Programmed cell death 4 (PDCD4) as a novel prognostic marker for papillary thyroid carcinoma

Background: The primary goal of papillary thyroid cancer (PTC) management was to stratify patients at pre- and post-surgical level to identify the small proportion of cases with potentially aggressive disease. Purpose: The aim of our study is to evaluate the possible role of programmed cell death 4 (PDCD4) and BRAF status as prognostic markers in PTC. Patients and methods: We investigate programmed cell death 4 (PDCD4) immunohistochemical expression in 125 consecutive PTCs with median follow-up of 75.3 months (range, 15\u201398 months) to verify the possible correlation between BRAF status and correlate the classical clinicopathological prognostic factors and PTC outcome with PDCD4 expression. To further support the data, miR-21 expression was tested (by quantitative real-time PCR and in situ hybridization) in a different series of 30 cases (15 PTCs BRAFwt and 15 PTCs BRAFV600E). Moreover, we validated our results using TGCA thyroid carcinoma dataset. Results: We found that 59.8% of the patients showed low-grade PDCD4 nuclear expression and low-grade expression correlated with BRAF V600E. Compared with BRAF 15 wild-type tissue samples, a significant miR-21 up-regulation was associated with BRAF V600E mutations. Lowgrade PDCD4 resulted, and was associated with aggressive histological variants, higher cancer size, extra-thyroidal extension, multifocality, lymph-node metastasis and lymph nodal ratio at the diagnosis. Concerning the outcome, the low-grade PDCD4 expression correlated at univariate and multivariate analysis, with lower levels of recurrence-free survival rate (RFS) and with poor outcome. Moreover, there was significant association between BRAF V600E patients with PDCD4 nuclear loss and lower RFS, whilet here was significant association between BRAF wild-type patients with PDCD4 nuclear expression and better outcome. Conclusion: These results showed that PDCD4 could predict PTC outcome and that the sum of PDCD4 and BRAF alterations increases the prognostic power of BRAF mutation alone

Calcitonin levels in autoimmune atrophic gastritis-related hypergastrinemia

Purpose: Calcitonin (Ct) is currently the most sensitive biochemical marker of C-cell disease (medullary thyroid cancer [MTC] and C-cell hyperplasia), but its specificity is relatively low. Our aim was to examine whether autoimmune atrophic gastritis (AAG) and chronic hypergastrinemia, with or without chronic autoimmune thyroiditis (AT), are conditions associated with increased Ct levels. Methods: Three groups of patients were consecutively enrolled in this multicentric study: group A consisted of patients with histologically-proven AAG (n = 13; 2 males, 11 females); group B fulfilled the criteria for group A but also had AT (n = 92; 15 males, 77 females); and group C included patients with AT and without AAG (n = 37; 6 males, 31 females). Results: Median Ct levels did not differ between the three groups. Ct levels were undetectable in: 8/13 cases (61.5%) in group A, 70/92 (76.1%) in group B, and 27/37 (73.0%) in group C. They were detectable but ≤ 10 ng/L in 4/13 (30.8%), 20/92 (21.7%) and 7/37 (18.9%) cases, respectively; and they were > 10 ng/L in 1/13 (7.7%), 2/92 (2.2%) and 3/37 (8.1%) cases, respectively (P = 0.5). Only three patients had high Ct levels (> 10 ng/L) and high gastrin levels and had an MTC. There was no correlation between Ct and gastrin levels (P = 0.353, r = 0.0785). Conclusions: High gastrin levels in patients with AAG do not explain any hypercalcitoninemia, regardless of whether patients have AT or not. This makes it mandatory to complete the diagnostic process to rule out MTC in patients with high Ct levels and AAG

The impact of recent next generation sequencing and the need for a new classification in gastric cancer

The phenotypical and molecular heterogeneity of gastric cancer has hampered the introduction in clinical practice of a unifying classification of the disease. However, as next generation sequencing (NGS) technologies enhanced the comprehension of the molecular landscape of gastric cancer, novel molecular classification systems have been proposed, allowing the dissection of molecular tumor heterogeneity and paving the way for the development of new targeted therapies. Moreover, the use of NGS analyses in the molecular profiling of formalin-fixed paraffin-embedded (FFPE) specimens will improve patient selection for the enrolment in novel clinical trials. In conclusion, the application of NGS in precision oncology will revolutionize the diagnosis and clinical management in gastric cancer patients

Current role of non-coding RNAs in the clinical setting

Non-coding RNAs (ncRNAs) have long been considered as \u201cjunk\u201d material of the human genome until functional studies have exposed them as critical regulators of gene expression in both physiological and pathological conditions. Mounting evidences have also shown that ncRNAs may serve as diagnostic markers for several disorders, predictor for drugs response, and targets for new therapeutic approaches. In this mini-review, we discuss the state of the art of non-coding RNAs in drug development and their involvement in conventional treatments response

Gastric xanthomatosis: a rare finding in the paediatric age.

