Perioperative outcomes and continence following robotic-assisted radical cystectomy with mainz pouch II urinary diversion in patients with bladder cancer.

PURPOSE: To present the widely unknown perioperative outcomes and continence status of bladder cancer patients following robotic-assisted radical cystectomy (RARC) with Mainz pouch II urinary diversion (UD). MATERIALS AND METHODS: From November 2020 to December 2023, 37 bladder cancer patients who underwent RARC with Mainz pouch II UD were retrospectively assessed (ChiCTR2300070279). The results, which included patient demographics, perioperative data, continence, and complications (early ≤ 30 days and late ≤ 30 days) were reported using the RC-pentafecta criteria. RC-pentafecta criteria included ≥ 16 lymph nodes removed, negative soft tissue surgical margins, absence of major (Grade III-IV) complication at 90 days, absence of clinical recurrence at ≤ 12 months, and absence of long-term UD-related sequelae. A numeric rating scale assessed patient satisfaction with urinary continence 30 days after surgery. The validated Patient Assessment of Constipation Symptoms (PAC-SYM) questionnaire was used to evaluate bowel function. The Kaplan-Meier curve was used to evaluate overall survival (OS). RESULTS: Of the 37 patients evaluated over a median (range) follow-up period of 23.0 (12.0-36.5) months. The median (range) age was 65 (40-81) years. The median (range) time to urinary continence after surgery was 2.3 (1.5-6) months. Of the 37 patients, 31 (83.8%) were continent both during the day and at night, 34 (91.9%) were continent during the day, 32 (86.5%) were continent at night, 35 (94.6%) were satisfied with their urinary continence status, and 21 (56.8%) were very satisfied. The mean (range) voiding frequency was 6 (4-10) during the day and 3 (2-5.5) at night. The mean (range) PAC-SYM total score was 9.50 (4.00-15.00). In 12 (32.4%) of the patients, RC-pentafecta was achieved, and achieving RC-pentafecta was linked to better satisfaction scores (7.3 vs. 5.5, p = 0.034). There was no significant difference between RC-pentafecta and No RC-pentafecta groups in terms of OS (25.6 vs. 21.5 months, p = 0.16). 7 (19.4%) patients experienced late complications. CONCLUSIONS: Mainz pouch II UD following RARC in bladder cancer patients results in a satisfactory continence rate. Achieving RC-pentafecta was correlated with better satisfaction scores. The intracorporeal approach to Mainz pouch II UD is beneficial for female patients due to its reduced invasiveness. TRIAL REGISTRATION: ChiCTR2300070279; Registration: 07/04/2023, Last updated version: 01/06/2023. Retrospectively registered.

Risk factors of high fluid absorption in patients treated with mini-PCNL: a single-center prospective study.

BACKGROUND: The factors influencing fluid absorption in mini-percutaneous nephrolithotripsy (mini-PCNL) are still unknown. We aim to investigate the factors that influence irrigation fluid absorption during mini-PCNL. METHODS: A total of 94 patients who underwent mini-PCNL were included in this prospective study. The endoscopic surgical monitoring system (ESMS) was used to measure the volume of irrigation fluid absorbed during the procedure. Irrigating time, the total volume of irrigation fluid, stone size, S.T.O.N.E. score, hemoglobin, electrolyte levels, and postoperative complications were recorded. RESULTS: A significant correlation was observed between fluid absorption and the presence of postoperative fever, and based on this phenomenon, patients were divided into low and high fluid absorption groups. The serum creatinine level in the high fluid absorption group was significantly high (7 vs. 16.5, p = 0.02). Significant differences were observed between the low and high fluid absorption groups in terms of mean stone size (21.70 mm vs. 26.78 mm), presence of stone burden ≥ 800 mm2 (4% vs. 23%), S.T.O.N.E. score > 8 (4% vs. 38%), the fluid used > 18,596 ml (19% vs. 78%), irrigation time (55.61 min vs. 91.28 min), and perfusion rate (24% vs. 45%) (all p < 0.05). The rates of postoperative fever and SIRS in the high fluid absorption group were significantly high (p < 0.05). CONCLUSIONS: Mean stone size, presence of stone burden ≥ 800 mm2, S.T.O.N.E. score > 8, the fluid used > 18596 mL, irrigation time, and perfusion rate are risk factors of intraoperative fluid absorption in mini-PCNL.

Transperitoneal vs retroperitoneal laparoscopic radical nephrectomy: a double-arm, parallel-group randomized clinical trial.

