Corticosterone implants produce stress-hyporesponsive birds.

In birds, the use of corticosterone (Cort) implants is a frequent tool aimed at simulating systemic elevations of this hormone and studying effects on biological traits (e.g. physiology, morphology, behavior). This manipulation may alter adrenocortical function, potentially changing both baseline (CortBAS) and stress-induced (CortSTRESS) plasma Cort levels. However, implant effects on the latter trait are rarely measured, disregarding downstream consequences of potentially altered stress responses. Here, we analyzed the effects of Cort implants on both CortBAS and CortSTRESS in nestling and adult European white storks, Ciconia ciconia In addition, we performed a review of 50 studies using Cort implants in birds during the last two decades to contextualize stork results, assess researchers' patterns of use and infer current study biases. High and low doses of Cort implants resulted in a decrease of both CortBAS (31-71% below controls) and CortSTRESS (63-79% below controls) in storks. Our literature review revealed that CortBAS generally increases (72% of experiments) whereas CortSTRESS decreases (78% of experiments) following implant treatment in birds. Our results challenge and expand the prevailing assumption that Cort implants increase circulating CortBAS levels because: (i) CortBAS levels show a quadratic association with implant dose across bird species, and decreased levels may occur at both high and low implant doses, and (ii) Cort implants also decrease CortSTRESS levels, thus producing stress-hyporesponsive phenotypes. It is time to work towards a better understanding of the effects of Cort implants on adrenocortical function, before addressing downstream links to variation in other biological traits.

Lifetime variation in feather corticosterone levels in a long-lived raptor.

In long-lived animals, the challenges that threaten individual homeostasis, and the way they are dealt with, are expected to vary in an age-related manner, encompassing the progressive selection of superior phenotypes and the acquisition and improvement of key skills (e.g. foraging, breeding and fighting abilities). Since exposure to homeostatic challenges typically elevates circulating glucocorticoid (GC) levels in vertebrates (modulating the behavioural and physiological responses that mediate allostasis), we may expect concomitant age-related changes in these hormones. Here, we investigated whether the level of corticosterone (the main avian GC) deposited in feathers during regular moult reflected the expected lifelong progression of energetic challenges in a long-lived raptor, the black kite (Milvus migrans). Feather corticosterone values were highest in the youngest birds, gradually declined to reach minimum levels in prime age, 7- to 11-year-old birds, and then increased again slightly among the oldest, senescent birds (≥12 years old). This pattern mirrored the age-related changes in reproductive success and survival rates previously reported for this population, suggesting that feather corticosterone levels captured the most vulnerable and challenging periods experienced by these birds as they proceeded through life. Moreover, feather corticosterone levels were negatively related to body size, suggesting that larger birds either experienced fewer homeostatic challenges, or were better able to cope with them. Feather corticosterone measures thus provided a valuable snapshot of how allostatic loads vary along the life of individuals, supporting the idea of a tight, long-term link between cumulative physiological responses to ecological challenges and demographic performance.

Response to treatment and interval to surgery after preoperative short-course radiotherapy in rectal cancer. / Respuesta al tratamiento e intervalo de tiempo hasta la cirugía con radioterapia preoperatoria de curso corto en el cáncer de recto.

INTRODUCTION: Preoperative short-course radiotherapy with immediate surgery improves local control in patients with rectal cancer. Tumor responses are smaller than those described with radiochemotherapy. Preliminary data associate this lower response to the short period until surgery. The aim of this study is to analyze the response to preoperative short-course radiotherapy and its correlation with the interval to surgery especially analyzing patients with mesorectal fascia involvement. METHODS: A total of 155 patients with locally advanced rectal cancer treated with preoperative radiotherapy (5×5Gy) were retrospectively analyzed. Tumor response in terms of rates of complete pathological response, downstaging, tumor regression grading and status of the circumferential resection margin were quantified. RESULTS: The mean interval from radiotherapy to surgery was 23 days. The rate of complete pathological response was 2.2% and 28% experienced downstaging (stage decreased). No differences between these rates and interval to surgery were detected. Eighty-eight patients had magnetic resonance imaging for staging (in 31 patients the mesorectal fascia was involved).The mean time to surgery in patients with involvement of the fascia and R0 surgery was 27 days and 16 days if R1 (P=.016). The cutoff of 20 days reached the highest probability of achieving a free circumferential resection margin between patients with mesorectal fascia involvement, with no statistically significant differences: RR 3.036 95% CI=(0.691-13.328), P=.06. CONCLUSIONS: After preoperative short-course radiotherapy, an interval>20 days enhances the likelihood of achieving a free circumferential resection margin in patients with mesorectal fascia involvement.

