tema, em 1902, alguns periódicos, instituições, países e autores foram configurados como referências no tema. Finalmente, o estudo fornece uma visão geral do progresso das publicações de impacto sobre Educação Física

In recent years, Physical Education has established itself as a field of study of great interest. Consequently, scientific production has been on the rise, reflected in the number of publications on the topic. This article analyzed scientific production on Physical Education indexed in Web of Science, from its beginnings until 2017. For this, a bibliometric study collected the indicators of production, dispersion and impact of the scientific production on Physical Education. Among the results, it found that the literature is in a stage of exponential growth. Furthermore, since scientific production on the topic began in 1902, certain journals, institutions, countries and authors have been established as benchmarks on the topic. Finally, the study reflects a general overview on the progress of impact publications on Physical Education

Alfabetización digital del profesorado de ciencias ambientales: un análisis de su competencia tecnológica / Digital literacy of environmental science teachers: an analysis of their technological competence

Introducción. En la actualidad el uso de los recursos tecnológicos en la educación es una práctica habitual e incluso de obligado cumplimiento. En la educación secundaria española la competencia digital es una de las habilidades clave que tienen que desarrollar los estudiantes. Este hecho se incrementa si tenemos en consideración que en el ámbito de las Ciencias Ambientales es primordial el uso sostenible de las TIC como factor para reducir el impacto medioambiental. Objetivo. Este trabajo tiene por objetivo analizar la competencia digital con base en el área de información y alfabetización informacional de los docentes de Ciencias Ambientales. Metodología. El estudio se centró en la provincia de Granada (España), contando con una muestra final de 106 profesores. La metodología empleada ha sido cuantitativa, utilizando como instrumento de recogida de datos el cuestionario. Resultados. Entre los resultados, se resalta el nivel satisfactorio en las diferentes subescalas competenciales del área de competencia digital analizada, estableciendo que el profesorado presenta un grado adecuado de formación tecnológica. Además, el modelo de ecuaciones estructurales verifica la correlación positiva entre las subescalas. Conclusión. Finalmente, el estudio sobre la competencia digital docente del profesorado de Ciencias Ambientales muestra una panorámica optimista en el desarrollo de competencias digitales en los estudiantes.

Introduction: Currently, the use of technological resources in education is a common and even mandatory practice. Digital competence is one of the key skills students have to develop in secondary education in Spain. Bearing in mind that in the field of Environmental Sciences the sustainable use of ICTs is essential as a factor in reducing environmental impact, this fact increases. Objective: This work aims to analyze digital competence based on the area of information and informational literacy of Environmental Science teachers. Methodology: This study focused on the province of Granada (Spain) with a final sample of 106 teachers. The methodology used was quantitative, using the questionnaire as a data collection instrument. Results: The satisfactory level in the different competence subscales of the area of digital competence analyzed is highlighted among the results, establishing that the teaching staff presents an adequate degree of technological training. In addition, the structural equation model verifies the positive correlation between the subscales. Conclusion: Finally, the study on the digital teaching competence of Environmental Science teachers shows an optimistic view on the development of digital competences in students.

Prognostic factors for survival with nab-paclitaxel plus gemcitabine in metastatic pancreatic cancer in real-life practice: the ANICE-PaC study.

BACKGROUND: Treatment with nab-paclitaxel plus gemcitabine increases survival in patients with metastatic pancreatic cancer. However, the assessment of treatment efficacy and safety in non-selected patients in a real-life setting may provide useful information to support decision-making processes in routine practice. METHODS: Retrospective, multicenter study including patients with metastatic pancreatic cancer, who started first-line treatment with nab-paclitaxel plus gemcitabine between December 2013 and June 2015 according to routine clinical practice. In addition to describing the treatment pattern, overall survival (OS) and progression-free survival (PFS) were assessed for the total sample and the exploratory subgroups based on the treatment and patients' clinical characteristics. RESULTS: All 210 eligible patients had a median age of 65.0 years (range 37-81). Metastatic pancreatic adenocarcinoma was recurrent in 46 (21.9%) patients and de novo in 164 (78.1%); 38 (18%) patients had a biliary stent. At baseline, 33 (18.1%) patients had an ECOG performance status ≥2. Patients received a median of four cycles of treatment (range 1-21), with a median duration of 3.5 months; 137 (65.2%) patients had a dose reduction of nab-paclitaxel and/or gemcitabine during treatment, and 33 (17.2%) discontinued treatment due to toxicity. Relative dose intensity (RDI) for nab-paclitaxel, gemcitabine, and the combined treatment was 66.7%. Median OS was 7.2 months (95% CI 6.0-8.5), and median PFS was 5.0 months (95% CI 4.3-5.9); 50 patients achieved either a partial or complete response (ORR 24.6%). OS was influenced by baseline ECOG PS, NLR and CA 19.9, but not by age ≥ 70 years and/or the presence of hepatobiliary stent or RDI < 85%. All included variables, computed as dichotomous, showed a significant contribution to the Cox regression model to build a nomogram for predicting survival in these patients: baseline ECOG 0-1 vs. 2-3 (p = 0.030), baseline NLR > 3 vs. ≤ 3 (p = 0.043), and baseline CA 19.9 > 37 U/mL vs. ≤37 U/mL (p = 0.004). CONCLUSIONS: Nab-Paclitaxel plus gemcitabine remain effective in a real-life setting, despite the high burden of dose reductions and poorer performance of these patients. A nomogram to predict survival using baseline ECOG performance status, NLR and CA 19.9 is proposed.

