Initial experience of transurethral-assisted laparoendoscopic single-site nephroureterectomy.

PURPOSE: We describe a new transurethral technique for distal ureter management and the improvement of intraoperative exposure during LESS-NU. METHODS: A total of 20 transurethral assisted LESS-NU were performed between May 2018 and December 2020 in our institution. The access route for the operation was via a single-port, with four channels placed through a transumbilical incision. After the lower ureter was separated from the bladder wall, a 1470 laser working channel was placed through the urethra to precisely cut the ureteral orifice. Following this, a self-made urethra auxiliary port was inserted through the bladder cuff opening to facilitate a resection of the ureter and kidney. The peri-operative and postoperative data were then retrospectively collected and analysed. RESULTS: All procedures were completed successfully and one patient needed an additional port. The mean operative time was 196.8 ± 45.8 min and the mean estimated blood loss was 58.9 ± 32.0 ml. The days required for the surgical drain removal and the hospital stay were 4.6 ± 4.6 and 11.1 ± 6.4 days, respectively. One patient developed a fever following surgery but there were no major complications. During the average follow-up period, which lasted 25.5 months, one patient developed spinal cord metastasis and died 8 months after surgery. No obvious abnormalities were found in any of the other patients. CONCLUSION: The tansurethral approach of the distal ureter for LESS-NU is deemed safe and efficient. The technique used offers accurate control of the distal ureter and good exposure of LESS.

Laparoendoscopic radical prostatectomy (LRP): stepwise transition from multi-site to single-site with the aid of the transurethral port.

PURPOSE: To describe our initial experience with laparoendoscopic radical prostatectomy (LRP) and a stepwise transition towards transurethral assisted laparoendoscopic single-site RP (TU-LESS RP). PATIENTS AND METHODS: From Jan. 2007 to Dec. 2016, 195 patients underwent RP, of which 89 patients were performed by LRP (Group A), 106 by TU-LESS RP (Group B). The peri-operative data were collected and analyzed. All data referring to patient demographics, surgery, pathology, and peri-operative outcomes were recorded. The cosmetic result was investigated by the Patient Scar Assessment Questionnaire (PSAQ). Analysis of variance or Chi squared test were adopted to analyze the data. RESULTS: 195 procedures were completed successfully. The operation time (109.6 ± 31.9 vs. 151.5 ± 87.3, P = 0.025) and anastomosis time (10.1 ± 4.8 vs. 21.8 ± 9.9, P < 0.001) of Group B was significantly reduced compared with Group A. Estimated blood loss in Group B was significantly lower than that in Group A (95.9 ± 11.1 vs. 180.2 ± 99.7, P = 0.006). About perioperative complications, Group B was also less compared with Group A (1.9% vs. 7.9%, P = 0.047). As to the usage of postoperative analgesics, Group B apparently used less than that in Group A (6.6% vs. 62.9%, P < 0.001), which is consistent with the visual analogue scale (VAS) of the two groups (1.7 ± 1.3 vs. 7.8 ± 1.1, P < 0.001). Patients in Group B were significantly more satisfied with incision healing than in group A (74.9 ± 9.3 vs. 49.7 ± 5.8, P < 0.001). There was no significant difference both in BCR rate and time between Group B and Group A. In urination control, more patients in Group B did not have urinary incontinence 3 month after RP compared with Group A (81.1% vs. 67.4%, P = 0.028). CONCLUSIONS: LESS RP is proved to be feasible for the proper patients, but it is difficult to popularized due to inconvenient operation. While by means of TU-LESS, operating difficulty can be significantly decreased. TU-LESS RP will be wildly accepted by surgeons and patients because of cosmetic satisfaction and quicker recovery.

Comparison of Laparoendoscopic Single-Site and Laparoscopic Radical Cystectomy for Male Patients with Bladder Cancer: Perioperative and Oncologic Outcomes.

