PCA3 score and prostate cancer diagnosis at repeated saturation biopsy. Which cut-off: 20 or 35?

PURPOSE: To compare PCA3 score cut-off of 35 vs 20 in PCa diagnosis in patients undergoing repeated saturation prostate biopsy (SPBx). MATERIALS AND METHODS: From January 2010 to May 2011, 118 patients (median 62.5 years) with primary negative extended biopsy underwent a transperineal SPBx (median 30 cores) for persistent suspicion of PCa. The indications for repeated biopsy were: persistently high or increasing PSA values; PSA > 10 ng/mL, PSA values between 4.1-10 or 2.6-4 ng/mL with free/total PSA ≤ 25% and ≤ 20%, respectively; moreover, before performing SPBx urinary PCA3 score was evaluated. RESULTS: All patients had negative DRE and median PSA was 8.5 ng/mL (range: 3.7-24 ng/mL). A T1c PCa was found in 32 patients (27.1%): PCA3 score was 59 (median; range: 7-201) in the presence of PCa and 35 (median; range: 3-253) in the absence of cancer (p < 0.05). In the presence of ASAP and HGPIN median PCA3 score was 109 (range: 42-253) and 40 (range: 30-140), respectively. Diagnostic accuracy, sensitivity, specificity, PPV and NPV of PCA3 score cut-off of 20 vs 35 in PCa diagnosis were 44.9 vs 50%, 90.6 vs 71.9%, 27.9 vs 41.8%, 31.9 vs 31.5% and 88.9 vs 80%, respectively. ROC analysis demonstrated an AUC for PCA3 ≥ 20 vs ≥ 35 of 0.678 and 0.634, respectively. CONCLUSIONS: Our data suggest that PCA3 is more useful as an exclusion tool; moreover, setting a PCA3 cut-off at 20 vs 35, would have avoided 22.9 vs 38.1% of biopsies while missing 9.4% and 28% diagnosis of PCa

Hypoxia inducible factor-1 alpha expression is increased in infected positive HPV16 DNA oral squamous cell carcinoma and positively associated with HPV16 E7 oncoprotein

<p>Abstract</p> <p>Background</p> <p>There is increasing evidence for the role of High Risk (HR) Human PapillomaVirus (HPV) in the pathogenesis of Oral Squamous Cell Carcinoma (OSCC). The E6 and E7 oncogenes from HR HPVs are responsible for the deregulation of p53 and pRB proteins involved in cell cycle and apoptotic pathways. In cell lines experiments, the HPV E7 protein seems to be able to enhance Hypoxia Inducible Factor-1 alpha (HIF-1α) activity, normally involved in the response to hypoxia and able to enhance angiogenesis.</p> <p>Results</p> <p>We studied tumor specimens from 62 OSCC; a higher prevalence of tumors in TNM stage II and also in pT2 class between OSCC infected positive HPV16 DNA than non-infected ones was observed. HIF-1α positivity was detected throughout the analysed fields, not associated with areas of necrosis and also observed in cells immediately adjacent to blood vessels. A significant increase in mean values of the HIF-1α labeling indexes was observed for pT1-T2, as well for stage I-II, in the infected positive HPV16 DNA tumors than non-infected ones. HIF-1α and HPV16 E7 labeling indexes showed a significantly positive correlation which suggested a positive association between HPV16 E7 and HIF-1α expression.</p> <p>Conclusions</p> <p>In our specimens HIF-1α immunoreactivity hints for an O₂-independent regulatory mechanism in infected positive HPV16 DNA tumors, especially for pT1-T2 and stage I-II tumors, suggesting a very early involvement in the development of HPV-induced OSCC. HIF-1α and HPV16 E7 labeling indexes suggest also a positive association between the two proteins in infected positive HPV16 DNA OSCC.</p

The Evaluation Culture to Build a Network of Competitive Cities in the Mediterranean

The gradual shift of the economic centre of gravity to the east, with the consequent marginalization of the majority parts of Europe, requires an approximation, in a short time, for the Mediterraneans peoples and their cultures to create a common space that will strengthen the interdependencies and complementarities

Implementation and Improvement of the Partial Sum Attack on 6-round AES

The Partial Sum Attack is one of the most powerful attacks, independent of the key schedule, developed in the last 15 years against reduced-round versions of AES. In this paper, we introduce a slight improvement to the basic attack which lowers the number of chosen plaintexts needed to successfully mount it. Our version of the attack on 6-round AES can be carried out completely in practice, as we demonstrate providing a full implementation. We also detail the structure of our implementation, showing the performances we achieve

