Hemangioblastoma of the gastrointestinal tract: A first case

We present the first documented case of hemangioblastoma located in the left colon. A 75-year-old woman undergoing adjuvant chemotherapy for breast cancer experienced rectal bleeding. Colonoscopy revealed a roundish mass covered with normal mucosa in the sigmoid colon. Endoscopic ultrasound showed an isoechoic lesion originating from the third layer of the intestinal wall; underlying layers were normal. Endoscopic ultrasound features were not suggestive of either cancer or malignant stromal tumor. Left hemicolectomy was subsequently performed due to repeated episodes of lower gastrointestinal bleeding. Grossly, a circumscribed submucosal yellowish nodule (13 mm) was observed, which was not attached to any peripheral nerve. Histologically, the lesion was composed of large, atypical cells traversed by a network of blood vessels. Immunohistochemically, the cells showed positivity for inhibin and NSE and weak positivity for S-100. A diagnosis of hemangioblastoma was made. This case highlights that hemangioblastoma of the gastrointestinal tract can also occur. © The Author(s) 2013

KRAS, BRAF and PIK3CA status in squamous cell anal carcinoma (SCAC)

Anti-EGFR therapy appears to be a potential treatment option for squamous cell anal carcinoma (SCAC). KRAS mutation is a rare event in SCAC, indicating the absence of the principal mechanism of resistance to this type of therapy. However, no information is available from the literature regarding the status of BRAF or PIK3CA in this cancer type. We analysed KRAS, BRAF and PIK3CA status in SCAC patients in relation to the clinical-pathological characteristics of patients and to the presence of the human papilloma virus (HPV). One hundred and three patients were treated with the Nigro scheme for anal cancer from March 2001 to August 2012. Fifty patients were considered for the study as there was insufficient paraffinembedded tumour tissue to perform molecular analysis the remaining 53. DNA was extracted from paraffin-embedded sections. KRAS, BRAF and PIK3CA gene status and HPV genotype were evaluated by pyrosequencing. KRAS and BRAF genes were wild-type in all cases. Conversely, PIK3CA gene was found to be mutated in 11 (22%) cases. In particular, 8 mutations occurred in exon 9 and 3 in exon 20 of the PIK3CA gene. These findings suggest that SCAC could potentially respond to an anti-EGFR drug. PIK3CA mutation may be involved in the process of carcinogenesis in some cases of SCAC. \ua9 2014 Casadei Gardini et al

Dynamic contrast-enhanced ultrasonography (D-CEUS) for the early prediction of bevacizumab efficacy in patients with metastatic colorectal cancer

Objectives: To investigate early changes in tumour perfusion parameters by dynamic contrast-enhanced ultrasonography (D-CEUS) and to identify any correlation with survival and tumour response in patients with metastatic colorectal cancer (CRC) treated with bevacizumab (B). Methods: Thirty-seven patients randomized to either chemotherapy (C) plus B or C alone were considered for this study. D-CEUS was performed at baseline and after the first treatment cycle (day 15). Four D-CEUS perfusion parameters were considered: derived peak intensity (DPI), area under the curve (AUC), slope of wash-in (A) and time to peak intensity (TPI). Results: In patients treated with C plus B, a ≥22.5 % reduction in DPI, ≥20 % increase in TPI and ≥10 % reduction in AUC were correlated with higher progression-free survival in the C+B arm (p = 0.048, 0.024 and 0.010, respectively) but not in the C arm. None of the evaluated parameter modifications had a correlation with tumour response or overall survival. Conclusions: D-CEUS could be useful for detecting and quantifying dynamic changes in tumour vascularity as early as 15 days after the start of B-based therapy. Although these changes may be predictive of progression-free survival, no correlation with response or overall survival was found. Key Points: • D-CEUS showed early changes in liver metastasis perfusion in colorectal cancer. • A decrease in tumour perfusion was associated with longer progression-free survival. • The decrease in perfusion was not correlated with higher overall survival