Objective: To compare the surgical and early oncological outcomes in patients with bladder cancer who had laparoendoscopic single-site radical cystectomy (RC) or laparoscopic RC. Materials and Methods: From July 2012 to May 2019, 28 consecutive men suffering from bladder cancer underwent laparoendoscopic single-site RC or laparoscopic RC with extracorporeally ileal conduit diversion. Data regarding the patient characteristics, surgical outcomes, and short-term oncological outcomes were analyzed retrospectively. Results: Compared with laparoscopic RC, laparoendoscopic single-site RC was associated with less postoperative pain (mean, 4.67 versus 6.08 scores; P = .004), and shorter convalescence (time to ambulation, mean, 1.13 days versus 2.15 days; P = .000; hospital stay after surgery, mean, 13 days versus 19 days; P = .001). In addition, differences in patient characteristics, mean total operation time, and mean estimated blood loss were not statistically significant between laparoendoscopic single-site RC and laparoscopic RC groups. There was no difference in the early or late complication rate between the two groups as well. It is also revealed that there was no significant difference in the overall survival rate at 24 months between laparoendoscopic single-site RC and laparoscopic RC groups. Conclusions: Based on our initial experience with laparoendoscopic single-site RC, it is a safe procedure with acceptable complications and oncological outcomes. Notably, laparoendoscopic single-site RC is associated with less postoperative pain and rapider convalescence compared with the historical series of laparoscopic RC. However, further comparative studies with longer follow-up period are warranted to validate this procedure.

Comparison of modified transumbilical laparoendoscopic single-site nephroureterectomy and retroperitoneal laparoscopic nephroureterectomy: initial experience.

INTRODUCTION: Owing to the development of the laparoendoscopic single-site (LESS) procedure, transumbilical LESS nephroureterectomy (LESS-NU) has become a new approach for treating upper tract urothelial carcinoma. AIM: The aim of this study is to introduce a modified LESS-NU procedure with bladder cuff excision for treating upper tract urothelial carcinoma (UTUC). We compared its clinical efficacy and postoperative outcomes in terms of follow-up time with traditional retroperitoneal laparoscopic nephroureterectomy (RL-NU). MATERIAL AND METHODS: From May 2014 to May 2019, we performed nephroureterectomy on 42 patients using the retroperitoneal approach and a modified LESS approach. A retrospective analysis was conducted for the evaluation of the clinical and postoperative outcomes between the two groups. RESULTS: The study included 25 LESS-NU and 17 RL-NU patients. All the procedures were completed successfully. The LESS-NU group had a significantly shorter mean operative time than the RL-NU group (204.4 min, 236.18 min, p = 0.005). The differences in skin incision length (2.88 cm, 8.94 cm, p < 0.001) and oral analgesic dose (n = 1.12, n = 2.75, p < 0.001) between LESS-NU and RL-NU were statistically significant. CONCLUSIONS: Modified LESS-NU is a feasible and safe procedure. Compared with the retroperitoneal laparoscopic approach, the single-site approach did not alter the patients' position. LESS-NU is a better procedure for treating UTUC than RL-NU in terms of cosmetic result and postoperative pain.

LncRNA00518 promotes cell proliferation through regulating miR-101 in bladder cancer.

The purpose of our study is to elucidate the expression of lncRNA00518 (lnc00518) in the bladder cancer, and its potential mechanism in regulating the development of bladder cancer. The expression of lnc00518 in bladder cancer tissues and cells was examined by qRT-PCR. Correlation between lnc00518 expression with clinicopathologic characteristics and prognosis of bladder cancer patients was analyzed. In vitro effects of lnc00518 on the cellular behaviors of bladder cancer cells were explored. Moreover, in vivo effect of lnc00518 was evaluated by subcutaneous tumorigenesis in nude mice. The possible miRNA targets of lnc00518 were predicted by bioinformatics and further confirmed by dual-luciferase reporter gene assay, RIP and rescue experiments. Lnc00518 was highly expressed in bladder cancer tissues and cells. Lnc00518 expression was correlated with TNM staging and histological grade of bladder cancer. Besides, the overall survival was lower in bladder cancer patients with high expression of lnc00518 relative to those with low expression. Overexpression of lnc00518 enhanced proliferative, invasive, migratory potentials and clonality, but shortened G0/G1 phase of bladder cancer cells. Lnc00518 knockdown obtained the opposite trends. In vivo experiments revealed that lnc00518 knockdown inhibited subcutaneous tumorigenesis in nude mice. QRT-PCR results indicated that lnc00518 expression was negatively correlated with miRNA-101 expression in bladder cancer cells. Through dual-luciferase reporter gene assay and RIP, we confirmed the binding between lnc00518 and miRNA-101. Furthermore, EZH2 was verified to be the target of miRNA-101. MiRNA-101 knockdown reversed the inhibitory roles of lnc00518 knockdown in proliferative, migratory and invasive potentials of bladder cancer cells. Lnc00518 is highly expressed in bladder cancer and can be served as a predictor of poor prognosis. Lnc00518 promotes the proliferative, invasive and migratory potentials of bladder cancer by upregulating EZH2 via competitively binding to miRNA-101.

