Final analysis of colorectal cancer patients treated with irinotecan and 5-fluorouracil plus folinic acid neoadjuvant chemotherapy for unresectable liver metastases

We have previously reported that neoadjuvant therapy with modified FOLFIRI enabled nearly a third of patients with metastatic colorectal cancer (mCRC) to undergo surgical resection of liver metastases. Here, we present data from the long-term follow-up of these patients. Forty patients received modified FOLFIRI: irinotecan 180 mg m−2, day 1; folinic acid, 200 mg m−2; and 5-fluorouracil: as a 400 mg m−2 bolus, days 1 and 2, and a 48-h continuous infusion 1200 mg m−2, from day 1. Treatment was repeated every 2 weeks, with response assessed every six cycles. Resected patients received six further cycles of chemotherapy postoperatively. Nineteen (47.5%) of 40 patients achieved an objective response; 13 (33%) underwent resection. After a median follow-up of 56 months, median survival for all patients was 31.5 months: for non-resected patients, median survival was 24 months and was not reached for resected patients. Median time to progression was 14.3 and 5.2 months for all and non-resected patients, respectively. Median disease-free (DF) survival in resected patients was 52.5 months. At 2 years, all patients were alive (8 DF), and at last follow-up, eight were alive (6 DF). Surgical resection of liver metastases after neoadjuvant treatment with modified FOLFIRI in CRC patients achieved favourable survival times

Comparison of the imaging performances for recently developed monolithic scintillators: CRY018 and CRY019 for dual isotope gamma ray imaging applications

The growing interest for new scintillation crystals with outstanding imaging performances (i.e. resolution and efficiency) has suggested the study of recently discovered scintillators named CRY018 and CRY019. The crystals under investigation are monolithic and have shown enhanced characteristics both for gamma ray spectrometry and for Nuclear Medicine imaging applications such as the dual isotope imaging. Moreover, the non-hygroscopic nature and the absence of afterglow make these scintillators even more attractive for the potential improvement in a wide range of applications. These scintillation crystals show a high energy resolution in the energy range involved in Nuclear Medicine, allowing the discrimination between very close energy values. Moreover, in order to prove their suitability of being powerful imaging systems, the imaging performances like the position linearity and the intrinsic spatial resolution have been evaluated obtaining satisfactory results thanks to the implementation of an optimized algorithm for the images reconstruction. © 2017 IOP Publishing Ltd and Sissa Medialab srl

Schedule-dependent activity of 5-fluorouracil and irinotecan combination in the treatment of human colorectal cancer: in vitro evidence and a phase I dose-escalating clinical trial

Several schedules of 5-fluorouracil (FU) and irinotecan (IRI) have been shown to improve overall survival in advanced colorectal cancer (CRC). Preclinical evidence suggests that the sequential administration of IRI and FU produces synergistic activity, although their clinical use has not been fully optimised. We investigated the interaction between short-term exposure to SN-38, the active metabolite of IRI, and prolonged exposure to FU in human CRC HT-29 cells and observed that the synergism of action between the two agents can be increased by extending the time of cell exposure to FU and reducing the interval between administration of the two agents. Based on these findings, we performed a phase I trial in 25 advanced CRC patients using a modified IRI/FU regimen as first-line therapy and evaluated three dose levels of IRI (150–300 mg/m2) and two of continuous infusion of FU (800–1000 mg/m2) in a 3-weekly schedule. The most severe grade III–IV toxicities were neutropoenia in four cycles and diarrhoea in three. One patient achieved complete response (4%), 12 a partial response (48%), the overall response rate was 52% (±20, 95% CI); seven of 25 patients had stable disease (28%), the overall disease control was 80% (±16, 95% CI). This modified IRI/FU schedule is feasible and exhibits potentially interesting clinical activity

Tephrochronology of core PRAD 1-2 from the Adriatic Sea: insights into Italian explosive volcanism for the period 200–80 ka

Core PRAD 1-2, located on the western flank of the Mid-Adriatic Deep, was investigated for tephra content within the part of the sequence assigned on biostratigraphic and sapropel-layer stratigraphy to MIS 5 and 6 (ca. 80–200 ka BP). A total of 11 discrete tephra layers are identified, 8 visible and 3 cryptotephra layers. 235 geochemical measurements obtained from individual glass shards using WDS-EPMA enabled 8 of the 11 tephras to be correlated to known eruption events, 5 of which are represented in the Lago Grande di Monticchio (LGdM) regional tephra archive sequence. Three of these layers are recognised ultra-distally for the first time, extending their known distributions approximately 210 km further north. The results provide an independent basis for establishing an age-depth profile for the MIS 5–6 interval in the PRAD 1-2 marine record. This approach allowed age estimates to be interpolated for the tephra layers that could not be correlated to known events. It also provides an independent test of, and support for, the broad synchroneity of sapropel-equivalent (S-E) events in the Adriatic Sea with the better-developed sapropel layers of the eastern Mediterranean, proposed by Piva et al. (2008a)

