A single-arm, multicenter, phase 2 clinical study of recombinant humanized anti-HER2 monoclonal antibody-MMAE conjugate (MRG002) in HER2-positive unresectable locally advanced or metastatic urothelial carcinoma.

BACKGROUND: MRG002 is a novel HER2-targeted antibody-drug conjugate being investigated in the MRG002-006 trial to evaluate the efficacy and safety in HER2-positive urothelial carcinoma patients. METHODS: This is an open-label, single-arm, multicenter phase II study. Eligibility criteria included: histologically confirmed HER2 IHC 2 + or 3 + UC, prior received ≥ 1 standard treatment. Patients in this study received MRG002 every 3 weeks until progressive disease or unacceptable toxicity. The primary endpoint was confirmed ORR per RECIST 1.1. RESULTS: As of February 24, 2023, a total of 43 patients were enrolled. The median age was 60. 9 patients were dosed at 2.6 mg/kg and 34 patients were dosed at 2.2 mg/kg. At baseline, most patients (29/43) received ≥ 2 lines of treatment and 35 (81.4%) patients had prior ICI therapy. FISH test was performed in 41 patients and 9 (22.0%) were positive. By the cut-off date, 41 patients were evaluable and the ORR was 53% (95%CI：38.9%-67.5%), with 6.9% CR, and the DCR was 83.7% (95%CI：70.0%-91.9%). The median PFS and OS for the 43 patients were 7.0 months (95%CI：5.4-NE) and 14.9 months (95%CI：11.9-NE), respectively. The ORR was 77.8% in 9 patients with positive HER2 FISH results. Most common treatment-related AEs were anemia (51.2%), alopecia (44.2%) and neutropenia (39.5%); most were grade 1 or 2. CONCLUSION: Preliminary results of MRG002 demonstrated a clinically meaningful response in pretreated HER-2 positive unresectable locally advanced or metastatic UC patients. MRG002 at 2.2 mg/kg was well tolerated with a manageable toxicity.

Activation of the cGMP/PKG/ERK signaling pathway associated with PDE5Is inhibits fibroblast activation by downregulating autophagy in early progressive benign prostatic hyperplasia.

PURPOSE: Benign prostatic hyperplasia (BPH) is one of the most prevalent diseases affecting aging males. However, approximately, 8% of the BPH patients under 50-year-old experience remarkably early progression, for reasons that remain elusive. Among the various factors implicated in promoting BPH advancement, the activation of fibroblasts and autophagy hold particular importance. Our research endeavors to explore the mechanisms behind the accelerated progression in these patients. METHODS: Immunohistochemistry and immunofluorescence were performed to detect the expression levels of LC3, p62, PDE5, and α-SMA in diverse BPH tissues and prostate stromal cells. The autophagy activator rapamycin, the autophagy suppressor chloroquine, and siRNA transfection were used to identify the impact of autophagy on fibroblast activation. RESULTS: Prostatic stromal fibroblasts in early progressive BPH tissues displayed activation of autophagy with an upregulation of LC3 and a concurrent downregulation of p62. After starvation or rapamycin treatment to a heightened level of autophagy, fibroblasts exhibited activation. Conversely, chloroquine treatment and ATG-7-knockdown effectively suppressed the level of autophagy and fibroblast activation. High expression of PDE5 was found in early progressive BPH stromal cells. The administration of PDE5 inhibitors (PDE5Is) hindered fibroblast activation through suppressing autophagy by inhibiting the ERK signaling pathway. CONCLUSION: Our findings suggest that autophagy plays a pivotal role in promoting BPH progression through fibroblast activation, while PDE5Is effectively suppress autophagy and fibroblast activation via the ERK signaling pathway. Nevertheless, further investigations are warranted to comprehensively elucidate the role of autophagy in BPH progression.

Prognostic value of Controlling Nutritional Status score for postoperative complications and biochemical recurrence in prostate cancer patients undergoing laparoscopic radical prostatectomy.

