Percutaneous ultrasound-guided renal biopsy in children: The need for renal biopsy in pediatric patients with persistent asymptomatic microscopic hematuria

Background: Percutaneous renal biopsy (PRB) is essential for the diagnosis, prognosis, and management of children with unknown kidney disease. In this study, the safety and efficacy of PRB is investigated, and also the common etiologies of childhood kidney disease, based on histological findings. In addition, we explored the role of PRBs in the diagnosis of children who presented with persistent asymptomatic hematuria. Methods: By chart review, from July 2005 to July 2009, a total of 99 PRBs were performed on 91 children (43 girls and 48 boys; mean age, 10.9 ± 4.4 years) under ultrasound (US) guidance, by a doctor, using an automated 18-gauge biopsy needle following the same protocol, at a medical center in northern Taiwan. Results: The accuracy of the histological diagnosis was excellent. The most common post-biopsy complications were perirenal hematoma (11.1%) and asymptomatic gross hematuria (3.0%), respectively. Nevertheless, these complications resolved spontaneously, and none had major bleeding episodes. Histological results showed that lupus nephritis, minimal change disease, and IgA nephropathy (IgAN) could be the current leading causes of childhood kidney diseases in Taiwan. Conclusions: Automated ultrasound (US)-guided PRB is a safe and reliable method of assessing childhood renal disease. A recent study shows that the presence of persistent asymptomatic isolated microhematuria in adolescents is a predictive marker of future end-stage renal disease. Hence, the emphasis of renal biopsy on children with persistent asymptomatic hematuria is beneficial for the early diagnosis of IgAN or other glomerulonephritis (GN), which tends toward progressive kidney disease in adulthood without prompt therapeutic intervention

Identification of patients with hormone receptor-positive breast cancer who need adjuvant tamoxifen therapy for more than 5 years

Extended hormonal therapy with tamoxifen for > 5 years has improved disease-free survival (DFS) and overall survival (OS) in hormone receptor (HR)-positive breast cancer patients. The aim of this study was to identify the HR-positive breast cancer women who need adjuvant tamoxifen for > 5 years. Methods: Between 1990 and 2004, 1104 HR-positive breast cancer patients who had received tamoxifen treatment at our institution and had been disease free for at least 6 years were included in this analysis. Univariate and multivariate analyses of prognostic factors for late recurrence were performed using the binary logistic regression model. Results: During a median follow-up period of 10.9 years after surgery, 70 patients died and 99 showed recurrence. In multivariate analysis, age  40 years and negative lymph node status, 566 patients) groups. The recurrence rates were 14.6% and 3.5% in the high-risk and low-risk groups, respectively. Patients in the high-risk group had poorer disease-free survival (p < 0.001) and overall survival (p = 0.010) than those in the low-risk group. Conclusion: Our findings suggest that HR-positive breast cancer women either aged  5 years

Tumor Stress-Induced Phosphoprotein1 (STIP1) as a Prognostic Biomarker in Ovarian Cancer

<div><p>Stress-induced phosphoprotein 1 (STIP1) has been recently identified as a released biomarker in human ovarian cancer. In addition, STIP1 secreted by human ovarian cancer cells has been shown to promote tumor cell proliferation by binding to ALK2 (activin A receptor, type II-like kinase 2) and activating the SMAD-ID3 signaling pathways. In this study, a total of 330 ovarian cancer tumor samples were evaluated for STIP1 expression by immunohistochemistry and analyzed for a possible correlation with patient characteristics and survival. The quantification of immunoreactivity was accomplished by applying an immunohistochemical scoring system (histoscore). Patients with high-level STIP1 expression (histoscore ≥169) had a significantly worse survival (high STIP1, mean survival time = 76 months; low STIP1, mean survival time = 112 months; <i>P</i><0.0001). Moreover, STIP1 histoscores were significantly higher in high-grade tumors (grade 3) than in low-grade (grade 1–2) malignancies (<i>P</i><0.0001), suggesting that STIP1 may be a proxy for tumor aggressiveness. The results of multivariable analysis revealed that high STIP1 histoscores, advanced stages, histologic types, and the presence of residual disease (≥2 cm) were independent predictors of poor prognosis. The addition of STIP1 histoscores improved the prediction of overall and progression-free survival rates in the multivariable Cox proportional hazard model. The treatment of ovarian cancer cells with recombinant STIP1 stimulated cell proliferation and migration, but co-treatment with anti-STIP1 antibodies abrogated this effect. Our findings suggest that STIP1 expression may be related to prognosis and that the STIP1 pathway may represent a novel therapeutic target for human ovarian cancer.</p> </div

The addition of STIP1 histoscores improves the prediction of patients’ outcomes.

<p>The time-dependent AUC (area under the ROC curve) of the model including STIP1 is reported as a red solid line, whereas the AUC of the model without STIP1 is shown as a blue dotted line. Other parameters included stage, type, serum CA125, and residual disease. (A) Overall survival, (B) Progression-free survival.</p

Multivariate analyses of clinicopathological parameters for overall and progression-free survivals.

<p>CI: confidence interval; HR, hazard ratio.</p

Clinicopathological characteristics and STIP1 histoscore^a in 330 patients with ovarian cancer.

*<p>Mann-Whitney U test.</p>**<p>Kruskal-Wallis test.</p>a<p>histoscore = percentage × intensity.</p>b<p>Clear cell carcinoma and borderline malignancies are not graded <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0057084#pone.0057084-Berek1" target="_blank">[3]</a>.</p><p>BOT, borderline ovarian tumor.</p

High STIP1 histoscores are associated with a reduced overall survival.

<p>Kaplan-Meier curve analyses for overall survival showed that women with a STIP1 histoscore >169 (red line) had a significantly lower overall survival than those with a STIP1 histoscore ≤169 (blue line). Statistical significances (<i>P</i><0.0001) were detected in the analyses of (A) all cases (n = 330) including invasive cancer and borderline tumor (BOT), (B) invasive ovarian cancers of all cell types (n = 280), and (C) only invasive serous type of ovarian cancers (n = 107).</p

Specificity of the anti-STIP1 antibody (panels A–D) and the intensity of immunostaining for STIP1 (panels E–G).

<p>STIP1 expressed in the cytoplasm of ovarian cancer cells is stained brown. The immunoreactivity of STIP1 to the anti-STIP1 antibody in cancer tissues (A, C) was abrogated by the addition of 15 µg of recombinant human STIP1 during incubation (B, D); these results support the specificity of the anti-STIP1 antibody. The intensity of the STIP1 staining was graded as 1 (E), 2 (F), and 3 (G). All of the slides presented here were from ovarian serous carcinomas. The scale bars represent 100 µm (A, B) or 20 µm (C–G).</p

The treatment of ovarian cancer cells with recombinant human STIP1 (rhSTIP1) stimulates cell proliferation.

<p>Two ovarian cancer cell lines (BG1 and MDAH2774) were treated with 400 nM of rhSTIP1 and analyzed by BrdU incorporation (A) and Ki67 immunostaining (B). Ki67-positive cells are shown in brown color; scale bars represent 20 µ.</p