Papillary renal neoplasm with reverse polarity: an observational study of histology, immunophenotypes, and molecular variation.

Background: Papillary renal neoplasm with reverse polarity (PRNRP) is a novel entity with unique clinicopathological characteristics, and only a small number of patients with PRNRP have been described. Methods: We retrospectively analyzed the data for nine patients with PRNRP and evaluated differences in the clinical, histomorphological, immunohistochemical, and molecular features; prognosis; and differential diagnosis of PRNRP from other renal tumors with papillary structure. Results: There were six males and three females aged 36 to 74 years (mean: 62.33 years; median: 68 years). All the tumors were solitary and ranged from 1 to 3.7 cm (mean: 2.17 cm; median: 2 cm), with three and six tumors arose in the left and right renal tract, respectively. Pathologically, PRNRP is a small, well-circumscribed neoplasm with predominant papillary formations. The lining epithelium is composed of a monolayer of cuboidal to low-columnar cells with low-grade nuclei arranged against the apical pole of the tumor cells. Edema, mucinous degeneration, and hyaline degeneration are found in the fibrovascular cores. Foamy macrophages, psammoma bodies, hemosiderin deposition, and infiltrative tumor boundaries were present in some patients. Immunohistochemically, all tumors showed diffuse positive staining for GATA3. Sanger sequencing confirmed the presence of KRAS mutation in seven patients. All patients had a good prognosis after surgery and were relapse free. Positive staining for GATA3 and negative staining for vimentin were the most significant markers for differentiating PRNRP from other renal tumors with analogous structure. Conclusions: These findings suggested that PRNRP is a distinctive subtype of renal tumor with specific pathological features and indolent behaviors that should be distinguished from other renal tumors, especially papillary renal cell carcinoma. A monolayer of tumor cells with an inverted nuclear pattern, positive staining for GATA3, and KRAS mutation are essential for pathological diagnosis. Owing to its satisfactory prognosis, the surveillance and follow-up of patients with PRNRP should be additionally formulated.

Simultaneous Determination of Celecoxib, Dezocine and Dexmedetomidine in Beagle Plasma Using UPLC-MS/MS Method and the Application in Pharmacokinetics.

BACKGROUND: An efficient, fast and sensitive ultra high-performance liquid chromatography-mass spectrometry (UPLC-MS/MS) method for simultaneous determination of celecoxib (CEL), dezocine (DEZ) and dexmedetomidine (DEX) in beagle plasma were established. METHODS: The beagle dogs plasmawas precipitated by acetonitrile. The column was Acquity UPLC BEH C18 column and the mobile phase was acetonitrile-formic acid with gradient mode, and the flow rate was set at 0.4 mL/min. Under the positive ion mode, CEL, DEZ, DEX and Midazolam (internal standard, IS) were monitored by multiple reaction monitoring (MRM) as the following mass transition pairs: m/z 381.10→282.10 for CEL, m/z 246.20→147.00 for DEZ, m/z 201.10→94.90 for DEX, and m/z 326.10→291.10 for IS. RESULTS: This UPLC-MS/MS method had good linearity for CEL, DEZ and DEX. The RSDs of inter-day and intra-day precision were the values of 0.31-7.66% and 0.11-9.63%, respectively; the RE values were from -6.05% to 10.98%. The extraction recovery was more than 79%, and the matrix effect was around 100%. The RSDs of stability were less than 8.96%. All of them met the acceptance standard of biological analysis method recommended by FDA. CONCLUSION: This UPLC-MS/MS method is an effective tool for the simultaneous determination of CEL, DEX and DEX, and has been successfully applied to the study of pharmacokinetics in beagle dogs.

The effectiveness of noninvasive biomarkers to predict hepatitis B-related significant fibrosis and cirrhosis: a systematic review and meta-analysis of diagnostic test accuracy.

Noninvasive biomarkers have been developed to predict hepatitis B virus (HBV)-related fibrosis owing to the significant limitations of liver biopsy. Those biomarkers were initially derived from evaluation of hepatitis C virus (HCV)-related fibrosis, and their accuracy among HBV-infected patients was under constant debate. A systematic review was conducted on records in PubMed, EMBASE and the Cochrane Library electronic databases, up until April 1st, 2013, in order to systematically assess the effectiveness and accuracy of these biomarkers for predicting HBV-related fibrosis. The questionnaire for quality assessment of diagnostic accuracy studies (QUADAS) was used. Out of 115 articles evaluated for eligibility, 79 studies satisfied the pre-determined inclusion criteria for meta-analysis. Eventually, our final data set for the meta-analysis contained 30 studies. The areas under the SROC curve for APRI, FIB-4, and FibroTest of significant fibrosis were 0.77, 0.75, and 0.84, respectively. For cirrhosis, the areas under the SROC curve for APRI, FIB-4 and FibroTest were 0.75, 0.87, and 0.90, respectively. The heterogeneity of FIB-4 and FibroTest were not statistically significant. The heterogeneity of APRI for detecting significant fibrosis was affected by median age (P = 0.0211), and for cirrhosis was affected by etiology (P = 0.0159). Based on the analysis we claim that FibroTest has excellent diagnostic accuracy for identification of HBV-related significant fibrosis and cirrhosis. FIB-4 has modest benefits and may be suitable for wider scope implementation.