Bilateral Single-session PCNL with Minimally Invasive Technique in Pediatric Nephrolithiasis.

PURPOSE: To assess outcomes of bilateral single-session percutaneous nephrolithotomy (PCNL) with minimally invasive techniques in pediatric population. MATERIALS AND METHODS: From August 2015 to July 2021, 45 children (including 12 infants) were treated with bilateral single-session PCNL, which included miniPCNL (12-16-Fr) and Microperc (4.8-Fr). Patient, stone and operation-related characteristics, stone-free rate (SFR) and complication rate (CR) were compared using ANOVA. Independent predictors were determined using multivariate linear regression. RESULTS: The mean stone burden was 3.2 cm in sum diameter for both kidneys. For bilateral kidneys, the mean operative time was 61.6min and SFR was 93.3%; CR was 53.3%, of which complications of Clavien grade 1 and 2 accounted for 46.7%. Bilateral Microperc, bilateral miniPCNL and Microperc plus miniPCNL was performed in 19, 14 and 12 children respectively. Both irrigation volume and postoperative stay were less in groups with Microperc. Both SFRs and CRs were satisfactory for the three groups. Self-limiting hematuria represented the most common complication of all cases (33.3%), especially in groups with miniPCNL. The stone burden was the only independent predictor for operative time (P < .001) and the postoperative complication (P = .008). Children with older age (P = .009), higher body mass index (P = .016) or a higher stone burden (P < .001) received larger irrigated fluid volume. Microperc was associated with less irrigated fluid volume (P = .001). Children with Clavien grade 3 complications (P = .004) spent prolonged postoperative hospital stay. CONCLUSION: With favourable SFR and acceptable CR, bilateral single-session PCNL with minimally invasive techniques might be an effective and safe procedure for pediatric nephrolithiasis.

Forgotten ureteral stents: a systematic review of literature.

BACKGROUND: The forgotten ureteral stents (FUS) is one of the late complications of stent placement. This systematic review summarized different aspects of FUS and focused on the problems and solutions related to FUS. METHODS: This systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement. PubMed® and Embase® were searched from inception until October 1st, 2022. Eligible studies were those defining FUS as a stent unintentionally left in situ longer than at least 2 months. RESULTS: Total 147 studies with 1292 patients were finally included. The mean indwelling time of FUS was 33.5 months (range from 3 months to 32 years). The most common initial cause for stent placement was adjunct treatment to urolithiasis (79.2%). The major forgetting reasons were patient-related (83.9%), which included poor compliance, lapse in memory, and misconceptions about the necessity of timely removal. Primary presenting complaints were flank pain (37.3%), lower urinary tract symptoms (33.3%), and hematuria (22.8%). Encrustation (80.8%) and urinary tract infections (40.2%) were the most common complications detected in patients with FUS. Computed tomography evolving as a preferred imaging test (76.1%) was indispensable for evaluating encrustation, migration, fracture and other complicated situations in patients with FUS. Besides, evaluation of kidney function and infection status was also of great importance. Multiple and multimodal procedures (59.0%) were often necessitated to achieve the stent-free status, and were mostly endoscopic procedures. Cystoscope was most commonly used (64.8%). Retrograde ureteroscopy (43.4%) and antegrade stent removal (31.6%) were often used when dealing with more complicated situations. Extracorporeal shockwave lithotripsy (30.4%) was often used as adjunctive to other endoscopic procedures, but it sometimes failed. The decision regarding the choice of treatment is based on the volume and site of encrustation, the direction of migration, the site of fracture, kidney function and other urinary comorbidities. CONCLUSIONS: FUS not only pose hazard to patients' health, but also impose a huge economic burden on medical care. Thorough preoperative evaluation is fundamental to developing the treatment strategy. The management of FUS should be individualized using different treatment modalities with their advantages to minimize patients' morbidities. Prevention is better than cure. Strengthening health education and setting a tracking program are of great importance to the prevention of FUS.

Learning Curves of Flexible Ureteroscopy (275 Cases) and Prone Percutaneous Nephrolithotomy (73 Cases) in Pediatric Stones: Data from 348 Children.

