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In the era of personalised medicine, testing for an increasing number of predictive biomarkers is becoming a priority. However, tissue biopsies from these patients are oftentimes insufficient for conventional approaches, a common issue that deprives them of the clinical benefits of biomarker-directed treatments. To tackle this problem, many clinical laboratories are resorting to circulating tumour DNA (ctDNA), which is becoming increasingly appreciated as a valuable source for biomarker testing. In this context, next-generation sequencing (NGS) has become essential. Indeed, different NGS systems are able to detect several clinically relevant low-frequency hot-spot mutations simultaneously in a single run. However, their reproducibility in the analysis of ctDNA has not yet been investigated. The purpose of this study was to evaluate the reproducibility of using Illumina MiSeq and Thermo Fisher Ion S5 Plus platforms to assess pathogenic alterations in non-small cell lung cancer (NSCLC) liquid biopsy specimens. Using the in vitro diagnostic (IVD) NGS panel Myriapod NGS Cancer panel DNA (Diatech Pharmacogenetics) on MiSeq platform (Illumina), we reanalysed ctDNA extracted from a retrospective series of n=40 patients with advanced NSCLC previously tested with a custom NGS panel (SiRe) on Thermo Fisher Ion S5 Plus system. Overall, 13 out of 40 (32.5%) ctDNA samples displayed pathogenic alterations in at least two genes, namely, EGFR and KRAS A concordance rate of 100% was identified between the two methodologies in terms of sample mutational status and total number of detected variables. All NGS platforms featured a high degree of concordance.

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In the present study, we analysed 44 formalin fixed paraffin embedded (FFPE) from different solid tumours by adopting two different next generation sequencing platforms: GeneReader (QIAGEN, Hilden, Germany) and Ion Torrent (Thermo Fisher Scientific, Waltham, Massachusetts, USA). We highlighted a 100% concordance between the platforms. In addition, focusing on variant detection, we evaluated a very good agreement between the two tests (Cohen's kappa=0.84) and, when taking into account variant allele fraction value for each variant, a very high concordance was obtained (Pearson's r=0.94). Our results underlined the high performance rate of GeneReader on FFPE samples and its suitability in routine molecular predictive practice.

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BACKGROUND AND AIMS: the diagnosis of celiac disease requires small bowel biopsies to identify the characteristic mucosal changes. The current biopsy practice among endoscopists for celiac disease is in most part unknown. The aim of this study was to compare the different diagnostic policies in various centers in their current practice. METHOD: information from a total of 931 confirmed celiac disease patients was retrospectively obtained retrospectively from nine centers in European and Middle Eastern countries. The number of small-bowel biopsies obtained from the duodenal bulb and the second part of the duodenum was compared among different centers. RESULTS: the most frequent stage of mucosal changes amongst Iranian subjects was Marsh IIIa whereas in the rest of the study population was Marsh IIIc. Marsh I and Marsh II were more prevalent in adults (P < 0.05) and Marsh IIIc was significantly higher in pediatric ages between 1 and 15 (P < 0.05). The most common number of biopsy specimens obtained from Romanian subjects was 1 (52% of cases), followed by 2 for Iranian (56%), 3 for Lithuanian (66.7%) and British patients (65%) and 4 for Italian patients (48.3%). For majority of cases, anemia was the most prevalent symptom (18.7%) followed by malabsorption (10.5%), diarrhea (9.3%) and dyspepsia (8.2%), respectively. CONCLUSIONS: despite the evidence-based recommendations, this study revealed a poor compliance with major guidelines on diagnosis of celiac disease. We emphasize that taking adequate number of duodenal biopsies should be implemented for an accurate diagnosis and also for the exclusion of celiac disease.

