Prognostic role of primary tumor size in Wilms tumor.

Wilms tumor (WT) is the most common childhood malignant kidney tumor. The aim of the present study was to determine the impact of primary tumor size on the survival of patients with WT. The data of 1,523 patients diagnosed with WT between 2000 and 2017 were retrieved from the Surveillance, Epidemiology, and End Results database. Receiver operating characteristic curves were plotted to determine the optimal cut-off value of primary tumor size. Overall survival (OS) and cancer-specific survival (CSS) were analyzed using the Kaplan-Meier method and the Cox proportional hazards regression model. The optimal cut-off value for primary tumor size was found to be 11.15 cm. No significant difference in the distribution of tumor size was detected between male and female patients. However, lymph node metastasis and distant metastasis were significantly more frequent in patients whose tumor was ≥11.15 cm in size compared with those with smaller tumors. In addition, patients with larger tumors exhibited significantly worse OS and CSS rates compared with those with smaller tumors. Furthermore, primary tumor size was identified as an independent prognostic factor for OS and CSS in the multivariate analyses. In summary, the present study indicates that primary tumor size is an independent prognostic factor for patients with WT, and tumors ≥11.15 cm are associated with worse OS and CSS.

The roles of pyroptosis in genitourinary diseases.

Pyroptosis, a form of programmed cell death distinct from apoptosis and necrosis, is thought to be closely associated with the pathogenesis of diseases. Recently, the association between pyroptosis and urinary diseases has attracted considerable attention, and a comprehensive review focusing on this issue is not available. In this study, we reviewed the role of pyroptosis in the development and progression of benign urinary diseases and urinary malignancies. Based on this, pyroptosis has been implicated in the development of urinary diseases. In summary, this review sheds light on future research directions and provides novel ideas for using pyroptosis as a powerful tool to fight urinary diseases.

The prognostic significance of primary tumor size in squamous cell carcinoma of the penis.

BACKGROUND: To evaluate the association of primary tumor size with clinicopathologic characteristics and survival of patients with squamous cell carcinoma of the penis (SCCP). METHODS: This study analyzed the data of 1001 patients with SCCP, obtained from the National Cancer Institute Surveillance, Epidemiology, and End Results (SEER) database between 2010 and 2014. The Kaplan-Meier method and the Cox proportional hazards regression model were used to analyze the effects of primary tumor size on overall survival (OS) and penile carcinoma-specific survival (PCSS). RESULTS: Advanced T stage (P < 0.001), lymph node metastasis (P < 0.001) and distant metastasis (P = 0.001) were more frequently associated with SCCP patients with tumor size ≥ 3 cm than those with tumor size < 3 cm. In Kaplan-Meier analyses, the patients with large tumors (≥ 3 cm) exhibited an inferior OS and PCSS than those with small tumors (< 3 cm). Moreover, tumor size was identified to be an independent prognostic factor for OS [hazard ratio (HR) 1.665, P < 0.001] and PCSS (HR 2.076, P = 0.003) of patients with SCCP in multivariate analyses. CONCLUSIONS: Large tumor size is associated with adverse clinicopathological characteristics of patients with SCCP. Besides, tumor size represents an independent prognostic factor for OS and PCSS. Therefore, clinical assessment of tumor size as a crucial prognostic factor might be highly beneficial for early intervention in patients with SCCP.

The Relationship between Urinary Stones and Gut Microbiomeby 16S Sequencing.