Background: Controlling Nutritional Status (CONUT) score was used for screening the preoperative nutritional status. The correlation between the CONUT score and the prognosis of patients with prostate cancer (PCa) has yet to be elucidated. Herein, we analyzed the prognostic value of CONUT scores in patients with PCa who underwent laparoscopic radical prostatectomy. Materials and methods: Data of 244 patients were retrospectively evaluated. Perioperative variables and follow-up data were analyzed. The patients were categorized into 2 groups according to their preoperative CONUT scores. Postoperative complication and incontinence rates were also compared. The Kaplan-Meier method was used to estimate the median biochemical recurrence-free survival (BCRFS) between the 2 groups. Univariate and multivariate Cox regression analyses were performed to identify the potential prognostic factors for BCRFS. Results: Patients were categorized into the low-CONUT group (CONUT score <3, n = 207) and high-CONUT group (CONUT score ≥3, n = 37). The high-CONUT group had a higher overall complication rate (40.5% vs.19.3%, p = 0.004), a higher major complication rate (10.8% vs. 3.9%, p = 0.013), and longer postoperative length of stay (8 days vs. 7 days, p = 0.017). More fever, urinary infection, abdominal infection, scrotal edema, rash, and hemorrhagic events (all p values < 0.05) were observed in the high-CONUT group. A higher rate of urinary incontinence was observed in the high-CONUT group at 1 (34.4% vs. 13.2%, p = 0.030) and 3 months (24.1% vs. 8.2%, p = 0.023) postoperatively. The high-CONUT group had shorter medium BCRFS (23.8 months vs. 54.6 months, p = 0.029), and a CONUT score ≥3 was an independent risk factor for a shorter BCRFS (hazards ratio, 1.842; p = 0.026). Conclusions: The CONUT score is a useful predictive tool for higher postoperative complication rates and shorter BCRFS in patients with PCa who undergo laparoscopic radical prostatectomy.

Exploring the Enigma of 5-ARIs Resistance in Benign Prostatic Hyperplasia: Paving the Path for Personalized Medicine.

PURPOSE OF REVIEW: Despite the widespread utilization of 5-alpha reductase inhibitors (5-ARIs) for managing benign prostatic hyperplasia (BPH), certain BPH patients exhibit unresponsiveness to 5-ARIs therapy. This paper provides a comprehensive overview of the current perspectives on the mechanisms of 5-ARIs resistance in BPH patients and integrates potential biomarkers and underlying therapeutic options for 5-ARIs resistance. These findings may facilitate the development of novel or optimize more effective treatment options, and promote personalized medicine for BPH. RECENT FINDINGS: The pathways contributing to resistance against 5-ARIs in certain BPH patients encompass epigenetic modifications, shifts in hormone levels, autophagic processes, and variations in androgen receptor structures, and these pathways may ultimately be attributed to inflammation. Promisingly, novel biomarkers, including intravesical prostatic protrusion, inflammatory factors, and single nucleotide polymorphisms, may offer predictive insights into the responsiveness to 5-ARIs therapy, empowering physicians to fine-tune treatment strategies. Additionally, on the horizon, GV1001 and mTOR inhibitors have emerged as potential alternative therapeutic modalities for addressing BPH in the future. After extensive investigation into BPH's pathological processes and molecular landscape, it is now recognized that diverse pathophysiological mechanisms may contribute to different BPH subtypes among individuals. This insight necessitates the adoption of personalized treatment strategies, moving beyond the prevailing one-size-fits-all paradigm centered around 5-ARIs. The imperative for early identification of individuals prone to treatment resistance will drive physicians to proactively stratify risk and adapt treatment tactics in future practice. This personalized medicine approach marks a progression from the current standard treatment model, emerging as the future trajectory in BPH management.

MRI-measured periprostatic adipose tissue volume as a prognostic predictor in prostate cancer patients undergoing laparoscopic radical prostatectomy.