2017 Research & Innovation Day Program

A one day showcase of applied research, social innovation, scholarship projects and activities.https://first.fanshawec.ca/cri_cripublications/1004/thumbnail.jp

New insights in the relation between climate and slope failures at high-elevation sites

Climate change is now unequivocal; however, the type and extent of terrestrial impacts are still widely debated. Among these, the effects on slope stability are receiving a growing attention in recent years, both as terrestrial indicators of climate change and implications for hazard assessment. High-elevation areas are particularly suitable for these studies, because of the presence of the cryosphere, which is particularly sensitive to climate. In this paper, we analyze 358 slope failures which occurred in the Italian Alps in the period 2000–2016, at an elevation above 1500 m a.s.l. We use a statistical-based method to detect climate anomalies associated with the occurrence of slope failures, with the aim to catch an eventual climate signal in the preparation and/or triggering of the considered case studies. We first analyze the probability values assumed by 25 climate variables on the occasion of a slope-failure occurrence. We then perform a dimensionality reduction procedure and come out with a set of four most significant and representative climate variables, in particular heavy precipitation and short-term high temperature. Our study highlights that slope failures occur in association with one or more climate anomalies in almost 92% of our case studies. One or more temperature anomalies are detected in association with most case studies, in combination or not with precipitation (47% and 38%, respectively). Summer events prevail, and an increasing role of positive temperature anomalies from spring to winter, and with elevation and failure size, emerges. While not providing a final evidence of the role of climate warming on slope instability increase at high elevation in recent years, the results of our study strengthen this hypothesis, calling for more extensive and in-depth studies on the subject

Landslide databases in the Geological Surveys of Europe

Acceso electrónico sólo desde el IGMELandslides are one of the most widespread geohazards in Europe, producing significant social and economic impacts. Rapid population growth in urban areas throughout many countries in Europe and extreme climatic scenarios can considerably increase landslide risk in the near future. Variability exists between European countries in both the statutory treatment of landslide risk and the use of official assessment guidelines. This suggests that a European Landslides Directive that provides a common legal framework for dealing with landslides is necessary. With this long-term goal in mind, this work analyzes the landslide databases from the Geological Surveys of Europe focusing on their interoperability and completeness. The same landslide classification could be used for the 849,543 landslide records from the Geological Surveys, from which 36% are slides, 10% are falls, 20% are flows, 11% are complex slides, and 24% either remain unclassified or correspond to another typology. Most of them are mapped with the same symbol at a scale of 1:25,000 or greater, providing the necessary information to elaborate European-scale susceptibility maps for each landslide type. A landslide density map was produced for the available records from the Geological Surveys (LANDEN map) showing, for the first time, 210,544 km2 landslide-prone areas and 23,681 administrative areas where the Geological Surveys from Europe have recorded landslides. The comparison of this map with the European landslide susceptibility map (ELSUS 1000 v1) is successful for most of the territory (69.7%) showing certain variability between countries. This comparison also permitted the identification of 0.98 Mkm2 (28.9%) of landslide-susceptible areas without records from the Geological Surveys, which have been used to evaluate the landslide database completeness. The estimated completeness of the landslide databases (LDBs) from the Geological Surveys is 17%, varying between 1 and 55%. This variability is due to the different landslide strategies adopted by each country. In some of them, landslide mapping is systematic; others only record damaging landslides, whereas in others, landslide maps are only available for certain regions or local areas. Moreover, in most of the countries, LDBs from the Geological Surveys co-exist with others owned by a variety of public institutions producing LDBs at variable scales and formats. Hence, a greater coordination effort should be made by all the institutions working in landslide mapping to increase data integration and harmonization.Earth Observation and Geohazards Expert Group (EOEG), EuroGeoSurveys, the Geological Surveys of Europe, BélgicaGeohazards InSAR Laboratory and Modeling Group, Instituto Geológico y Minero de España, EspañaRisk and Prevention Division, Bureau de Recherches Géologiques et Minières, FranciaEngineering Geology Department, Institute of Geology and Mineral Exploration, GreciaGeoHazard team, Geological Institute of Romania, RumaníaGeological Survey of Slovenia, EsloveniaCroatian Geological Survey, CroaciaItalian Institute for Environmental Protection and Research, Geological Survey of Italy, ItaliaSwiss Federal Office for the Environment, SuizaGeological Survey of Austria, AustriaPolish Geological Institute, National Research Institute, PoloniaGeological Survey of Ireland, IrlandaCzech Geological Survey, República ChecaFederal Institute for Geosciences and Natural Resources, AlemaniaGeological Survey of Norway, NoruegaCyprus Geological Survey, ChipreGeological Survey of Sweden, SueciaInstitut Cartogràfic i Geològic de Catalunya, EspañaBritish Geological Survey, Reino UnidoGeological Survey of Slovakia, EslovaquiaGeological Survey of Lithuania, LituaniaFederalni zavod za geologiju, Bosnia y HerzegovinaGeological Survey of Estonia, EstoniaLaboratório Nacional de Energia e Geologia, PortugalGeological Survey of Hungary, HungríaNorwegian Water and energy Directorate of Norway, Norueg