OBJECTIVE: To understand the relationship between urinary stones and the gut microbiome and to screen for microbial species that may be involved in stone formation. METHODS: Stool samples were collected from patients with urolithiasis and healthy patients between March and December 2017. The samples were analyzed by 16S sequencing to determine differences in the microbiome profiles between the two groups. The mouse model was established and was divided into two groups. Fecal samples were collected from the mice before gavage and three weeks postgavage for microbiome analysis. The microbial population of each group was analyzed to screen for microbial species that may affect the formation of urinary stones. Differences in the number of crystals in the renal tubules of the mice were examined by necropsy. RESULTS: The microbial composition was different between urolithiasis patients and healthy controls. The urolithiasis patients had significantly reduced microbial abundance; however, increased proportions of Bacteroidetes and Actinobacteria were detected compared to healthy controls. Furthermore, the abundance of Alistipesindistinctus and Odoribactersplanchnicus was significantly increased in the urolithiasis patients compared to the healthy controls. In addition, the incidence of urolithiasis was much higher in the experimental mouse group (stone solution + urolithiasis patient stool) than in the control mouse group. However, the microbial abundance before gavage was not significantly different from that seen three weeks postgavage. CONCLUSION: Theurolithiasis patients in this study had a different gut microbiome when compared with that of healthy individuals. The altered microbiome increased the rate of crystal formation in renal tubules and accelerated urinary stone formation in the mouse model of urolithiasis.

Prognostic value of lymphovascular invasion in patients with squamous cell carcinoma of the penis following surgery.

BACKGROUND: To evaluate the prognostic value of Lymphovascular Invasion (LVI) in patients with squamous cell carcinoma of the penis (SCCP) following surgery. PATIENTS AND METHODS: This retrospective study analyzed the data of 891 eligible patients with SCCP who were diagnosed between 2010 and 2014, obtained from the Surveillance, Epidemiology, and End Results (SEER) database. The patients were categorized by LVI, age, grade, T stage, lymph nodes status, distant metastasis, regional lymph nodes removed, and surgery. Overall survival (OS) and penile carcinoma-specific survival (PCSS) were evaluated by Kaplan-Meier method and Cox proportional hazards regression model. RESULTS: The presence of LVI was significantly associated with increased risk of advanced T stage, high grade, lymph node metastasis, and distant metastasis (P < 0.001 for all). In Kaplan-Meier analyses, patients with the presence of LVI had significantly lower OS and PCSS than those with the absence of LVI (P < 0.001 for both,). The presence of LVI was also significantly associated with poorer OS and worse PCSS in patients with Tx + Ta + T1 stage (P = 0.007, P < 0.001), N0 stage (P < 0.001, P = 0.040), grade 1 (P = 0.001, P < 0.001), grade 2 (P = 0.001, P = 0.014), no distant metastasis (P < 0.001 for both), no regional lymph nodes removed (P < 0.001 for both), Non-radical surgery (P < 0.001 for both) and radical surgery(P = 0.037, P = 0.002). In multivariate analyses, the presence of LVI in patients with SCCP following surgery was found to be a significant independent predictor of decreased OS (hazard ratio 1.403, P = 0.039). CONCLUSIONS: The LVI status might be a crucial prognostic indicator for overall survival in patients with SCCP.

B7-H3 promoted proliferation of mouse spermatogonial stem cells via the PI3K signaling pathway.

OBJECTIVE: We found seminal B7-H3 was associated with human sperm concentration. However, the mechanism is unclear. The purpose of this study was to investigate the expression of B7-H3 in mouse testis and determine the effects of B7-H3 on the proliferation of mouse spermatogonial stem cells (SSCs) and the underlying mechanisms. METHODS: B7-H3 expression in the testis of mice at different ages (3 weeks, 8 weeks, 4 months and 9 months) was detected by western blot and immunohistochemistry. CCK-8 were used to measure mouse SSCs proliferation after incubation with different concentrations of B7-H3 for 1-72 h in vitro. Flow cytometry was used to analyze the cell cycle of mouse SSCs after incubation with different concentrations of B7-H3 for 48 and 72 h. The signaling pathways involved were assessed by western blot. RESULTS: Four-month-old mice had the highest expression of B7-H3 in the testis, while 3-week-old mice had the lowest expression of B7-H3. B7-H3 was predominantly detected on the membrane and in the cytoplasm of Sertoli cells. Furthermore, B7-H3 promoted mouse SSCs proliferation and increased the percentage of cells in S+G2/M phase in a time- and dose-dependent manner in vitro. These effects were inhibited by LY294002, indicating the involvement of the phosphoinositide 3-kinase signaling pathway. CONCLUSIONS: The expression of B7-H3 in mouse testis, especially Sertoli cells, was associated with mouse age. In vitro, B7-H3 promoted the proliferation and accelerated the cell cycle of mouse SSCs via the PI3K pathway, indicating a critical role of B7-H3 expressed by Sertoli cells in mouse spermatogenesis.

