Energy and Environmental Monitoring of a School Building Deep Energy Renovation in Italy

Abstract The Tito M. Plauto school in Cesena is the Italian case study in the FP7 School of the Future project. Objective was the energy renovation of school buildings with high energy and indoor environment targets, to be demonstrated by monitoring before and after the retrofit. Measures involved envelope components and energy systems, including renewable. The energy monitoring started in January 2014 and included thermal and electricity uses; as well the electricity produced by the PV plant. Data were compared to those registered for the 2008-2010 period. The environmental quality was addressed by thermal comfort and CO 2 concentration instrumental monitoring

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

AB012. Transcriptional and chromatin profiling reveals the molecular architecture and druggable vulnerabilities of thymic epithelial tumors (TETs)

Thymic epithelial tumors (TETs) have been profiled to the present moment mainly through several analyses of FFPE samples. Despite the leap forward brought by the TCGA, several questions remain still unsolved. Among these, TETs are characterized by a strong component of immune infiltrate which makes the transcriptomic analyses conducted so far scarcely interpretable to profile stromal subpopulations constitutive of the tumor. Furthermore, rarely correspondent healthy tissue is available due to the lipomatous atrophy of aged thymi. Therefore, the recent report of (I) isolation, (II) propagation (III) and characterization of human thymic epithelial cells (TECs) and their capacity to reconstitute the functional organ ex vivo and in vivo, represents a novel approach to study the biology of both healthy and neoplastic thymi. Human thymic biopsies (both healthy and neoplastic) were digested and plated on a lethally irradiated murine feeder layer. Both RNA-Seq and CUTANDTAG were performed on cultivated TECs at different passages. Cultured TECs were injected with human thymic interstitial cells into rat decellularized scaffolds and cultivated for 10–12 days. sc-RNA Seq is currently being performed on both healthy and neoplastic thymic mini-organs and their correspondent primary tissues. Here show that we successfully cultivated a cohort of 21 clonogenic TECs in vitro including adult neoplastic TECs, their non-tumoral counterpart and pediatric TECs. We show that at the transcriptome level each class of TECs clusters independently and that neoplastic TECs belong to the same cloud independently from thymoma histotype. Around 1,400 differentially expressed genes (DEGs) can be found when comparing adult neoplastic and non-neoplastic counterpart, among which around 70 are transcription factors. Importantly, we prove for the first time that clonogenic TECs derived from TETs can repopulate a decellularized rat scaffold and recreate a 3D architecture mimicking the primary tumor. This work demonstrates that this culture system allows the expansion of clonogenic TECs from both tumor samples and their non-tumoral counterpart. Those cells, when transplanted into decellularized thymi, reproduce the architecture of the primary tissue, showing that TETs contain progenitor/stem epithelial cells. We are currently characterizing TECs at the transcriptomic and epigenomic level with aim of identifying new druggable targets prior to clinical trials

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

Predictive role of multiple gene alterations in response to cetuximab in metastatic colorectal cancer: A single center study

<p>Abstract</p> <p>Background</p> <p><it>KRAS</it> mutations negatively affect outcome after treatment with cetuximab in metastatic colorectal cancer (mCRC) patients. As only 20% of <it>KRAS</it> wild type (WT) patients respond to cetuximab it is possible that other mutations, constitutively activating the EGFR pathway, are present in the non-responding <it>KRAS</it> WT patients. We retrospectively analyzed objective tumor response rate, (ORR) progression-free (PFS) and overall survival (OS) with respect to the mutational status of <it>KRAS</it>, <it>BRAF</it>, <it>PIK3CA</it> and PTEN expression in mCRC patients treated with a cetuximab-based regimen.</p> <p>Methods</p> <p>67 mCRC patients were enrolled onto the study. DNA was extracted from paraffin-embedded sections derived from primary or metastatic lesions. Exon 2 of <it>KRAS</it> and exon 15 of <it>BRAF</it> were analyzed by direct sequencing, <it>PIK3CA</it> was evaluated by pyrosequencing and PTEN expression by immunohistochemistry.</p> <p>Results</p> <p><it>BRAF</it> and <it>PIK3CA</it> mutations were independently associated with worse PFS (<it>p</it> = 0.006 and <it>p</it> = 0.028, respectively) and OS (<it>p</it> = 0.008 and <it>p</it> = 0.029, respectively). No differences in clinical outcome were found between patients who were positive or negative for PTEN expression. Conversely, patients negative for <it>KRAS</it>, <it>BRAF</it> and <it>PIK3CA</it> mutations were characterized by significantly better ORR, PFS and OS than patients with at least one of these mutations.</p> <p>Conclusions</p> <p><it>BRAF</it> and <it>PIK3CA</it> mutations would seem to be independent predictors of anti-EGFR therapy effectiveness and could be taken into consideration during treatment decision making.</p