Prognostic role of a new inflammatory index with neutrophil-to-lymphocyte ratio and lactate dehydrogenase (CII: Colon Inflammatory Index) in patients with metastatic colorectal cancer: results from the randomized Italian Trial in Advanced Colorectal Cancer (ITACa) study

Aim: The aim of this study was to investigate the role of a new inflammatory index (Colon Inflammatory Index [CII]) as a predictor of prognosis and treatment efficacy in patients with metastatic colorectal cancer (mCRC) enrolled in the prospective multicenter randomized ITACa (Italian Trial in Advanced Colorectal Cancer) trial to receive first-line chemotherapy (CT)+ bevacizumab or CT alone. Patients and methods: Between November 14, 2007 and March 6, 2012, 276 patients diagnosed with CRC were available for baseline neutrophil-to-lymphocyte ratio (NLR) and lactate dehydrogenase (LDH). We divided the population into three groups on basis of the CII index. Results: At baseline in all populations, median PFS and OS was predictive of clinical outcome (p<0.0001). Following adjustment for clinical covariates, multivariate analysis confirmed CII index as an independent prognostic factor. The CII index was also predictive when we evaluated the two distinct arms with (p=0.0009) or without bevacizumab (p=0.0001). When we divided right side versus left side for treatment regimen (CT plus bevacizumab versus only bevacizumab), we found a benefit of bevacizumab versus only CT in the right side in patients treated with bevacizumab and not in patients treated with only chemotherapy. Conversely, we found no difference the left side, but we found a difference in the poor group of 4 months in favor to only chemotherapy. Conclusion: Our results indicate that the CII index is a good prognostic marker for mCRC patients in first line treatment with CT with or without bevacizumab

MIPAS observations of ozone in the middle atmosphere

This work is distributed under the Creative Commons Attribution 4.0 License.In this paper we describe the stratospheric and mesospheric ozone (version V5r-O3-m22) distributions retrieved from MIPAS observations in the three middle atmosphere modes (MA, NLC, and UA) taken with an unapodized spectral resolution of 0.0625 cm from 2005 until April 2012. O is retrieved from microwindows in the 14.8 and 10 μm spectral regions and requires non-local thermodynamic equilibrium (non-LTE) modelling of the O and vibrational levels. Ozone is reliably retrieved from 20 km in the MA mode (40 km for UA and NLC) up to ∼105 km during dark conditions and up to ∼95 km during illuminated conditions. Daytime MIPAS O has an average vertical resolution of 3-4 km below 70 km, 6-8 km at 70-80 km, 8-10 km at 80-90, and 5-7 km at the secondary maximum (90-100 km). For nighttime conditions, the vertical resolution is similar below 70 km and better in the upper mesosphere and lower thermosphere: 4-6 km at 70-100 km, 4-5 km at the secondary maximum, and 6-8 km at 100-105 km. The noise error for daytime conditions is typically smaller than 2% below 50 km, 2-10% between 50 and 70 km, 10-20% at 70-90 km, and ∼30% above 95 km. For nighttime, the noise errors are very similar below around 70 km but significantly smaller above, being 10-20% at 75-95 km, 20-30% at 95-100 km, and larger than 30% above 100 km. The additional major O errors are the spectroscopic data uncertainties below 50 km (10-12 %) and the non-LTE and temperature errors above 70 km. The validation performed suggests that the spectroscopic errors below 50 km, mainly caused by the O air-broadened half-widths of the band, are overestimated. The non-LTE error (including the uncertainty of atomic oxygen in nighttime) is relevant only above ∼85 km with values of 15-20 %. The temperature error varies from ∼3% up to 80 km to 15-20% near 100 km. Between 50 and 70 km, the pointing and spectroscopic errors are the dominant uncertainties. The validation performed in comparisons with SABER, GOMOS, MLS, SMILES, and ACE-FTS shows that MIPAS O has an accuracy better than 5% at and below 50 km, with a positive bias of a few percent. In the 50-75 km region, MIPAS O has a positive bias of ∼10 %, which is possibly caused in part by O spectroscopic errors in the 10 μm region. Between 75 and 90 km, MIPAS nighttime O is in agreement with other instruments by 10 %, but for daytime the agreement is slightly larger, ∼10-20 %. Above 90 km, MIPAS daytime O is in agreement with other instruments by 10 %. At night, however, it shows a positive bias increasing from 10% at 90 km to 20% at 95-100 km, the latter of which is attributed to the large atomic oxygen abundance used. We also present MIPAS O distributions as function of altitude, latitude, and time, showing the major O features in the middle and upper mesosphere. In addition to the rapid diurnal variation due to photochemistry, the data also show apparent signatures of the diurnal migrating tide during both day-and nighttime, as well as the effects of the semi-Annual oscillation above ∼70 km in the tropics and mid-latitudes. The tropical. daytime O at 90 km shows a solar signature in phase with the solar cycle. © Author(s) 2018.The IAA team was supported by the Spanish MICINN under the project ESP2014-54362-P and EC FEDER funds. The IAA and IMK teams were partially supported by ESA O3-CCI and MesosphEO projects. Maya Garcia-Comas was financially supported by MINECO through its >Ramon y Cajal> subprogram. Funding for the Atmospheric Chemistry Experiment comes primarily from the Canadian Space Agency. Work at the Jet Propulsion Laboratory was performed under contract with the National Aeronautics and Space Administration