Different expression of B7-H3 in the caput, corpus, and cauda of the epididymis in mouse.

BACKGROUND: B7-H3, a member of the B7 family of the Ig superfamily of proteins, has been detected in the epididymis, which is a storage organ related to sperm maturation. However, the characteristics of its expression in different regions of the epididymis remain unknown. Our aim was to investigate the expression of B7-H3 in the caput, corpus, and cauda of the epididymis. METHODS: We extracted epididymis specimens from adult male C57BL/6 mice. The expression of B7-H3 was then measured with immunohistochemistry, enzyme-linked immunosorbent assay (ELISA) and western blotting. RESULTS: B7-H3 protein was predominantly detected on the membrane and in the cytoplasm of the principal cells in the epididymis. Moreover, the level of B7-H3 in the corpus of the mouse epididymis was significantly higher than that in the caput (p < 0.05) or the cauda of the epididymis (P < 0.05). However, there was no remarkable difference in the level of B7-H3 between the caput and the cauda (p > 0.05). CONCLUSIONS: The caput, corpus, and cauda of the mouse epididymis all expressed B7-H3 protein. However, the levels of B7-H3 were different in the three regions of the epididymis.

Overexpression of B7-H3 in CD14+ monocytes is associated with renal cell carcinoma progression.

Renal cell carcinoma (RCC) is well known as a typical hypervascular tumor and has a high mortality rate. Tumor-induced angiogenesis is crucial for tumor growth and metastasis. It also plays an important role in the development and progression of RCC. However, the molecular mechanism is still unclear. In our study, we evaluated the expression level of B7-H3 in CD14(+) monocytes in 56 paired RCC samples and distant normal tissues by flow cytometry and located the co-expression of B7-H3 and CD14 by immunohistochemistry. In addition, we analyzed its association with clinical pathologic features through Chi-square test and Fisher exact test. Results showed that B7-H3 and CD14 co-expressed in tumor stroma surrounding the vessels and that the level of B7-H3 expression was higher in tumor than in normal tissues (63.42 ± 11.92 vs. 15.59 ± 3.01, P < 0.0001). Furthermore, the expression level was significantly associated with RCC stage (P = 0.000), nodal metastasis (P = 0.003), distant metastasis (P = 0.020), and nuclear grade (P = 0.004). Conclusively, we found the phenomenon that B7-H3 and CD14 co-expressed in RCC tissues. The level of expression was closely associated with the tumor's progression, indicating that B7-H3 might play an important role in angiogenesis of RCC mediated by CD14(+) monocytes.

Staged microvascular anastomosis training program for novices: transplantation of both kidneys from one rat donor.