In this study, we evaluated the association between the PPAT volume and the prognosis of PCa patients after LRP. We retrospectively analysed data of 189 PCa patients who underwent LRP in Beijing Chaoyang Hospital. Volumes of PPAT and prostate were measured by magnetic resonance imaging (MRI), and normalized PPAT volume was computed (PPAT volume divided by prostate volume). Patients were then stratified into the high-PPAT group (n = 95) and low-PPAT group (n = 94) by the median of normalized PPAT volume (73%). The high-PPAT group had significantly higher Gleason score (total score 8 or more, 39.0% vs. 4.3%, p < 0.001) and pathological stage (stage T3b, 28.4% vs. 13.8%, p = 0.048). No significant correlation between normalized PPAT volume and body mass index (ρ = -0.012, p = 0.872) was observed. Kaplan-Meier curve analysis showed the high-PPAT group had significantly shorter biochemical recurrence (BCR) interval (median progression-free survival time 15.9 months vs. 32.7 months, p = 0.001). Univiarate and multivariate Cox regression analyses showed high normalized PPAT volume (>73%) (hazard ratio 1.787 [1.075-3.156], p = 0.002) were independent risk factors for BCR post-operatively. In conclusion, MRI-measured PPAT volume is of significant prognostic value for PCa patients undergoing LRP.

Skull metastasis is a poor prognostic factor for prostate cancer patients with bone metastasis: a retrospective study based on a Chinese population.

BACKGROUND: Skull is a relatively rare metastasis site for prostate cancer (PCa). There is no evidence regarding the prognostic indication of skull metastasis (SM) in PCa patients. In this study, we analyzed the prognostic value of SM for metastatic PCa patients receiving androgen deprivation therapy (ADT). METHODS: 107 consecutive patients were included from September 2008 to August 2021. All patients were administered with standard ADT. Abiraterone plus glucocorticoid and/or docetaxel chemotherapy were given after failure to castration-resistant prostate cancer. Clinical parameters and follow-up prognostic data were retrospectively analyzed. The association of clinical and pathological parameters with SM were analyzed. The progression-free survival (PFS) and overall survival (OS) were assessed using Kaplan-Meier analysis and Cox regression analyses. RESULTS: Patients with SM (n = 26) had significantly higher biopsy Gleason scores, higher clinical T stage, higher prostate-specific antigen level at diagnosis, and were more likely to have high-burden metastasis and lymph node metastasis, compared with those without SM (n = 81). They also showed significantly lower level of hemoglobin, albumin and serum calcium, along with higher level of alkaline phosphatase. SM was significantly associated with shorter medium PFS (9.4 vs. 18.3 months, p < 0.001) and OS (22.2 vs. 58.2 months, p < 0.001). Cox analysis demonstrated that SM was an independent risk factor for shorter PFS (hazard ratio 2.327 [1.429-3.789], p = 0.001) and shorter OS (hazard ratio 2.810 [1.615-4.899], p < 0.001). CONCLUSION: In this study, we found that SM was significantly correlated with more aggressive disease and indicated poor prognosis in PCa patients with bone metastasis. Our study may provide useful reference for the risk stratification of PCa patients.

MRI-measured adipose features as predictive factors for detection of prostate cancer in males undergoing systematic prostate biopsy: a retrospective study based on a Chinese population.

In this study, we retrospectively evaluated the data of 901 men undergoing ultrasonography-guided systematic prostate biopsy between March 2013 and May 2022. Adipose features, including periprostatic adipose tissue (PPAT) thickness and subcutaneous fat thickness, were measured using MRI before biopsy. Prediction models of all PCa and clinically significant PCa (csPCa) (Gleason score higher than 6) were established based on variables selected by multivariate logistic regression and prediction nomograms were constructed. Patients with PCa had higher PPAT thickness (4.64 [3.65-5.86] vs. 3.54 [2.49-4.51] mm, p < 0.001) and subcutaneous fat thickness (29.19 [23.05-35.95] vs. 27.90 [21.43-33.93] mm, p = 0.013) than those without PCa. Patients with csPCa had higher PPAT thickness (4.78 [3.80-5.88] vs. 4.52 [3.80-5.63] mm, p = 0.041) than those with non-csPCa. Adding adipose features to the prediction models significantly increased the area under the receiver operating characteristics curve for the prediction of all PCa (0.850 vs. 0.819, p < 0.001) and csPCa (0.827 vs. 0.798, p < 0.001). Based on MRI-measured adipose features and clinical parameters, we established two nomograms that were simple to use and could improve patient selection for prostate biopsy in Chinese population.

