Laparoscopic prostatectomy with complete urethral reconstruction for sexual active BPH patients.

OBJECTIVE: To describe our technique of transvesical laparoscopic simple prostatectomy (LSP) plus complete urethral reconstruction(CUR). MATERIAL AND METHODS: From May 2019 to May 2021, 28 BPH patients with prostate volumes > 80 ml and the requirement to preserve the ejaculatory function (EF) received LSP plus CUR. Baseline demographics, pathology data, perioperative and postoperative complications, and functional outcomes were assessed. Data were analyzed with the Wilcoxon test. RESULTS: The median prostate volume was 106 ml. All patients successfully underwent LSP with no intraoperative complications or conversions to open surgery. The median operative time was 146 min. A total of five Clavien-Dindo Grade1-2 postoperative complications were noted, including infection, prolonged urine leakage and cardiac arrhythmia. No patient reported postoperative urgent or stress urinary incontinence. Functional outcomes at one-year follow-up demonstrated significant improvement from baseline with median IPSS and Qmax (p both < 0.001). Compared with baseline, no significant difference was observed in IIEF and MSHQ-EjD-SF at 6 and 12 months postoperatively. CONCLUSIONS: Our data support transperitoneal-transvesical LSP plus CUR as a safe and effective surgical technique for treating BPH with large prostate adenoma, regardless of the volume of the median lobe, especially for patients requiring to preserve antegrade ejaculation.

Comparison of RLP and PCNL for large pelvis calculi with CKD.

OBJECTIVES: To compare the effect and safety of retroperitoneal laparoscopic pyelolithotomy (RLP) and percutaneous nephrolithotomy (PCNL) for large pelvis calculi with chronic kidney disease (CKD). MATERIAL AND METHODS: Between June 2017 and July 2021, 62 patients with CKD and large renal pelvis calculi (>4 cm2) were treated with RLP. Another 62 patients receiving PCNL served as controls. The perioperative parameters were compared. All patients were followed up for at least 6 months with the stone-free rate and the recovery of renal function evaluated. RESULTS: Significantly longer operation time (101.47 ± 9.25 vs 62.55 ± 7.54 min), less drop in hemoglobin level (0.90 ± 0.38 vs 2.13 ± 0.80 g/dl), staged operations (0% vs 12.9%), postoperative fever (3.23% vs 16.13%) and delayed bowel movement (3.23% vs 14.52), and shorter hospitalization time (3.90 ± 1.66 vs 4.72 ± 1.80 days) were observed in the RLP group (p < 0.05). The stone-free rates were 100% in the RLP group and 88.7% in the PCNL group at the 3-months follow-up (p < 0.05). The serum creatinine level was significantly lower in the RLP group at 24 h (2.81 ± 1.18 vs 3.00 ± 1.15 mg/dl) and 1 week (2.08 ± 1.13 vs 2.34 ± 1.01 mg/dl) postoperatively (p < 0.05). CONCLUSIONS: Although associated with a longer operation time, RLP is a safer and more efficient surgical option for CKD patients with large pelvic stones than PCNL.

Pan-cancer Analysis of NEDD4L and Its Tumor Suppressor Effects in Clear Cell Renal Cell Carcinoma.

The expression level of NEDD4L, an E3 ubiquitin ligase, has changed significantly in human cancers. In this study, we aimed to study the expression of NEDD4L in pan-carcinoma and its function in malignant tumors. We analyzed the gene expression level of NEDD4L in pan-cancer from The Cancer Genome Atlas (TCGA) microarray data set, the correlation between gene expression and overall survival, disease-specific survival, and tumor immune microenvironment changes. NEDD4L expression changes in half of the cancer types. Low expression of NEDD4L gene predicts poor overall survival and disease-specific survival (DSS) in renal clear cell carcinoma (KIRC) and renal chromophobe cell carcinoma (KIRP). NEDD4L is negatively related to interstitial cell infiltration and immune cell infiltration in most common cancers. Furthermore, the low expression of NEDD4L was verified in our clear cell renal cell carcinoma (ccRCC) clinical tissues. In ccRCC cells, NEDD4L overexpression significantly reduced cell proliferation and migration. In the functional analysis, we proved that NEDD4L could inhibit ERBB3 and MAPK signaling pathways. When cells are deficient in nutrition, NEDD4L promoted the degradation of the autophagy regulatory protein ULK1. Our study provides novel insights into the role of NEDD4L in pan-cancer. NEDD4L may play a tumor suppressor effect in ccRCC, through tumor immune regulation and ubiquitination of key intracellular kinases.