Genetic variant of MAML2 in the NOTCH signaling pathway and the risk of bladder cancer: A STROBE-compliant study.

The NOTCH signaling pathway plays a crucial role in cell phenotype and transformation. Single nucleotide polymorphisms (SNPs) may regulate gene expression to trigger bladder cancer susceptibility. Here, we aimed to explore the relationships between genetic variants in the NOTCH pathway and bladder cancer progression.We screened SNPs located in NOTCH pathway genes using the 1000 Genomes Project dataset (CHB). A case-control cohort study including 580 bladder cancer cases and 1101 controls was conducted to genotype the candidate SNPs. The expression quantitative trait locus (eQTL) and bioinformatics analyses were performed to explore the biological function of the SNPs' host gene and their relationship. Kaplan-Meier analysis was performed to assess the association between host gene expression and bladder cancer patient prognosis.The rs7944701 in the intron of mastermind-like 2 (MAML2) had the strongest signal and was related to bladder cancer risk (OR = 1.329, 95% CI = 1.115-1.583, P = .001). eQTL analysis showed that rs7944701 with a C allele was negatively associated with mastermind-like 2 (MAML2) expression (TT versus TC/CC). Bioinformatics analysis indicated that MAML2expression was lower in bladder cancer tissues than in non-tumor tissues (P = 5.46 × 10). Additionally, bladder cancer patients with high MAML2 expression had a significantly poorer prognosis (HR = 1.53, 95% CI = 1.29-1.82, P = .010).The rs7944701 in MAML2 was strongly associated with bladder cancer susceptibility in a Chinese population. This genetic variant and its host gene could be a potential novel biomarker for individuals suffering from bladder cancer.

Transurethral-Assisted Transumbilical Laparoendoscopic Single-Site Radical Cystectomy: Initial Short-Term Experience.

INTRODUCTION: Laparoendoscopic single-site (LESS) technique is a less invasive approach for radical cystectomy (RC), which is promising in reducing the incisional morbidity and improving the cosmesis of laparoscopic surgery. This study aimed to investigate the clinical and oncological outcomes for patients with malignant urinary bladder tumors that underwent the transurethral-assisted transumbilical LESS-RC. METHODS: From December 2014 to June 2017, 47 patients underwent LESS-RC combined with unilateral or bilateral cutaneous ureterostomy were enrolled in this study. The urethra was used as a potential approach without additional incision, which could allow for trocar insertion through natural orifices. Assessments were also conducted on preoperative, perioperative, postoperative, pathologic, and functional outcome data. RESULTS: Mean patient age was 73 years. Mean body mass index was 24.0 kg/m2. Median operating time and estimated blood loss measure 217 min and 178 mL, respectively. Four patients were diagnosed with positive lymph nodes. Two patients had positive surgical margins. No major perioperative complications occurred. Median postoperative follow-up time was 20.1 months. Two patients died due to their progressive disease. CONCLUSION: LESS can serve as a feasible and effective surgical procedure for RC to treat bladder cancer. With increasing experience and improvements, LESS-RC is promising to be a relatively acceptable alternative for minimally invasive surgery in some specific patients (with generally poor conditions that cannot be tolerated for a long time surgery, short life expectancy, advanced cancer, or associated with intestinal disease).