Radiation therapy for vulvar cancer: consensus guidelines of the GINECOR working group of the Spanish Society of Radiation Oncology. Part 1: clinical recommendations.

PURPOSE: The present consensus statement was developed by the GINECOR working group on behalf of the Spanish Society of Radiation Oncology (SEOR). Given the lack of prospective data on the management of vulvar carcinoma, this document provides an up-to-date review of radiotherapy treatment in vulvar cancer and a series of consensus-based recommendations from a group of experts. METHODS: A two-round, online modified Delphi study was conducted to reach consensus treatment recommendations in three clinical settings: 1) adjuvant treatment, 2) locally-advanced vulvar cancer (LAVC), and 3) recurrent disease. After the first round, we comprehensively reviewed the available medical literature from peer-reviewed journals to assess and define the evidence-based treatment options. In the second round, participants were asked to indicate their level of agreement with the preliminary recommendations according to the GRADE (Grade of Recommendation, Assessment, Development, and Evaluation) criteria, as follows: strongly agree; agree; neither agree nor disagree; disagree; strongly disagree. RESULTS: The main recommendations were as follows: 1) following surgical resection, adjuvant radiotherapy is recommended with the presence of adverse risk factors (primarily positive margins and lymph node involvement); 2) radiotherapy (with or without chemotherapy) should be considered in LAVC; and 3) in recurrent disease, radiotherapy should be individualised on a case-by-case basis. A high level of agreement over 80% was reached. CONCLUSIONS: In the absence of robust clinical data, these final recommendations may help to select the optimal radiotherapy approach for this relatively rare cancer.

Radiation therapy for vulvar cancer: consensus technical guidelines of the GINECOR working group of the Spanish Society of Radiation Oncology. Part 2: radiotherapy recommendations.

PURPOSE: The present consensus statement was developed by the GINECOR working group on behalf of the Spanish Society of Radiation Oncology (SEOR). This document provides an up-to-date review of the technical aspects in radiation treatment of vulvar cancer. METHODS: A two-round modified Delphi study was conducted to reach consensus on the appropriateness of technical aspects of external beam radiotherapy and brachytherapy. Three clinical scenarios were proposed: adjuvant treatment of vulvar cancer, radiation treatment of locally advanced vulvar carcinoma and locoregional recurrences. After the first round, an extensive analysis of current medical literature from peer-reviewed journal was performed to define evidence-based treatment options. In the second round, participants were asked to indicate their level of agreement with the preliminary recommendations according to the GRADE (Grade of Recommendation, Assessment, Development, and Evaluation) criteria, as follows: strongly agree; agree; neither agree nor disagree; disagree and strongly disagree. RESULTS: The main recommendations on external beam radiotherapy and brachytherapy, both in adjuvant setting and local advanced disease are summarized. Recommendations include treatment technique, treatment volume, and doses in target and organs at-risk. Taking into consideration the different clinical scenarios of recurrent disease, the radiation treatment should be individualized. CONCLUSIONS: In the absence of robust clinical data, these recommendations may help to select the optimal radiotherapy approach for this relatively rare cancer.

Eurasian otter (Lutra lutra) as sentinel species for the long-term biomonitoring of the Guadiamar River after the Aznalcóllar mine spill.