OBJECTIVE: To compare the outcomes of patients undergoing Retroperitoneal laparoscopic Radical nephrectomy (RLRN) and Transperitoneal laparoscopic Radical nephrectomy (TLRN). METHODS: A total of 120 patients with localized renal cell carcinoma were randomized into either RLRN or TLRN group. Mainly by comparing the patient perioperative related data, surgical specimen integrity, pathological results and tumor results. RESULTS: Each group comprised 60 patients. The two group were equivalent in terms of perioperative and pathological outcomes. The mean integrity score was significantly lower in the RLRN group than TLRN group. With a median follow-up of 36.4 months after the operation, Kaplan-Meier survival analysis showed no significant difference between RLRN and TLRN in overall survival (89.8% vs. 88.5%; P = 0.898), recurrence-free survival (77.9% vs. 87.7%; P = 0.180), and cancer-specific survival (91.4% vs. 98.3%; P = 0.153). In clinical T2 subgroup, the recurrence rate and recurrence-free survival in the RLRN group was significantly worse than that in the TLRN group (43.2% vs. 76.7%, P = 0.046). Univariate and multivariate COX regression analysis showed that RLRN (HR: 3.35; 95%CI: 1.12-10.03; P = 0.030), male (HR: 4.01; 95%CI: 1.07-14.99; P = 0.039) and tumor size (HR: 1.23; 95%CI: 1.01-1.51; P = 0.042) were independent risk factor for recurrence-free survival. CONCLUSIONS: Our study showed that although RLRN versus TLRN had roughly similar efficacy, TLRN outperformed RLRN in terms of surgical specimen integrity. TLRN was also significantly better than RLRN in controlling tumor recurrence for clinical T2 and above cases. TRIAL REGISTRATION: Chinese Clinical Trial Registry ( https://www.chictr.org.cn/showproj.html?proj=24400 ), identifier: ChiCTR1800014431, date: 13/01/2018.

Knockdown of AMIGO2 suppresses proliferation and migration through regulating PPAR-γ in bladder cancer.

PURPOSE: This study aims to reveal the relationship between AMIGO2 and proliferation, migration and tumorigenicity of bladder cancer, and explore the potential molecular mechanisms. METHODS: The expression level of AMIGO2 is measured by qRT-PCR and immunohistochemistry (IHC). Stable AMIGO2 knockdown cell lines T24 and 5637 were established by lentivirus transfection. Cell Counting Kit (CCK-8 assay) was produced to determine cell proliferation, flow cytometry analysis was utilized to detect cell cycle, and wound healing assay was proceeded to test migration ability of bladder cancer cells. Xenograft mouse model was established for investigating the effect of AMIGO2 on tumor formation in vivo. The RNA Sequencing technology was applied to explore the underlying mechanisms. The expression level of PPAR-γ was measured by Western Blot. RESULTS: AMIGO2 was upregulated in bladder cancer cells and tissues. Inhibited expression of AMIGO2 suppresses cell proliferation and migration. Low AMIGO2 expression inhibited tumorigenicity of 5637 in nude mice. According to RNA-Seq and bioinformatics analysis, 917 DEGs were identified. The DEGs were mainly enriched in cell-cell adhesion, peroxisome proliferators-activated receptors (PPARs) signaling pathway and some other pathways. PPAR-γ is highly expressed in bladder cancer cell lines T24 and 5637, but when AMIGO2 is knocked down in T24 and 5637, the expression level of PPAR-γ is also decreased, and overexpression of PPAR-γ could reverse the suppression effect of cell proliferation and migration caused by the inhibition of AMIGO2. CONCLUSION: AMIGO2 is overexpressed in bladder cancer cells and tissues. Knockdown of AMIGO2 suppresses bladder cancer cell proliferation and migration. These processes might be regulated by PPAR-γ signaling pathway.

Comparison of 3 and 4 cycles of neoadjuvant gemcitabine and cisplatin for muscle-invasive bladder cancer: a systematic review and meta-analysis.