Propensity score-matched analysis for ileal conduit and orthotopic neobladder intracorporeally accomplished following laparoscopic radical cystectomy.

PURPOSE: To compare perioperative results of intracorporeal ileal conduit (ICIC) and intracorporeal orthotopic neobladder (ICONB) following laparoscopic radical cystectomy. MATERIALS AND METHODS: A total of 51 ICIC patients and 32 ICONB patients were included. Propensity score matching was performed based on: age, body mass index, gender, age-adjusted Charlson comorbidity index, history of neoadjuvant chemotherapy, history of abdominal surgery, history of smoking and enhanced recovery protocols. Primary outcomes were length of stay and 30-day complications. Secondary outcomes were operative time and estimated blood loss. RESULTS: ICONB was more likely to be performed in younger patients (P < 0.001). Other baseline characteristics in the 2 groups were similar (P > 0.05). ICIC showed shorter length of stay (11 days vs. 14 days, P = 0.031) and faster pelvic drainage tube removal (6 days vs. 9 days, P = 0.014). Operative time, estimated blood loss, 30-day complications were similar in the 2 groups (P > 0.05). However, postoperative fever was significantly lower in ICIC group (19.6% vs. 62.5%, P < 0.001). After propensity score matching, ICIC still showed shorter length of stay (10 days vs. 15 days, P = 0.002) and less postoperative fever (15% vs. 65%, P = 0.003). In multivariable analysis, ICONB was independently associated with length of stay≥14 days and postoperative fever both before and after propensity score matching (P < 0.05). CONCLUSIONS: In our research, ICONB was more likely to be performed in younger patients. ICIC and ICONB showed no difference on 30-day complications, operative time and estimated blood loss. ICIC group showed shorter length of stay, faster pelvic drainage tube removal and less postoperative fever.

Impact of preoperative body mass index on perioperative outcomes is optimized by enhanced recovery protocols in laparoscopic radical cystectomy with intracorporeal urinary diversion.

BACKGROUND: We aimed to examine whether body mass index (BMI) had an impact on clinical outcomes of laparoscopic radical cystectomy with intracorporeal urinary diversion. Furthermore, we analyzed the optimization of enhanced recovery protocols (ERPs) on the impact of BMI on clinical outcomes. METHODS: By searching our database, data of 83 consecutive patients were retrospectively collected, including 37 patients with a BMI <24 kg/m2 (group A) and 46 patients with a BMI ≥24 kg/m2 (group B). The baseline and peri-operative variables of the two groups were compared. Subgroup analysis was conducted for ERPs (11 patients in group A1, 18 patients in group B1) and conventional recovery protocols (CRPs; 26 patients in group A2, 28 patients in group B2). The primary outcomes were 30-day overall complication rate and ΔALBmin (reduction proportion of minimum albumin). The secondary outcomes were operative time and length of stay. RESULTS: The baseline variables were similar between the two groups (P>0.05). The 30-day overall complication rate, operative time, and length of stay were similar between the two groups (P>0.05). But post-operative nausea and vomiting (PONV) was higher in group A than in group B (32.4% vs. 8.7%, P=0.014). Group A was associated with lower serum albumin level pre-operatively and on post-operative days 1-3. ΔALBmin was higher in group A than in group B (33.08%±9.88% vs. 27.92%±8.52%, P<0.05). In the subgroup analysis, the CRPs group presented similar results, with group A2 showing higher PONV rate, lower albumin level pre- and post-operatively, and higher level of reduction proportion (P<0.05). For the ERPs group, the PONV rate, pre-operative albumin level, and reduction proportion were similar between group A1 and B1 (P>0.05). Multivariable analysis showed that PONV and CRPs were independently associated with ΔALBmin ≥34% (P<0.05). CONCLUSIONS: BMI had no impact on the 30-day overall complication rate, operative time, and length of stay of patients who underwent laparoscopic radical cystectomy with intracorporeal urinary diversion. BMI <24 kg/m2 was associated with higher PONV rate and more albumin loss, both of which could be optimized by ERPs.