ABAT and ALDH6A1, regulated by transcription factor HNF4A, suppress tumorigenic capability in clear cell renal cell carcinoma.

BACKGROUND: Clear cell renal cell carcinoma (ccRCC) is a malignancy characterized by metabolic reprogramming. ABAT and ALDH6A1 are metabolic enzymes. In this study, we aim to investigate the associations of ABAT and ALDH6A1 with the malignancy of ccRCC cells. METHODS: The gene expression levels of ABAT and ALDH6A1 in ccRCC were analyzed from gene expression microarray datasets and RNA sequencing data. Clinical information was analyzed from The Cancer Genome Atlas (TCGA) data. The distributions of ABAT and ALDH6A1 in ccRCC clinical tissues were screened by reverse transcription-quantitative polymerase chain reaction (RT-QPCR) and immunohistochemical assays. The effect of overexpression of ABAT or ALDH6A1 was measured by detecting the cell viability, migration ability, and the ratio of lactate and nicotinamide adenine dinucleotide phosphate (NADPH). Chromatin immunoprecipitation (ChIP) and luciferase reporter assays were carried out to investigate the transcript regulation of HNF4A in ABAT and ALDH6A1. RESULTS: Remarkable downregulated ABAT and ALDH6A1 expression levels were observed in ccRCC patients and low expression of ABAT and ALDH6A1 was correlated with poor survival. Overexpression of ABAT or ALDH6A1 significantly attenuated cell proliferation and migration, and impaired lactate production. In ABAT increased ccRCC cells, the ratio of NADPH/NADP+ was reduced. Finally, we demonstrated that ABAT and ALDH6A1 were directly regulated by a tumor suppressor, HNF4A. CONCLUSIONS: These observations identified HNF4A-regulated low-expressed ABAT and ALDH6A1 as promising diagnostic and prognostic biomarkers for ccRCC.

miR-192/215-5p act as tumor suppressors and link Crohn's disease and colorectal cancer by targeting common metabolic pathways: An integrated informatics analysis and experimental study.

MicroRNAs have emerged as key regulators involved in a variety of biological processes. Previous studies have demonstrated that miR-192/215 participated in progression of Crohn's disease and colorectal cancer. However, their concrete relationships and regulation networks in diseases remain unclear. Here, we used bioinformatics methods to expound miR-192/215-5p macrocontrol regulatory networks shared by two diseases. For data mining and figure generation, several miRNA prediction tools, Human miRNA tissue atlas, FunRich, miRcancer, MalaCards, STRING, GEPIA, cBioPortal, GEO databases, Pathvisio, Graphpad Prism 6 software, etc . are extensively applied. miR-192/215-5p were specially distributed in colon tissues and enriched biological pathways were closely associated with human cancers. Emerging role of miR-192/215-5p and their common pathways in Crohn's disease and colorectal cancer was also analyzed. Based on results derived from multiple approaches, we identified the biological functions of miR-192/215-5p as a tumor suppressor and link Crohn's disease and colorectal cancer by targeting triglyceride synthesis and extracellular matrix remodeling pathways.

Influence of prostate size on the perioperative and postoperative outcome of transurethral plasmakinetic enucleation of the prostate: Results of 892 patients with 3 years of follow-up.

To explore the influence of prostate size on the outcome of Plasmakinetic enucleation of the prostate (PkEP) for the treatment of benign prostate hyperplasia (BPH), The data of 892 patients with symptomatic BPH who underwent PkEP were retrospectively reviewed. Among them, 199 (22.31%) had the prostate size smaller than 40 g (Group 1), 409 (45.85%) between 40 and 79 g (Group 2), 197 (22.09%) between 80 and 120 g (Group 3), and 87 (9.75%) larger than 120 g (Group 4). Perioperative variables, perioperative and postoperative complications were recorded. Patients were followed up for 36 months postoperatively. The efficiency of the surgery increased as the prostate size increased. Greater decreases in hemoglobin were noted in groups with larger prostates, while the duration of catheterization after the operation was similar across all groups. During the 3-year follow-up, the postoperative improvement in International Prostate Symptom Score (IPSS), Quality of Life (QOL), maximal flow rate (Qmax) and post-void residual urine volume (PVR), as well as longterm complications including urethral stricture and bladder-neck contracture were comparable across the 4 groups. These findings revealed that PkEP is more efficient for large prostate and can treat all prostates regardless of the size with equivalent symptom relief and micturition improvement.

