Extra-osseous Ewing sarcoma of the thyroid gland mimicking lymphoma recurrence: a case report

Extra-osseous Ewing sarcomas/peripheral primitive neuroectodermal tumors (EOES/pPNETs) are high-grade malignant tumors found in various organs, such as the lung, skin, intestine, kidney and female genital tract; however, to the best of our knowledge, only two cases have previously been identified in the thyroid gland. We describe a case of primary EOES/PNET of the thyroid gland in a 66-year-old man with a previous history of large B cell lymphoma. During a routine follow-up examination, the patient underwent an ultrasound cervical scan showing a solid nodule of the left thyroid lobe. The fine-needle aspiration biopsy of the nodule suggested a neuroendocrine tumor. Histological and immunohistochemical examination of the surgical specimen supported a diagnosis of EOES/PNET, which was further confirmed by the demonstration of EWSR1 gene translocation by means of fluorescent in situ hybridization and by the detection of glycogen particles and neurosecretory granules by means of electron microscopy. Total body computed tomography and magnetic resonance imaging excluded the involvement of other sites, and therefore a diagnosis of primary EOES/PNET of the thyroid gland was made.This paper also discusses the main differential diagnoses, including lymphoma recurrence, other small round cell tumors (primary or metastatic), and a thyroid localization of an EWS/PNET from another organ

KRAS mutational analysis in ductal adenocarcinoma of the pancreas and its clinical significance.

Mutations of KRAS are detectable in 70-90% of pancreatic duct adenocarcinomas (PDAC), using direct sequencing. We used a highly sensitive molecular method in order to investigate: (a) the frequency and prognostic significance of different KRAS mutations and, (b) whether the presence of KRAS mutations in histologically-negative resection margins of PDAC could explain local tumor recurrence after surgery. Twenty-seven patients with histologic diagnosis of PDAC, radical pancreaticoduodenectomy and histologically-negative margins were evaluated. KRAS mutations were searched for mutant-enriched PCR in tumor and negative resection margins. KRAS mutations were detected in 85.2% of the cases; the most frequent mutation was G12D (48.1%). Shorter OS was found in patients with G12D (25 months; 95% CI, 20.5-29.5), vs patients with other mutations (31.5 months; 95% CI, 25.6-37.1) (N.S.). KRAS mutation in histologically-negative margins was detected in one patient who died of locoregional recurrence; six patients had tumor recurrence but no mutations in surgical margins. The high frequency of KRAS mutations suggests a search for KRAS status to improve the diagnosis in suspected cases; the G12D mutation could be related to poor prognosis, but without statistical significance. No correlation was found between the frequency of cancer recurrence and KRAS mutations in surgical margins

Georgian yeasts and grape cultivars do edit the wine quality in a precision oenology

Georgia, a country of the South Caucasus region, is recognised to be the oldest place with winemaking practice since the Neolithic period. Eight-thousand years of winemaking experience has led to a continuous progress in both the local oenological techniques and the breeding programs of autochthonous grape varieties, consequently becoming the basis for vini-viticuture of this country. Moreover, the home made production of wine is still very popular in rural families and spontaneous fermentation of must is the norm in Georgia. Five Georgian regions, Guria, Imereti, Ratcha-Lechkhumi, Kartli and Kakheti, were chosen for grape and wines sampling; 22 different native cultivars, in 26 vineyards and 19 family cellars were analysed. This study allowed the isolation of one hundred and eighty-two novel wine-associated yeasts from Georgia. Yeast of the collection were ascribed to 15 different species; Metschnikowia pulcherrima (F\u2019 = 0.56, I\u2019 = 0.32), Hanseniaspora guilliermondii (F\u2019 = 0.49, I\u2019 = 0.27), and Cryptococcus flavescens (F\u2019 = 0.31, I\u2019 = 0.11) were the dominant yeasts found on grapes, whereas Saccharomyces cerevisiae showed the highest prevalence into wine samples. Seventy four isolates with fermentative potential were screened for oenological traits such as ethanol production, resistance to SO2, and acetic acid, glycerol and H2S production. Three yeast strains belonging to the Kluyveromyces marxianus, S. cerevisiae and Torulaspora delbrueckii species were selected and separately inoculated in vinifications experiments at a Georgian cellar, using musts from healty grapes of two local cultivars Goruli Mtsvane (B) and Saperavi (N). Physical (\ub0Brix) and microbial analyses (plate counts) were performed to monitor the fermentative process. The results from quantitative GC-FID analysis of volatile compounds revealed that the highest amount of fermentation flavors were significantly more produced in fermentation conducted in Saperavi variety inoculated with K. marxianus, whereas other aromatic compounds showed a higher content in Goruli Mtsvane variety samples fermented by S. cerevisiae. The selected yeast strains have proved to be promising for enhancing the flavor potential in low aromatic Georgian cultivars. This work intends to be a knowledge contribution for a precision oenology toward the strategic concept of \u201cone grape variety-one yeast\u201d

Prognostic Value of QFR Measured Immediately After Successful Stent Implantation: The International Multicenter Prospective HAWKEYE Study

The aim of this study was to investigate the potential role of post-percutaneous coronary intervention (PCI) quantitative flow ratio (QFR) measurements to predict clinical outcomes in patients with successful PCI

Epidermal growth factor receptor gene analysis with a highly sensitive molecular assay in routine cytologic specimens of lung adenocarcinoma