Current Trends in Percutaneous Nephrolithotomy in China: A Spot Survey.

OBJECTIVE: To describe trends in the procedure of percutaneous nephrolithotomy (PCNL) in China to identify training needs. METHODS: A spot survey with 36 questions, which revealed demographic data, patterns of PCNL practice, and opinions regarding specific clinical cases, was administered to Chinese urologists during the 17th National Urological Urolithiasis Symposium held in Dandong in 2018. RESULTS: Out of 400 participants, 221 responses to the survey were received. PCNL was performed by 80.5% of the participants, and 70.2% of them were senior clinicians. It was found that 91% used the prone decubitus in training programs and 27.6% the modified supine, and 46.6% were apprenticeship trained for PCNL, while 5.6% trained during their residency. The prone position was the preferred decubitus, even for obese patients. All of the urologists established their own access, 93.7% used ultrasonography guidance alone, 70.7% used ultrasonic and/or pneumatic lithotripters, and 29.2% used laser. When exiting the kidney, 73.8% placed a nephrostomy tube whereas 26.2% used the tubeless technique. For postoperative follow-up, 51.3% used computed tomography (CT) or ultrasonography plus kidney-ureter-bladder (KUB) to monitor the results of procedures, while 45% used KUB alone. Colonic injury was reported by 8.9%. Average hospital stays of >3 days were reported for 81.2% of procedures. CONCLUSION: Chinese urologists obtain their own access during PCNL, with ultrasonic guidance in most cases, and almost a half of them are apprenticeship trained. They prefer the prone position, use fascial dilators, and place a nephrostomy tube when exiting the kidney. Most urologists follow the official management guidelines in special cases. Skilled use of urological ultrasound examination, flexible nephroscopy, postoperative CT, tubeless procedures in selected patients, and urology residency training are recommended for PCNL practice.

Modified ileal conduit intracorporeally accomplished following laparoscopic radical cystectomy with enhanced recovery protocols: experience with 48 cases.

BACKGROUND: This study introduces the results of laparoscopic radical cystectomy with modified intracorporeal ileal conduit (mICIC), which was accompanied by enhanced recovery after surgery (ERAS) protocols. METHODS: From March 2014 to June 2020, 48 patients underwent mICIC. Patients were divided into ERAS (n=17) and non-ERAS groups (n=31). Baseline and perioperative variables were analyzed. The primary outcome was 90-day complications. Secondary outcomes were operative time, length of stay, two-year overall survival, cancer-specific survival, and disease-free survival. RESULTS: Forty-eight patients underwent intracorporeal ileal conduit with no transition to open surgery. Twenty-five patients (52.1%) experienced at least one complication, including 22 minor cases (45.8%) and three major cases (6.2%). The median operative time, urinary diversion time, estimated blood loss, and length of stay were 320 min, 135 min, 200 mL, and 10.5 days, respectively. The median time to flatus and normal diet were two days and three days, respectively. A comparison between ERAS and non-ERAS groups indicated that ERAS implementation was associated with less complications (29.4% vs. 64.5%, P=0.018), faster time to flatus (2 vs. 3 days, P=0.016) and liquid diet (2 vs. 4 days, P<0.001). The results of hydronephrosis and compromised renal function showed no difference between the preoperative period and six months after surgery. The mean follow-up time was 25.4 months, and the two-year overall survival, cancer-specific survival, and disease-free survival rates were 61.3%, 73.2%, and 58.4%, respectively. CONCLUSIONS: The complication rate and operative time of the mICIC were acceptable. Clinical outcomes can be optimized with ERAS pathway.

A potential panel of five mRNAs in urinary extracellular vesicles for the detection of bladder cancer.