Overexpression of ULK1 Represents a Potential Diagnostic Marker for Clear Cell Renal Carcinoma and the Antitumor Effects of SBI-0206965.

BACKGROUND: Uncoordinated 51-like kinase 1 (ULK1) plays a vital role in autophagy. ULK1 dysregulation has recently been found in several human cancers. METHODS: mRNA expression levels of ULK1 and clinical information were analysed from The Cancer Genome Atlas data. ULK1 expression levels were verified in 36 paired fresh ccRCC tissue specimens by western blot analysis. Expression of ULK1 was knockdown by shRNA lentivirus. ULK1 activity was inhibited by SBI-0206965. The effect of inhibition of ULK1 was measured by detecting the apoptotic rate, autophagy, and the ratio of ROS and NADPH. The efficacy of SBI-0206965 in vivo was assessed by the murine xenograft model. FINDINGS: ULK1 mRNA expression was significantly upregulated in clear cell renal cell carcinoma (ccRCC) and overexpression of ULK1 correlated with poor outcomes. We found that ULK1 was highly expressed in 66.7% of ccRCC tumours (p < 0·05). Knockdown of ULK1 and selective inhibition of ULK1 by SBI-0206965 induced cell apoptosis in ccRCC cells. We demonstrated that SBI-0206965 triggered apoptosis by preventing autophagy and pentose phosphate pathway (PPP) flux. Furthermore, blocking the kinase activity of ULK1 with SBI-0206965 resulted in a level of anticancer effect in vivo. INTERPRETATION: Taken together, our results suggested that ULK1 was upregulated in ccRCC tumours and may be a potential therapeutic target. Therefore, SBI-0206965 should be further considered as an anti-ccRCC agent. FUND: This work was supported in part by The National Natural Science Foundation of China (No. 81570748) and Natural Science Foundation of Fujian Province (No. 2018J01345, 2017XQ1194).

Cytoreductive cryosurgery in patients with bone metastatic prostate cancer: A retrospective analysis.

The current study is a retrospective analysis of 49 patients with bone metastatic prostate cancer: 26 receiving androgen deprivation therapy (ADT) alone versus 23 receiving cytoreductive cryosurgery of the primary tumor plus ADT treatment. Progression-free survival (PFS) was the primary outcome variable, and Cox proportional hazards regression analysis was used to identify predictors for PFS. The baseline characteristics were generally comparable between the 2 groups. Median follow-up time was 41 months (range 24-56) and 37 months (range 19-53) in ADT alone group and cryosurgery groups, respectively. Patients receiving cryosurgery had significantly longer PFS (35 vs 25 months, P = 0.0027) and time to castration resistance (36 vs 25 months, P = 0.0011). Cox multivariate analysis associated longer PFS with the following factors: cryosurgery (HR0.207, 95% CI 0.094-0.456), lower prostate specific antigen at diagnosis (≤100 ng/ml, HR0.235, 95% CI 0.072-0.763) and lower Gleason score (≤7, HR0.195, 95% CI 0.077-0.496). Cryosurgery reduced the risk of progression by 79.3%. In conclusion, cytoreductive cryosurgery of the primary tumor in patients with bone metastatic prostate cancer could reduce the risk of progression and delay time to castration-resistant prostate cancer.

Plasmakinetic enucleation of the prostate compared with open prostatectomy for prostates larger than 100 grams: a randomized noninferiority controlled trial with long-term results at 6 years.