Estudio bibliométrico sobre la realidad virtual aplicada a la neurorrehabilitación y su influencia en la literatura científica / Bibliometric study about virtual reality applied to neurorehabilitation and its presence in scientific literature

Desde los años 90 la realidad virtual se ha aplicado en el ámbito de la salud para tratar fobias y trastornos mentales. Actualmente se utiliza para la neurorrehabilitación, ya que es capaz de engañar al cerebro y extrapolar al usuario a un mundo virtual. Dado el interés creciente por la temática, este trabajo tiene como objetivo analizar la producción científica en la Web of Science y Scopus sobre la realidad virtual aplicada a la neurorrehabilitación durante los últimos 10 años. Para esto, se ha empleado una metodología propia de los estudios bibliométricos a partir del establecimiento de una serie de palabras clave comprobadas en bases de datos y utilizadas por distintos autores en sus publicaciones. Se analizaron 8 variables siguiendo la línea de estudios previos: número total de documentos, producción por años, tipología de los archivos, títulos de las fuentes, instituciones, países, autores y artículos más citados. Entre los resultados se destaca el creciente interés de la temática a partir del año 2013 y el auge de la producción en el año 2016, así como la implicación de las principales potencias mundiales en la investigación y publicación sobre la realidad virtual para la rehabilitación. El análisis de los metadatos muestra un panorama incipiente en las publicaciones sobre la realidad virtual en el ámbito de la salud, donde Estados Unidos se destaca como el país con mayor producción científica(AU)

Ever since the 1990s virtual reality has been applied in healthcare to treat phobias and mental disorders, and is currently used for neurorehabilitation, as it is able to deceive the brain and extrapolate the user to a virtual world. Given the growing interest in the topic, this study aims to analyze the high-impact scientific production about virtual reality applied to neurorehabilitation included in the Web of Science and Scopus in the last 10 years. To achieve this end, a bibliometric methodology was used based on a number of keywords checked in databases and used by different authors in their publications. Eight variables were analyzed, in line with previous studies: total number of documents, production per year, document type, source title, affiliation, countries, authors and most cited articles. Among the results is the growing interest in the topic as of the year 2013 and the boom in production in 2016, as well as the involvement of the main world powers in research and publication about the use of virtual reality for rehabilitation. Finally, analysis of the metadata shows an incipient panorama in publications about virtual reality in healthcare, with the United States as the country with the greatest scientific production(AU)

Análisis organizativo de las clases de inclusión escolar en Francia / Organizational analysis of school inclusion classes in France

El objetivo de esta investigación se centra en la percepción que poseen los profesores sobre las Clases de Inclusión Escolar (CLIS) de Centros Públicos de Educación “Élémentaire” de la Loire (Francia) en relación con distintos aspectos organizativos. Contamos con una muestra de 40 profesores a quienes se les pasó el instrumento, un cuestionario ad hoc. Seguimos un diseño metodológico de carácter no experimental; concretamente, un diseño de encuesta transversal. Los resultados nos han acercado al contexto real de las CLIS obteniendo datos significativos sobre su tipología, el número de alumnos y alumnas escolarizados, el tiempo dedicado por los profesores y las profesoras a la planificación e implementación, y el grado de adecuación de las relaciones interpersonales de los individuos docentes respecto al resto de miembros implicados en el proceso de enseñanza-aprendizaje del alumnado de las CLIS...

Screening of hormone-like activities in bottled waters available in Southern Spain using receptor-specific bioassays.