BACKGROUND: Extracellular vesicles (EVs) have showed promising potential in liquid biopsy of cancer. In present study, we evaluate the feasibility to diagnose bladder cancer using EVs RNA markers identified from public tissue RNA sequencing data. METHODS: We used urine samples from a cohort of population with suspected bladder cancer. Disease status (i.e., primary or recurrent bladder cancer) was diagnosed by cystoscopy. A prediction model including the expression of multiple RNAs in urinary EVs were developed in training cohort (n=368, 126 bladder cancer and 242 negative controls). The performance of optimal model (ExoPanel) consists of five mRNAs (MYBL2, TK1, UBE2C, KRT7, S100A2) was further assessed by a validation cohort (n=155, 56 bladder cancer and 99 negative controls). RESULTS: The performance of ExoPanel in training cohort was AUC 0.7759 (95% CI: 0.7259-0.8260), NPV 90.34% (95% CI: 84.04-94.42%), SN 88.89% (95% CI: 81.75-93.57%), and SP 54.13% (95% CI: 47.63-60.50%) respectively. In the validation cohort, the performance of this model was AUC 0.8402 (95% CI: 0.7690-0.9114), NPV 90.91% (95% CI: 79.29-96.60%), SN 91.07% (95% CI: 79.63-96.67%), and SP 50.51% (95% CI: 40.34-60.63%). Using this model, it is possible to rule out a significant number of non cancer patients, thus reduce the unnecessary operation of cystoscopy. CONCLUSIONS: We discovered a panel of five mRNAs, and evaluated its potential to facilitate bladder cancer diagnosis by analyzing their expression in urinary EVs.

Methylated CpG dinucleotides in the 5-α reductase 2 gene may explain finasteride resistance in benign prostatic enlargement patients.

The inhibition of 5-α reductase type 2 (SRD5A2) by finasteride is commonly used for the management of urinary obstruction resulting from benign prostatic enlargement (BPE). Certain BPE patients showing no SRD5A2 protein expression are resistant to finasteride therapy. Our previous work showed that methylated cytosine-phosphate-guanine (CpG) islands in the SRD5A2 gene might account for the absence or reduction of SRD5A2 protein expression. Here, we found that the expression of the SRD5A2 protein was variable and that weak expression of the SRD5A2 protein (scored 0-100) occurred in 10.0% (4/40) of benign adult prostates. We showed that the expression of SRD5A2 was negatively correlated with DNA methyltransferase 1 (DNMT1) expression. In vitro SRD5A2-negative BPH-1 cells were resistant to finasteride treatment, and SRD5A2 was re-expressed in BPH-1 cells when SRD5A2 was demethylated by 5-Aza-2'-deoxycytidine (5-Aza-CdR) or N-phthalyl-L-tryptophan (RG108). Furthermore, we determined the exact methylation ratios of CpG dinucleotides in a CpG island of SRD5A2 through MassArray quantitative methylation analysis. Ten methylated CpG dinucleotides, including four CpG dinucleotides in the promoter and six CpG dinucleotides in the first exon, were found in a CpG island located from -400 bp to +600 bp in SRD5A2, which might lead to the silencing of SRD5A2 and the absence or reduction of SRD5A2 protein expression. Finasteride cannot exert a therapeutic effect on patients lacking SRD5A2, which may partially account for the resistance to finasteride observed in certain BPE patients.

The long-term efficacy of one-shot neoadjuvant intra-arterial chemotherapy combined with radical cystectomy versus radical cystectomy alone for bladder cancer: a propensity-score matching study.

