Comparison of outcomes between flexible ureteroscopy and mini-percutaneous nephrolithotomy in the management of upper calyceal calculi larger than 2 cm.

OBJECTIVE: To compare the outcomes of FURSL and m-PNL in the management of upper calyceal calculi larger than 2 cm. METHODS: A total of 75 patients with upper calyceal calculi larger than 2 cm that were treated by FURSL (n = 37) or mini-PNL (n = 38) were retrospectively analysed. The mean age, sex, stone burden, operative time, complications, length of hospitalization, and stone-free rate (SFR) were compared between the groups. The success of the procedure was defined by the absence of residual stones or residual fragments smaller than 4 mm on computed tomography at 4 weeks postoperatively. RESULTS: The two groups had comparable preoperative parameters. The mean operative time was significantly longer in the mini-PNL group than in the FURSL group (87.8 vs. 69.8 min, p < 0.001). The length of hospitalization was greater in the mini-PNL group than in the FURSL group (2.5 vs. 1.3 days, p < 0.001). Although the perioperative complication rate was higher in the mini-PNL group (23.7%) than in the FURSL group (13.5%), this difference was not statistically significant (p = 0.258). The SFR for the mini-PNL group was 89.5%, and that of the FURSL group was 81.1%; the difference was not significantly different (p = 0.304). CONCLUSIONS: Both FURSL and mini-PNL are effective and safe for the management of upper calyceal calculi larger than 2 cm. Of these two procedures, mini-PNL is less time consuming, FURSL is associated with faster recovery. FURSL can be considered a good alternative treatment in selected patients.

Downregulation of miR-221, -30d, and -15a contributes to pathogenesis of prostate cancer by targeting Bmi-1.

Prostate cancer is the second leading cause of cancer-related deaths of men. Bmi-1, a member of PcG family of proteins, has been implicated in the pathogenesis of prostate cancer, and disturbed profile of microRNAs (miRNAs) has been found in prostate cancer tissues. How Bmi-1 is regulated by miRNAs is unclear. In this study, we screened 18 miRNAs that potentially repress the expression of Bmi-1 using a dual luciferase system and found that 12 miRNAs could bind with the 3'-untranslated region of Bmi-1 mRNA. Using qRT-PCR, we found that expression of miR-221, -15a, and -30d was significantly reduced in prostate cancer tissues. Subsequent functional study indicated that miR-221 and miR-30d can repress prostate cancer cell proliferation, and this effect can be partially rescued by Bmi-1 overexpression. Our study constructs the relation between downregulated miR-221 and miR-30d and prostate cancer pathogenesis. These results indicate that miR-221 and miR-30d are candidate tumor suppressor miRNAs in prostate cancer and therefore serve as potential clinical classification markers and therapeutic targets for human prostate cancer.

Synergistic effect and mechanism of vitamin A and vitamin D on inducing apoptosis of prostate cancer cells.

To explore the mechanism and synergistic effect of vitamin A and vitamin D in inducing apoptosis of prostate cancer cells. The cell proliferation activity was determined by MTT assay. The proportion of apoptotic cells was analyzed by FACS and fluorescence intensity. TUNEL was used to evaluate vitamin A and vitamin D's induction of apoptosis in prostate cancer cells. The protein and mRNA expression level of Cyclin D1 and Bax were determined by real time-PCR and western blot. The results of MTT showed vitamin A and vitamin D's inhibition on proliferation ratio in prostate cancer cells is time and concentration dependent. FACS and fluorescence intensity analysis proved that the proportion of apoptotic cells increased after vitamin A and vitamin D treatment. TUNEL showed vitamin A and vitamin D induced prostate cancer cells apoptosis. The combination of vitamin A and vitamin D markedly enhanced the expression of Bax and reduced the expression of Cyclin D1 by real time-PCR and western blot assay. In conclusion, vitamin A and vitamin D could synergistically induce apoptosis in prostate cancer cells.

The efficacy and safety of one-stage endoscopy combined with intrarenal surgery (mini-nephrostomy tract) in the prone split-leg position for complex renal calculi.