BACKGROUND: Rat renal transplantation is an essential experimental model and requires greater microsurgical skills. Thus, training novices to perform quick and reliable microvascular anastomosis is of vital importance for rat renal transplantation. In this study, we developed and evaluated a staged microvascular anastomosis training program for novices, harvesting and transplanting both kidneys from one rat donor. METHODS: Five trainees without any prior microsurgical experience underwent a training program in which the goals were staged according to difficulty. Each trainee had to achieve satisfactory results as evaluated by a mentor before entering the next stage. Rat renal transplantation was accomplished by end-to-end technique with a bladder patch. In the intensive rat renal transplantation stage, the trainees required an average of 20 independent attempts at isotransplantation as final training assessment. RESULTS: After 2 months of intensive practice, all trainees had achieved stable and reproducible rat renal transplantation, with a satisfactory survival rate of 85.9% at postoperative Day 7. The total mean operative time was 78.0 minutes and the mean hot ischemia time was 26.2 minutes. With experience increasing, the operative time for each trainee showed a decreasing trend, from 90-100 minutes to 60-70 minutes. After 20 cases, the mean operative time of the trainees was not statistically significantly different from that of the mentor. CONCLUSION: Harvesting and transplanting both kidneys from one rat donor after a staged microvascular anastomosis training program is feasible for novices without any prior microsurgical skills.

B7-H3 promoted sperm motility in humans.

OBJECTIVE: To determine whether seminal B7-H3 levels are correlated to semen parameters and affect human sperm functions. METHODS: A total of 83 healthy donors of proven fertility (aged 22-37 years) and 176 infertile men (aged 21-38 years) were recruited. Computer-assisted semen analysis and enzyme-linked immunosorbent assay were used to assess the correlations between seminal B7-H3 levels and semen parameters. Flow cytometry and fluorescence microscopy were used to detect the putative receptor for B7-H3. Computer-assisted semen analysis and FITC-conjugated pisum sativum agglutinin staining were performed for assessing sperm motility, capacitation, and acrosome reaction (AR) after incubation with various concentrations of B7-H3 for 0-4 hours in vitro. RESULTS: Seminal B7-H3 level was significantly higher in the healthy donors than that in the infertile men (P <.05), and closely associated with sperm concentrations and progressive motility (all P <.05), but not the other parameters examined (all P >.05). A putative receptor for B7-H3 was detected on the surface of sperm, with no significant differences in expression between the healthy donors and infertile men (P >.05). Seminal B7-H3 promoted sperm progressive motility in a time- and dose-dependent manner in vitro, although having no significant influence on sperm capacitation and AR. CONCLUSION: B7-H3 showed a favorable effect on human sperm motility, without affecting sperm capacitation and AR.

The frequency of tumor-infiltrating Tie-2-expressing monocytes in renal cell carcinoma: its relationship to angiogenesis and progression.

OBJECTIVE: To examine the frequency of tumor-infiltrating Tie-2-expressing monocytes (TEMs) in renal cell carcinoma (RCC) and its association with microvessel density (MVD) and other clinical-pathologic features. MATERIALS AND METHODS: This study enrolled 65 consecutive patients with RCC treated with radical nephrectomy. The frequency of tumor-infiltrating TEMs, which was defined as CD14(+) Tie-2(+) cells, was assessed using flow cytometry. MVD was measured by immunohistochemistry using anti-CD34 antibody. The association between clinicopathologic parameters, MVD, and the frequency of tumor-infiltrating TEMs in RCC was assessed. RESULTS: High frequency of tumor-infiltrating TEMs was significantly associated with advanced stage (P = .018), positive lymph nodes (P = .013), high grade (P = .019), and metastases (P = .006). Correlation analysis revealed that the frequency of TEMs was positively correlated with MVD. CONCLUSION: Our findings revealed a significant association between prognostic tumor features, MVD, and the frequency of tumor-infiltrating TEMs in RCC and indicated that TEMs may play an important role in angiogenesis and progression of RCC.

Is the impact of the extent of lymphadenectomy in radical prostatectomy related to the disease risk? A single center prospective study.