BACKGROUND: Bladder cancer is a complex disease associated with high morbidity and mortality. Management of bladder cancer before radical cystectomy continues to be controversial. We compared the long-term efficacy of one-shot neoadjuvant intra-arterial chemotherapy (IAC) versus no IAC (NIAC) before radical cystectomy (RC) for bladder cancer. METHODS: We performed a retrospective review of patients who underwent either one-shot IAC or NIAC before RC between October 2006 and November 2015. A propensity-score matching (1:3) was performed based on key characters. The Kaplan-Meier method was utilized to estimate survival probabilities, and the log-rank test was used to compare survival outcomes between different groups. A multivariable Cox proportional hazard model was used to estimate survival outcomes. RESULTS: Twenty-six patients were treated using IAC before RC, and 123 NIAC patients also underwent RC. After matching, there was no significant difference between groups in baseline characteristics, perioperative variables, complication outcomes or tumor characteristics. Compared with clinical tumor stages, pathological tumor stages demonstrated a significant decrease (P = 0.002) in the IAC group. There was no significant difference in overall survival (OS, p = 0.354) or cancer-specific survival (CSS, p = 0.439) between the groups. Among all patients, BMI significantly affected OS (p = 0.004), and positive lymph nodes (PLN) significantly affected both OS (p<0.001) and CSS (p = 0.010). CONCLUSIONS: One-shot neoadjuvant IAC before RC shows safety and tolerability and provides a significant advantage in pathological downstaging but not in OS or CSS. Further study of neoadjuvant combination therapeutic strategies with RC is needed.

Surgical techniques for facilitating laparoscopic intracorporeal orthotopic neobladder: initial experience

ABSTRACT Purpose: To describe our technique and outcomes for laparoscopic intracorporeal ileal neobladder (ICNB) reconstruction. Materials and Methods: From April 2014 to November 2016, 21 patients underwent laparoscopic ICNB at our tertiary referral centre. ICNB with bilateral isoperistaltic afferent limbs and several technique improvements were introduced. Demographics, clinical, and pathological data were collected. Perioperative, 1-year oncologic, 1-year Quality of life and 1-year functional outcomes were reported. Results: ICNB was successfully performed in all 21 patients without open conversion and transfusion. Mean operative time was 345.6±66.9 min, including 106±22 min for LRC and PLND and 204±46.4 min for ICNB, respectively. Mean established blood loss was 192±146 mL. The overall incidence of 90-d complication was 33.3%, while major complication occurred in 4.8%. One-year daytime and night-time continence rates were 85.7% and 57.1%, respectively. One patient died from myocardial infarction six months postoperatively, and two patients had lung metastasis five months and six months respectively. Conclusions: We described our experience of 3D LRC with a novel intracorporeal orthotopic ileal neobladder, and the technique improvements facilitate the procedure. However, further studies are required to evaluate long-term outcomes of the intracorporeal neobladder with bilateral isoperistaltic afferent limbs.

Surgical techniques for facilitating laparoscopic intracorporeal orthotopic neobladder: initial experience.

PURPOSE: To describe our technique and outcomes for laparoscopic intracorporeal ileal neobladder (ICNB) reconstruction. MATERIALS AND METHODS: From April 2014 to November 2016, 21 patients underwent laparoscopic ICNB at our tertiary referral centre. ICNB with bilateral isoperistaltic afferent limbs and several technique improvements were introduced. Demographics, clinical, and pathological data were collected. Perioperative, 1-year oncologic, 1-year Quality of life and 1-year functional outcomes were reported. RESULTS: ICNB was successfully performed in all 21 patients without open conversion and transfusion. Mean operative time was 345.6±66.9 min, including 106±22 min for LRC and PLND and 204±46.4 min for ICNB, respectively. Mean established blood loss was 192±146 mL. The overall incidence of 90-d complication was 33.3%, while major complication occurred in 4.8%. One-year daytime and night-time continence rates were 85.7% and 57.1%, respectively. One patient died from myocardial infarction six months postoperatively, and two patients had lung metastasis five months and six months respectively. CONCLUSIONS: We described our experience of 3D LRC with a novel intracorporeal orthotopic ileal neobladder, and the technique improvements facilitate the procedure. However, further studies are required to evaluate long-term outcomes of the intracorporeal neobladder with bilateral isoperistaltic afferent limbs.

Comparison of Radical Nephroureterectomy and Partial Ureterectomy for the Treatment of Upper Tract Urothelial Carcinoma.