Background: The goal of this study was to determine the safety and efficacy of endoscopic combined intrarenal surgery (ECIRS) performed in the prone split-leg position for the treatment of complex renal stones. Materials and methods: A mature ECIRS protocol was designed. Retrospective analysis was conducted of medical records between January 2020 and December 2021 of patients with complex renal stones at one center who underwent ECIRS by 2 skilled surgeons using retrograde flexible ureteroscopy and mini-percutaneous nephrolithotomy in the prone split-leg position. Results: A total of 44 patients were included in this study. Mean stone size was 26.1 ± 12.7 mm, and the number of calyces involved was 4.36 ± 2.09. Mean operative time was 71.1 ± 21.8 minutes. Postoperative decline in hemoglobin was 15.8 ± 9.8 g/L. Seventy-five percent of patients achieved stone-free status. The mean number of residual stones was 2.8 ± 2.3, and the mean residual stone size was 10.30 ± 4.76 mm. Six patients (13.6%) developed postoperative complications, including 4 with fever during the first 2 days postoperatively and 2 patients with transient postoperative pain. No patients developed severe complications. Conclusions: Endoscopic combined intrarenal surgery in the prone split-leg position can be performed safely by experienced surgeons using retrograde flexible ureteroscopy in conjunction with mini-percutaneous nephrolithotomy as a successful technique for the treatment of complex renal stones.

Comprehensive analysis based in silico study of organophosphate flame retardants - environmental explanation of bladder cancer progression.

Brominated flame retardants are associated with increased toxicity and high concerns for environmental pollution. Therefore, organophosphate flame retardants (OPFRs) are considered safer alternatives and are widely used in building materials and electronics. This study aimed to determine whether organophosphate flame retardants are implicated in bladder cancer development and progression. Data of interactive genes associated with OPFRs was obtained from the CTD database (http://ctdbase.org/) in July 2021. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis revealed that organophosphate flame retardants were closely linked to bladder cancer. Furthermore, the immune-related genes showed a strong correlation with bladder cancer. Further analysis revealed that the immune-related genes were associated with the prognosis, clinical characteristics, and response to immunotherapies in bladder cancer. In conclusion, OPFRs and their metabolites could promote the progression of bladder cancer by affecting the expression of immune genes.

Computational Analysis of Influencing Factors and Multiple Scoring Systems of Stone Clearance Rate after Flexible Ureteroscopic Lithotripsy.

Our research aims at the analysis of various stone scoring systems which are referred to as STONE scoring system (SSS) in this study. GUY's scoring system and RUSS scoring system (RSS) are utilized to predict stone-free status (SFS) after surgery and problems after percutaneous nephrolithotomy (PCNL) for harder stones. The data of 68 patients with renal calculi who received FURL in Ren Ji Hospital from Jan 2020 to Mar 2021 are collected as the study subjects. There were 44 male and 24 female patients, with an average age of 55.6 ± 11.4 years. Reliability analysis of related influencing factors (IF) of stone clearance rate (SCR) and multiple scoring systems after flexible ureteroscopic lithotripsy (FURL) was performed. Relevant factors with statistical significance for postoperative SCR were selected for logistic regression analysis (RA). According to the SSS score, GSS classification, and RUSS score, the SCR after FURL was statistically analyzed. The results showed that the P values corresponding to stone position (lower caliceal), cumulative stone diameter (CSD), urinary tract infection, and external physical vibration lithecbole (EPVL) were less than 0.05. The area under the ROC curve of RUSS score, SSS score, and GSS grading was 0.932, 0.841, and 0.533, respectively. The main IF of SCR after FURL were stone location (lower caliceal), CSD, urinary tract infection, and EPVL. The RUSS score system was the best in the evaluation of SCR after FURL. In the previous research, the score systems such as CROES (CRS), SSS, S-ReS, C, and GSS for the prediction of SFS were compared. In our analysis, we have compared the RUSS scoring system which has proven to be giving better results as compared to SSS and GSS. We also performed the regression analysis and found that the stone location shows the strongest correlation of all the other factors for stone clearing rate.

Bile Acids Elevated in Chronic Periaortitis Could Activate Farnesoid-X-Receptor to Suppress IL-6 Production by Macrophages.