BACKGROUND: In muscle-invasive bladder cancer (MIBC), neoadjuvant chemotherapy (NAC) combined with radical cystectomy (RC) is critical in reducing disease recurrence, with GC (gemcitabine and cisplatin) being one of the most commonly used NACs. Different GC schedules have been used, but the best neoadjuvant regimen is still unknown. The clinical outcomes of 3 and 4 cycles of neoadjuvant GC are compared in this systematic review and meta-analysis to determine which is best for patients with MIBC. METHODS: We searched PubMed, Embase, Web of Science, Cochrane Library, CBM, CNKI, WAN FANG DATA, and meeting abstracts to identify relevant studies up to March 2023. Studies that compared 3 and 4 cycles of neoadjuvant GC for MIBC were included. The primary outcomes were pCR, pDS, OS, and CSS. The secondary outcome was recurrence and SAEs. RESULTS: A total of 3 studies, with 1091 patients, were included in the final analysis. Patients that received 4 cycles of GC had a higher pCR (OR = 0.66; 95% CI, 0.50-0.87; p = 0.003) and pDS (OR = 0.63; 95% CI, 0.48-0.84; p = 0.002) than those who received 3 cycles. Regarding recurrence rate (OR = 1.23; 95% CI, 0.91-1.65; p = 0.18), there were no appreciable differences between the 3 and 4 cycles of GC. Survival parameters such as OS (HR, 1.35; 95% CI, 0.86-2.12; p = 0.19) and CSS (HR, 1.06; 95% CI, 0.82-1.38; p = 0.20) were similar. Only one trial reported on the outcomes of SAEs. And there were no statistically significant differences in thrombocytopenia, infection rate, neutropenic fever, anemia, or decreased renal function between patients. The neutropenia of patients was statistically different (OR = 0.72; 95% CI, 0.52-0.99; p = 0.04). CONCLUSION: The 4-cycle GC regimen was superior to the 3-cycle regimen in only the pCR and pDS results. Survival and recurrence rates were similar between the two regimens. In both treatment regimes, the toxicity profile was manageable. However, due to the inherent drawbacks of retrospective research, this should be regarded with caution.

Is Anti-Reflux Anastomosis an Advantage in an Orthotopic Ileal Neobladder? A Systematic Review and Meta-Analysis.

INTRODUCTION: We conducted a systematic review and meta-analysis to assess the available literature regarding the postoperative effects of anti-reflux anastomosis and direct anastomosis in orthotopic ileal neobladder (ONB). METHODS: We searched PubMed, Embase, and the Cochrane Library in October 2021. We included 11 studies of patients with bladder cancer who underwent radical cystectomy and ONB as urinary diversion. Outcomes evaluated in this review were ureteroenteric anastomotic stricture (UEAS), vesicoureteral reflux, renal function (RFn) impairment, and pyelonephritis. All data were analyzed using Review Manager 5.4.4 and subgroup analyses were applied. RESULTS: A total of 11 studies were eligible for meta-analysis. The synthetic data suggested that anti-reflux anastomosis and direct anastomosis were comparable in terms of RFn impairment (odds ratio (OR) = 1.69; 95% confidence interval (CI): 0.18-15.6; p = 0.65, I2 = 69%) and pyelonephritis (OR = 1.13; 95% CI: 0.65-1.99; p = 0.66, I2 = 1%) without significant difference in each group statistically. The pooled study data showed a significantly higher incidence of UEAS (OR = 2.84; 95% CI: 1.75-4.61, p < 0.0001, I2 = 50%) and a lower incidence of vesicoureteral reflux (OR = 0.24; 95% CI: 0.10-0.59; p = 0.002, I2 = 75%) in anti-reflux anastomosis compared to direct anastomosis. In subgroup analysis, anti-reflux anastomosis was more likely to result in UEAS than direct anastomosis, especially when ureteral stent was removed within 14 days. CONCLUSION: Although meta-analysis showed that overall incidence of vesicoureteral reflux was higher with direct anastomosis than anti-reflux anastomosis, the rate of vesicoureteral reflux was not directly related to impairment of RFn. The anti-reflux mechanism of ONB was positively associated with a higher incidence of significant UEAS compared to the direct approach, which can lead to kidney damage and an increased risk of secondary surgical procedures.

Aldehyde dehydrogenase 6 family member A1 negatively regulates cell growth and to cisplatin sensitivity in bladder cancer.

Aldehyde dehydrogenase 6 family member A1 (ALDH6A1) is a highly conserved member of aldehyde dehydrogenase (ALDHs) family. Recent studies reveal that it broadly involved in tumorigenesis and drug metabolism in kinds of cancer. However, the critical role of ALDH6A1 in bladder cancer progression and cisplatin resistance of cancer cells are still poorly understood. In this study, we researched the significant function of ALDH6A1 in bladder cancer. Our results showed that ALDH6A1 exhibited a decreased expression in clinical bladder cancer tissues and bladder cancer cell lines. Stable ALDH6A1 knockdown not only could promote cell growth and colony formation in bladder cancer cells, but also enhance drug resistance to cisplatin treatment. On the contrary, we found the active transcript factor hepatocyte nuclear factor 4α (HNF4α, NR2A1) by alveriene could upregulate ALDH6A1 expression, significantly inhibit the cell growth and colony formation of bladder cancer cells, and improve cisplatin sensitivity of bladder cancer cells. Together, our results show that ALDH6A1 plays as a tumor suppressor in bladder cancer, which regulated by HNF4a. ALDH6A1 could be a promising diagnostic marker and treatment target in bladder cancer.

