Hydropenia may accelerates the progression of orthotopic bladder cancer induced by N-methyl-N-nitrosourea by increasing the expression levels of AQP1, AQP3, and AQP4.

BACKGROUND: Increasing evidence has demonstrated aquaporins (AQPs) to be critical players in carcinogenesis. Here, we aimed to explore the role of hydropenia in the progression of bladder cancer (BCa), as well as to assess the expression of AQP1, AQP3, and AQP4 in bladder tissues from hydropenic and N-methyl-N-nitrosourea (MNU)-treated rats. METHODS: An orthotopic BCa model was induced by administering Sprague Dawley rats with MNU. A hydropenic rat model was established by administrating rats with 2/3 of the amount of water given to the control group. At week 8, the rats were sacrificed and their bladder tissues were collected. Then, pathological alterations in the rat bladders were assessed by hematoxylin and eosin staining. The RNA and protein expression levels of AQP1, AQP3, and AQP4 were determined by using qRT-PCR and western blot assays. RESULTS: All of the rats (100%) administrated with MNU developed tumors, of which 5 were large (diameter, 0.5-1.0 cm), 10 were medium (diameter, 0.2-0.5 cm), and 5 were small (diameter, <0.2 cm) in size. The tumors were nodular and cauliflower shaped, with multiple satellite focus, and were accompanied by bleeding, ulcers, stones, and residual urine. Hematoxylin and eosin staining revealed that the bladder mucosa was incomplete, with a large amount of necrotic tissue and obvious leukocytic infiltration. The tumor volume in the MNU + hydropenia group was significantly larger than that in the MNU group. Noticeably, hydropenia exacerbated pathological changes induced by MNU administration. QRT-PCR and western blot analysis revealed that the MNU group, hydropenia group, and MNU + hydropenia group had significantly increased levels of AQP1, AQP3, and AQP4 compared to the control group, with the most dramatic increase seen in the MNU + hydropenia group. CONCLUSIONS: Hydropenia exacerbates pathological alterations induced by MNU in rats with orthotopic BCa by increasing the expression levels of AQP1, AQP3, and AQP4. This study reveals a possible mechanism of the occurrence of BCa.

Comparison of mini-percutaneous nephrolithotomy and retroperitoneal laparoscopic ureterolithotomy for treatment of impacted proximal ureteral stones greater than 15 mm.

BACKGROUND: The optimal treatment for large impacted proximal ureteral stones remains controversial. The aim of this study was to evaluate the efficacy, safety, and potential complications of mini-percutaneous nephrolithotomy (MPCNL) and retroperitoneal laparoscopic ureterolithotomy (RPLU) in the treatment of impacted proximal ureteral stones with size greater than 15 mm. METHODS: A total of 268 patients with impacted proximal ureteral stones greater than 15 mm who received MPCNL or RPLU procedures were enrolled consecutively between January 2014 and January 2019. Data on surgical outcomes and complications were collected and analyzed. RESULTS: Demographic and ureteral stone characteristics found between these two groups were not significantly different. The surgical success rate (139/142, 97.9% vs. 121/126, 96.0%, P = 0.595) and stone-free rate after 1 month (139/142, 97.9% vs. 119/126, 94.4%, P = 0.245) of RPLU group were marginally higher than that of the MPCNL group, but there was no significant difference. There was no significant difference in the drop of hemoglobin between the two groups (0.8 ±â€Š0.6 vs. 0.4 ±â€Š0. 2 g/dL, P = 0.621). The mean operative time (68.2 ±â€Š12.5 vs. 87.2 ±â€Š16.8 min, P = 0.041), post-operative analgesics usage (2/121, 1.7% vs. 13/139, 9.4%, P = 0.017), length of hospital stay after surgery (2.2 ±â€Š0.6 vs. 4.8 ±â€Š0.9 days, P < 0.001), double J stent time (3.2 ±â€Š0.5 vs. 3.9 ±â€Š0.8 days, P = 0.027), time of catheterization (1.1 ±â€Š0.3 vs. 3.5 ±â€Š0.5 days, P < 0.001), and time of drainage tube (2.3 ±â€Š0.3 vs. 4.6 ±â€Š0.6 days, P < 0.001) of MPCNL group were significantly shorter than that of the RPLU group. The complication rate was similar between the two groups (20/121, 16.5% vs. 31/139, 22.3%, P = 0.242). CONCLUSIONS: MPCNL and RPLU have similar surgical success and stone clearance in treating impacted proximal ureteral stones greater than 15 mm, while patients undergoing MPCNL had a lower post-operative pain rate and a faster recovery.

Needle Adjustment Free (NAF) running suture technique (PAN suture) in laparoscopic partial nephrectomy.