Accidents at mines involving stored tailings have produced catastrophic environmental damage. In April 1998 the dam of the Aznalcóllar mine tailings pond in the surroundings of the Doñana National Park (southwestern Spain) broke, discharging into the Guadiamar River more than 6 million m3 of toxic mud and acidic water with high concentrations of heavy metals and arsenic. We used the Eurasian otter (Lutra lutra) as sentinel species to assess the potential impact of the toxic spill on the river ecosystems and their recovery with time by studying the spatial and temporal variation (1999-2003, 2006) of selected trace element (Cu, Zn, Cd, Pb and As) concentrations in feces. Throughout the sampling period, the highest heavy metal and As levels were found in the most spill-affected reaches of the Guadiamar River (i.e., the Middle and, to a lesser extent, the Lower reaches), pointing out the mining accident as the main origin of the contamination. Overall, levels of trace elements decreased with the time elapsed since the toxic spill, except for Cd (F1,352 = 0.29, P = 0.59). However, rebounds for some elements (Pb, As, and Cu) were also observed, especially in the Middle and Lower reaches of the river, which might be attributed to the residual contamination in abiotic compartments and/or new inputs from industrial and agricultural activities in the nearby areas. Concentrations were relatively high when compared to those reported for both our reference area (Guadalete River) and other metal-polluted zones. We found that the estimated amounts of Pb and As ingested during the first years after the spill in the Guadiamar Middle reach would be high enough to cause reproductive issues. This could affect the local population recovery, although evidence on distribution range and numbers suggests otherwise, with thriving populations at regional scale. Our results support the role of otters as sentinel species for biomonitoring contaminants and thus to evaluate fluvial ecosystem health.

Re-irradiation for high-grade gliomas: Has anything changed?

Optimal management after recurrence or progression of high-grade gliomas is still undefined and remains a challenge for neuro-oncology multidisciplinary teams. Improved radiation therapy techniques, new imaging methods, published experience, and a better radiobiological knowledge of brain tissue have positioned re-irradiation (re-RT) as an option for many of these patients. Decisions must be individualized, taking into account the pattern of relapse, previous treatment, and functional status, as well as the patient's preferences and expected quality of life. Many questions remain unanswered with respect to re-RT: Who is the most appropriate candidate, which dose and fractionation are most effective, how to define the target volume, which imaging technique is best for planning, and what is the optimal timing? This review will focus on describing the most relevant studies that include re-RT as salvage therapy, with the aim of simplifying decision-making and designing the best available therapeutic strategy.

Selection on individuals of introduced species starts before the actual introduction.

Biological invasion is a global problem with large negative impacts on ecosystems and human societies. When a species is introduced, individuals will first have to pass through the invasion stages of uptake and transport, before actual introduction in a non-native range. Selection is predicted to act during these earliest stages of biological invasion, potentially influencing the invasiveness and/or impact of introduced populations. Despite this potential impact of pre-introduction selection, empirical tests are virtually lacking. To test the hypothesis of pre-introduction selection, we followed the fate of individuals during capture, initial acclimation, and captivity in two bird species with several invasive populations originating from the international trade in wild-caught pets (the weavers Ploceus melanocephalus and Euplectes afer). We confirm that pre-introduction selection acts on a wide range of physiological, morphological, behavioral, and demographic traits (incl. sex, age, size of body/brain/bill, bill shape, body mass, corticosterone levels, and escape behavior); these are all traits which likely affect invasion success. Our study thus comprehensively demonstrates the existence of hitherto ignored selection acting before the actual introduction into non-native ranges. This could ultimately change the composition and functioning of introduced populations, and therefore warrants greater attention. More knowledge on pre-introduction selection also might provide novel targets for the management of invasive species, if pre-introduction filters can be adjusted to change the quality and/or quantity of individuals passing through such that invasion probability and/or impacts are reduced.

Differences in adrenocortical responses between urban and rural burrowing owls: poorly-known underlying mechanisms and their implications for conservation.

The hypothalamus-pituitary-adrenal/interrenal (HPA) axis of vertebrates integrates external information and orchestrates responses to cope with energy-demanding and stressful events through changes in circulating glucocorticoid levels. Urbanization exposes animals to a wide variety of ever-changing stimuli caused by human activities that may affect local wildlife populations. Here, we empirically tested the hypothesis that urban and rural owls (Athene cunicularia) show different adrenocortical responses to stress, with urban individuals showing a reduced HPA-axis response compared to rural counterparts to cope with the high levels of human disturbance typical of urban areas. We applied a standard capture-restraint protocol to measure baseline levels and stress-induced corticosterone (CORT) responses. Urban and rural owls showed similar circulating baseline CORT levels. However, maximum CORT levels were attained earlier and were of lower magnitude in urban compared to rural owls, which showed a more pronounced and long-lasting response. Variability in CORT responses was also greater in rural owls and contained the narrower variability displayed by urban ones. These results suggest that only individuals expressing low-HPA-axis responses can thrive in cities, a pattern potentially mediated by three alternative and non-exclusive hypotheses: phenotypic plasticity, natural selection and matching habitat choice. Due to their different conservation implications, we recommend further research to properly understand wildlife responses to humans in an increasingly urbanized world.