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Background and aims: the diagnosis of celiac disease requires small bowel biopsies to identify the characteristic mucosal changes. The current biopsy practice among endoscopists for celiac disease is in most part unknown. The aim of this study was to compare the different diagnostic policies in various centers in their current practice. Method: information from a total of 931 confirmed celiac disease patients was retrospectively obtained retrospectively from nine centers in European and Middle Eastern countries. The number of small-bowel biopsies obtained from the duodenal bulb and the second part of the duodenum was compared among different centers. Results: the most frequent stage of mucosal changes amongst Iranian subjects was Marsh IIIa whereas in the rest of the study population was Marsh IIIc. Marsh I and Marsh II were more prevalent in adults (P < 0.05) and Marsh IIIc was significantly higher in pediatric ages between 1 and 15 (P < 0.05). The most common number of biopsy specimens obtained from Romanian subjects was 1 (52% of cases), followed by 2 for Iranian (56%), 3 for Lithuanian (66.7%) and British patients (65%) and 4 for Italian patients (48.3%). For majority of cases, anemia was the most prevalent symptom (18.7%) followed by malabsorption (10.5%), diarrhea (9.3%) and dyspepsia (8.2%), respectively. Conclusions: despite the evidence-based recommendations, this study revealed a poor compliance with major guidelines on diagnosis of celiac disease. We emphasize that taking adequate number of duodenal biopsies should be implemented for an accurate diagnosis and also for the exclusion of celiac disease(AU)

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BACKGROUND: Celiac disease (CD) may have a variety of different presentations. This study has aimed to explore the prevalence of gastrointestinal (GI) and non-GI symptoms in patients with CD according to data collected in Italy and Romania (Europe) and Iran (Middle East). METHODS: This is a retrospective cross-sectional study conducted in Iran, Romania and Italy with data collection during the period from May 2009 - May 2011. For each center we included only patients with CD that was confirmed by endoscopy, small bowel biopsies and positive serology. GI symptoms such as abdominal pain, diarrhea, constipation, nausea and vomiting, weight loss and flatulence, as well as additional signs and symptoms of iron deficiency anemia (IDA), osteoporosis, hypertransaminasemia, and other related abnormalities were collected. RESULTS: Overall, 323 women and 127 men, whose mean age at diagnosis was 34.2 ± 16.47 years were included in this study. Of these, 157 subjects (34.9%) reported at least one GI symptom. The majority of cases had the following primary presenting GI symptoms: diarrhea (13.6%), dyspepsia and constipation (4.0%). Other disease symptoms were reported by 168 (37.3%) patients. The most presenting non-GI symptoms in the majority of cases were anemia (20.7%) and osteopenia (6%). There were statistically significant differences between the majority of symptoms when we compared the reported clinical symptoms from different countries. CONCLUSION: This study indicated that upper abdominal disorders such as abdominal pain and dyspepsia were the most common primary complaints among European patients, whereas Iranian patients had complaints of diarrhea and bloating as the classic presentations of CD. For non-GI symptoms, anemia was the most frequent complaint for both Iranian and Italian patients; however it was significantly higher in Iranians.

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The aim of this study is to evaluate the prognostic values of some biological parameters in a population based series of female breast cancer patients. Through the Tuscan Cancer Registry all the invasive breast cancer cases diagnosed during the period 2004-2005 in the provinces of Florence and Prato, central Italy, were retrieved. Molecular subtypes were analyzed defined by immunohistochemical markers, by age, tumor size, lymph node status, histotype, grade of differentiation and proliferative marker. Out of 1487 patients 70.3% were luminal A subtype (ER/PR + HER2-), 15.6% luminal B (ER/PR + HER2+), 8.1% triple negative (ER/PR-HER2-), 6.0% HER2+ (ER/PR-HER2+); the 3 year survival rates were 93.3%, 89.5%, 86.3%, 82.7% respectively (p < 0.001). Analysis of survival by the Cox proportional hazards model showed an independent prognostic value of molecular classification. Our study revealed significant differences in clinicopathological characteristics among breast cancer molecular subtypes and confirmed their prognostic independent role.