BACKGROUND: It is proposed a new running suture technique called Needle Adjustment Free (NAF) technique, or PAN suture. The efficiency and the safety were evaluated in laparoscopic partial nephrectomy. METHODS: This new running suture technique avoids the Needle Adjustment method used in traditional techniques. The new continuous suture technique (11 patients) was compared with the traditional continuous suture method (33 patients) used in both transperitoneal and retroperitoneal laparoscopic partial nephrectomy (LPN) in terms of suture time (ST), warm ischemia time (WIT), blood loss (BL), open conversion rate and post-op discharge time, post-op bleeding, post-op DVT, ΔGFR (affected side, 3 months post-op). Differences were considered significant when P < 0.05. RESULTS: ST in the PAN suture group was 30.37 ± 16.39 min, which was significant shorter (P = 0.0011) than in the traditional technique group which was 13.68 ± 3.33 min. WIT in the traditional technique group was 28.73 ± 7.89 min, while in the PAN suture group was 20.64 ± 5.04 min, P = 0.0028. The BL in entirety in the traditional technique group was 141.56 ± 155.23 mL, and in the PAN suture group was 43.18 ± 31.17 mL (P = 0.0017). BL in patients without massive bleeding in the traditional technique group was significantly greater than in the PAN suture group at 101.03 ± 68.73 mL versus 43.18 ± 31.17 mL (P = 0.0008). The open conversion rate was 0 % in both groups. There was no significant difference between the two groups in postoperative discharge time, post-op bleeding, post-op DVT, ΔGFR (affected side, 3 months post-op). CONCLUSIONS: The NAF running suture technique, or PAN suture, leading to less ST, WIT and BL, which was shown to be more effective and safer than the traditional technique used for LPN. A further expanded research with larger sample size is needed.

An experimental model of the epithelial to mesenchymal transition and pro-fibrogenesis in urothelial cells related to bladder pain syndrome/interstitial cystitis.

BACKGROUND: Suitable in vitro models are needed to investigate urothelial epithelial to mesenchymal transition (EMT) and pro-fibrogenesis phenotype in bladder pain syndrome/interstitial cystitis (BPS/IC). This study is to establish a novel experimental BPS/IC cell model and explore how different concentrations of tumor necrosis factor (TNF)-α influence the EMT and pro-fibrogenesis phenotype of urothelial cells. METHODS: SV-HUC-1 urothelial cells were cultured with 2, 10, or 50 ng/mL TNF-α to mimic chronic inflammatory stimulation. The EMT and pro-fibrogenesis phenotype, including production of collagen I and pro-fibrosis cytokines, were estimated after 72 h of culture. RESULTS: The bladder urothelial cells of BPS/IC exhibited upregulated vimentin, TNF-α and TNF receptor, downregulated E-cadherin, and increased collagen I. Higher concentrations of TNF-α (10 and 50 ng/mL) produced an obvious mesenchymal morphology, enhanced invasion and migratory capacity, increased expression of vimentin, and decreased expression of E-cadherin. Collagen I was increased in cells treated with 2 and 10 ng/mL TNF-α after 72 h. Secretion of interleukin (IL)-6 and IL-8 was promoted with 10 and 50 ng/mL TNF-α, while that of IL-1ß or transforming growth factor-ß was unaffected. Slug and Smad2 were upregulated by TNF-α after 72 h. The Smad pathway was activated most strongly with 10 ng/mL TNF-α and Slug pathway activation was positively correlated with the concentration of TNF-α. CONCLUSIONS: Sustained 10 ng/mL TNF-α stimulation induced the EMT and pro-fibrogenesis phenotype resembling BPS/IC in SV-HUC-1 cells. Minor inflammatory stimulation induced the pro-fibrogenesis phenotype while severe inflammatory stimulation was more likely to produce significant EMT changes. Different degrees of activation of the Slug and Smad pathways may underlie this phenomenon.

Beforehand transection and suturing (BTS) of the dorsal vascular complex: a novel technique in laparoscopic radical prostatectomy.