Bottled water consumption is a putative source of human exposure to endocrine-disrupting chemicals (EDCs). Research has been conducted on the presence of chemicals with estrogen-like activity in bottled waters and on their estrogenicity, but few data are available on the presence of hormonal activities associated with other nuclear receptors (NRs). The aim of this study was to determine the presence of endocrine activities dependent on the activation of human estrogen receptor alpha (hERa) and/or androgen receptor (hAR) in water in glass or plastic bottles sold to consumers in Southern Spain. Hormone-like activities were evaluated in 29 bottled waters using receptor-specific bioassays based on reporter gene expression in PALM cells [(anti-)androgenicity] and cell proliferation assessment in MCF-7 cells [(anti-)estrogenicity] after optimized solid phase extraction (SPE). All of the water samples analyzed showed hormonal activity. This was estrogenic in 79.3% and anti-estrogenic in 37.9% of samples and was androgenic in 27.5% and anti-androgenic in 41.3%, with mean concentrations per liter of 0.113pM 17ß-estradiol (E2) equivalent units (E2Eq), 11.01pM anti-estrogen (ICI 182780) equivalent units (ICI 182780Eq), 0.33pM methyltrienolone (R1881) equivalent units (R1881Eq), and 0.18nM procymidone equivalent units (ProcEq). Bottled water consumption contributes to EDC exposure. Hormone-like activities observed in waters from both plastic and glass bottles suggest that plastic packaging is not the sole source of contamination and that the source of the water and bottling process may play a role, among other factors. Further research is warranted on the cumulative effects of long-term exposure to low doses of EDCs.

Assessment of estrogenic and anti-androgenic activities of the mycotoxin zearalenone and its metabolites using in vitro receptor-specific bioassays.

Zearalenone (ZEN) is a well-known mycotoxin present in numerous agricultural products. Humans and animals are therefore at a risk of exposure to zearalenone through consumption of contaminated food. After intake, ZEN is reduced to α- and ß-zearalenol (α-ZEL and ß-ZEL), zearalanone (ZAN), and α- and ß-zearalanol (α-ZAL and ß-ZAL). Although their estrogenicity has been well characterized, much less is known about their interaction with other nuclear receptors. This study was undertaken to investigate interactions of ZEN and its five metabolites, with the human androgen receptor (hAR) and estrogen receptor alpha (hERα). Their ability to induce hAR-mediated reporter gene expression was examined in androgen-sensitive PALM cells, whereas the effects on hERα function were assessed in MCF-7 cells using the E-Screen bioassay. We confirm that ZEN and its metabolites are full agonists for hERα and demonstrate that all six compounds tested possess hAR-mediated antagonistic activity in PALM cells, in which ZAN, α-ZAL, and ß-ZAL were the most effective hAR antagonists. Overall, the observed estrogenic and anti-androgenic potencies of ZEN and its metabolites suggest that these compounds may interfere with the endocrine system by various modes of action and that further investigation is warranted into their role as endocrine disrupters in animals and humans.

Toxicity Associated with Capecitabine in Patients Suffering from Dihydropyrimidine Dehydrogenase Deficiency.

Dihydropyrimidine dehydrogenase (DPD) is a metabolic enzyme that is crucial in 5-fluorouracil (5-FU) degradation. A deficiency in it is associated with the occurrence of adverse events following fluoropyrimidine-based therapies. We describe a case of toxicity grade 5 after the administration of capecitabine and oxaliplatin in a patient with stage III colorectal cancer and DPD congenital deficiency, which was identified later. Several polymorphisms have been associated with the global toxicity of 5-FU; however, genetic tests are low in sensitivity and therefore they cannot as yet be used as prescreening techniques in clinical practice.

Segmental heterogeneity in Bcl-2, Bcl-xL and Bax expression in rat tubular epithelium after ischemia-reperfusion.

AIMS: Studies in rats with bilateral clamping of renal arteries showed transient Bcl-2, Bcl-xL and Bax expression in renal tubular epithelium following ischemia-reperfusion. However, current data on the preferential localization of specific mRNAs or proteins are limited because gene expression was not analysed at segmental level. This study analyses the mRNA expression of Bcl-2, Bcl-xL and Bax in four segments of proximal and distal tubules localized in the renal cortex and outer medulla in rat kidneys with bilateral renal clamping for 30 min and seven reperfusion times versus control animals without clamp. METHODS: Proximal convoluted tubule (PCT), distal convoluted tubule (DCT), proximal straight tubule (PST) and medullary thick ascending limb (MTAL) were obtained by manual microdissection. RT-PCR was used to analyse mRNA expression at segmental level. RESULTS: Proximal convoluted tubule and MTAL showed early, persistent and balanced up-regulation of Bcl-2, Bcl-xL and Bax, while PST and DCT revealed only Bcl-2 and Bcl-xL, when only Bax was detected in PST. DCT expressed Bcl-xL initially, and persistent Bcl-2 later. CONCLUSION: These patterns suggest a heterogeneous apoptosis regulatory response in rat renal tubules after ischemia-reperfusion, independently of cortical or medullary location. This heterogeneity of the expression patterns of Bcl-2 genes could explain the different susceptibility to undergo apoptosis, the different threshold to ischemic damage and the different adaptive capacity to injury among these tubular segments.