Concomitant Small Cell Neuroendocrine Carcinoma of Gallbladder and Breast Cancer

The neuroendocrine carcinoma is defined as a high-grade malignant neuroendocrine neoplasm arising from enterochromaffin cells, usually disposed in the mucosa of gastric and respiratory tracts. The localization in the gallbladder is rare. Knowledge of these gallbladder tumors is limited and based on isolated case reports. We describe a case of an incidental finding of small cell neuroendocrine carcinoma of the gallbladder, observed after cholecystectomy for cholelithiasis, in a 55-year-old female, who already underwent quadrantectomy and sentinel lymph-node biopsy for breast cancer. The patient underwent radiotherapy for breast cancer and six cycles of chemotherapy with cisplatin and etoposide. Eighteen months after surgery, the patient was free from disease. Small cell neuroendocrine carcinoma of the gallbladder has poor prognosis. Because of the rarity of the reported cases, specific prognostic factors have not been identified. The coexistence of small cell neuroendocrine carcinoma of the gallbladder with another malignancy has been reported only once.The contemporary presence of the two neoplasms could reflect that bioactive agents secreted by carcinoid can promote phenotypic changes in susceptible cells and induce neoplastic transformation

Biological aggressiveness evaluation in prostate carcinomas: Immunohistochemical analysis of PCNA and p53 in a series of Gleason 6 (3+3) adenocarcinomas

We selected 63 prostate tumors with Gleason's grade 6 (3+3), commonly showing both tubular and cribrous patterns. We compared in both patterns the expression of two of the most used biologic markers: PCNA and p53, with the aim to verify the validity of the Gleason's grading system to compare the morphologic grade with biologic aggressiveness and prognostic value. We did not find any statistical difference in the protein immunopositivity, indicating that both patterns could have identical biologic behaviour; then we confirmed the validity of Gleason's system for considering both tubular and cribrous patterns as an intermediate grade of tumoral differentiation. Moreover, we found a linear relationship between the increase of PCNA and the accumulation of mutated p53; this datum could confirm the hypothesis that p53 mutation is a late event in prostate carcinogenesis

Gut microbiota profiles and characterization of cultivable fungal isolates in IBS patients

Studies so far conducted on irritable bowel syndrome (IBS) have been focused mainly on the role of gut bacterial dysbiosis in modulating the intestinal permeability, inflammation, and motility, with consequences on the quality of life. Limited evidences showed a potential involvement of gut fungal communities. Here, the gut bacterial and fungal microbiota of a cohort of IBS patients have been characterized and compared with that of healthy subjects (HS). The IBS microbial community structure differed significantly compared to HS. In particular, we observed an enrichment of bacterial taxa involved in gut inflammation, such as Enterobacteriaceae, Streptococcus, Fusobacteria, Gemella, and Rothia, as well as depletion of health-promoting bacterial genera, such as Roseburia and Faecalibacterium. Gut microbial profiles in IBS patients differed also in accordance with constipation. Sequence analysis of the gut mycobiota showed enrichment of Saccharomycetes in IBS. Culturomics analysis of fungal isolates from feces showed enrichment of Candida spp. displaying from IBS a clonal expansion and a distinct genotypic profiles and different phenotypical features when compared to HS of Candida albicans isolates. Alongside the well-characterized gut bacterial dysbiosis in IBS, this study shed light on a yet poorly explored fungal component of the intestinal ecosystem, the gut mycobiota. Our results showed a differential fungal community in IBS compared to HS, suggesting potential for new insights on the involvement of the gut mycobiota in IBS. KEY POINTS: Comparison of gut microbiota and mycobiota between IBS and healthy subjects Investigation of cultivable fungi in IBS and healthy subjects Candida albicans isolates result more virulent in IBS subjects compared to healthy subjects

Extrafoveal Müller cells detection in vivo in the human retina: A pilot study based on optical coherence tomography.