Objectives: To evaluate learning curves in pediatric flexible ureteroscopy (FURS) and pediatric prone percutaneous nephrolithotomy (PCNL) by a single surgeon with experience in adult endourologic procedures. Materials and Methods: Children who were found to have nephrolithiasis and treated with PCNL or FURS from June 2014 to April 2019 were analyzed. Patient demographics, stone characteristics, stone-free rate (SFR), and complication rate (CR) were reported. Learning curves were generated to estimate the effect of a surgeon's experience on outcomes. Results: Seventy-three children underwent PCNL on 86 sides in 77 operations and 275 children underwent FURS on 320 sides in 288 operations. The SFRs were 88.1% (282/320) for FURS procedures and 89.5% (77/86) for PCNL procedures. CRs were 19.8% (57/288) and 35.1% (27/77), respectively. Learning curves showed that the SFRs of the two procedures increased with the accumulation of cases. There was an apparent improvement of SFR for PCNL procedures after ∼60 surgeries. A favorable SFR of FURS could be achieved at the start of learning. No apparently decreased CRs were observed for either PCNL or FURS. Conclusions: Both PCNL and FURS could achieve satisfactory SFRs and accepted CRs in pediatric stones. Increased surgical experience was associated with improved SFRs of both PCNL and FURS procedures, and the surgeon's experience of adult FURS translating to that of pediatric FURS was better than adult PCNL translating to pediatric PCNL. A surgeon needs ∼60 cases of PCNL to achieve competence. For FURS, a favorable SFR could be achieved at the start of learning.

Old men with prostate cancer have higher risk of Gleason score upgrading and pathological upstaging after initial diagnosis: a systematic review and meta-analysis.

BACKGROUND: To evaluate the predictive performance of age for the risk of Gleason score change and pathologic upstaging. EVIDENCE ACQUISITION: Ovid MEDLINE, Ovid Embase, and the Cochrane Library were searched from inception until May 2020. Quality of included studies was appraised utilizing the Newcastle-Ottawa Quality Assessment Scale for case-control studies. The publication bias was evaluated by funnel plots and Egger's tests. EVIDENCE SYNTHESIS: Our search yielded 27 studies with moderate-to-high quality including 84296 patients with mean age of 62.1 years. From biopsy to prostatectomy, upgrading and upstaging occurred in 32.3% and 9.8% of patients, respectively. Upgrading from diagnostic biopsy to confirmatory biopsy was found in 16.8%. Older age was associated with a significant increased risk of upgrading (OR 1.04, 95% CI 1.03-1.05), and similar direction of effect was found in studies focused on upgrading from diagnostic biopsy to confirmatory biopsy (OR 1.06, 95% CI 1.04-1.08). For pathologic upstaging within older men compared with younger, the pooled odds was 1.03 (95% CI 1.01-1.04). CONCLUSION: Thorough consideration of age in the context of effect sizes for other factors not only prompts more accurate risk stratification but also helps providers to select optimal therapies for patients with prostate cancer.

Predicting Gleason sum upgrading from biopsy to radical prostatectomy pathology: a new nomogram and its internal validation.

BACKGROUND: To explore the rate of Gleason sum upgrading (GSU) from biopsy to radical prostatectomy pathology and to develop a nomogram for predicting the probability of GSU in a Chinese cohort. METHODS: We retrospectively reviewed our prospectively maintained prostate cancer (PCa) database from October 2012 to April 2020. 198 patients who met the criteria were enrolled. Multivariable logistic regression analysis was performed to determine the predictors. Nomogram was constructed based on independent predictors. The receiver operating curve was undertaken to estimate the discrimination. Calibration curve was used to assess the concordance between predictive probabilities and true risks. RESULTS: The rate of GSU was 41.4%, whilst GS concordance rate was 44.4%. The independent predictors are prostate specific antigen (PSA), greatest percentage of cancer (GPC), clinical T-stage and Prostate Imaging Reporting and Data System (PI-RADS) score. Our model showed good discrimination (AUC of 0.735). Our model was validated internally with good calibration with bias-corrected C-index of 0.726. CONCLUSIONS: Utilization of basic clinical variables (PSA and T-stage) combined with imaging variable (PI-RADS) and pathological variable (GPC) could improve performance in predicting actual probabilities of GSU in the 24-core biopsy scheme. Our nomogram could help to assess the true risk and make optimal treatment decisions for PCa patients.

Men with High Prostate Specific Antigen Have Higher Risk of Gleason Upgrading after Prostatectomy: A Systematic Review and Meta-analysis.