Chronic periaortitis (CP) is a rare autoimmune disease without effective treatment. By analyzing the serum bile acid spectrum in 28 CP patients with the ultra-performance liquid chromatography-tandem mass spectrometry, we found that the bile acids were significantly altered in CP patients, with significant increases in chenodeoxycholic acid (CDCA) and glycochenodeoxycholic acid (GCDCA) and decrease in deoxycholic acid (DCA). Signaling pathway enrichment analysis from the RNA sequencing results suggested that the altered gene sets in PBMC of CP patients were associated with bile acid metabolism. Furthermore, we found that pathological concentration of CDCA could significantly inhibited IL-6 expression in RAW 264.7 cells after LPS stimulation. Since CDCA is a well-known natural high-affinity ligand for the bile acid receptor farnesoid-x-receptor (FXR) while GW4064 is the synthetic specific agonist of this receptor, we then revealed that GW4064 significantly decreased IL-6 expression in RAW 264.7 cells and bone marrow-derived macrophages but not in FXR-/- macrophages upon LPS stimulation. The western blot results with the anti-FXR antibody showed significantly increased expression in the nuclear proportion, suggesting that FXR agonist promoted the transportation of FXR into the nucleus but did not increase the FXR expression in macrophages. Dual-luciferase report assay and ChIP assay demonstrated that upon activation, FXR could directly bind to the promoter site of IL-6, leading to the decreased expression of IL-6. Thus, bile acids, especially CDCA, may operate to damp inflammation via FXR-mediated downregulation of IL-6 in mononuclear cells and provide a protective mechanism for CP patients.

The retrospective experience of day-surgery semi tubeless ultra-mini percutaneous nephrolithotomy.

BACKGROUND: To retrospectively assess the experience of day-surgery semi tubeless ultra-mini percutaneous nephrolithotomy (UMP) for the treatment of kidney stones by experienced surgeons. METHODS: Clinical data of 358 patients with kidney stones (254 males and 104 females; mean age: 59.60±11.70) who were performed UMP surgery in Shanghai Jiao Tong University School of Medicine affiliated Renji Hospital from June 2015 to December 2018. Patient demographics, operative data, complications, and readmission rates were recorded. Day-surgery UMP was defined as discharge of patients either the same day or within 24 h after surgery. Semi tubeless UMP was defined as no placement of DJ and nephrostomy tube after surgery. RESULTS: The average size of stones was 14.56±6.24 mm (range, 4-30 mm). There are solitary stones in 192 cases, multiple stones in 142 cases and 29 cases with Staghorn stones. F13 outer sheath was used for all operations; 358 patients completed UMP on the day of admission; 326 (91.06%) patients achieved same-day discharge or received overnight observation prior to discharge, and 32 patients (8.94%) required full admission (longer than 24 h). The readmission rate was 0.56% (2 patients). The postoperative complications within 1 week occurred in 36 (10.06%) patients, including 23, 10, 3 of grades I, II, IIIa complications (Clavien-System). The average operation time was 29.64 min and the hemoglobin drop were 13.42±9.55 g/L. The stone clearance rate was 91.62% (328/358). The semi tubeless rate war 95.25% (341/358). CONCLUSIONS: For day-surgery semi tubeless UMP, experienced surgeons gain excellent patient outcomes in appropriately selected patients. Day-surgery semi tubeless UMP is worth promoting.

Treatment of large fibroepithelial polyps in the proximal ureter with antegrade plus retrograde endoscopic laser polypectomy.

The diagnosis and treatment of large fibroepithelial polyps in the proximal ureter have been the clinical challenges. This study retrospectively summarized the clinical diagnosis and treatment of fibroepithelial polyps >5 cm in length in the proximal ureter of 6 patients who received treatment in the Affiliated Renji Hospital of Shanghai Jiaotong University School of Medicine between December 2010 and February 2017. The length of fibroepithelial polyps ranged from 5.8 to 8.2 cm. There were 4 males and 2 females with the mean age of 32.6 ±â€Š9.8 years. Unilateral polyps were found in all patients (right: n = 4; left: n = 2). Hydronephrosis of different extents was noted in these patients, 4 complained of back pain and 2 were diagnosed with hydronephrosis by ultrasonography. 1 patient had macroscopic hematuria. All these patients received antegrade plus retrograde endoscopic laser polypectomy after admission. Symptoms were significantly improved after surgery, and ultrasonography showed hydronephrosis was attenuated to different extents 2 weeks later. Three months later, computed tomography urography revealed favorable recovery in 5 patients and deterioration of hydronephrosis due to ureteropelvic stenosis in 1 patient.