BACKGROUND: Studies have demonstrated that plasmakinetic enucleation of the prostate (PKEP) and open prostatectomy (OP) have equivalent short-term efficacy for large prostates, but no comparison concerning their long-term results was reported. OBJECTIVE: To demonstrate the noninferiority of PKEP to OP concerning maximum urinary flow rate (Qmax) at 1 yr postoperatively and to compare the long-term results of both procedures. DESIGN, SETTING, AND PARTICIPANTS: From 2004 to 2007, 160 patients with prostates >100g were randomized to receive PKEP or OP. A total of 153 patients (95.6%) completed the noninferiority study, and 123 patients (76.9%) finished a 6-yr follow-up assessment. INTERVENTION: The PKEP procedures were performed with 27F Karl Storz continuous flow resectoscopy and the Gyrus PlasmaKinetic device. OP was performed by a suprapubic transvesical approach. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary end point was Qmax at 1 yr postoperatively. Secondary end points included other perioperative parameters and postoperative micturition variables. The student t test, Mann-Whitney U test, chi-square test, or Fisher exact probability test was used as appropriate. RESULTS AND LIMITATIONS: PKEP was noninferior to OP regarding Qmax at 1 yr postoperatively. Compared with OP, PKEP was associated with less perioperative hemoglobin decrease, shorter catheterization time, and shorter postoperative hospital stay (1.0 vs 3.2g/dl, 40 vs 148h, and 3 vs 8 d, respectively; p<0.001 for all), as well as fewer short-term complications (22.5% vs 42.5%, p=0.031). On intention-to-treat analysis, both the PKEP and OP groups had equivalent Qmax (25.2±7.0ml/s vs 25.7±7.6ml/s, respectively; p=0.688), International Prostate Symptom Score (3.5 [2-5] vs 3 [2-5], respectively p=0.755), quality of life (2 [1-3] vs 2 [1-3], respectively; p=0.950), and postvoid residual urine (20 [9-33.5] vs 16.5 [7-31] ml, respectively; p=0.469) at 72 mo postoperatively. No patients required reoperation because of recurrence of BPH. The relatively small sample size is the limitation. CONCLUSIONS: PKEP is a durable procedure with short- to long-term micturition improvement equivalent to OP and significantly lower perioperative morbidity. PATIENT SUMMARY: We compared PKEP with OP for large prostates and found that PKEP is less invasive, with short- to long-term micturition improvement equivalent to OP. TRIAL REGISTRATION: Plasmakinetic Enucleation of the Prostate and Open Prostatectomy to Treat Large Prostates. ClinicalTrials.gov identifier NCT01952912. http://www.clinicaltrials.gov/ct2/show/NCT01952912?term=NCT016301952912&rank=1.

Y-type partial duplication of a vaginal ectopic ureter with ipsilateral hypoplastic pelvic kidney and bicornuate uterus.

We present a case of vaginal ectopic ureter with ipsilateral partial duplication of the upper ureter (Y-type ureter), ipsilateral hypoplastic pelvic kidney and bicornuate uterus in a 20-year-old woman who presented with mild urinary incontinence since infancy. Ultrasonography, computed tomography and intravenous pyelography examination showed a left kidney with no evidence of a right kidney. Cystourethroscopy showed absence of the right hemitrigone. Magnetic resonance (MR) urography demonstrated the presence of a bicornuate uterus, an ectopic dysplastic right kidney in the pelvic cavity, and a right ureter that terminates in the vaginae fornix. The patient underwent right nephroureterectomy and urinary continence was restored completely. Although congenital malformations of the urinary tract are frequently associated with genital tract abnormalities, to best our knowledge, this is the first report of the coexistence of all of these anomalies in an individual. Our report also highlights the importance of MR urography in the diagnosis of such rare and complex anomalies.

Use of the ImmuKnow assay to evaluate the effect of alemtuzumab-depleting induction therapy on cell-mediated immune function after renal transplantation.

