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Background and aims: Diagnosis of the biliary stricture remains a challenge. In view of the low sensitivity of brush cytology (BC), fluorescence in situ hybridization (FISH) has been reported as a useful adjunctive test in patients with biliary strictures. We aimed to determine performance characteristics of BC and FISH individually and in combination (BC + FISH) in the primary diagnosis of biliary strictures. Methods: This single-center prospective study was conducted between April 2019 and January 2021. Consecutive patients with unsampled biliary strictures undergoing first endoscopic retrograde cholangiopancreatography in our institution were included. Tissue specimens from two standardized transpapillary brushings from the strictures were examined by routine cytology and FISH. Histopathological confirmation after surgery or 12-month follow-up was regarded as the reference standard for final diagnosis. Results: Of 109 enrolled patients, six were excluded and one lost from the final analysis. In the remaining 102 patients (60.8% males, mean age 67.4, range 25–92 years), the proportions of benign and malignant strictures were 28 (27.5%) and 74 (72.5%), respectively. The proportions of proximal and distal strictures were 26 (25.5%) and 76 (74.5%), respectively. In comparison to BC alone, FISH increased the sensitivity from 36.1% to 50.7% (p = 0.076) while maintaining similar specificity (p = 0.311). Conclusions: Dual-modality tissue evaluation using BC + FISH showed an improving trend in sensitivity for the primary diagnosis of biliary strictures when compared with BC alone. [ABSTRACT FROM AUTHOR]

During endoscopic procedures for suspected urothelial tumors of the upper urinary tract, radiographic imaging using an iodinated contrast medium is often required. However, following ureteropyelography, we detected changes in cytology characteristics not correlating with real cytology findings in naive urine. The aim of our study was to assess cytology changes between naive and postcontrast urine according to The Paris System of cytology classification. Methods: We prospectively assessed urine samples from 89 patients (23 patients with histologically proven urothelial cancer and 66 healthy volunteers). The absence of malignancy was demonstrated by CT urography and/or ureteroscopy. The study was single blind (expert cytopathologist) and naïve Paris system for urine cytology assessment was used. Furthermore, additional cytological parameters were analyzed (e.g., specimen cellularity, degree of cytolysis, cytoplasm and nucleus color, chromatin and nucleo-cytoplasmic ratio). Results: Our study showed statistically significant differences when comparing naïve and postcontrast urine in healthy volunteers (only 51 % concordance, p = 0.001) versus malignant urine specimens (82 % concordance). The most important differences were in the shift from The Paris System category 2 (negative) to 1 (non-diagnostic) and from category 2 (negative) to 3 (atypia). Other significant changes were found in the assessment of specimen cellularity (p = 0.0003), degree of cytolysis (p = 0.001), cytoplasm color (p = 0.003), hyperchromasia (p = 0.001), course chromatin (p = 0.002), nucleo-cytoplasmatic ratio (p = 0.001) and nuclear borders' irregularity (p = 0.01). Conclusion: Our unique study found crucial changes in the cytological assessment of naive and postcontrast urine and we confirm that postcontrast urine is more often assessed as abnormal, suspect or non-diagnostic. Therefore, before urine collection for cytology, the clinician should avoid administration of iodinated contrast into the urinary tract. [ABSTRACT FROM AUTHOR]

Prostate cancer (PCa) is the second leading cause of cancer-related deaths in men in Western countries, and there is still an urgent need for a better understanding of PCa progression to inspire new treatment strategies. Skp2 is a substrate-recruiting component of the E3 ubiquitin ligase complex, whose activity is regulated through neddylation. Slug is a transcriptional repressor involved in the epithelial-to-mesenchymal transition, which may contribute to therapy resistance. Although Skp2 has previously been associated with a mesenchymal phenotype and prostate cancer progression, the relationship with Slug deserves further elucidation. We have previously shown that a high Gleason score (≥8) is associated with higher Skp2 and lower E-cadherin expression. In this study, significantly increased expression of Skp2, AR, and Slug, along with E-cadherin downregulation, was observed in primary prostate cancer in patients who already had lymph node metastases. Skp2 was slightly correlated with Slug and AR in the whole cohort (Rs 0.32 and 0.37, respectively), which was enhanced for both proteins in patients with high Gleason scores (Rs 0.56 and 0.53, respectively) and, in the case of Slug, also in patients with metastasis to lymph nodes (Rs 0.56). Coexpression of Skp2 and Slug was confirmed in prostate cancer tissues by multiplex immunohistochemistry and confocal microscopy. The same relationship between these two proteins was observed in three sets of prostate epithelial cell lines (PC3, DU145, and E2) and their mesenchymal counterparts. Chemical inhibition of Skp2, but not RNA interference, modestly decreased Slug protein in PC3 and its docetaxel-resistant subline PC3 DR12. Importantly, chemical inhibition of Skp2 by MLN4924 upregulated p27 and decreased Slug expression in PC3, PC3 DR12, and LAPC4 cells. Novel treatment strategies targeting Skp2 and Slug by the neddylation blockade may be promising in advanced prostate cancer, as recently documented for other aggressive solid tumors. [ABSTRACT FROM AUTHOR]