Incidental prostate cancer at the time of cystectomy: the incidence and clinicopathological features in Chinese patients.

OBJECTIVES: To evaluate the incidence and the clinicopathological features of incidental prostate cancer detected in radical cystoprostatectomy (RCP) specimens in Chinese men and to estimate the oncological risk of prostate apex-sparing surgery for such patients. METHODS: The clinical data and pathological feature of 504 patients who underwent RCP for bladder cancer from January 1999 to March 2013 were retrospectively reviewed. Whole mount serial section of the RCP specimens were cut transversely at 3-4 mm intervals and examined in same pathological institution. RESULTS: Thirty-four out of 504 patients (6.8%) had incidental prostate cancer with a mean age of 70.3 years. 12 cases (35.2%) were diagnosed as significant disease. 4 cases were found to have apex involvement of adenocarcinoma of the prostate while in 5 cases the prostate stroma invasion by urothelial carcinoma were identified (one involved prostate apex). The mean follow-up time was 46.4±33.8 months. Biochemical recurrence occurred in 3 patients but no prostate cancer-related death during the follow-up. There was no statistical significance in cancer specific survival between the clinically significant and insignificant cancer group. CONCLUSIONS: The prevalence of incidental prostate cancer in RCP specimens in Chinese patients was remarkably lower than in western people. Most of the incidental prostate cancer was clinically insignificant and patient's prognosis was mainly related to the bladder cancer. Sparing the prostate apex was potentially associated with a 1.0% risk of leaving significant cancer of the prostate or urothelial carcinoma.

Feasibility and preliminary experience of quantitative T2* mapping at 3.0 T for detection and assessment of aggressiveness of prostate cancer.

RATIONALE AND OBJECTIVES: To assess the feasibility of quantitative T2* mapping at 3.0 T for prostate cancer detection and to investigate the use of T2* values to characterize tumor aggressiveness, with whole-mount step-section pathologic analysis as the reference standard. MATERIALS AND METHODS: Prostate multiecho T2* was performed in 55 consecutive patients with prostate cancer using a multishot fast-field echo sequence at 3.0 T magnetic resonance imaging. T2* mapping was obtained by exponentially fitting the multiecho T2* images pixel by pixel with different echo times for each slice. Generalized estimating equations were used to test the T2* value difference between normal and malignant prostate regions and the association between T2* value and tumor Gleason scores. RESULTS: The T2* values of the cancerous prostatic regions (mean: 42.51 ± 0.65 milliseconds) were significantly lower (P < .001) than those of the normal prostatic regions (mean: 74.87 ± 0.99 milliseconds). Adopting a threshold value of 59.27 milliseconds, T2* mapping resulted in 94.8% sensitivity and 77.3% specificity in the identification of prostate cancer. A lower mean T2* value was significantly associated with a higher tumor Gleason score (mean T2* values of 53.53, 43.75, 33.66, and 22.95 milliseconds were associated with Gleason score of 3 + 3, 3 + 4, 4 + 3, and ≥8, respectively P < .05). CONCLUSIONS: From these preliminary data, quantitative T2* mapping seems to be a potential method in the characterization of prostate cancer. T2* mapping may provide additional quantitative information that significantly correlated with prostate cancer aggressiveness.

Ductal adenocarcinoma of the prostate: immunohistochemical findings and clinical significance.