PURPOSE: To examine the correlation between prostate specific antigen (PSA) and the risk of Gleason sum upgrading (GSU) from biopsy Gleason sum (bGS) to prostatectomy Gleason sum (pGS). MATERIALS AND METHODS: Five electronic databases (Web of Science, Ovid Medline, Ovid Embase, SCOPUS and the Cochrane Library) were searched from inception until March 2020. Studies were included if they focused on the relationship between PSA and GSU analyzed in multivariable analysis. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were utilized. Quality of included studies was appraised utilizing the Newcastle-Ottawa Quality Assessment Scale (NOS) for case-control studies. The publication bias was evaluated by funnel plot and Egger's test. RESULTS: Our search yielded 19 studies with high quality including 42193 patients. GSU was found in 28.2% of patients. Higher PSA level was associated with a significant increased risk of GSU (pooled OR = 1.14, 95% CI: 1.10-1.18; P < .05; I2 = 92%). For the definition of upgrading from bGS ≤ 6 to pGS ≥ 7, the odds of upgrading with higher PSA level as opposed to lower PSA level was 1.12 (95% CI: 1.11-1.14; P < .05; I2 = 13%), while the odds of upgrading with other definitions were 1.11 (95% CI: 1.05-1.18; P < .05; I2 = 89%). CONCLUSION: Patients with high level of serum PSA are at high risk of undergoing pathologic upgrading at prostatectomy. Combined with other risk factors, PSA prompts risk reclassification and improve confidence of urologists in management decisions for optimal therapy. Nevertheless, further robust studies are necessitated to confirm these results.

Genistein inhibited the proliferation of kidney cancer cells via CDKN2a hypomethylation: role of abnormal apoptosis.

INTRODUCTION: Genistein is recognized as a potent anti-oxidant in soybean-enriched foods, which is a kind of phytoestrogen involved in anticancer activity in various cancers. OBJECTIVE: The objective of this study was to investigate the molecular mechanism of CDKN2a hypomethylation involved in the anti-tumor effect of genistein on kidney cancer. METHODS: The CDKN2a expression was measured using qRT-PCR. The level of CDKN2a methylation was detected using methylation-specific PCR. The apoptosis was detected via flow-cytometric analysis. The cell viability was detected using the 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. RESULTS: Our results indicated that genistein induced cell apoptosis and inhibited the cell proliferation of kidney cancer cells. Moreover, genistein increased the expression of CDKN2a and decreased CDKN2a methylation. CONCLUSIONS: Our results demonstrated that the anti-tumor effect of genistein might induce cell apoptosis and inhibit the proliferation of kidney cancer cells via regulating CDKN2a methylation.

The prognostic value of vascular endothelial growth factor in patients with renal cell carcinoma: a systematic review of the literature and meta-analysis.

OBJECTIVE: Vascular endothelial growth factor (VEGF) serum level or tumor expression may be prognostic in renal cell carcinoma (RCC). The purpose of this meta-analysis was to examine the prognostic value of serum VEGF level and tumor expression in patients with RCC. METHODS: PubMed and EMBASE databases were searched until September 26, 2016. Prospective and retrospective studies of RCC patients that had VEGF levels measured were included. Outcome measures were overall survival (OS), disease-specific survival (DSS), and progression-free survival (PFS). RESULTS: A total of 14 studies were included in the meta-analysis. In patients with RCC, elevated serum VEGF level was not associated with OS (pooled hazard ratio [HR] = 1.16; 95% confidence interval [CI]: 0.52 to 2.60; p = 0.716), but was associated with poor DSS (pooled HR = 4.22; 95% CI: 2.02 to 8.79; p < 0.001) and PFS (pooled HR = 1.50; 95% CI: 1.22 to 1.85; p < 0.001). Removal of one study, however, resulted in elevated serum level being associated with poorer OS. Tumor VEGF expression was not associated with OS (pooled HR = 1.48; 95% CI: 0.74 to 2.95; p = 0.263), but was associated with worse DSS (pooled HR = 1.83; 95% CI: 1.24 to 2.71; p = 0.003). CONCLUSION: In patients with RCC, elevated serum VEGF level is associated with worse OS, DSS, and PFS, while tumor expression is only associated with worse DSS. The number of studies, however, was limited and the results should be interpreted with caution.

Synergistic roles of p53 and HIF1α in human renal cell carcinoma-cell apoptosis responding to the inhibition of mTOR and MDM2 signaling pathways.