Counteracting health risks by Modulating Homeostatic Signaling.

Homeostasis was initially conceptualized by Bernard and Cannon around a century ago as a steady state of physiological parameters that vary within a certain range, such as blood pH, body temperature, and heart rate [1,2]. The underlying mechanisms that maintain homeostasis are explained by negative feedbacks that are executed by the neuronal, endocrine, and immune systems. At the cellular level, homeostasis, such as that of redox and energy steady state, also exists and is regulated by various cell signaling pathways. The induction of homeostatic mechanism is critical for human to adapt to various disruptive insults (stressors); while on the other hand, adaptation occurs at the expense of other physiological processes and thus runs the risk of collateral damages, particularly under conditions of chronic stress. Conceivably, anti-stress protection can be achieved by stressor-mimicking medicinals that elicit adaptive responses prior to an insult and thereby serve as health risk countermeasures; and in situations where maladaptation may occur, downregulating medicinals could be used to suppress the responses and prevent subsequent pathogenesis. Both strategies are preemptive interventions particularly suited for individuals who carry certain lifestyle, environmental, or genetic risk factors. In this article, we will define and characterize a new modality of prophylactic intervention that forestalls diseases via modulating homeostatic signaling. Moreover, we will provide evidence from the literature that support this concept and distinguish it from other homeostasis-related interventions such as adaptogen, hormesis, and xenohormesis.

Prognostic value of preoperative platelet-related parameters and plasma fibrinogen in patients with non-muscle invasive bladder cancer after transurethral resection of bladder tumor.

Aim: To investigate the prognostic value of preoperative mean platelet volume (MPV), MPV/lymphocyte ratio (MPVLR), MPV/platelet count ratio and plasma fibrinogen in patients with non-muscle invasive bladder cancer (NMIBC) after transurethral resection of bladder tumor (TURBT). Methods: A total of 371 patients who underwent TURBT were enrolled. The main end points were disease-free survival (DFS) and overall survival (OS). Results: MPVLR, tumor size, tumor number and pathological grade were independent risk factors for postoperative DFS. Age and pathological grade were independent risk factors for postoperative OS. Conclusion: MPVLR is an independent risk factor for DFS in NMIBC patients and could be used as a parameter to predict postoperative tumor recurrence in patients after TURBT.

The current study investigated the prognostic value of preoperative mean platelet volume (MPV), MPV/lymphocyte ratio (MPVLR), MPV/platelet count ratio (MPVPCR) and plasma fibrinogen (PF) in peripheral blood of patients with non-muscle invasive bladder cancer (NMIBC) after transurethral resection of bladder tumor (TURBT). Included were 371 patients who underwent TURBT and were followed up. A high level of PF indicated worse survival and age and pathological grade were independent risk factors for postoperative survival. High levels of MPV, MPVLR and MPVPCR were associated with recurrence. MPVLR, tumor size, tumor number and pathological grade were independent risk factors for postoperative recurrence. MPVLR could be used as a parameter to predict postoperative tumor recurrence in patients after TURBT.

Transurethral plasmakinetic resection versus enucleation for benign prostatic hyperplasia: comparison of intraoperative safety profiles based on endoscopic surgical monitoring system.