Background: Gastric xanthoma are rare benign lesions most frequently found in the antrum. They can be associated with inflammation of the gastric mucosa, especially in patients with chronic gastritis, Helicobacter pylori, intestinal metaplasia, bile reflux. Their etiology is nevertheless not completely known as they are rarely described. Just a few number of adult cases aging >35 years has been reported [1], whereas to our knowledge only one previous paediatric case was described as yet [2]. Specific aim: We report a rare paediatric case of gastric xanthomatosis, whose endoscopic follow-up demonstrates the evolution of lesions and their correlation with Proton Pump Inhibitors (PPI) treatment administered. Case Report: A 13 year old girl came to our attention for disphagia, chest burning, feeling of regurgitation and rumination after each meal. Neither abdominal pain, nor alteration in stool frequency were referred. The clinical assessment was normal, except for a mild decrease in body weight (from 25th to 10th percentile) with respect to the height (50th percentile). The general blood tests performed were all negative, gastro-panel included [3]. A first upper-GI tract endoscopy previously performed had identified two whitish kissing lesions with diameter of 0.3 cm surrounded by hyperhaemic mucosa, in the middle of the small gastric curve, and a mild hyperhaemic antral mucosa. The histologic examination demonstrated inactive chronic gastritis at the antrum as well as in the areas next to the two lesions; no Helicobacter pylori was detected. A therapeutic trial with PPI was suggested and performed for one month, with only partial remission of symptoms. Given a relapse of symptoms fifteen days after the suspension of the PPI treatment, we decided to perform at our Unit another upper-GI-tract endoscopy two months after the previous one, in order to evaluate the effect of the ongoing treatment on the gastric lesions. Six gastric lesions were found this time: they appeared as nodules and soft pseudo-polyps and measuring 0.5 121 cm, with a greyish-whitish top resembling a papilloma. The presence of bile reflux was observed. The histologic examination evidenced foamy histiocytes being compatible with gastric xanthoma. Discussion: It is important not to misrecognize the nature of these lesions, since they may present at endoscopy an ulcer-like aspect, so that an anti-acidic treatment could be therefore inappropriately prescribed. Taking biopsies during upper GI-endoscopy is thus fundamental to diagnose gastric xanthoma as well as to exclude gastric tumors. Reference(s) [1] Gravina AG, Iacono A, Alagia I, D\u2019Armiento FP, Sansone S, Romano M. Image of the Month: Gastric xanthomatosis associated with gastric intestinal metaplasia in a dyspeptic patient. Dig Liv Dis 2009; 41: 765. [2] Wetzler G, Felix AA, Lipton JF. Image of the Month: Gastric Xanthelasma. Jour Ped Gastroenterol Nutr 2010; 51: 1. [3] Guariso G, Basso D, Bortoluzzi CF, Meneghel A, Schiavon S, Fogar P, Farina M, Navaglia F, Greco E, Mescoli C, Zambon CF, Plebani M. GastroPanel: evaluation of the usefulness in the diagnosis of gastroduodenal mucosal alterations in children. Clin Chim Acta 2009; 402(1 122): 54 1260

Identification of Influential User Locations for Smart Meter Installation to Reconstruct the Urban Demand Pattern

This paper aims to show how the total demand signal (i.e., the sum of all user demands) of a district metered area (DMA) can be reconstructed using simple linear models starting from the readings taken at influential user locations with a preassigned temporal resolution (e.g., 1 h). By comparing the total reconstructed demand pattern with the inflow into the DMA, which is usually monitored at DMA boundaries using flowmeters, water utilities have the potential to identify occurrences of anomalous events, such as pipe bursts, unauthorized consumption, and leakage increases. To address this issue, two procedures are proposed that are applicable when smart meters at the end of life were previously installed at all locations and when no smart meter was present, respectively. The first procedure is based on the application of the stepwise regression that measures the demand time series aimed at both the selection of user locations and the model calibration, whereas Fisher's test or economic considerations is used as stopping criterion. The second methodology consists of the application of criteria to identify the subset of representative locations on the basis of available data and practical considerations (user typology and consumption on the annual bill). In addition, a new method to calibrate the model using billed annual consumptions is provided. Both methodologies enable the construction of linear models that express the total pattern as a function of single-user consumption patterns, allowing the reconstruction of the original signal. Both procedures were applied to a case study in Naples (Italy) with a total of 1,406 users, that is, 1,067 residential users and 339 non-residential users. The results proved that, as expected, the accuracy of the total demand pattern reconstruction of both procedures increases as the sample size of the representative locations grows. However, the results indicating the trade-off between the sample size and the goodness of the fit reveal that the accuracy is good even for low model order (25-50 users selected). Indeed, the coefficient of determination, R2, of the fit increases from 0.66 to 0.83 for 25 and 50 users selected, respectively, and the accuracy becomes almost perfect for a size of 100 (i.e., approximately 7% of the total number of users considered). Overall, this paper demonstrates that an effective strategy for the accurate characterization of the total demand in a DMA consists of distributing the preassigned number of smart meters between the different categories of users present in that DMA (i.e., residential and non-residential) and privileging users with the highest annual consumption