High LINC00536 expression promotes tumor progression and poor prognosis in bladder cancer.

Growing evidences demonstrate that long non-coding RNAs (lncRNAs) contribute to the cancer initiation and progression and are considered as promising diagnostic and therapeutic targets of multiple cancers. However, the definite role of LINC00536 in bladder cancer (BC) remains unclear. In the present study, we found LINC00536 expression was highly expressed in BC tissues compared with controls and negatively associated with survival rate in BC patients. Gain-of-function assays indicated that LINC00536 overexpression promoted the proliferation, migration and invasion, whereas LINC00536 knockdown attenuated the cell phenotypes above in BC cell lines. In vivo assay illustrated that LINC00536 knockdown inhibited BC growth in vivo. Mechanistically, Wnt3a was identified as the target of LINC00536. LINC00536 promoted malignant phenotypes via activating the Wnt3a/ß-Catenin signaling. Wnt3a knockdown reversed the increase of proliferation, migration, and invasion abilities of BC cells induced by LINC00536 overexpression. In summary, our findings demonstrated that LINC00536 promoted BC progression by modulating the Wnt3a/ß-Catenin signaling.

Laparoendoscopic single-site nephrectomy with the aid of intraabdominal retractors.

OBJECTIVES: To evaluate the feasibility and clinical efficacy of a novel intraabdominal retractor device in laparoendoscopic single-site nephrectomy(LESS-N). METHODS: Between February 2012 and February 2017, 98 patients underwent LESS-N in our institution, including 38 patients with benign renal disease and 60 patients with malignant renal disease. 39 were performed conventional LESS-N(C-LESS-N) and 59 were performed intraabdominal retractor-assisted LESS-N(IAR-LESS-N). Demographic data, and perioperative and postoperative data were collected and analyzed retrospectively. RESULTS: All the procedures were completed successfully. In C-LESS-N group, four patients were added one 5-mm additional trocar and two patients were converted to open surgery. In IAR-LESS-N group, no patients required additional trocars or conversion to open surgery. The mean operative time was lower in IAR-LESS-N group than that in C-LESS-N group (94.2 min vs 127.4 min, P < 0.05). The mean renal vascular management time declined from 25.4 min in C-LESS-N group to 18.4 min in IAR-LESS-N group (P < 0.05). The mean estimated blood loss was 128.6 ml in C-LESS-N group and 102.3 ml in IAR-LESS-N group (P < 0.05). Two patients in C-LESS-N group required blood transfusion, while none of the patients in IAR-LESS-N group did. No severe postoperative complications occurred in both groups. Study limitations included retrospective study, short follow-up, and accumulated surgical experience and skills. CONCLUSIONS: Intraabdominal retractors allow performance of LESS-N with improved working space, quicker renal hilar management, and shortened total operative time. It is expected that the application of intraabdominal retractors, along with the new robotic platform might revive LESS and translate into a renewed future interest of LESS.

[Transurethral transumbilical laparoendoscopic single-site surgery for radical prostatectomy].

OBJECTIVE: To investigate the feasibility and advantages of transurethral transumbilical laparoendoscopic single-site surgery (TU-LESS) for radical prostatectomy. METHODS: Five patients with prostate cancer underwent TU-LESS for radical prostatectomy, with a four-channel single-port device inserted into a 2. 5 cm periumbilical incision and another placed through the urethra, followed by analysis of the perioperative data. RESULTS: All the operations were successfully accomplished, with neither conversion to open surgery nor additional channel. The mean operation time, intraoperative blood loss, and postoperative hospital stay were 168 min, 120 ml, and 15 d, respectively. No severe perioperative complications were observed. TNM stage classification manifested T2cN0M0 in 2 cases and T2bN0M0 in the other 3. Postoperative pathology showed no negative surgical margins in any of the cases. CONCLUSION: TU-LESS is safe and feasible for radical prostatectomy and can reduce the complication of low urinary tract surgery by single-site laparoendoscopy.

