L.B. Liu

Diagnosis and Surgical Treatment of Nutcracker Syndrome: A Single-Center Experience

OBJECTIVES To report our experience in the diagnosis and surgical treatment of the nutcracker syndrome, which is uncommon, with few larger series published. METHODS We retrospectively analyzed 23 patients with the nutcracker syndrome who presented to our institution from July 1998 to July 2007. A diagnosis of the nutcracker syndrome was suspected from the clinical examination, ultrasound, computed tomography, and magnetic resonance imaging findings. The diagnosis was confirmed by determination of the renocaval gradient using phlebography of the left renal vein (LRV). Because of recurrent gross hematuria and persistent orthostatic proteinuria, 7 patients (4 females and 3 males) underwent LRV transposition. Other patients with mild and tolerable symptoms were treated conservatively. The follow-up range was 14-122 months (mean 42.6). RESULTS All 23 patients met the criteria for establishing the diagnosis of the nutcracker syndrome. Ultrasonography, computed tomography, and magnetic resonance imaging revealed entrapment of the LRV between the superior mesenteric artery and aorta. The renocaval pressure gradient was > or = 4 mm Hg (normal < 1 mm Hg) in all patients. The hematuria and proteinuria disappeared in the 7 patients who underwent LRV transposition, and only 1 patient continued to have pelvic pain. No complications occurred during surgery. The postoperative complications included paralytic ileus in 2 and retroperitoneal hematoma in 1 patient. No improvement or only partial improvement was observed in most patients receiving conservative treatment. CONCLUSIONS The diagnosis of the nutcracker syndrome is determined from the clinical examination and radiographic findings. In patients who require surgical treatment, LRV transposition is an efficient surgical approach with an acceptable risk of complications. However, in some cases, pelvic pain may persist despite removal of the obstruction of the renal venous backflow.

miRNA-205 is a candidate tumor suppressor that targets ZEB2 in renal cell carcinoma.

SummaryBackground: This study aims to characterize the function of downregulated MicroRNA miR-205 in renal cell carcinoma (RCC), and show how the downstream zinc finger E-box-binding homeobox 2 (ZEB2) is negatively regulated by miR-205. Materials and Methods: The expression of miR-205 was detected in RCC and adjacent non-tumor tissues using real-time polymerase chain reaction (PCR). The expression of miR-205 and ZEB2 was detected in RCC cell lines using real-time PCR. The luciferase reporter assay was used to assess ZEB2 as a target of miR-205. Protein levels of ZEB2, E-cadherin, and vimentin were measured by western blot after overexpression of miR-205 in ACHN cells. In vivo functions of miR-205 in ACHN cells were measured by MTT assays, migration and invasion assays, and flow cytometry. Results: MiR-205 was significantly downregulated in RCC samples and cell lines compared with matched non-tumor tissues and HK-2 cells, respectively. No significant difference was found in miR-205 expression between well differentiated and poorly to moderately differentiated groups or between phase I and phase II-III. ZEB2 was upregulated in RCC cell lines compared with expression in HK-2 cells. Upregulation of miR-205 expression caused the downregulation of ZEB2 and vimentin, and the upregulation of E-cadherin in ACHN cells. miR-205 also inhibited proliferation, migration, and invasion, and induced apoptosis of ACHN cells. Conclusion: miR-205 is a candidate tumor suppressor that targets ZEB2 in RCC.

Tumor microenvironment B cells increase bladder cancer metastasis via modulation of the IL-8/androgen receptor (AR)/MMPs signals

While B cells in the tumor microenvironment may play important roles in cancer progression, their impacts on the bladder cancer (BCa) metastasis remain unclear. Here we found from human clinical BCa samples that BCa tissues could recruit more B cells than the surrounding normal bladder tissues and the in vitro co-culture assay also demonstrated that B cells could be recruited more easily towards BCa cells compared to normal bladder cells. Chamber invasion and 3D invasion assays showed the recruited B cells could then significantly increase the BCa cell invasion. Mechanism dissection found that recruited B cells could increase IL-8/androgen receptor (AR) signals in BCa cells that could then promote the expression of metastasis genes including MMP1 and MMP13. Blocking the IL-8/AR/MMPs signals either by anti-IL-8 neutralizing antibody, AR-siRNA, or MMPs inhibitors all partially reversed the infiltrating B cells capacity to increase the BCa cell invasion. The in vivo data from orthotopically xenografted BCa mouse model also confirmed that infiltrating B cells could increase BCa cell invasion via increasing AR signals. Together, these results demonstrate the key roles of B cells within the bladder tumor microenvironment that increase the BCa metastasis and may help us to develop the potential therapies via targeting these newly identified IL-8/AR/MMPs signals to better battle the BCa progression.