BACKGROUND: Controversy exists regarding the extent of pelvic lymph node dissection (PLND) in radical prostatectomy (RP) for prostate cancer. Impact of the extent of PLND may be determined by the disease risk. The aim of our study was to find the association between the extent of PLND on biochemical progression and disease risk. METHODS: The study included 360 consecutive patients treated with RP for clinically localized prostate cancer at our department between 2000 and 2003. Patients were randomized to receive extended PLND (n = 180) and standard PLND (n = 180) at RP. Clinical and pathological data were prospectively collected. The patients did not receive any neoadjuvant or adjuvant therapy. The relation of disease risk and the extent of PLND to biochemical progression-free survival (BPFS) were examined. RESULTS: There were no significant differences in age, prostate-specific antigen, and other preoperative features in patients who underwent standard and extended PLND. Mean patient age was 68 y old and median follow-up was 74 mo. BPFS for the standard PLND group and the extended PLND group was 90.1% and 91.3% in low risk disease (log rank P = 0.807), 73.1% and 85.7% in intermediate risk disease (log rank P = 0.042), and 51.1% and 71.4% in high risk disease (log rank P = 0.036), respectively. In multivariate Cox proportional hazard analysis, extended PLND was an independent prognostic factor of biochemical progression-free survival when adjusting for other clinical and pathologic features. CONCLUSIONS: In intermediate and high risk patients, extended PLND positively affects BPFS. In low risk patients, extended PLND may be omitted to reduce operation time and complications.

B7-H3 over expression in prostate cancer promotes tumor cell progression.

PURPOSE: We compared B7-H3 expression in benign prostatic hyperplasia and prostate cancer tissue specimens, and determined the effects of low B7-H3 expression on the PC-3 human prostate cancer cell line using RNA interference. MATERIALS AND METHODS: B7-H3 expression in prostate specimens was determined by enzyme-linked immunosorbent assay. A PC-3 cell line with low B7-H3 expression was established by RNA interference to investigate the effect of B7-H3 on cell proliferation, adhesion, migration and invasion in vitro. RESULTS: B7-H3 in tissue samples was significantly higher in the prostate cancer group than in the benign prostatic hyperplasia group (mean±SEM 174.73±56.80 vs 82.69±46.19 ng/gm, p<0.001). B7-H3 expression down-regulated by small interfering RNA decreased cell adhesion to PC-3 fibronectin more than 30%, and migration and Matrigel™ invasion up to 50%. No apparent impact was observed on cell proliferation. CONCLUSIONS: B7-H3 is aberrantly expressed in prostate cancer. In addition to modulating tumor immunity, B7-H3 may have a novel role in regulating PC-3 cell progression.

Pure natural orifice translumenal endoscopic surgery management of simple renal cysts: 2-year follow-up results.

BACKGROUND AND PURPOSE: Retrograde ureteroscopic marsupialization is a pure natural orifice translumenal endoscopic surgery (NOTES). We retrospectively examined the feasibility and safety of this technique to manage symptomatic simple renal cysts. PATIENTS AND METHODS: Sixteen patients with simple renal cysts were selected and treated by incising the cyst wall to drain into the collecting system through retrograde ureteroscopy. A retrospective observational study was performed to evaluate the patient's symptomatic and radiologic results after ureteroscopic marsupialization. Symptomatic success based on pain relief was evaluated using a visual analog pain scale preoperatively and postoperatively. Radiologic success was defined as no recurrence of the cyst or a reduction in cyst size by at least half. RESULTS: There were no intraoperative or postoperative complications observed. The mean operative time was 35 minutes (range 20-50 min). The mean hospital stay was 3.4 days (range 2-5 d). Of the 16 patients, one patient was lost at follow-up. The symptoms based on pain had resolved in 13 (83%) cases but remained in 2 cases at a mean follow-up of 24.2 months (range 6-36 mos). The average visual analog pain scale decreased from 6.7 (range 4-9) to 1.1 (range 0-5) at the sixth month. The mean size of all cysts decreased from 6.8 cm (range 4-10 cm) to 1.3 cm (range 0-5 cm). Radiographic success was achieved in 93% (14/15) of patients. Cytology and cyst wall pathology reports revealed no evidence of malignancy. CONCLUSIONS: Retrograde ureteroscopic marsupialization is a complete transurethral NOTES marsupialization. With appropriate patient selection, the minimally invasive retrograde ureteroscopic marsupialization is feasible, safe, and effective. It can be preferred to more invasive laparoscopic or open surgical approaches.