BACKGROUND: Beforehand transection and suturing (BTS) of the dorsal vascular complex (DVC), a novel technique in non-neurovascular bundle sparing (NVB-sparing) extraperitoneal laparoscopic radical prostatectomy (eLRP), had been proposed; this study aimed to evaluate this technique in clinical laparoscopic procedures. METHODS: Using this new technique, the DVC was transected and sutured after dissection of the pelvic fascia and before dissection of the prostate, especially before ligation of the bilateral prostatic pedicles. This study retrospectively analyzed the data of 90 non NVB-sparing eLRP patients [traditional technique (n=60) and BTS technique (n=30)]. RESULTS: The surgical time in the BTS technique group was 121.73±24.53 min, which was significantly shorter (P=0.0015) than the traditional technique group (144.12±39.68 min). The calculated blood loss in the traditional technique group was 388.45±232.78 mL, and 264.16±130.70 mL in the BTS technique group (P=0.0016). The estimated blood loss in the traditional technique group was 350.34±311.80 mL, which was significantly greater than the BTS technique group (250.33±145.31 mL, P=0.0422). The transfusion rate in the traditional technique group was significantly greater than the BTS technique group (15.00% vs. 0.00%; P=0.0266). The biochemical recurrence rate in traditional technique group was 48.33%, which was higher than in the BTS group (30.00%) (P=0.0465). There was no significant difference between the 2 groups with respect to the pre-operative hemoglobin (Hb) concentration, pre-operative hematocrit (HCT), post-operative Hb concentration, post-operative HCT, ΔHCT, pre-operative blood volume, rectal perforation, open conversion, apical capsule residue, false suture, post-operative bleeding, urinary leakage, re-operation, surgical site infection, post-operative stay, and emission time of urinary incontinence. CONCLUSIONS: In managing the relationship between the DVC and prostate in patients undergoing non NVB-sparing eLRP, the BTS technique was shown to be more effective and safer than the traditional technique.

The Effects of Neurokinin-1 Receptor Antagonist in an Experimental Autoimmune Cystitis Model Resembling Bladder Pain Syndrome/Interstitial Cystitis.

To identify the effects of the neurokinin-1 receptor (NK1R) antagonist aprepitant in treating pelvic pain, micturition symptoms, and bladder inflammation in mice with experimental autoimmune cystitis (EAC) similar to bladder pain syndrome/interstitial cystitis (BPS/IC). Female C57BL/6 mice were divided into the following three groups: normal control, EAC, and EAC plus aprepitant. EAC was induced in mice by duplicate immunization with bladder homogenate. In the EAC model group, EAC mice were given PBS by gavage once a day during the fourth week. In the EAC plus aprepitant group, aprepitant was administered instead of PBS in the same way. After 4 weeks, pelvic pain threshold and urination habits of mice were analyzed, as well as the bladder weight to body weight ratio, and histologic assessment of the expression of IL-1ß, TNF-α, intercellular adhesion molecule 1 (ICAM-1), and NK1R in bladder tissue. EAC mice mimicked the phenotype and pathophysiologic lesions of BPS/IC well. Compared to PBS-treated EAC mice, the mice treated with aprepitant exhibited higher pain threshold values, less number of total urine spots or small urine spots, lower bladder weight to body weight ratio, and reduced bladder inflammation with less mast cell infiltration and decreased expressions of IL-1ß, TNF-α, and ICAM-1 in bladder tissue. There was no difference in NK1R expression in bladders treated with or without aprepitant. The NK1R antagonist aprepitant relieved pelvic pain, urinary symptoms, and bladder inflammation in EAC mice. This indicated that NK1R may be a novel therapeutic target in BPS/IC treatment.

Establishment of a Novel Autoimmune Experimental Model of Bladder Pain Syndrome/Interstitial Cystitis in C57BL/6 Mice.

The aim of this study is to identify whether vaccinating twice with bladder homogenate can establish a new model of experimental autoimmune cystitis (EAC) in C57BL/6 strain mice. C57BL/6 mice were vaccinated with bladder homogenate in complete Freund's adjuvant (CFA) and boost immunized with bladder homogenate in incomplete Freund's adjuvant (IFA) after 2 weeks were used as the EAC model. Mice immunized with phosphate-buffered saline (PBS) in CFA or IFA were used as the control. Micturition habits and suprapubic-pelvic pain threshold were measured 4 weeks after primary immunization. Bladder to body weight ratios and expression of inflammatory cytokines and neurokinin 1 receptor (NK1R) were then examined. Histologic and immunohistochemical examination of the bladder was carried out, and IL-1ß, IFN-γ, and TNF-α production by the kidneys, liver, and lungs was also tested. Double-immunized mice were extensively sensitive to pressure applied on the pelvic area (P < 0.001). Compared to single-immunized mice or controls, double-immunized mice showed more micturition frequency, lower urine output per micturition, higher bladder to body weight ratio, and significant elevation in the expression of inflammatory cytokines, including IL-1ß, IL-4, IL-6, IL-10, IFN-γ, and TNF-α (all P < 0.05). NK1R gene expression was significantly increased in double-immunized mice compared to the other three groups (P < 0.001). A nonspecific immune response occurred in the liver but was much weaker than bladder inflammation. Our dual immunization EAC model in C57BL/6 mice can effectively mimic the symptoms and pathophysiologic characteristics of BPS/IC and thus can be widely used to investigate the pathogenesis and therapeutic strategies of BPS/IC.