This study aimed to compare the oncological and renal outcomes of partial ureterectomy (PU) versus radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC). UTUC patients' clinical information was reviewed, and progression-free survival (PFS), overall survival (OS), and kidney function were collected. The mean follow-up period was 59 (6-135) months in the RNU group and 34.5 (5-135) months in the PU group. The mean operation time in the PU group was 141 (64-340) min, which is significantly shorter than the RNU group (P < 0.01). Regarding kidney function at one year or two years after operation, the PU group had significantly improved mean estimated glomerular filtration rate (eGFR) levels and a remarkably decreased constitution of patients with chronic kidney disease (CKD) III or higher group (P < 0.05). There was no significant difference in PFS and OS between the RNU group and the PU group (P > 0.05). Multifactor Cox regression analysis indicated that age and the preoperative CKD stages were independent risk factors for poor kidney functions of UTUC patients. Compared to patients in RNU group, patients in PU have no significant difference in survival time but have shorter operation time, shorter hospital stay, and improved kidney functions.

Increased H2S and its synthases in urothelial cell carcinoma of the bladder, and enhanced cisplatin-induced apoptosis following H2S inhibition in EJ cells.

H2S, synthesized by cystathionine ß-synthase (CBS), cystathionine γ-lyase (CSE) and 3-mercaptopyruvate sulfurtransferase (MPST), functions as a signalling molecule in mammalian cells. H2S serves complex functions in physiological and pathological processes, including in bladder cancer. In the present study, H2S production, the expression of the associated enzymes and the effect of H2S on human urothelial cell carcinoma of the bladder (UCB) tissue and cell lines were evaluated, and whether decreasing H2S levels influenced cell viability and tumour growth following treatment with cisplatin (CDDP) was assessed in UCB cells in vitro and in vivo. H2S production and the expression of CBS, CSE and MPST in bladder tissue specimens and the UCB cell lines 5637, EJ and UM-UC-3 were analysed using a sulfur-sensitive electrode and western blotting. UCB cells were subjected to different treatments, and viability and protein expression were determined. H2S production was inhibited to examine its influence on EJ cell tumour growth following CDDP treatment in vivo. It was identified that CBS, CSE and MPST protein were up-regulated in UCB tissues and cells. The H2S production and enzyme expression levels were the highest in UCB tissue and EJ cells. The inhibition of endogenous H2S biosynthesis decreased EJ cell viability and tumour growth in response to CDDP treatment. H2S levels and the associated biosynthetic enzymes were increased in human UCB tissue and cells compared with adjacent tissue and normal cells, which may have increased the resistance to CDDP-induced apoptosis in UCB. Therefore, H2S and its production may be an alternative therapeutic target for UCB.

Expression of CD74 in bladder cancer and its suppression in association with cancer proliferation, invasion and angiogenesis in HT-1376 cells.

The aim of the present study was to investigate the expression and potential roles of CD74 in human urothelial cell carcinoma of the bladder (UCB) in vitro and in vivo. CD74 and macrophage migration inhibitory factor (MIF) were located and assayed in normal and UCB samples and cell lines using immunostaining. CD74 was knocked down using CD74 shRNA lentiviral particles in HT-1376 cells. The proliferative, invasive potential and microvessel density (MVD) of knockdown-CD74 HT-1376 cells were analyzed in vitro or in vivo. The expression of CD74 in an additional high grade UCB J82 cell line was also verified in vivo. All experiments were repeated at least 3 times. The majority of muscle-invasive bladder cancer (MIBC) samples, and only one high grade UCB cell line, HT-1376, expressed CD74, compared with normal, non-muscle-invasive bladder cancer (NMIBC) samples and other cell lines. The levels of proliferation and invasion were decreased in the CD74 knockdown-HT-1376 cells, and western blotting assay indicated that the levels of proteins associated with proliferation, apoptosis and invasion in the cells were affected correspondingly by different treatments in vitro. The tumorigenesis and MVD assays indicated less proliferation and angiogenesis in the knockdown-HT-1376 cells compared with the scramble cells. Notably, J82 cells exhibiting no signal of CD74 in vitro presented the expression of CD74 in vivo. The present study revealed the potential roles of CD74 in the proliferation, invasion and angiogenesis of MIBC, and that it may serve as a potential therapeutic target for UCB, but additional studies are required.