Detection and quantitation of soluble B7-H3 in expressed prostatic secretions: a novel marker in patients with chronic prostatitis.

PURPOSE: We determined the soluble B7-H3 level and its clinical significance in serum and expressed prostatic secretions of patients with chronic prostatitis, including chronic bacterial prostatitis (type II) and chronic pelvic pain syndrome. MATERIALS AND METHODS: Using enzyme-linked immunosorbent assay we measured soluble B7-H3 in 11 patients with chronic prostatitis (type II), and 26 with inflammatory (type IIIA) and 54 with noninflammatory (type IIIB) chronic pelvic pain syndrome, and healthy donors. We assessed differences between these groups using Student's t test. As determined by the National Institutes of Health-Chronic Prostatitis Symptom Index, we correlated soluble B7-H3 with clinical pain using the Pearson test. RESULTS: We found no significant difference between serum soluble B7-H3 in healthy donors and patients with chronic prostatitis (p = 0.897). However, soluble B7-H3 in expressed prostatic secretions was statistically significantly decreased in patients with chronic prostatitis vs controls (p <0.001). ROC using soluble B7-H3 greater than 38.82 ng/ml in expressed prostatic secretions distinguished patients with chronic prostatitis from healthy donors with 90.9% sensitivity and 83.5% specificity. Also, soluble B7-H3 levels in expressed prostatic secretions correlated negatively with the Chronic Prostatitis Symptom Index and the pain subscore. Compared to the pretreatment level soluble B7-H3 in expressed prostatic secretions was significantly increased in patients with a greater than 25% decrease in the Chronic Prostatitis Symptom Index total score (p = 0.016). CONCLUSIONS: Data indicate that the soluble B7-H3 level in expressed prostatic secretions is a novel chronic prostatitis marker that correlates negatively with subjective symptoms.

[Gene transfer-induced human heme oxygenase-1 over-expression protects kidney from ischemia-reperfusion injury in rats].

OBJECTIVE: To study the protection of gene transfer-induced human heme oxygenase-1 over-expression against renal ischemia reperfusion injury in rats. METHODS: The model of kidney ischemia-reperfusion injury was established with Sprague-Dawley rats. In the therapy group (n=18), the left kidney was perfused and preserved with Ad-hHO-1 at 2.5×10(9) pfu/1.0 ml after flushed with 0-4°C HC-A organ storage solution via donor renal aorta. The rats in control groups were perfused with 0.9% saline solution (n=12) or the vector carrying no interest gene Ad-EGFP 2.5×10(9) pfu/1.0 ml (n=18) instead of Ad-hHO-1. BUN and Cr in serum were measured by slide chemical methods. The kidney samples of rats were harvested for assay of histology, immunohistochemistry and quantification of HO enzymatic activity. Apoptosis cells in the kidney were measured by TUNEL. RESULTS: Ad-hHO-1 via donor renal aorta could transfect renal cells of rats effectively, enzymatic activity of HO in treated group [(1.62±0.07) nmol×mg(-1)×min(-1)] is higher than in control groups treated with saline solution team [(1.27±0.07) nmol×mg(-1)×min(-1)] and vector EGFP team [(1.22±0.06) nmol×mg(-1)×min(-1)] (P<0.01). Immunohistochemically, we found that the rats treated with Ad-hHO-1 expressed hHO-1 in kidneys at a high level. Corresponding to this, the level of BUN and Cr, as well as the number of apoptosis cells, were decreased, and the damage in histology by HE staining was ameliorated. CONCLUSION: Over-expression of human HO-1 can protect the kidney from ischemia/reperfusion injury in rats.