INTRODUCTION: To investigate the clinical features, diagnosis, treatment, and prognosis of ductal adenocarcinoma of the prostate. METHODS: The clinicopathological and immunohistochemical data of seven patients with ductal adenocarcinoma of the prostate were retrospectively analyzed. All patients underwent physical examination, magnetic resonance imaging (MRI), bone scan, cystoscopy, and computed tomography (CT) scan. The level of prostate-specific antigen (PSA) before and after surgery was assessed. Different prostate cancer markers were used for immunohistochemical staining. RESULTS: The mean age of the seven patients diagnosed with prostatic ductal adenocarcinoma in this study was 76.2 years (range 57-88). Five patients presented with intermittent and painless gross hematuria, one patient with progressive dysuria, and one patient with elevated serum PSA on routine health examination. The level of PSA before surgery ranged from 1.3 to 45.0 ng/mL. Immunohistochemical staining results of the prostatic ductal adenocarcinoma confirmed positivity for PSA, prostatic acid phosphatase, androgen receptor, and alpha-methyacyl co-enzyme A (CoA)-reductase markers. Two of the patients underwent bilateral orchiectomy combined with anti-androgen therapy, three underwent transurethral resection of prostate, one received radical prostatectomy, and one received medical castration therapy. The clinical outcomes of all patients were satisfactory, based on follow-up data. The symptoms of hematuria and dysuria were ameliorated well, and the postoperative PSA level decreased below 4.0 ng/mL. Recurrence or metastasis of disease was not detected on MRI and bone scan. CONCLUSION: Ductal adenocarcinoma of the prostate is a rare subtype of prostate carcinoma, the diagnosis of which could be based on pathological and immunohistochemical examination. Earlier management promises better prognosis.

Increased expression of forkhead box M1 protein is associated with poor prognosis in clear cell renal cell carcinoma.

Forkhead box protein M1 (FoxM1) is crucial in the regulation of various biological processes, including cell proliferation, organogenesis, and angiogenesis. Overexpression of FoxM1 is associated with carcinogenesis. In this study, immunohistochemistry was carried out to examine FoxM1 expression in clear cell renal cell carcinoma (ccRCC), and these data were examined for correlation with clinicopathological parameters and prognosis. FoxM1 protein had high expression in 37 of 87 cases of ccRCC (42.5 %), which was significantly higher than in normal tissues, and FoxM1 overexpression was significantly associated with tumor stage (P = 0.005) and recurrence (P = 0.027). The Kaplan-Meier survival analysis demonstrated that FoxM1 expression was significantly associated with shorter recurrence-free survival and overall survival (P = 0.007 and P = 0.008, respectively). Multivariate analysis further demonstrated that FoxM1 was an independent prognostic factor for patients with ccRCC. So FoxM1 might be a potential molecular marker to predict the prognosis of patients with ccRCC.

PLZF mediates the PTEN/AKT/FOXO3a signaling in suppression of prostate tumorigenesis.

Promyelocytic leukemia zinc finger (PLZF) protein expression is closely related to the progression of human cancers, including prostate cancer (PCa). However, the according context of a signaling pathway for PLZF to suppress prostate tumorigenesis remains greatly unknown. Here we report that PLZF is a downstream mediator of the PTEN signaling pathway in PCa. We found that PLZF expression is closely correlated with PTEN expression in a cohort of prostate cancer specimens. Interestingly, both PTEN rescue and phosphoinositide 3-kinase (PI3K) inhibitor LY294002 treatment increase the PLZF expression in prostate cancer cell lines. Further, luciferase reporter assay and chromatin immunoprecipitation assay demonstrate that FOXO3a, a transcriptional factor phosphorylated by PI3K/AKT, could directly bind to the promoter of PLZF gene. These results indicate that PTEN regulates PLZF expression by AKT/FOXO3a. Moreover, our animal experiments also demonstrate that PLZF is capable of inhibiting prostate tumorigenesis in vivo. Taken together, our study defines a PTEN/PLZF pathway and would shed new lights for developing therapeutic strategy of prostate cancer.

Application of pyrosequencing technique for improved detection of K-Ras mutation in formalin-fixed and paraffin-embedded prostate carcinoma tissues in Chinese patients.