Epidermal growth factor receptor (EGFR) gene mutational analysis is critical for guiding the treatment of lung adenocarcinoma. In everyday clinical practice, EGFR testing is frequently centralized in referral laboratories that may receive paucicellular cytologic specimens, often fixed in various ways. We conducted a search for EGFR mutations in 108 cytologic samples of lung adenocarcinoma from different hospitals using the TheraScreen EGFR29 kit. These samples included 80 (74.1%) fine-needle aspirations, 13 (12%) pleural/ascitic fluids, 13 (12%) bronchial washings, and 2 bronchial brushings. The samples were fixed in ethanol (n = 79), Duboscq-Brasil (n = 18) or formalin (n = 10); 1 was unfixed. Ninety-two (85.2%) were amplified, 16 (14.8%) were not. Mutations were detected in 22 (23.9%) of 92 amplified samples, 9 containing less than 200 cancer cells, and 4 with less than 50% cancer cells. DNA was amplified in 12 of 18 Duboscq-Brasil-fixed samples. These findings indicate that cytologic specimens are adequate for EGFR testing when a highly sensitive assay is used, even if they are paucicellular or not optimally fixed

Mutation analysis of the EGFR gene and downstream signalling pathway in histologic samples of malignant pleural mesothelioma.

BACKGROUND: As epidermal growth factor receptor (EGFR) is involved in the pathogenesis of malignant pleural mesotheliomas (MPMs), the anti-EGFR drugs may be effective in treating MPM patients. Mutations of the EGFR gene or its downstream effectors may cause constitutive activation leading to cell proliferation, and the inhibition of apoptosis and metastases. Consequently, molecular profiling is essential for select patients with MPM who may respond to anti-EGFR therapies. METHODS: After manual macrodissection, genomic DNA was extracted from 77 histological samples of MPM: 59 epithelioid, 10 biphasic, and 8 sarcomatoid. Epidermal growth factor receptor gene mutations were sought by means of real-time polymerase chain reaction (PCR) and direct sequencing, KRAS gene mutations by mutant-enriched PCR, and PIK3CA and BRAF gene mutations by direct sequencing. RESULTS: Gene mutations were identified in nine cases (12%): five KRAS, three BRAF, and one PI3KCA mutation; no EGFR gene mutations were detected. There was no difference in disease-specific survival between the patients with or without gene mutations (P=0.552). CONCLUSIONS: Mutations in EGFR downstream pathways are not rare in MPM. Although none of those found in this study seemed to be prognostically significant, they may support a more specific selection of patients for future trials

Mutation analysis of KRAS in primary colorectal cancer and matched metastases by means of highly sensitivity molecular assay.

Mutation analysis of KRAS is needed before starting treatment with anti-EGFR monoclonal antibodies in patients with metastatic colorectal cancer (CRC). In most of the cases, testing is performed on primary tumors, assuming that KRAS mutation status does not change in metastasis although correlation studies gave conflicting results. We evaluated the KRAS status concordance rate between primary tumors and related metastasis using a highly sensitive molecular assay. Forty-five primary tumors and related metastases from patients with CRC (28/45 male-62.2% and 17/45 female-37.8%; mean age 66.4 years) were analyzed by using TheraScreen: KRAS mutational kit. Metastatic samples were collected from lymph nodes (8/45-17.8%) and visceral sites (37/45-82.2%); 23 were synchronous (49%) and 22 were metachronous (51%), obtained after a mean of 30.8 months after the first diagnosis of CRC. Twenty-eight patients had KRAS mutations in both primary CRC and related metastases (62.2%). No differences in type and frequency of mutations were identified, despite different metastatic sites and time of onset of metastatic disease. Our results indicate that the mutation status of KRAS is the same in primary CRC and metastasis, suggesting that in clinical practice, KRAS testing can be performed on both tumor tissues when using a highly sensitive molecular assay

Eranshahr: Uomo, ambiente e società nell’Iran arsacide e sasanide. Testimonianze scritte, cultura materiale e società da Arsace a Yazdegard III

L’arco temporale che si pone a cavallo tra due transizioni politiche di notevole importanza, la prima tra la dinastia dei Seleucidi e quella degli Arsacidi, la seconda tra la dinastia dei Sasanidi e il califfato islamico, costituisce un contesto cruciale per la messa in pratica di diversi approcci metodologici volti alla comprensione delle relazioni tra uomo, potere politico e territorio nell’Iran tra III sec. a.C. e VII d.C. In tale quadro si è scelto di focalizzare l’attenzione su tre aree nodali dell’Iran antico: le regioni storiche dell’Elimaide (Khuzestan), della Persia (Pars) e della Media (Mad e Pahlaw). Le regioni prese in considerazione, pur caratterizzate da notevoli differenze, furono al centro delle trasformazioni del periodo e forniscono informazioni utili per la ricostruzione di specifiche dinamiche storico-culturali

Human malignant mesothelioma is recapitulated in immunocompetent BALB/c mice injected with murine AB cells

Malignant Mesothelioma is a highly aggressive cancer, which is difficult to diagnose and treat. Here we describe the molecular, cellular and morphological characterization of a syngeneic system consisting of murine AB1, AB12 and AB22 mesothelioma cells injected in immunocompetent BALB/c mice, which allows the study of the interplay of tumor cells with the immune system. Murine mesothelioma cells, like human ones, respond to exogenous High Mobility Group Box 1 protein, a Damage-Associated Molecular Pattern that acts as a chemoattractant for leukocytes and as a proinflammatory mediator. The tumors derived from AB cells are morphologically and histologically similar to human MM tumors, and respond to treatments used for MM patients. Our system largely recapitulates human mesothelioma, and we advocate its use for the study of MM development and treatment