Gemcitabine and vinorelbine followed by weekly docetaxel in patients with advanced non-small-cell lung cancer: a phase II trial of sequential chemotherapy.

UNLABELLED: Objective. We conducted this phase II trial to evaluate the efficacy and toxicity of the sequential nonplatinum combination chemotherapy consisting of gemcitabine (GEM) and vinorelbine (VNR) followed by weekly docetaxel (DOC) in patients with advanced non-small-cell lung cancer (NSCLC). Patients and methods. ELIGIBILITY CRITERIA: stage IV NSCLC, Performance status =/< 2, adequate renal, hepatic and bone marrow function. Treatment consisted on: VNR 25 mg/m(2) plus gemcitabine 1000 mg/m(2), on days 1 and 8 of each 21-day cycle, followed by docetaxel 36 mg/m(2) weekly until progression or unacceptable toxicity. Results. 21 stage IV patients were enrolled. All patients are evaluable for treatment response and toxicity profile. The mean age of the patients was 63 years (range: 51 to 72) with 18 (86%) males and 3 (14%) females. Histology types were: adenocarcinoma in 8 patients (38%), large cell carcinoma in 1 patients (5%) and squamous cell carcinoma in 12 patients (57%). The majority of the patients had and ECOG PS of 1. Eight patients (38%) did not complete six cycles of gemcitabine-navelbine. The median number of cycles of gemcitabine-navelbine was 4 (range 2-6) Of the 13 patients (61%) who completed six cycles of gemcitabine-navelbine, all of them went on to receive weekly docetaxel and received at least 3 cycles, with a median number of 8 cycles (range 3- 16). The overall response rate was 33%. Respect survival, the minimum follow-up was 6 months (range, 6-25 months). The median survival time (MST) was 7.9 months, and the 1-year survival was 30%, and the median progression-free survival was 4.7 months. Toxicity was mild, well tolerated and mostly hematologic. In the GEM/VNR cycle, grade 3/4 neutropenia occurred in 14%, two patients with febrile neutropenia. Grade 3 anaemia in 1 patients (5%) and grade 3 thrombocytopenia in 1 patient (5%). Nonhematologic toxicity was also mild: 1 patient with Grade 3 skin toxicity with docetaxel, 1 patient with grade 3 infection, 2 patients with grade 3 astenia and 1 patient with a mild allergic reaction postchemotherapy treatment with docetaxel. Conclusion. The sequential triplet nonplatinum chemotherapy consisted of GEM/VNR followed by weekly DOC is active and can be administered safely in advanced NSCLC. Our results are similar with other sequential regimens and did not represent a significant improvement in the treatment of this disease.

Solitary metastasis in a nasal fossa as the first manifestation of a renal carcinoma.

Renal cell carcinoma is an uncommon tumor in adults. Metastasis in the nasal fossa is rare, and can become apparent as a result of repeated epistaxis. We report a patient with renal cell carcinoma presenting with epistaxis secondary to a metastasis in the right nasal fossa. The primary tumor was treated with nephrectomy and the nasal fossa metastasis was treated successfully with embolization, chemoimmunotherapy, surgery, and radiotherapy. The presence of repeated epistaxis may very occasionally be the first symptom of renal cell carcinoma, and systemic treatment combined with local treatment may enable adequate control of the disease.

Secondary signet-ring cell tumour of the prostate derived from a primary gastric malignancy.

Primary signet-ring cell carcinoma of the prostate is infrequent and even more so as secondary spread of this pathologic sub-type to the prostate. We describe the sixth reported case with a diagnosis of a secondary signet-ring cell tumour of the prostate secondary to a gastric cancer. Five years post-gastrectomy to resect signet-ring cell carcinoma, we detected a secondary intra-prostatic spread with urinary tract obstruction. The physical appearance of the tumour cells was similar to that of the previously-resected signet-cell carcinoma of the stomach. There were no metastases in other sites and the patient was treated with radiotherapy. When confronted with intra-prostatic signet-ring cell adenocarcinoma it is necessary to distinguish between primary and secondary aetiology since this would reflect in the choice of treatment and prognosis.