Oligometastases in prostate cancer: Ablative treatment.

Technological advances in radiotherapy have led to the introduction of techniques such as stereotactic body radiation therapy (SBRT), allowing the administration of ablative doses. The hypothesis that oligometastatic disease may be cured through local eradication therapies has led to the increasing use of SBRT in patients with this type of disease. At the same time, scientific advances are being made to allow the confirmation of clinically suspected oligometastatic status at molecular level. There is growing interest in identifying patients with oligometastatic prostate cancer (PCa) who may benefit from curative intent metastasis-directed therapy, including SBRT. The aim is to complement, replace or delay the introduction of hormone therapy or other systemic therapies. The present review aims to compile the evidence from the main ongoing studies and results on SBRT in relation to oligometastatic PCa; examine aspects where gaps in knowledge or a lack of consensus persist (e.g., optimum schemes, response assessment, identification and diagnosis of oligometastatic patients); and document the lack of first-level evidence supporting the use of such techniques.

Intimal sarcoma of the pulmonary artery with multiple lung metastases: Long-term survival case.

Pulmonary artery intimal sarcoma (PAIS) is a rare tumor with a very poor prognosis. Clinical and radiological findings usually mimic thromboembolic disease, leading to diagnostic delays. The treatment of choice is surgery, and adjuvant chemotherapy and radiotherapy have limited results. We report the case of a 48-year-old male patient, initially suspected with pulmonary thromboembolism. The angio-CT revealed a filling defect in the pulmonary artery trunk. The patient underwent surgery, resulting in with complete resection of the mass with a diagnosis of PAIS. The tumor progressed rapidly in the lung, requiring surgery of multiple lung metastases. The patient was treated with stereotactic body radiation therapy (SBRT) on two occasions for new pulmonary lesions. In the last followup (4 years after initial diagnosis), the patient was disease-free. In conclusion, SBRT proved to be an alternative treatment to metastasectomy, allowing palliative chemotherapy to be delayed or omitted, which may result in improved quality of life.

Effects of Ontogeny, Diel Rhythms, and Environmental Variation on the Adrenocortical Physiology of Semialtricial Black Kites (Milvus migrans).

We examined whether hypothalamic-pituitary-adrenal axis activity in the nestlings of a semialtricial raptor, the black kite (Milvus migrans), varied with advancing age, throughout the day, and in response to a number of socioecological factors presumed to affect allostatic load. Both baseline corticosterone (CORT) titers and maximum CORT levels during 30 min of handling and restraint augmented across all sampled ages, suggesting that nestlings' energetic demands and capacity to respond to perturbations increase progressively throughout development. CORT secretion also peaked in the early morning, reached minimum levels in the central hours of the day, and increased again before dusk, suggesting a possible role of CORT in the regulation of activity-inactivity patterns. Finally, nestlings raised in a year of low marsh inundation, implying lower food availability and heightened allostatic loads, exhibited higher adrenocortical responsiveness to stress than nestlings raised in years of intermediate or high flooding. The nondetectable effect of other socioecological variables, such as territory quality, temperature, or brood order, suggests that parents may be able to buffer their nestlings from adverse environmental conditions or that the effect of such factors may have been obscured by selective mortality operating before sampling. We propose that future studies increase the simultaneous use of complementary techniques (fecal sampling, feather analysis) to reach firmer and more comprehensive conclusions, especially for planning the management and conservation of sensitive species.

Oligometastatic disease, the curative challenge in radiation oncology.