Measurements of global distributions of polar mesospheric clouds during 2005–2012 by MIPAS/Envisat

We have analysed MIPAS (Michelson Interferometer for Passive Atmopheric Sounding) infrared measurements of PMCs for the summer seasons in the Northern (NH) and Southern (SH) hemispheres from 2005 to 2012. Measurements of PMCs using this technique are very useful because they are sensitive to the total ice volume and independent of particle size. For the first time, MIPAS has provided coverage of the PMC total ice volume from midlatitudes to the poles. MIPAS measurements indicate the existence of a continuous layer of mesospheric ice, extending from about ~ 81 km up to about 88–89 km on average and from the poles to about 50–60° in each hemisphere, increasing in concentration with proximity to the poles. We have found that the ice concentration is larger in the Northern Hemisphere than in the Southern Hemisphere. The ratio between the ice water content (IWC) in both hemispheres is also latitudedependent, varying from a NH= SH ratio of 1.4 close to the poles to a factor of 2.1 around 60°. This also implies that PMCs extend to lower latitudes in the NH. A very clear feature of the MIPAS observations is that PMCs tend to be at higher altitudes with increasing distance from the polar region (in both hemispheres), particularly equatorwards of 70°, and that they are about 1 km higher in the SH than in the NH. The difference between the mean altitude of the PMC layer and the mesopause altitude increases towards the poles and is larger in the NH than in the SH. The PMC layers are denser and wider when the frost-point temperature occurs at lower altitudes. The layered water vapour structure caused by sequestration and sublimation of PMCs is present at latitudes northwards of 70° N and more pronounced towards the pole. Finally, MIPAS observations have also shown a clear impact of the migrating diurnal tide on the diurnal variation of the PMC volume ice density

HEPPA-II model-measurement intercomparison project : EPP indirect effects during the dynamically perturbed NH winter 2008-2009