[Indirubin inhibits the proliferation of prostate cancer PC-3 cells].

OBJECTIVE: To explore the antitumoral effect of indirubin on androgen-independent prostate cancer PC-3 cells and its possible mechanisms. METHODS: We measured the inhibitory effect of indirubin on the proliferation of prostate cancer PC-3 cells using MTT assay, detected their cell cycles by flow cytometry, and determined the expressions of the cell cycle regulatory protein cyclin D1 and its related downstream gene c-myc by Western blot. RESULTS: The viability of the PC-3 cells was significantly decreased by indirubin in a concentration-dependent manner, reduced to 52. 2% and 13. 6% at 5 and 10 µmol/L, respectively. The cell cycle of the PC-3 cells was markedly inhibited by indirubin at 5 µmol/L, with the cells remarkably increased in the G0 and G1 phases and decreased in the S and G2/M phases. Meanwhile, indirubin also inhibited the expressions of cyclin D1 and c-myc in the Wnt signaling pathway. CONCLUSION: Indirubin can suppress the proliferation of androgen-independent prostate cancer PC-3 cells, which may be associated with its inhibitory effect on the cell cycle and Wnt signaling pathway.

Prognostic role of microRNA-205 in multiple human malignant neoplasms: a meta-analysis of 17 studies.

OBJECTIVE: MicroRNA-205 (miRNA-205) was revealed as an attractive prognostic tumour biomarker in recent studies. However, the results of different studies have been inconsistent. We conducted a meta-analysis to elucidate the precise predictive value of miRNA-205 in various human malignant neoplasms. DESIGN: Meta-analysis. DATA SOURCES: Qualified studies were identified up to 5 June 2014 by performing online searches in PubMed, EMBASE and Web of Science, and additional quality evaluations. PARTICIPANTS: Seventeen eligible studies with 4827 patients were ultimately enrolled in this meta-analysis. OUTCOME MEASURES: The heterogeneity between studies was assessed using I(2) statistics. Pooled HRs with 95% CIs for patient survival and disease recurrence were calculated to investigate the correlation between miRNA-205 expression and cancer prognosis. RESULTS: Our results indicate that elevated miRNA-205 was significantly associated with enhanced overall survival in the breast cancer subgroup (HR=0.78, 95% CI 0.67 to 0.91) and superior disease-free survival/recurrence-free survival in the adenocarcinoma subgroup (HR=0.68, 95% CI 0.49 to 0.94). CONCLUSIONS: miRNA-205 is a promising biomarker for predicting the recurrence and progression of patients with adenocarcinomas or breast cancer. Owing to its complex roles, further relevant studies are warranted.

Osteopontin mediating cyclosporine A induced epithelial-to-mesenchymal transition on rat renal tubular epithelial cells.

Osteopontin (OPN) is highly correlated with cyclosporine A (CsA) nephrotoxicity. As epithelial-to-mesenchymal transition (EMT) of renal tubular epithelial cells plays an important role in CsA nephropathy, we investigated whether OPN mediated EMT of renal tubular epithelial cells upon CsA stimulation. OPN knockdown suppresses CsA induced EMT on NRK52E cells, and it also attenuates downregulation of E-cadherin and upregulation of α-smooth muscle actin (α-SMA) and fibronectin (FN) that are induced by CsA. OPN alone can induce EMT on NRK52E cells, which also results in upregulation of TGF-ß1. Thus, OPN is a causative factor in mediating CsA induced EMT on NRK52E cells.

MTHFR C677T polymorphisms are associated with aberrant methylation of the IGF-2 gene in transitional cell carcinoma of the bladder.