The concept of oligometastatic disease was first described by Hellman and Weichselbaum in 1995. The mere insight of this concept led to the hypothesis that this disease may be cured using local ablative weapons. Surgery has already demonstrated this hypothesis. Surgery limitations, either technical or due to refusal or associated comorbidity, have led to implement alternative ablative options such as stereotactic body radiation therapy (SBRT). SBRT evolved from (stereotactic radiosurgery) because of the need to irradiate extracranial lesions and has been shown to be safe and effective. SBRT achieves local control rates ranging from 70%-90%, but highly variable survival rates depending on the group analyzed. Series with heterogeneous metastatic sites and tumor origin have reported 20% survival rates at 2-3 years, similar to those achieved with surgery. Despite its excellent results, SBRT still faces significant clinical challenges. Its optimal integration with systemic treatment is unknown, and response assessment is very difficult. However, the greatest challenge lies in selection of patients most likely to remain oligometastatic, those who will most benefit from the technique. Biomarkers, molecular signatures, that accurately predict the biological behavior of malignancy are needed. The expression profile of specific miRNAs has been shown to have a potential in this regard.

Rosette-forming glioneuronal tumour (RGNT) of the fourth ventricle: a highly aggressive case.

BACKGROUND: The rosette-forming glioneuronal tumour (RGNT) is a rarely encountered tumour that has been included as a new entity in the 2007 edition of the "World Health Organization (WHO) Classification of Tumours of the Central Nervous System". We describe a rather unusual case of multifocal cerebellar RGNT, located in the spinal cord and displaying leptomeningeal spread. CLINICAL PRESENTATION: Twenty-four-year-old male with history of long-lasting headaches. A magnetic resonance scan revealed three heterogeneous lesions located within both cerebellar hemispheres and the left cerebellopontine angle, in addition to a spinal cord lesion at the level of the cervical region, and images of leptomeningeal spread. Interventions were performed in two stages; these involved resection of two cerebellar lesions, with a histopathological diagnosis of RGNT with atypical microvascular proliferation and focal necrosis. Although these tumours appear to be benign, our case debuted in an aggressive form, both from the radiological point of view and with respect to its histopathological characteristics. For this reason, the patient received adjuvant therapy with chemotherapy and radiotherapy. CONCLUSIONS: Experience of RGNT is limited. The prognostic significance of the histological findings of vascular proliferation and necrosis is still unknown. The clinical improvement in our patient endorses our decision to perform aggressive treatment.

Links between fear of humans, stress and survival support a non-random distribution of birds among urban and rural habitats.

Urban endocrine ecology aims to understand how organisms cope with new sources of stress and maintain allostatic load to thrive in an increasingly urbanized world. Recent research efforts have yielded controversial results based on short-term measures of stress, without exploring its fitness effects. We measured feather corticosterone (CORTf, reflecting the duration and amplitude of glucocorticoid secretion over several weeks) and subsequent annual survival in urban and rural burrowing owls. This species shows high individual consistency in fear of humans (i.e., flight initiation distance, FID), allowing us to hypothesize that individuals distribute among habitats according to their tolerance to human disturbance. FIDs were shorter in urban than in rural birds, but CORTf levels did not differ, nor were correlated to FIDs. Survival was twice as high in urban as in rural birds and links with CORTf varied between habitats: while a quadratic relationship supports stabilizing selection in urban birds, high predation rates may have masked CORTf-survival relationship in rural ones. These results evidence that urban life does not constitute an additional source of stress for urban individuals, as shown by their near identical CORTf values compared with rural conspecifics supporting the non-random distribution of individuals among habitats according to their behavioural phenotypes.

Characterization and adequacy of the use of radiotherapy and its trend in time.

BACKGROUND AND PURPOSE: Characterization of radiotherapy activity and its trend over time. Gathering of parameters for future planning of our resources, applicable to similar population areas. Performing a clinical audit of appropriate use of radiotherapy. MATERIAL AND METHODS: Analysis of 9782 patients treated between 1998 and 2008. Descriptive statistics of pathologies and social/demographic characteristics. Intention of treatment. The rate of radiotherapy utilization was estimated and compared with those considered optimal. Rate of reirradiation. RESULTS: The average global rate of radiotherapy utilization for the period was 32.7%. It increased by 23% between 1998 and 2008, while the population of the area rose by 1.04%, equaling an average 1.13 irradiations/1000 inhabitants/year. Radiation treatment has increased by 13.6, 2.3, 1.6 and 1.06 times in patients with prostate, breast, rectal and lung cancer, respectively. Eight percent of radiotherapy treatments involve concurrent chemotherapy. The proportion of treatments with palliative intent was 18.2%. The overall underutilization of radiation therapy in our environment was an estimated 13.4%. CONCLUSIONS: The grade of adequacy of radiation rates in relation with scientific evidence was globally considered suboptimal, especially in lung cancer. There was an upward trend of irradiation in breast and prostate cancer, tending toward rates considered optimal.