INTRODUCTION: mTOR and MDM2 signaling pathways are frequently deregulated in cancer development, and inhibition of mTOR or MDM2 independently enhances carcinoma-cell apoptosis. However, responses to mTOR and MDM2 antagonists in renal cell carcinoma (RCC) remain unknown. MATERIALS AND METHODS: A498 cells treated with MDM2 antagonist MI-319 and/or mTOR inhibitor rapamycin were employed in the present study. Cell apoptosis and Western blot analysis were performed. RESULTS AND CONCLUSION: We found that the MDM2 inhibitor MI-319 induced RCC cell apoptosis mainly dependent on p53 overexpression, while the mTOR antagonist rapamycin promoted RCC cell apoptosis primarily through upregulation of HIF1α expression. Importantly, strong synergistic effects of MI-319 and rapamycin combinations at relatively low concentrations on RCC cell apoptosis were observed. Depletion of p53 or HIF1α impaired both antagonist-elicited apoptoses to differential extents, corresponding to their expression changes responding to chemical treatments, and double knockdown of p53 and HIF1α remarkably hindered MI-319- or rapamycin-induced apoptosis, suggesting that both p53 and HIF1α are involved in MDM2 or mTOR antagonist-induced apoptosis. Collectively, we propose that concurrent activation of p53 and HIF1α may effectively result in cancer-cell apoptosis, and that combined MDM2 antagonists and mTOR inhibitors may be useful in RCC therapy.

Nuclear expression and clinical significance of phosphohistidine phosphatase 1 in clear-cell renal cell carcinoma.

OBJECTIVE: To explore expression and clinical relevance of phosphohistidine phosphatase 1 (PHPT1) in clear-cell renal cell carcinoma. METHODS: Patients with clear-cell renal cell carcinoma who underwent radical or nephron-sparing nephrectomy were enrolled. Correlations between PHPT1 expression and demographic and clinical characteristics were analysed prospectively. RESULTS: In total, 122 patients (78 male/44 female) were included. In normal kidney tissue, PHPT1 expression was observed only in the proximal tubule. High PHPT1 expression levels were associated with larger tumour size, higher Fuhrman nuclear grade and advanced pathological tumour-node-metastasis (pTNM) stage compared with low PHPT1 expression levels. Patients with low PHPT1 expression showed better overall survival and progression-free survival compared with those with high PHPT1 expression. In addition, multivariate analysis showed that nuclear grade and pTNM stage were independent predictors of progression-free survival and overall survival in patients with clear-cell renal cell carcinoma. PHPT1 expression was also an independent predictor of overall survival but not progression-free survival. CONCLUSIONS: PHPT1 was expressed in the epithelium of proximal tubuli and nuclei of clear-cell renal cell carcinoma tissue samples. High levels of 14 kDa phosphohistidine phosphatase protein were negatively associated with overall survival and progression-free survival in patients with clear-cell renal cell carcinoma.

Protein interactions of cortactin in relation to invadopodia formation in metastatic renal clear cell carcinoma.

In the present study, we wanted to examine the predominant factor/s in the initiation of metastasis. We used samples of advanced grades of renal clear cell carcinoma with documented clinical history of vena caval spread as the experimental group. The major rationale for this selection is the fact that renal cell carcinoma metastasize extensively through the inferior vena cava up to the pulmonary bed and often exist as a continuous mass of metastatic tissue. As cortactin plays a significant role in invadopodia formation during initiation of metastasis, in the present study, we tested expression of cortactin and phospho(tyr421)-cortactin in different grades of renal cell clear carcinoma and examined its property to bind to actin. The findings of the present study suggest that the variations of the local physiological milieu are the driving forces for metastasis by enhancing molecular mechanisms for lamellipodia formation. We conclude that localization of cortactin in cancer cells and interaction between actin and its nucleators are crucial for cancer progression.

miR-144 downregulation increases bladder cancer cell proliferation by targeting EZH2 and regulating Wnt signaling.

microRNAs (miRNAs) have been proposed to be key regulators of diverse biological processes such as transcriptional regulation, cell growth and tumorigenesis. Wnt signaling plays an important role in the regulation of tumorigenesis and cancer progression. However, little is known about whether miR-144 regulates bladder cancer cell proliferation by controlling Wnt signaling. In this study, we found that the miR-144 expression level is significantly decreased in bladder cancer cell lines as well as in clinical cancer tissues. miR-144 inhibitor blocks the expression of endogenous miR-144 and promotes cancer cell proliferation, whereas miR-144 overexpression is sufficient to inhibit cell proliferation. We further demonstrated that enhancer of zeste homolog 2 (EZH2) is a target gene of miR-144. miR-144 downregulation relieves miR-144-mediated repression of EZH2, which results in activation of Wnt/ß-catenin signaling and subsequent cell proliferation. These data suggest miR-144 is an essential mediator of bladder cancer cell proliferation, thus offering a new target for the development of therapeutic agents against bladder cancer.

Laparoscopic retroperitoneal dismembered pyeloplasty: single-center experience in China.