OBJECTIVE: To compare the intraoperative safety profiles of transurethral plasmakinetic resection of the prostate (PK-TURP) with transurethral plasmakinetic endoscopic enucleation of the prostate (PK-EEP) in the treatment of benign prostatic hyperplasia (BPH) based on endoscopic surgical monitoring system (ESMS). METHODS: A total of 128 patients who were diagnosed with BPH were stratified based on prostate volume (PV) and accepted PK-EEP or PK-TURP treatment at 1:1 ratio. The ESMS as a novel method was used to monitor blood loss and fluid absorption during the operation. Clinical parameters such as intraoperative blood loss volume, fluid absorption volume, operation time, tissue weight of resection, preoperative and postoperative red blood cell count (RBC), hemoglobin concentration (HB), hematocrit (HCT), electrolyte, postoperative bladder irrigation time, indwelling catheter time, hospital stay time and other associated complications were documented and compared between two groups. RESULTS: No significant differences in majority of baseline characteristics were observed among patients with different prostate volumes between two surgical methods. For patients with prostate volume < 40 ml, the average operation time of patients who received PK-EEP treatment was much more than those who received PK-TURP (P = 0.003). On the other hand, for patients with prostate volume > 40 ml, the PK-TURP surgery was associated with a significant increase in intraoperative blood loss (P = 0.021, in PV 40-80 ml group; P = 0.014, in PV > 80 ml group), fluid absorption (P = 0.011, in PV 40-80 ml group; P = 0.006, in PV > 80 ml group) and postoperative bladder irrigation time as well as indwelling catheter time but decrease in resected tissue weight compared to the PK-EEP treatment. CONCLUSION: The ESMS plays an important role in comparison of intraoperative safety profiles between PK-TURP and PK-EEP. Our data suggest that PK-TURP treatment is associated with a decreased operation time in patients with prostate volume < 40 ml and the PK-EEP treatment is associated with decreased intraoperative blood loss, fluid absorption and increased tissue resection for patients with prostate volume > 40 ml. Our results indicate that the size of prostate should be considered when choosing the right operation method.

Construction of a novel mRNA-signature prediction model for prognosis of bladder cancer based on a statistical analysis.

BACKGROUND: Bladder cancer (BC) is a common malignancy neoplasm diagnosed in advanced stages in most cases. It is crucial to screen ideal biomarkers and construct a more accurate prognostic model than conventional clinical parameters. The aim of this research was to develop and validate an mRNA-based signature for predicting the prognosis of patients with bladder cancer. METHODS: The RNA-seq data was downloaded from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). Differentially expressed genes (DEGs) were screened in three datasets, and prognostic genes were identified from the training set of TCGA dataset. The common genes between DEGs and prognostic genes were narrowed down to six genes via Least Absolute Shrinkage and Selection Operator (LASSO) regression, and stepwise multivariate Cox regression. Then the gene-based risk score was calculated via Cox coefficient. Time-dependent receiver operating characteristic (ROC) and Kaplan-Meier (KM) survival analysis were used to assess the prognostic power of risk score. Multivariate Cox regression analysis was applied to construct a nomogram. Decision curve analysis (DCA), calibration curves, and time-dependent ROC were performed to assess the nomogram. Finally, functional enrichment of candidate genes was conducted to explore the potential biological pathways of candidate genes. RESULTS: SORBS2, GPC2, SETBP1, FGF11, APOL1, and H1-2 were screened to be correlated with the prognosis of BC patients. A nomogram was constructed based on the risk score, pathological stage, and age. Then, the calibration plots for the 1-, 3-, 5-year OS were predicted well in entire TCGA-BLCA patients. Decision curve analysis (DCA) indicated that the clinical value of the nomogram was higher than the stage model and TNM model in predicting overall survival analysis. The time-dependent ROC curves indicated that the nomogram had higher predictive accuracy than the stage model and risk score model. The AUC of nomogram time-dependent ROC was 0.763, 0.805, and 0.806 for 1-year, 3-year, and 5-year, respectively. Functional enrichment analysis of candidate genes suggested several pathways and mechanisms related to cancer. CONCLUSIONS: In this research, we developed an mRNA-based signature that incorporated clinical prognostic parameters to predict BC patient prognosis well, which may provide a novel prognosis assessment tool for clinical practice and explore several potential novel biomarkers related to the prognosis of patients with BC.

Comparison of open and intracorporeal modified ureterosigmoidostomy (Mainz II) after laparoscopic radical cystectomy with bladder cancer.