Radiotherapy in rectal cancer: development, adequacy and radiotherapy utilisation rate. A comparative analysis with the most frequent tumour sites.

INTRODUCTION: Radiotherapy is a basic weapon in the local treatment of multiple solid tumors. The radiotherapy activity has been evaluated in our centre during the past eleven years. The study focused on rectal cancer. MATERIALS AND METHODS: This is a descriptive study of all radiotherapy procedures performed between January 1998 and December 2008. It quantifies the workload of each pathology treated, the rate of irradiation and its adequacy with optimal rates of irradiation according to the best available scientific evidence. RESULTS: We quantified 9,622 external radiotherapy procedures of which 6,009 were associated with the five pathologies that involved the highest workloads. Of these, 905 were performed in rectal cancer. The workloads due to cancers of the breast, prostate, lung, gynaecological pathologies and rectal cancers were 23.2%, 11.8%, 11.6%, 6.3% and 9.3% respectively. The real "radiotherapy utilisation rates" of these pathologies were 62%, 20.2%, 34.3%, 21% and 64% respectively, while the "rates of adequacy" were 74.7%, 33.6%, 45.1%, 60% and 104.8%. CONCLUSIONS: The "radiotherapy utilisation rate" for rectal cancer was equivalent to the estimated optimum rate as defined on the basis of reference groups. The therapy utilised developed chronologically in parallel with the available scientific evidence. The radiotherapy utilisation rates for breast and prostate cancer gradually increased, with a tendency to reach optimal rates. Radiotherapy as a treatment for lung cancer was underutilised. In global terms, the rate of utilisation of radiation therapy was low, although it displayed a tendency to increase.

Tracking stress: localisation, deposition and stability of corticosterone in feathers.

How animals cope with stressors is an important determinant of their well being and fitness. Understanding what environmental perturbations are perceived as stressors, and quantifying how they are responded to, how often they occur and the negative consequences of exposure to glucocorticoids, has been problematic and limited to short-term physiological measures. By contrast, the quantification of corticosterone (CORT) in feathers represents a long-term, integrated measure of hypothalamic-pituitary-adrenal activity. In the present study, we show that by understanding how the hormone is deposited in feathers, in combination with specific sampling protocols, one can identify localised patterns of CORT deposition that reveal different temporal patterns of a bird's response to stressors. CORT in feathers appears to be stable over time, is resistant to heat exposure and is useful in determining both the overall exposure of the bird to the hormone over days or weeks, as well as identifying discrete, punctuated, stressful events. Variation in feather CORT can also be examined among individuals of a population at one point in time, as well as over years by using museum specimens. The ability to track stress over time allows for new questions to be asked about the health and ecology of birds and their environment.

Physiological stress levels predict survival probabilities in wild rabbits.

Among vertebrates, short-term elevations of glucocorticoid hormones (corticosterone or cortisol) facilitate a suite of physiological and behavioral changes aimed at overcoming environmental perturbations or other stressful events. However, chronically elevated glucocorticoids can have deleterious physiological consequences, and it is still unclear as to what constitutes an adaptive physiological response to long-term stress. In this study, we experimentally exposed European wild rabbits Oryctolagus cuniculus to a source of long-term stress (simulated through a 2- to 4-week period of captivity) and tested whether glucocorticoid physiology predicted two major components of rabbit fitness: body condition and survival probability. Following exposure to long-term stress, moderately elevated serum corticosterone and fecal glucocorticoid metabolites levels in the wild rabbits were negatively associated with body condition, but positively associated with subsequent survival upon release. Our results suggest that the cost of maintaining elevated corticosterone levels in terms of decreased body condition is balanced by the increased chance of survival upon release.