Botulinum Toxin-A Injections for Idiopathic Overactive Bladder: A Systematic Review and Meta-Analysis

Objective: To review the current evidence on the efficacy and safety of botulinum toxin-A in the management of idiopathic overactive bladder (OAB). Methods: A systematic search of PubMed, Embase and the Cochrane Central Search Library was performed. All randomized controlled trials comparing botulinum toxin-A with placebo, different doses and injection techniques, in patients with idiopathic OAB was included. The analyzed outcomes were quantification of symptoms, urodynamic outcomes, quality of life and adverse events. Result: A total of 1,020 participants from 12 randomized controlled trials were included. Botulinum toxin-A was associated with less urinary frequency, less incontinence episodes, improvement in quality of life, higher post-void residual-related catheterization and higher urinary tract infection. Doses of 100-300 U were not consistently differentiated from each other in voiding diary, quality of life and urge urinary incontinence. No statistically significant difference was seen between bladder body and bladder base, bladder body and bladder body plus trigone in urinary retention and urinary tract infection. Conclusion: Botulinum toxin-A is associated with significant improvement in OAB symptoms in patients with idiopathic OAB. However, there is a higher incidence of postoperative urinary retention and urinary infection compared to placebo. Low-dose botulinum toxin-A seems to be the optimum dose that appropriately balances the benefits with adverse events. Trigone inclusion seems as safe and effective as trigone-sparing injection.

CORRIGENDUM: A Comparative Study of Fast-Track Versus Conventional Surgery in Patients Undergoing Laparoscopic Radical Cystectomy and Ileal Conduit Diversion: Chinese Experience.

Fast-track surgery (FTS), which combines various techniques with evidence-based adjustments, is aimed to reduce postoperative morbidity, attenuate surgical stress response, thereby accelerating recovery and shorting length of stay. To further investigate the effectiveness of fast-track surgery, we compared the short-term outcomes of laparoscopic radical cystectomy and ileal conduit diversion for Chinese bladder cancer patients with FTS or with CS in our hospital. Patients with bladder cancer were included and divided into two consecutive groups: CS group and FTS group. Duration to first flatus and regular diet, postoperative hospital days, hospital expense, incidence of complications and postoperative surgical stress response were compared. There was no significant difference between the two groups in age, sex, BMI and postoperative TNM classification. Compared with the CS group, the FTS group had significantly shorter duration to first flatus, time to regular diet, postoperative hospital days and hospital expense, less complications, lower white blood count (WBC) and serum of C-reactive protein (CRP) on postoperative day 5 and 7. Our study indicates that FTS program is safe and efficacious for Chinese patients undergoing laparoscopic radical cystectomy and ileal conduit diversion. It can accelerate recovery, reduce stress action, shorten postoperative hospitals days and reduce hospital expenses.

Ergonomic status of laparoscopic urologic surgery: survey results from 241 urologic surgeons in china.

Background The prolonged and frequent use of laparoscopic equipment raises ergonomic risks that may cause physical distress for surgeons. We aimed to assess the prevalence of urologic surgeons’ physical distress associated with ergonomic problems in the operating room (OR) and their awareness of the ergonomic guidelines in China. Methods A sample of 300 laparoscopic urologists in China was assessed using a questionnaire on demographic information, ergonomic issues in the OR, musculoskeletal symptoms, and awareness of the ergonomic guidelines for the OR. Results There were 241 survey respondents (86.7%) with valid questionnaires. Among the respondents, only 43.6% placed the operating table at pubic height during the actual operation. The majority of the respondents (63.5%) used only one monitor during the procedure. Only 29.9% placed the monitor below the eye level. More than half of the respondents (50.6%) preferred to use manual control instead of the foot pedal. Most of the respondents (95.0%) never used the body support. The respondents experienced discomfort in the following regions, in ascending order: leg (21.6%), hand (30.3%), wrist (32.8%), shoulder (33.6%), back (53.1%), and neck (58.1%). The respondents with over 250 total operations experienced less discomfort than those with less than 250 total operations. Most of the respondents (84.6%) were unaware of the ergonomic guidelines. However, almost all of the respondents (98.3%) regarded the ergonomic guidelines to be important in the OR. Conclusions Most of the laparoscopic urologists were not aware of the ergonomic guidelines for the OR; hence, they have been suffering from varying degrees of physical discomfort caused by ergonomic issues. There is an urgent need for education regarding ergonomic guidelines in the OR for laparoscopic urologists in China.

CCL21/CCR7 enhances the proliferation, migration, and invasion of human bladder cancer T24 cells.

Objective To investigate the effects of CCL21/CCR7 on the proliferation, migration, and invasion of T24 cells and the possible associated mechanisms: expression of MMP-2 and MMP-9, and regulation of BCL-2 and BAX proteins. Methods T24 cells received corresponding treatments including vehicle control, antibody (20ng/mL CCR7 antibody and 50 ng/ml CCL21), and 50, 100, and 200 ng/ml CCL21. Proliferation was evaluated by MTT assay; cell migration and invasion were assayed using a transwell chamber. Cell apoptosis was induced by Adriamycin (ADM). The rate of cell apoptosis was examined by flow cytometry using annexin V-FITC/PI staining. Western-blot was used to analyze MMP-2 and MMP-9 and BCL-2 and BAX proteins. Results CCL21 promoted T24 cell proliferation in concentration-dependent manner with that 200 ng/mL induced the largest amount of proliferation. Significant differences of cell migration were found between CCL21treatment groups and the control group in both the migration and invasion studies (P < 0.001 for all). The expressions of MMP-2 and MMP-9 proteins were significantly increased after CCL21 treatment (p < 0.05 for all). Protein expression of Bcl-21 follows an ascending trend while the expression of Bax follows a descending trend as the concentration of CCL21 increases. No difference was found between the control group and antibody group for all assessments. Conclusion CCL21/CCR7 promoted T24 cell proliferation and enhanced its migration and invasion via the increased expression of MMP-2 and MMP-9. CCL21/CCR7 had antiapoptotic activities on T24 cells via regulation of Bcl-2 and Bax proteins. CCL21/CCR7 may promote bladder cancer development and metastasis.