OBJECTIVE: To compare perioperative and oncologic outcomes of open modified ureterosigmoidostomy urinary diversion (OMUUD) and intracorporeal modified ureterosigmoidostomy urinary diversion (IMUUD) following laparoscopic radical cystectomy (LRC). PATIENTS AND METHODS: We retrospectively reviewed our single institutional collected database patients undergoing LRC from October 2011 to October 2019. The perioperative characteristics were compared between OMUUD and IMUUD, and overall survival (OS) and progression-free survival (PFS) were evaluated by the Kaplan-Meier method. RESULTS: Overall, 84 patients were included. OMUUD and IMUUD were performed in 63 (75%) and 21 (25%) patients, respectively. IMUUD patients demonstrated shorter postoperative length of stay (16.24 ± 3.91 days vs. 18.98 ± 7.41 days, P = 0.033), similar operation time (498.57 ± 121.44 vs. 462.24 ± 99.71, P = 0.175), similar estimated blood loss [400 (200-475) ml vs. 400 (200-700) ml, P = 0.095], and similar overall complication rate within 30 days (19.05% vs. 25.40%, P = 0.848) and 90 days (23.81% vs. 17.46%, P = 0.748). Complete urinary control rate was 87.3% (55/63) in the OMUUD group. In IMUUD, the complete urinary control rate was 90.5% (19/21). There was no significant difference in OS (χ2 = 0.015, P = 0.901) and PFS (χ2 = 0.107, P = 0.743) between the two groups. CONCLUSION: IMUUD postoperative recovery is faster; other perioperative outcomes and oncology results are not significantly different with OMUUD. It is indicated that IMUUD can be utilized safely and effectively in the urinary diversion after LRC.

A novel bladder cancer - specific oncolytic adenovirus by CD46 and its effect combined with cisplatin against cancer cells of CAR negative expression.

BACKGROUND: Conditionally replicative oncolytic adenoviruses (CRAds) display significant anti-tumor effects. However, the traditional adenovirus of serotype 5 (Ad5) entering cancer cells via coxsackie virus and adenovirus receptor (CAR) can't be utilized for bladder cancer with low expression of CAR, which limits the application of Ad5. METHODS: We utilized Ad5/F11p containing the chimeric fiber gene encoding the Ad5 fiber tail domain and Ad11p fiber shaft and knob domains to construct bladder cancer-specific chimeric type viruses Ad5/F11p-PSCAE-UPII-E1A, which can infect bladder cancer cells mediated by CD46 molecule. We carried out series of experiments in vitro to research anti-tumor effect of Ad5/F11p-PSCAE-UPII-E1A and the interaction in combination with cisplatin. RESULTS: The results demonstrated Ad5/F11p-PSCAE-UPII-E1A could infect bladder cancer cells (T24, EJ and 5637) in a CAR-independent way, and exert anti-tumor effect by blocking the cancer cells in G1 phase and inducing apoptosis. Ad5/F11p-PSCAE-UPII-E1A plus cisplatin enhanced the anti-proliferative effect and increased the number of apoptotic cells compared with viruses or cisplatin alone. Ad5/F11p-PSCAE-UPII-E1A plus cisplatin could upregulate the proteins expression of p53, Bax, and cleaved caspase-3, and downregulated Bcl-2 protein expression in T24, EJ and 5637 cells. CONCLUSION: We constructed a bladder cancer-specific oncolytic adenovirus and provided new combination treatment strategies for bladder cancer.

Accuracy of Percutaneous Core Biopsy in the Diagnosis of Small Renal Masses (≤ 4.0 cm): A Meta-analysis.

OBJECTIVE: To use meta-analysis to determine the accuracy of percutaneous core needle biopsy in the diagnosis of small renal masses (SMRs ≤ 4.0 cm). MATERIALS AND METHODS: Studies were identified by searching PubMed, Embase, and the Cochrane Library database up to March 2013. Two of the authors independently assessed the study quality using QUADAS-2 tool and extracted data that met the inclusion criteria. The sensitivity, specificity, likelihood ratios, diagnostic odds ratio (DOR) and also summary receiver operating characteristic (SROC) curve were investigated and draw. Deek's funnel plot was used to evaluate the publication bias. RESULT: A total of 9 studies with 788 patients (803 biopsies) were included. Failed biopsies without repeated or aborted from follow-up/surgery result were excluded (232 patients and 353 biopsies). For all cases, the pooled sensitivity was 94.0% (95% CI: 91.0%, 95.0%), the pooled positive likelihood was 22.57 (95 % CI: 9.20-55.34), the pooled negative likelihood was 0.09 (95 % CI: 0.06-0.13), the pooled DOR was 296.52(95 % CI: 99. 42-884.38). The area under the curve of SROC analysis was 0.959 ± 0.0254. CONCLUSION: Imaging-guided percutaneous core needle biopsy of small renal masses (SMRs ≤ 4.0 cm) is highly accurate to malignant tumor diagnosis with unknown metastatic status and could be offered to some patients after clinic judgment prior to surgical intervention consideration.

A tissue graft model of DNA damage response in the normal and malignant human prostate.