BACKGROUND: The purpose of this study was to comparatively evaluate the efficacy of pyrosequencing (PS) and Sanger sequencing (SS) methods for detecting K-Ras codon 12 and 13 mutations in formalin-fixed paraffin-embedded (FFPE) prostate cancer (PCa) samples from Chinese patients. METHODS: The cancer cell lines, including the LS174T G12D mutant (GGT to GAT) and the COLO320 wild-type, were tested to determine the limitation of detection and reproducibility of the PS method. In addition, 101 PCa patient samples, 13 benign prostatic hyperplasia (BPH) and 12 normal adjacent tissue samples, were assayed by PS and SS to evaluate their detection abilities for K-Ras mutations in codons 12 and 13. RESULTS: The PS assay was able to reproducibly detect 5% mutant alleles and had an intra-assay variability of 4.21% and inter-assay variability of 11.37%. The PS assay detected a higher number of K-Ras mutations in PCa samples than the SS assay (8.91% vs. 3.96%). Correlation and stratification analyses of the PCa samples and K-Ras mutation status revealed no associations between age, serum prostate specific antigen (PSA), depth of invasion (pT category), or Gleason score. CONCLUSIONS: We demonstrated that the PS method detected more K-Ras mutations in codons 12 and 13 of FFPE prostate cancer samples from Chinese patients than the traditional SS method. In addition, the K-Ras mutation was more frequent in Chinese population than in Western populations but was similar to that of other Eastern populations, suggesting that these K-Ras mutations may contribute to the pathogenesis of prostate carcinoma in Asian patients.

Germline mutations in the von Hippel-Lindau disease (VHL) gene in mainland Chinese families.

BACKGROUND: von Hippel-Lindau (VHL) disease is a hereditary cancer syndrome caused by germline mutations in the VHL gene. To date, more than 500 VHL families have been reported worldwide. However, few information is available about VHL germline mutations in mainland Chinese families. OBJECTIVE: To provide some preliminary information about the germline VHL mutations in mainland Chinese population. METHODS: A total of 27 index patients suspected of having VHL disease from unrelated Chinese families were studied by using direct DNA sequencing analysis and universal primer quantitative fluorescent multiplex polymerase chain reaction. RESULTS: The VHL germline mutations were detected in 26 (96%) probands. A total of 20 intragenic mutations (77%) were identified consisting of 12 missenses, 5 nonsenses, 2 micro-deletions and 1 novel intron mutation (IVS1-38C>T). Six large deletions (23%) were detected including four partial deletions and two complete deletions. Furthermore, a C>T substitution at nucleotide 470 (Pro86Leu) was observed in two unrelated Chinese families. Of note, two mutations (Asn78Ser and Ser80Ile) previously characterized as VHL type I mutations in Western VHL were associated with the type II Chinese family. In addition, a VHL germline mutation was also identified in a proband who did not fulfill the clinical diagnostic criteria for VHL disease. CONCLUSIONS: The spectrum of VHL germline mutations in mainland Chinese population is similar to that observed in Western population, and Genetic testing can be powerful in diagnosis and clinical management of VHL disease.

Metabonomic profiling of renal cell carcinoma: high-resolution proton nuclear magnetic resonance spectroscopy of human serum with multivariate data analysis.

Metabonomic profiling using proton nuclear magnetic resonance ((1)H NMR) spectroscopy and multivariate data analysis of human serum samples was used to characterize metabolic profiles in renal cell carcinoma (RCC). We found distinct, easily detectable differences between (a) RCC patients and healthy humans, (b) RCC patients with metastases and without metastases, and (c) RCC patients before and after nephrectomy. Compared to healthy human serum, RCC serum had higher levels of lipid (mainly very low-density lipoproteins), isoleucine, leucine, lactate, alanine, N-acetylglycoproteins, pyruvate, glycerol, and unsaturated lipid, together with lower levels of acetoacetate, glutamine, phosphatidylcholine/choline, trimethylamine-N-oxide, and glucose. This pattern was somewhat reversed after nephrectomy. Altered metabolite concentrations are most likely the result of the cells switching to glycolysis to maintain energy homeostasis following the loss of ATP caused by impaired TCA cycle in RCC. Serum NMR spectra combined with principal component analysis techniques offer an efficient, convenient way of depicting tumour biochemistry and stratifying tumours under different pathophysiological conditions. It may be able to assist early diagnosis and postoperative surveillance of human malignant diseases using single blood samples.