The purpose of this study was to determine the relationship between methylation status of the insulin-like growth factor 2 (IGF-2) gene and methylenetetrahydrofolate reductase (MTHFR) C677T gene polymorphisms in bladder transitional cell carcinoma tissues in a Chinese population. The polymorphisms of the folate metabolism enzyme gene MTHFR were studied by restrictive fragment length polymorphism (RFLP). PCR-based methods of DNA methylation analysis were used to detect the CpG island methylation status of the IGF-2 gene. The association between the methylation status of the IGF-2 gene and clinical characteristics, as well as MTHFR C677T polymorphisms, was analyzed. Aberrant hypomethylation of the IGF-2 gene was found in 68.3% bladder cancer tissues and 12.4% normal bladder tissues, respectively, while hypomethylation was not detected in almost all normal bladder tissues. The hypomethylation rate of the IGF-2 gene in cancer tissues was significantly higher in patients with lymph node metastasis than in those without lymph node metastasis (46.3% vs 17.2%, P = 0.018). No association was found between aberrant DNA methylation and selected factors including sex, age, tobacco smoking, alcohol consumption and green tea consumption. After adjusting for potential confounding variables the variant allele of MTHFR C677T was found to be associated with hypomethylation of the IGF-2 gene. Compared with wildtype CC, the odds ratio was 4.33 (95% CI=1.06-10.59) for CT and 4.95 (95% CI=1.18-12.74) for TT. MTHFR 677 CC and CT genotypes might be one of the reasons that cause abnormal hypomethylation of the IGF-2 gene, and the aberrant CpG island hypomethylation of the IGF-2 gene may contribute to the genesis and progression of bladder transitional cell carcinoma.

The role of aberrant promoter hypermethylation of DACT1 in bladder urothelial carcinoma.

The purpose of this study was to determine the relationship between hypermethylation of DACT1 gene promoter and lower mRNA expression in bladder urothelial carcinoma tissue. The methylation status of 29 urothelial carcinoma samples and 29 normal tissue samples were examined by methylation-specific polymerase chain reaction (MSP). The DACT1 mRNA transcript levels and DACT1 protein levels in all samples were then evaluated to define the relationship between the methylation status of the DACT1 promoter and its expression at the transcriptional and translational levels. Decreased expression of DACT1 was detected in 89.66% of urothelial carcinomas (26/29; P < 0.005). Promoter hypermethylation was found in 58.62% (17/29) urothelial carcinomas and 25% (7/29) normal tissues, respectively (P < 0.05). DACT1 expression was lower in tissues where the DACT1 gene promoter was hypermethylated than in unmethylated tissues (0.25±0.17 vs 0.69±0.30, P < 0.05). DACT1 gene hypermethylation was closely related to tumor size, grade and stage (P < 0.05). Our results indicate that silencing and downregulation of DACT1 mRNA may be implicated in carcinogenesis and the progression of bladder urothelial carcinoma, and may be a potential prognostic factor.

Lateral lymph node dissection with radical surgery versus single radical surgery for rectal cancer: a meta-analysis.

OBJECTIVES: To assess the value of lateral lymph node dissection( LLND) in the radical surgery of rectal cancer. METHODS: The published Chinese and English literature was retrieved. A total of 15 papers fitted the selection criteria, including 4,858 patients. Among them 2,401 were in the LLND group and 2,457 in the non- LLND (NLLND) group. Evaluation parameters included 5-year survival rate recurrence rate, peri-operative outcomes, postoperative urinary and sexual functions. RESULTS: The operating time was significantly shorter in the NLLND group than that in the LLND group (weighted mean difference (WMD)=109 min, 95 confidence interval(CI):90-129, P <0.001). Intra-operative blood loss was greater in the LLND group, but the difference was not significant (WMD=429 mL, 95 CI:325-854, P = 0.05).The frequency of peri-operative morbidity(OR, 1.57 95 CI:1.06-2.33, P = 0.02) was also significantly higher in the LLND group. There were no significant differences in 5-year survival rate and recurrence rate between the two groups. Data from individual studies(three)showed that the frequency of male urinary dysfunction (OR=5.12, 95CI 2.15-12.19, P=0.0002) and sexual dysfunction (P < 0.05) were greatly lower in the NLLND group. CONCLUSION: Meta analysis showed that LLND did not have specific advantage in decreasing postoperative recurrence and prolonging survival time. Furthermore it was associated with prolonged operation time, increased blood loss and elevated incidence of peri-operative complications and urinary and sexual dysfunction.