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The widespread implementation of mammography screening has resulted in an increased frequency of needle core biopsies (NCB). The aim of this study was that of evaluating the diagnostic reproducibility on breast NCB, according to the B-classification, among several pathologists from different Italian regions. Fifty single slides of NCBs performed for non palpable breast lesions were selected to evaluate the diagnostic reproducibility, according to the B classification, among 31 pathologists from different Italian areas, involved in the pathologic diagnosis of screen-detected breast lesions. According to the study majority diagnosis (MD), 21 cases were classified as B2 (benign lesion), 23 B3 (lesion of uncertain malignant potential) and 6 B5 (malignant lesion). Overall, individual kappa coefficients in comparison to MD were good (mean 0.61, range 0.31-0.88). The level of inter-observer agreement, however, appeared lower in differentiating the two intermediate categories B2 and B3, thus potentially leading to over-treatment (false-positives: 26%) or under-treatment (false-negatives: 17%) of individual patients. Specific sub-types of B3 need an improvement of the diagnostic definition. A multidisciplinary approach and consultation with expert colleagues are recommended.

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BACKGROUND: The association between intestinal-type sinonasal adenocarcinoma and the occupational exposure to leather dusts has been widely documented, but the identification of precursor lesions in exposed workers has remained controversial. The purpose of this study was to investigate the histological changes and modifications in the phenotype of epithelial cells in nasal mucosa of leather workers. METHODS: Biopsy specimens of the mucosa of the middle turbinate were obtained from 139 subjects who had been employed in leather factories for 10-48 years (median, 29 years). Tissue fragments were routinely processed for histological examination and immunostainings for cytokeratin 20, CDX-2, and MUC-2 were performed. RESULTS: Regarding the surface epithelium, the most common histopathological finding was the presence of squamous metaplasia (64.7%), which was associated with mild to moderate dysplasia in 37 cases (41.1%), and goblet cell hyperplasia was identified in 30 biopsy specimens (21.6%). Positivity for MUC-2 was detected in goblet cells of 20 of the 30 samples with goblet cell hyperplasia (66.6%), whereas no immunostaining was observed for cytokeratin 20 and CDX-2. Presence of goblet cell hyperplasia was significantly associated with longer occupational exposure in leather tanning activities (p = 0.03). None of the alterations observed (squamous metaplasia, dysplasia, or goblet cell hyperplasia) showed correlation with smoking habits. Similarly, there was no correlation between squamous metaplasia with or without dysplasia and type and duration of occupational exposure. CONCLUSION: Our data identify goblet cell hyperplasia as possible work-related alterations of nasal mucosa in leather workers. Additional investigations are needed to clarify the significance of these findings in the development of sinonasal intestinal-type carcinoma.

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BACKGROUND: Imatinib mesylate represents a real major paradigm shift in cancer therapy, targeting the specific molecular abnormalities, crucial in the etiology of tumor. Intra-arterial hepatic chemotherapy (IAHC) followed by embolization, has been considered an interesting palliative option for patients with liver metastases from gastrointestinal stromal tumor (GIST), due to the typically hypervascular pattern of the tumor. AIMS: We report our experience with IAHC followed by Imatinib mesylate, in order to show the superiority of the specific molecular approach in liver metastases from GIST. MATERIALS AND METHODS: Three patients (pts) with pretreated massive liver metastases from GIST, received IAHC with Epirubicin 50 mg/mq, every 3 weeks for 6 cycles. At the evidence of progression, they received Imatinib mesylate. RESULTS: We observed progressive diseases in all cases. In 1998, one patient underwent Thalidomide at 150 mg orally, every day for 4 months, with evidence of stable disease and clinical improvement. In 2001, two patients received Imatinib mesylate at 400 mg orally, every day, with evidence of partial response lasting 18+ months and 16 months. One of them had grade 3 neutropenia, with suspension of therapy for 3 weeks. CONCLUSION: No patient treated with IAHC, reported objective responses, but two of them obtained partial response after the assumption of Imatinib mesylate and one showed temporary stabilization with thalidomide. Imatinib mesylate represents a new opportunity in GIST therapy, targeting the specific molecular alteration. It seems to be superior to conventional intra arterial hepatic chemotherapy.

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