OBJECTIVE: To report on our experience with laparoscopic retroperitoneal dismembered pyeloplasty in the treatment of ureteropelvic junction (UPJ) obstruction. Special attention was paid to the technical features associated with the procedure. SUBJECTS AND METHODS: From May 2004 to April 2012, in total, 117 consecutive patients (64 men and 53 women) with a mean age of 33.5 years (range, 12-60 years) underwent laparoscopic retroperitoneal dismembered pyeloplasty for symptomatic and radiologically proved UPJ obstruction. Follow-up studies were performed with diuretic renography at 3 and 6 months postoperatively and annually thereafter. Success was defined as symptomatic relief and improvement of the diuresis renogram without evidence of obstructed drainage. RESULTS: The mean operative time was 170 minutes (range, 90-310 minutes), and the mean estimated blood loss was 40 mL (range, 20-100 mL). Crossing vessels were encountered in 21 patients (18.0%). In all cases, the ureter was transposed anteriorly. From 9 patients, including 4 cases of horseshoe kidney, coexisting renal calculi were successfully removed. The mean hospital stay was 7 days (range, 5-14 days). There were no intraoperative complications. Postoperative complication was recorded in 2 patients with leakage at the anastomosis. Seven patients developed anastomotic strictures, which required open surgery or ureteral stent. The success rate was 94% (110/117) at a mean follow-up of 43 months (range, 3-95 months). CONCLUSIONS: In our experience, laparoscopic retroperitoneal dismembered pyeloplasty is effective and feasible. With the improvement of technique, we believe that it would become a new standard treatment for UPJ obstruction.

Horseshoe kidney with retrocaval ureter: one case report.

Horseshoe kidney and retrocaval ureter are uncommon congenital anomalies of the genitourinary system that are easily diagnosed by typical imaging features. Both anomalies presenting in one patient is a rare disease characterized by isthmus of horseshoe kidney between the abdominal aorta and inferior vena cava. The clinical diagnosis and treatment of horseshoe kidney with retrocaval ureter remain a challenge. Here, we reported a case of a 44-year-old man with the two anomalies who was preoperatively diagnosed by unenhanced computed tomography scanning immediately after retrograde pyelography. The literatures on such combined anomalies are reviewed and the diagnostic evaluation and surgical management of this rare entity are discussed.

TGFBI-promoted adhesion, migration and invasion of human renal cell carcinoma depends on inactivation of von Hippel-Lindau tumor suppressor.

OBJECTIVE: To investigate the role of transforming growth factor-ß-induced (TGFBI) in metastasis of renal cell carcinoma (RCC) and the associations between TGFBI expression and von Hippel-Lindau (VHL) status. METHODS: In null type VHL cells stably transfected with the VHL vector, the expression of VHL in cells with wild type VHL was decreased by siRNA. We investigated the effects of hypoxia-inducible transcription factor (HIF) on TGFBI in RCC cells by decreasing the expression levels of HIF-1α and HIF-2α through siRNA. The secretion of transforming growth factor-ß1 (TGF-ß1) in RCC cells with different VHL status was analyzed by enzyme-linked immunosorbent assay. The role of TGFBI in metastasis and the effect of VHL activation on TGFBI-induced adhesion, migration, and invasion in RCC cells were examined using matrigel, chemotaxis, and the transwell system, respectively. RESULTS: Our results suggested that TGF-ß1 and TGFBI might be targets of VHL, and the suppression of TGFBI by VHL is not by way of the HIF-1α or HIF-2α pathway. The expression of TGFBI was significantly enhanced by TGF-ß1 in VHL-inactive RCC cells compared with VHL-active cells. In addition, these results indicate that TGFBI participated in the adhesion, migration, and invasion of RCC cells, which are dependent on the inactivation of VHL. CONCLUSION: The results of the present study suggest that TGFBI-promoted metastasis of RCC cells depends on inactivation of the VHL tumor suppressor and that TGFBI could be a therapeutic target against RCC in the future.

Interferon-α induces G1 cell-cycle arrest in renal cell carcinoma cells via activation of Jak-Stat signaling.

The purpose of this study was to clarify the mechanism of IFN-α resistance in RCC. The effects of IFN-α on induction of apoptosis and cell-cycle arrest were analyzed by flow cytometric analysis. Jak-Stat pathway components induced by IFN-α was evaluated using Western blotting. The results suggested that IFN-α caused growth inhibition of RCC cell lines via arrest in the G1 phase without inducing apoptosis. The resistance of RCC to IFN-α was associated with the low expression of Stat1. This study indicated that the Jak-Stat pathway should be considered a primary target for improving the response of RCC to IFN-α treatment.