BACKGROUND: Good outcomes after renal transplantation are dependent on effective immunosuppression while minimizing infection. Alemtuzumab (Campath or Campath-1H) is an anti-CD52 humanized monoclonal IgG1 antibody which induces rapid and sustained depletion of circulating lymphocytes and has been effectively used as an immunosuppressant in post-transplant induction therapy. METHODS: We used the ImmuKnow assay to compare cell-mediated immune function in renal transplant patients treated with alemtuzumab or with conventional immunosuppressive tri-therapy. The ImmuKnow method determines the levels of adenosine triphosphate (ATP) released from CD4 cells following stimulation with a mitogen. RESULTS: We showed a statistically significant difference in the distribution of outcome after transplantation between the conventional and the Campath groups (P = 0.010). A significantly higher number of patients treated with alemtuzumab induction therapy were stable after transplantation compared to those treated with conventional immunosuppressive tri-therapy (96.6 vs. 75.7 %). ATP values were significantly higher in the conventional group compared to the Campath group at 180 days after transplantation (P < 0.001). ATP levels did not change significantly over time in clinically stable kidney recipients treated with alemtuzumab induction therapy (P = 0.554). CONCLUSIONS: The ImmuKnow assay is a useful tool for evaluating the global immune response in alemtuzumab-treated renal transplant patients. Alemtuzumab-depleting induction therapy remains effective for at least 180 days.

Electrosurgical enucleation versus bipolar transurethral resection for prostates larger than 70 ml: a prospective, randomized trial with 5-year followup.

PURPOSE: We compared the perioperative and postoperative characteristics of prostate PlasmaKinetic™ enucleation and bipolar transurethral resection for large volume benign prostatic hyperplasia. MATERIALS AND METHODS: In this prospective, randomized, controlled trial 80 patients with benign prostatic hyperplasia and a prostate of larger than 70 ml were randomly assigned to prostate bipolar transurethral resection or PlasmaKinetic enucleation. Operative time, resected adenoma weight, changes in hemoglobin, catheterization time and postoperative hospital stay were recorded and compared. Patients were followed 1, 6, 12, 24, 36, 48 and 60 months after surgery. RESULTS: Greater resected prostate weight (mean ± SD 64.2 ± 19.0 vs 50.6 ± 20.0 gm, p = 0.03), less blood loss (mean 0.87 ± 0.42 vs 1.74 ± 0.63 gm, p <0.01), and shorter catheterization time (mean 35.5 ± 5.8 vs 60.1 ± 5.8 hours, p <0.01) and postoperative hospital stay (mean 3 vs 4 days, [corrected] p <0.01) were recorded in the enucleation group than in the resection group. The postoperative improvement in International Prostate Symptom Score, quality of life, maximal flow rate and post-void residual urine volume was similar in the 2 groups at 1, 6, 12 and 24 months but significantly better in the enucleation group at 36, 48 and 60 months. During the 5-year followup no patient in the enucleation group but 2 in the resection group experienced recurrence. CONCLUSIONS: For large volume benign prostatic hyperplasia PlasmaKinetic enucleation of the prostate is associated with less blood loss, shorter hospital stay and catheterization time than bipolar transurethral resection of the prostate. Moreover, PlasmaKinetic enucleation seems to be superior at long-term followup with fewer reoperations necessary.

High- vs low-power holmium laser lithotripsy: a prospective, randomized study in patients undergoing multitract minipercutaneous nephrolithotomy.

OBJECTIVE: To determine the efficacy and safety of high-power holmium: yttrium aluminum-garnet (Ho:YAG) laser lithotripsy for multitract modified minimally invasive percutaneous nephrolithotomy (MPCNL) in the treatment of patients with large staghorn renal calculi. METHODS: A randomized, prospective study was conducted. Two-hundred seventy-three consecutive patients (291 renal units) with large staghorn renal calculi were randomized to undergo multitract MPCNL with 30-W low-power or 70-W high-power Ho:YAG laser lithotripsy. Both groups were compared in terms of perioperative findings and postoperative outcomes, including procedure time, stone-free rate, length of hospital stay, transfusion rates, renal function recovery, and other complications. RESULTS: The average patient age was 49.2 years (range 22-73) and mean stone size was 5.54±0.7 cm. The 2 groups had some comparable perioperative findings and outcome, including tracts required per operated renal unit (n), blood loss, postoperative fever, postoperative hospital stay, stone-free rate, and improvement of operated renal function. The operation time in the high-power group was significantly shorter than that in the low-power group (129.20±17.2 vs 105.18±14.2, P<.01). CONCLUSION: A combination of multitract MPCNL and high-power Ho:YAG laser lithotripsy can greatly decrease the operative time without increasing the intraoperative complications or delaying postoperative renal function recovery when compared with low-power Ho:YAG laser lithotripsy.

