Variant histology is associated with more non-urothelial tract recurrence but less intravesical recurrence for upper tract urothelial carcinoma after radical nephroureterectomy.

PURPOSE: To investigate the prognostic impact of variant histology (VH) on oncological outcomes in patients with upper urinary tract urothelial carcinoma (UTUC) who had undergone radical nephroureterectomy (RNU). PATIENTS AND METHODS: A total of 1239 patients with clinically localized UTUC who underwent RNU at a single institution between January 2005 and June 2020 were included. The VH was reviewed by a uro-pathologist at our institution. The Cox regression model was used to perform multivariate analysis, including VH and other established prognostic factors for post-RNU oncological outcomes (intravesical recurrence [IVR], non-urothelial recurrence, and cancer-specific death). RESULTS: Of the 1239 patients with UTUC, 384 patients (31%) were found to have VH. Advanced tumor stage, lymph node metastasis, high tumor grade, lymphovascular invasion, open surgery, and renal pelvis had a significantly larger proportion of UTUC with VH compared to pure UTUC (all p < 0.05). VH was an independent prognostic factor associated with less IVR identified by multivariate analysis, more non-urothelial recurrence, and more cancer-specific mortality. CONCLUSION: Patients with VH account for 31% with UTUC treated with RNU in this cohort. VH was an independent prognostic factor associated with more non-urothelial recurrence and cancer-specific mortality but less IVR.

MicroRNA-26a-5p Restoration Ameliorates Unilateral Ureteral Obstruction-Induced Renal Fibrosis in Mice Through Modulating TGF-ß Signaling.

Renal fibrosis is a hallmark of chronic and progressive renal diseases characterized by excessive fibroblast proliferation, extracellular matrix accumulation, and a loss of renal function, eventually leading to end-stage renal diseases. MicroRNA-26a-5p (miR-26a-5p) downregulation has been previously noted in the sera of unilateral ureteral occlusion (UUO)-injured mice, and exosome-mediated miR-26a-5p reportedly attenuated experimental pulmonary and cardiac fibrosis. This study evaluated the expression patterns of miR-26a in a human tissue microarray with kidney fibrosis and in tissues from a mouse model of UUO-induced renal fibrosis. Histologic analyses showed that miR-26a-5p was downregulated in human and mouse tissues with renal interstitial nephritis and fibrosis. Moreover, miR-26a-5p restoration by intravenous injection of a mimic agent prominently suppressed the expression of transforming growth factor ß1 (TGF-ß1) and its cognate receptors, the inflammatory transcription factor NF-κB, epithelial-mesenchymal transition, and inflammatory markers in UUO-injured kidney tissues. In vitro, miR-26a-5p mimic delivery significantly inhibited TGF-ß1-induced activation of cultured normal rat kidney NRK-49F cells, in terms of downregulation of TGF-ß1 receptors, restoration of the epithelial marker E-cadherin, and suppression of mesenchymal markers, including vimentin, fibronectin, and α-smooth muscle actin, as well as TGF-ß1/SMAD3 signaling activity. Our findings identified miR-26a-5p downregulation in kidney tissues with human interstitial nephritis and UUO-induced mouse kidney fibrosis. MiR-26a-5p restoration may exhibit an antifibrotic effect through the blockade of both TGF-ß and NF-κB signaling axes and is considered a novel therapeutic target for treating obstruction-induced renal fibrosis.

Impaired insulin signaling at the bladder mucosa facilitates metabolic syndrome-associated bladder overactivity in rats with maternal and post-weaning fructose exposure.