We compare simulations from three high-top (with upper lid above 120 km) and five medium-top (with upper lid around 80 km) atmospheric models with observations of odd nitrogen (NOx D NO+NO2), temperature, and carbon monoxide from seven satellite instruments (ACE-FTS on SciSat, GOMOS, MIPAS, and SCIAMACHY on Envisat, MLS on Aura, SABER on TIMED, and SMR on Odin) during the Northern Hemisphere (NH) polar winter 2008/2009. The models included in the comparison are the 3-D chemistry transport model 3dCTM, the ECHAM5/MESSy Atmospheric Chemistry (EMAC) model, FinROSE, the Hamburg Model of the Neutral and Ionized Atmosphere (HAMMO-NIA), the Karlsruhe Simulation Model of the Middle Atmosphere (KASIMA), the modelling tools for SOlar Climate Ozone Links studies (SOCOL and CAO-SOCOL), and the Whole Atmosphere Community Climate Model (WACCM4). The comparison focuses on the energetic particle precipitation (EPP) indirect effect, that is, the polar winter descent of NOx largely produced by EPP in the mesosphere and lower thermosphere. A particular emphasis is given to the impact of the sudden stratospheric warming (SSW) in January 2009 and the subsequent elevated stratopause (ES) event associated with enhanced descent of mesospheric air. The chemistry climate model simulations have been nudged toward reanalysis data in the troposphere and stratosphere while being unconstrained above. An odd nitrogen upper boundary condition obtained from MIPAS observations has further been applied to medium-top models. Most models provide a good representation of the mesospheric tracer descent in general, and the EPP indirect effect in particular, during the unperturbed (pre-SSW) period of the NH winter 2008/2009. The observed NOx descent into the lower mesosphere and stratosphere is generally reproduced within 20 %. Larger discrepancies of a few model simulations could be traced back either to the impact of the models' gravity wave drag scheme on the polar wintertime meridional circulation or to a combination of prescribed NOx mixing ratio at the uppermost model layer and low vertical resolution. In March-April, after the ES event, however, modelled mesospheric and stratospheric NOx distributions deviate significantly from the observations. The too-fast and early downward propagation of the NO x tongue, encountered in most simulations, coincides with a temperature high bias in the lower mesosphere (0.2-0.05 hPa), likely caused by an overestimation of descent velocities. In contrast, upper-mesospheric temperatures (at 0.05-0.001 hPa) are generally underestimated by the high-top models after the onset of the ES event, being indicative for too-slow descent and hence too-low NOx fluxes. As a consequence, the magnitude of the simulated NOx tongue is generally underestimated by these models. Descending NOx amounts simulated with mediumtop models are on average closer to the observations but show a large spread of up to several hundred percent. This is primarily attributed to the different vertical model domains in which the NOx upper boundary condition is applied. In general, the intercomparison demonstrates the ability of state-of- the-art atmospheric models to reproduce the EPP indirect effect in dynamically and geomagnetically quiescent NH winter conditions. The encountered differences between observed and simulated NOx, CO, and temperature distributions during the perturbed phase of the 2009 NH winter, however, emphasize the need for model improvements in the dynamical representation of elevated stratopause events in order to allow for a better description of the EPP indirect effect under these particular conditions.Peer reviewe

HEPPA-II model–measurement intercomparison project: EPP indirect effects during the dynamically perturbed NH winter 2008-2009