Abstract Muller cells (MC) represent a key element for the metabolic and functional regulation of the vertebrate retina. The aim of the present study was to test the feasibility of a new method for the in-vivo detection and quantification of extrafoveal MC in human retina. We developed a new approach to isolate and analyse extrafoveal MC in vivo, starting from structural optical coherence tomography data. Our pilot investigation was based on the optical properties of MC, which are known to not interfere with the light reaching the outer retinal structures. We reconstructed MC in the macular region of 18 healthy subjects and the quantitative analyses revealed ~42,000/9 mm2 cells detected. Furthermore, we included 2 patients affected by peripheral intraocular melanoma, with macular sparing, needing surgical enucleation. We used these two eyes to perform a qualitative comparison between our reconstructions and histological findings. Our study represents the first pilot investigation dedicated on the non-invasive isolation and quantification of MC, in-vivo, in human retina. Although we are aware that our study has several limitations, first of all related with the proper detection of foveal MC, because of the peculiar z-shape morphology, this approach may open new opportunities for the non-invasive in vivo analysis of MC, providing also potential useful perspectives in retinal diseases

Accuracy of 3 Tesla pelvic phased-array multiparametric MRI in diagnosing prostate cancer at repeat biopsy.

Introduction. Multiparametric pelvic magnetic resonance imaging (mpMRI) accuracy in prostate cancer (PCa) diagnosis was evaluated. Materials and Methods. From June 2011 to December 2013, 168 patients (median 65 years) with negative digital rectal examination underwent repeat transperineal saturation biopsy (SPBx; median 28 cores) for persistently high or increasing PSA values, PSA &gt;10 ng/ml or PSA values between 4.1-10 o r 2.6-4 ng/ml with free/total PSA &lt; 25% and &lt; 20%, respectively. All patients underwent mpMRI using a 3.0 Tesla scanner equipped with surface 16 channels phased-array coil and lesions suspicious for PCa were submitted to additional targeted biopsies. Results. A T1c PCa was found in 66 (39%) cases; SPBx and mpMRI-suspicious targeted biopsy diagnosed 60 (91%) and 52 (78.8%) cancers missing 6 (all of the anterior zone) and 14 cancers (12 and 2 of the lateral margins and anterior zone), respectively; in detail, mpMRI missed 12 (18.1%) PCa charaterized by microfocal (1 positive core with greatest percentage of cancer and Gleason score equal to 5% and 6, respectively) disease at risk for insignificant cancer. The diameter of the suspicious mpMRI lesion was directly correlated to the diagnosis of PCa with poor Gleason score (p &lt; 0.05); detection rate of cancer for each suspicious mpMRI core was 35.3%. Diagnostic accuracy, sensitivity, specificity, positive and negative predictive value of mpMRI in diagnosing PCa was 75.7%, 82.5%, 71.8%, 78.9%, 87.9%, respectively. Conclusion. Multiparametric pMRI improved SPBx accuracy in diagnosing significant anterior PCa; the diameter of mpMRI suspicious lesion resulted significantly predictive of aggressive cancers

Rapid molecular assay for the evaluation of clove essential oil antifungal activity against wheat common bunt

Common bunt of durum wheat (DW), Triticum turgidum L. ssp. durum (Desf.) Husn., is caused by the two closely related fungal species belonging to Tilletia genus (Tilletiales, Exobasidiomycetes, Ustilaginomycotina): Tilletia laevis Kühn (syn. T. foetida (Wallr.) Liro.) and T. caries (DC) Tul. (syn. T. tritici (Bjerk.) G. Winter). This is one of the most devastating diseases in wheat growing areas worldwide, causing considerable yield loss and reduction of wheat grains and flour quality. For these reasons, a fast, specific, sensitive, and cost-effective method for an early diagnosis of common bunt in wheat seedlings is urgent. Several molecular and serological methods were developed for diagnosis of common bunt in wheat seedlings but at late phenological stages (inflorescence) or based on conventional PCR amplification, with low sensitivity. In this study, a TaqMan Real Time PCR-based assay was developed for rapid diagnosis and quantification of T. laevis in young wheat seedlings, before tillering stage. This method, along with phenotypic analysis, was used to study conditions favoring pathogen infection and to evaluate the effectiveness of clove oil-based seed dressing in controlling the disease. The overall results showed that: i) the Real Time PCR assay was able to quantify T. laevis in young wheat seedlings after seed dressing by clove oil in different formulations, greatly reducing times of analysis. It showed high sensitivity, detecting up to 10 fg of pathogen DNA, specificity and robustness, allowing to directly analyze crude plant extracts and representing a useful tool to speed up the tests of genetic breeding for disease resistance; ii) temperature was a critical point for disease development when using wheat seeds contaminated by T. laevis spores; iii) at least one of the clove oil-based formulations tested was able to efficiently control wheat common bunt, suggesting that clove oil dressing could represent a promising tool for managing the disease, especially in sustainable farming