High Expression of Long Noncoding RNA MALAT1 Indicates a Poor Prognosis and Promotes Clinical Progression and Metastasis in Bladder Cancer

Micro‐Abstract Bladder cancer is the second most common malignancy of the urinary system, after prostate cancer. The expression of long noncoding RNA MALAT1 can promote cancer cell proliferation, invasion, and metastasis in many tumor types. High MALAT1 expression could serve as an independent prognostic factor for bladder cancer and could be a potential therapeutic target of bladder cancer. Background: Recent studies have demonstrated that the expression of long noncoding RNA metastasis‐associated lung adenocarcinoma transcript 1 (MALAT1) promotes cancer cell proliferation, invasion, and metastasis in many tumor types, but the association between bladder cancer and MALAT1 remains unknown. Materials: The expression of MALAT1 was tested by in situ hybridization (ISH) in 120 bladder cancer specimens. The association between MALAT1 expression and clinicopathological features and prognosis of the patients with bladder cancer was analyzed. Quantitative real‐time polymerase chain reaction (qRT‐PCR) was performed to verify the relationship between the expression of MALAT1 and progression and metastasis of bladder cancer. Results: ISH showed that high MALAT1 expression was associated with advanced histological grade, high tumor stage, and positive lymph nodes. Kaplan‐Meier survival analysis and Cox regression analysis indicated that high tumor stage, positive lymph nodes, and high MALAT1 expression were independent prognostic indicators for overall survival (OS) of patients with bladder cancer. qRT‐PCR showed that the expression of MALAT1 in bladder cancer tissues was 2.85 times higher than those measured in adjacent normal tissues (P < .001). The expression of MALAT1 was 2.673 ± 0.254 in non–muscle‐invasive bladder cancer and 2.987 ± 0.381 in muscle‐invasive bladder cancer (P = .018). In bladder cancer specimens with positive lymph nodes, MALAT1 expression was 3.167 ± 0.297 versus 2.896 ± 0.329 in bladder cancer specimens with negative lymph nodes (P = .020). Conclusion: High MALAT1 expression could serve as an independent prognostic factor for OS of patients with bladder cancer and could be considered as a potential therapeutic target of bladder cancer.

Development and Validation of an Animal Model of Prostate Inflammation-Induced Chronic Pelvic Pain: Evaluating from Inflammation of the Prostate to Pain Behavioral Modifications

Background Chronic prostatitis/Chronic pelvic pain syndrome (CP/CPPS) is the most common type of prostatitis. Due to the lack of a suitable animal model partly, the pathogenesis for this condition is obscure. In the current study we developed and validated an animal model for nonbacterial prostatitis and prostate inflammation-induced chronic pelvic pain in rats with the use of intraprostatic injection of λ-carrageenan. Methods Male Sprague-Dawley rats weighing 250–350 g were used for the experiments. After intraprostatic injection of 3% λ-carrageenan, at different time points(after 24 h, 7d, 14d and 30d of injection), radiant heat and von Frey filaments were applied to the scrotum of rats to measure the heat and mechanical thresholds respectively. Then the prostate was removed for histology, and cyclooxygenase (COX) 2 protein expression was determined by Western-blot. Evans blue(50 mg/kg) was also injected intravenously to assess for plasma protein extravasation at different time points after injection of λ-carrageenan. Results Compared to control group, inflamed animals showed a significant reduction in mechanical threshold (mechanical allodynia) at 24 h and 7d(p = 0.022,0.046, respectively), and a significant reduction in heat threshold (thermal hyperalgesia) at 24 h, 7d and 14d(p = 0.014, 0.018, 0.002, respectively) in the scrotal skin. Significant increase of inflammatory cell accumulation,COX2 expression and Evans blue extravasation were observed at 24 h, 7d and 14d after injection. Conclusions Intraprostatic λ-carrageenan injection induced neurogenic prostatitis and prostate inflammation pain, which lasted at least 2 weeks. The current model is expected to be a valuable preclinical tool to study the neurobiological mechanisms of male chronic pelvic pain.

Right retrocaval ureter and left nutcracker syndrome: a case report.

We report a rare case of right retrocaval ureter and left nutcracker syndrome in a young man who was accurately diagnosis preoperatively with the help of intravenous urogram and gray-scale and color flow Doppler ultrasonography, and confirmed by computed tomography. Surgery that involves resection of the retrocaval segment and relocation of the anastomosis anterior to the inferior vena cave was performed for the right retrocaval ureter, whereas surveillance was adopted for the left nutcracker syndrome.