PURPOSE: DNA damage responses are relevant to prostate cancer initiation, progression and treatment. Few models of the normal and malignant human prostate that maintain stromal-epithelial interactions in vivo exist in which to study DNA damage responses. We evaluated the feasibility of maintaining tissue slice grafts at subcutaneous vs subrenal capsular sites in RAG2(-/-)γC(-/-) mice to study the DNA damage responses of normal and malignant glands. MATERIALS AND METHODS: We compared the take rate and histology of tissue slice grafts from fresh, precision cut surgical specimens that were maintained for 1 to 4 weeks in subcutaneous vs subrenal capsular sites. Induction of γH2AX, p53, ATM and apoptosis was evaluated as a measure of the DNA damage response after irradiation. RESULTS: The take rate of subcutaneous tissue slice grafts was higher than typically reported but lower than at the subrenal capsular site. Subcutaneous tissue slice grafts frequently showed basal cell hyperplasia, squamous metaplasia and cystic atrophy, and cancer did not survive. In contrast, normal and malignant histology was well maintained in subrenal capsular tissue slice grafts. Regardless of implantation site the induction of γH2AX and ATM occurred in tissue slice graft epithelium 1 hour after irradiation and decreased to basal level by 24 hours, indicating DNA damage recognition and repair. As observed previously in prostatic ex vivo models, p53 was not activated. Notably, tumor but not normal cells responded to irradiation by undergoing apoptosis. CONCLUSIONS: To our knowledge this is the first study of DNA damage responses in a patient derived prostate tissue graft model. The subrenal capsular site of RAG2(-/-)γC(-/-) mice optimally maintains normal and malignant histology and function, permitting novel studies of DNA damage responses in a physiological context.

Waist circumference and risk of lower urinary tract symptoms: a meta-analysis.

BACKGROUND AND OBJECTIVE: Epidemiological studies have reported conflicting results concerning the role of central obesity in lower urinary tract symptoms. We performed a meta-analysis to determine whether larger waist circumference (WC) is a predicted signal for Lower Urinary Tract Symptoms (LUT). Data resource: Eligible studies were retrieved by searching PubMed, Web of science, and the Cochrane Library database up to January 2014. STUDY ELIGIBILITY CRITERIA: Prospective and retrospective cohort, case-controlled trials and observational studies. DATA EXTRACTION: Data were extracted and analyzed using random effect models to reveal an array of risk factors. Dose-response meta-analysis was performed for studies reporting categorical risk estimates at multiple exposure levels. Study heterogeneity and publication biases were assessed. DATA SYNTHESIS: A total of 12 studies met the inclusion criteria of the meta-analysis. A positive association with waist circumference (WC) was observed between WC and LUTS at an odds ratio of 1.49, (95% confidence intervals 1.34-1.64). In subgroup analysis, WC exhibited a positive dose-dependent relationship with LUTS in mostly study design, region and primary outcomes. LIMITATION: Potential biases from preferential publication and selective reporting. CONCLUSION: Large WC is associated with increased risk of LUTS. Further studies are needed to confirm this finding and to define related biological mechanisms.

PA-MSHA improves prognosis of patients undergoing radical cystectomy: a retrospective cohort study using inverse probability of treatment weighting.

Objective: To observe the effect of Pseudomonas aeruginosa mannose-sensitive hemagglutinin (PA-MSHA) on the prognosis and the incidence of lymphatic leakage in patients undergoing radical cystectomy (RC). Method: A total of 129 patients who underwent RC in Lanzhou University Second Hospital from 2013 to 2022 were enrolled in this study. They were divided into 43 patients treated with PA-MSHA and 86 patients in the control group. Inverse probability of treatment weighting (IPTW) was applied to reduce potential selection bias. Kaplan-Meier method and Cox regression analysis were used to analyze the effect of PA-MSHA on the survival of patients and the incidence of postoperative lymphatic leakage. Results: The PA-MSHA group exhibited improved overall survival (OS) and cancer-specific survival (CSS) rates compared to the control group. The 3-year and 5-year overall survival (OS) rates for the PA-MSHA group were 69.1% and 53.2%, respectively, compared to 55.6% and 45.3% for the control group (Log-rank=3.218, P=0.072). The 3-year and 5-year cancer-specific survival (CSS) rates for the PA-MSHA group were 73.3% and 56.5%, respectively, compared to 58.0% and 47.3% for the control group (Log-rank=3.218, P=0.072). Additionally, the 3-year and 5-year progression-free survival (PFS) rates for the PA-MSHA group were 74.4% and 56.8%, respectively, compared to 57.1% and 52.2% for the control group (Log-rank=2.016, P=0.156). Multivariate Cox regression analysis indicates that lymph node metastasis and distant metastasis are poor prognostic factors for patients, while the use of PA-MSHA can improve patients' OS (HR: 0.547, 95%CI: 0.304-0.983, P=0.044), PFS (HR: 0.469, 95%CI: 0.229-0.959, P=0.038) and CSS (HR: 0.484, 95%CI: 0.257-0.908, P=0.024). The same trend was observed in the cohort After IPTW adjustment. Although there was no significant difference in the incidence of postoperative lymphatic leakage [18.6% (8/35) vs. 15.1% (84.9%), P=0.613] and pelvic drainage volume [470 (440) ml vs. 462.5 (430) ml, P=0.814] between PA-MSHA group and control group, PA-MSHA could shorten the median retention time of drainage tube (7.0 d vs 9.0 d) (P=0.021). Conclusion: PA-MSHA may improve radical cystectomy in patients with OS, PFS, and CSS, shorten the pelvic drainage tube retention time.