We compare simulations from three high-top (with upper lid above 120 km) and five medium-top (with upper lid around 80 km) atmospheric models with observations of odd nitrogen (NOx  =  NO + NO2), temperature, and carbon monoxide from seven satellite instruments (ACE-FTS on SciSat, GOMOS, MIPAS, and SCIAMACHY on Envisat, MLS on Aura, SABER on TIMED, and SMR on Odin) during the Northern Hemisphere (NH) polar winter 2008/2009. The models included in the comparison are the 3-D chemistry transport model 3dCTM, the ECHAM5/MESSy Atmospheric Chemistry (EMAC) model, FinROSE, the Hamburg Model of the Neutral and Ionized Atmosphere (HAMMONIA), the Karlsruhe Simulation Model of the Middle Atmosphere (KASIMA), the modelling tools for SOlar Climate Ozone Links studies (SOCOL and CAO-SOCOL), and the Whole Atmosphere Community Climate Model (WACCM4). The comparison focuses on the energetic particle precipitation (EPP) indirect effect, that is, the polar winter descent of NOx largely produced by EPP in the mesosphere and lower thermosphere. A particular emphasis is given to the impact of the sudden stratospheric warming (SSW) in January 2009 and the subsequent elevated stratopause (ES) event associated with enhanced descent of mesospheric air. The chemistry climate model simulations have been nudged toward reanalysis data in the troposphere and stratosphere while being unconstrained above. An odd nitrogen upper boundary condition obtained from MIPAS observations has further been applied to medium-top models. Most models provide a good representation of the mesospheric tracer descent in general, and the EPP indirect effect in particular, during the unperturbed (pre-SSW) period of the NH winter 2008/2009. The observed NOx descent into the lower mesosphere and stratosphere is generally reproduced within 20 %. Larger discrepancies of a few model simulations could be traced back either to the impact of the models\u27 gravity wave drag scheme on the polar wintertime meridional circulation or to a combination of prescribed NOx mixing ratio at the uppermost model layer and low vertical resolution. In March–April, after the ES event, however, modelled mesospheric and stratospheric NOx distributions deviate significantly from the observations. The too-fast and early downward propagation of the NOx tongue, encountered in most simulations, coincides with a temperature high bias in the lower mesosphere (0.2–0.05 hPa), likely caused by an overestimation of descent velocities. In contrast, upper-mesospheric temperatures (at 0.05–0.001 hPa) are generally underestimated by the high-top models after the onset of the ES event, being indicative for too-slow descent and hence too-low NOx fluxes. As a consequence, the magnitude of the simulated NOx tongue is generally underestimated by these models. Descending NOx amounts simulated with medium-top models are on average closer to the observations but show a large spread of up to several hundred percent. This is primarily attributed to the different vertical model domains in which the NOx upper boundary condition is applied. In general, the intercomparison demonstrates the ability of state-of-the-art atmospheric models to reproduce the EPP indirect effect in dynamically and geomagnetically quiescent NH winter conditions. The encountered differences between observed and simulated NOx, CO, and temperature distributions during the perturbed phase of the 2009 NH winter, however, emphasize the need for model improvements in the dynamical representation of elevated stratopause events in order to allow for a better description of the EPP indirect effect under these particular conditions

Systematic versus on-demand early palliative care: results from a multicentre, randomised clinical trial

Background Early palliative care (EPC) in oncology has been shown to have a positive impact on clinical outcome, quality-of-care outcomes, and costs. However, the optimal way for activating EPC has yet to be defined. Methods This prospective, multicentre, randomised study was conducted on 207 outpatients with metastatic or locally advanced inoperable pancreatic cancer. Patients were randomised to receive ‘standard cancer care plus on-demand EPC’ (n = 100) or ‘standard cancer care plus systematic EPC’ (n = 107). Primary outcome was change in quality of life (QoL) evaluated through the Functional Assessment of Cancer Therapy – Hepatobiliary questionnaire between baseline (T0) and after 12 weeks (T1), in particular the integration of physical, functional, and Hepatic Cancer Subscale (HCS) combined in the Trial Outcome Index (TOI). Patient mood, survival, relatives' satisfaction with care, and indicators of aggressiveness of care were also evaluated. Findings The mean changes in TOI score and HCS score between T0 and T1 were −4.47 and −0.63, with a difference between groups of 3.83 (95% confidence interval [CI] 0.10–7.57) (p = 0.041), and −2.23 and 0.28 (difference between groups of 2.51, 95% CI 0.40–4.61, p = 0.013), in favour of interventional group. QoL scores at T1 of TOI scale and HCS were 84.4 versus 78.1 (p = 0.022) and 52.0 versus 48.2 (p = 0.008), respectively, for interventional and standard arm. Until February 2016, 143 (76.9%) of the 186 evaluable patients had died. There was no difference in overall survival between treatment arms. Interpretations Systematic EPC in advanced pancreatic cancer patients significantly improved QoL with respect to on-demand EPC