Giant primary vaginal calculus secondary to vesicovaginal fistula with partial vaginal outlet obstruction in a 12-year-old girl.

A vesicovaginal fistula with vagina obstruction associated with vaginal calculi is an extremely rare medical condition. We report a giant primary vaginal calculus resulting from vesicovaginal fistula with partial vaginal outlet obstruction secondary to perineum trauma and surgery in a 12-year-old girl. Episiotomy was performed and the adhesive labia minora was split. After the removal of a giant calculus in the vagina, approximately 8 cm in diameter, the fistula tract was completely excised, followed by the repair of the vesicovagina fistula and the vagina. The patient was symptom-free at 6-month follow-up examination.

Analysis of HK-2 cells exposed to oxalate and calcium oxalate crystals: proteomic insights into the molecular mechanisms of renal injury and stone formation.

Exposure to high levels of oxalate and calcium oxalate monohydrate (COM) crystals is injurious to renal epithelial cells and triggers serial responses related to stone formation. Multiple molecules and proteins are involved in this process, but previous studies have generally been limited, without an overall understanding of protein expression alteration after oxalate and/or crystal exposure as well as its role in stone formation. We used proteomic analysis to reveal the changes in the proteome of HK-2 cells induced by oxalate and COM crystals, so as to provide candidate proteins involved in the molecular mechanisms concerning HK-2 cell injury and kidney stone formation. HK-2 cells were exposed to oxalate plus COM crystals at different concentrations in various samples. Cell viability was determined using a Cell Counting Kit-8 assay kit. For proteomic analysis, cells were exposed to oxalate (2 mM) and COM crystals (200 ug/ml) for 12 h. The proteins were separated by two-dimensional electrophoresis and the differentially expressed proteins were identified by liquid chromatography electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS). Validation of protein expression was further performed by Western blot analysis. Oxalate and COM crystals showed concentration-dependent toxicity on HK-2 cells. A total of 12 differentially expressed proteins in HK-2 cells induced by oxalate and COM crystals were identified, which were involved in various aspects of cellular processes. Our study provides a platform for further studying the molecular mechanism of renal epithelial cell injury and kidney stone formation.

70 W holmium: yttrium-aluminum-garnet laser in percutaneous nephrolithotomy for staghorn calculi.

PURPOSE: To investigate the safety and efficacy of the high-power (70 W) holmium laser in percutaneous nephrolithotripsy (PCNL) for staghorn calculi. PATIENTS AND METHODS: From December 2004 to March 2008, 438 consecutive patients (456 renal units) with > or =4-cm staghorn stones underwent PCNL with a pulsed holmium:yttrium-aluminum-garnet (Ho:YAG) laser using a 1000-microm end-firing optical fiber. For the first 106 patients (group A; average stone size 5.6 +/- 0.8 cm), a 30 W (3.0 J/pulse; 10 pulse/sec) laser was used, whereas for the other 332 patients (group B; average stone size 5.8 +/- 0.8 cm), the laser power was set at 3.0 J/pulse with a frequency of 20 pulses/sec. For stones in a calix visible with the nephroscope but unreachable with a laser, the mucosa of the calix was split with a 100 W holmium laser to fragment the stones further. Moreover, a porcine model for assessing the safety of the high-power holmium laser was developed. RESULTS: All patients had successful PCNL. The average lithotripsy time in group B was significantly shorter than that in group A (44 +/- 11.5 minutes vs 69 +/- 14.8 minutes; P < 0.05). No patient had a severe complication. In addition, 39 patients underwent calix splitting with no hemorrhage during or after the operation. The glomerular filtration rate of the treated kidney, reexamined 6 months after the operation, had improved greatly (45.12 vs 31.91 mL/min; P < 0.05). Pathologic evaluation of porcine kidneys exposed to high-power laser firing showed no damage. CONCLUSIONS: The high-power Ho:YAG laser enhances lithotripsy efficacy by "vaporizing" and "bursting" the stone quickly, reducing lithotripsy time significantly. This is an effective and safe treatment for patients with large renal stones.