Safety of low-intensity extracorporeal shock wave therapy in prostate disorders: in vitro and in vivo evidence.

ABSTRACT: Recent evidence suggests that low-intensity extracorporeal shock wave therapy (Li-ESWT) is a promising treatment for chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS); however, its safety in pelvic organs, particularly prostate tissues and cells, remains unclear. The current study evaluates the risks of prostate cell damage or oncogenesis following the administration of Li-ESWT for prostatitis. To this end, a robust in vitro model (Cell Counting Kit-8 [CCK-8] assay, clone formation assay, cell scratch assay, lactate dehydrogenase [LDH] release assay, flow cytometry, and immunoblotting assay) was designed to examine the effects of Li-ESWT on cell proliferation, clonogenicity, migration, membrane integrity, and DNA damage. Exome sequencing of Li-ESWT-treated cells was performed to determine the risk of carcinogenesis. Furthermore, an in vivo rat model ( n = 20) was employed to assess the effects of Li-ESWT on cancer biomarkers (carcinoembryonic antigen [CEA], Ki67, proliferating cell nuclear antigen [PCNA], and gamma-H2A histone family member X, phosphorylation of the H2AX Ser-139 [ γ -H2AX]) in prostate tissue. Based on our findings, Li-ESWT promotes cellular growth and motility without inducing significant cell membrane or DNA damage or alterations. Genetic analyses did not demonstrate an increase in mutations, and no damage to prostate tissue or upregulation of cancer biomarkers was detected in vivo. This comprehensive in vitro and in vivo assessment confirms the safety of Li-ESWT in managing prostate disorders.

Targeting DAD1 gene with CRISPR-Cas9 system transmucosally delivered by fluorinated polylysine nanoparticles for bladder cancer intravesical gene therapy.

Background: Intravesical chemotherapy is highly recommended after transurethral resection of bladder tumor for patients with bladder cancer (BCa). However, this localized adjuvant therapy has drawbacks of causing indiscriminate damage and inability to penetrate bladder mucosal. Methods: Fluorinated polylysine micelles (PLLF) were synthesized by reacting polylysine (PLL) with heptafluorobutyrate anhydride. Anti-apoptotic gene defender against cell death 1 (DAD1) was selected by different gene expression analysis between BCa patients and healthy individuals and identified by several biological function assays. The gene transfection ability of PLLF was verified by multiple in vitro and in vivo assays. The therapeutic efficiency of PLLF nanoparticles (NPs) targeting DAD1 were confirmed by intravesical administration using an orthotopic BCa mouse model. Results: Decorated with fluorinated chains, PLL can self-assemble to form NPs and condense plasmids with excellent gene transfection efficiency in vitro. Loading with the CRISPR-Cas9 system designed to target DAD1 (Cas9-sgDAD1), PLLF/Cas9-sgDAD1 NPs strongly inhibited the expression of DAD1 in BCa cells and induced BCa cell apoptosis through the MAPK signaling pathway. Furthermore, intravesical administration of PLLF/Cas9-sgDAD1 NPs resulted in significant therapeutic outcomes without systemic toxicity in vivo. Conclusion: The synthetized PLLF can transmucosally deliver the CRISPR-Cas9 system into orthotopic BCa tissues to improve intravesical instillation therapy for BCa. This work presents a new strategy for targeting DAD1 gene in the intravesical therapy for BCa with high potential for clinical applications.