BACKGROUND/PURPOSE: Metabolic syndrome (MetS) and overactive bladder might share common pathophysiologies. Environmental fructose exposure during pre- and postnatal periods of rats may program MetS-associated bladder overactivity. We explored the dysregulated insulin signalling at bladder mucosa, as a common mechanism, in facilitating bladder overactivity in rats with MetS induced by maternal and post-weaning fructose diet. METHODS: Male offspring of Sprague-Dawley rats were subject into 4 groups by maternal and post-weaning diets (i.e., Control/Control, Fructose/Control, Control/Fructose and Fructose/Fructose by diets). Micturition behavior was evaluated. Acidic ATP solution was used to elicit cystometric reflex along with insulin counteraction. Concentration-response curves to insulin were plotted. The canonical signalling pathway of insulin was evaluated in the bladder mucosal using Western blotting. Levels of detrusor cGMP and urinary NO2 plus NO3 were measured. RESULTS: Male offspring with any fructose exposure presents traits of MetS and bladder overactivity. We observed all fructose exposure groups have the poor urodynamic response to insulin during ATP solution stimulation and poor insulin-activated detrusor relaxation in organ bath study. Compared to controls, the Control/Fructose and Fructose/Fructose groups showed the increased phosphorylation levels of IRS1 (Ser307) and IRS2 (Ser731); thus, suppressed the downstream effectors and urinary NOx/detrusor cGMP levels. The Fructose/Control group showed the compensatory increase of phospho-AKT (Ser473) and phospho-eNOS/eNOS levels, but decreased in eNOS, phospho-eNOS, urinary NOx, and detrusor cGMP levels. CONCLUSION: Our results show dysregulated insulin signalling at bladder mucosa should be a common mechanism of MetS-associated bladder overactivity programmed by pre-and postnatal fructose diet.

Prevalence and oncologic impact of chronic kidney disease for upper tract urothelial carcinoma in endemic area.

OBJECTIVE: This study aimed to assess the impact of preoperative chronic kidney disease (CKD) on the oncological outcomes of patients with upper tract urothelial carcinoma (UTUC) who underwent standard radical nephroureterectomy (RNU). METHODS: A total of 1172 UTUC patients who received RNU at a single center in Taiwan between February 2005 and August 2019 were included. The patients were categorized into two groups based on their preoperative CKD stage: CKD stage ≤3 (811 patients) and CKD stage >3 (361 patients). The estimated glomerular filtration rate (eGFR) was calculated using the Modification of Diet in Renal Disease (MDRD) formula. The study investigated the oncological outcomes, including intravesical recurrence, non-urothelial recurrence, and cancer-specific mortality, stratified by preoperative CKD status. RESULTS: The main findings indicated that UTUC patients with CKD stage >3 in Taiwan exhibited a higher proportion of females (p < 0.001), a greater history of concurrent bladder cancer (p = 0.003), more multifocal tumor behavior (p < 0.001), a higher incidence of carcinoma in situ (p = 0.008), increased rates of intravesical recurrence (p < 0.001), a lower prevalence of smoking history (p = 0.003), lower utilization of adjuvant chemotherapy (p < 0.001), reduced occurrence of non-urothelial recurrence (p < 0.001), and lower cancer-specific mortality (p = 0.006) compared to patients with CKD stage ≤3. Multivariate Cox regression analysis revealed significant differences in intravesical recurrence (p = 0.014) and non-urothelial recurrence (p = 0.006) between the CKD stage >3 and CKD stage ≤3 groups. The study also demonstrated that patients with concurrent bladder cancer and variant histology had higher rates of intravesical recurrence, non-urothelial recurrence, and cancer-specific mortality. The CKD stage >3 group exhibited lower rates of intravesical recurrence (p = 0.0014), higher rates of non-urothelial recurrence (p < 0.0001), and increased cancer-specific mortality (p = 0.0091) compared to the CKD stage ≤3 group in the 5-year free survival analysis. CONCLUSION: In Taiwan, UTUC patients with CKD stage >3 exhibit distinct characteristics compared to the general population with urothelial carcinoma. They are associated with a non-smoking status, a higher proportion of females, and less aggressive pathological features. Additionally, CKD stage >3 can serve as a clinical indicator for intravesical and non-urothelial recurrence. Further investigation into molecular aspects and treatment modifications for these patients is warranted.

Genetic Interference of FGFR3 Impedes Invasion of Upper Tract Urothelial Carcinoma Cells by Alleviating RAS/MAPK Signal Activity.

Upper tract urothelial cancer (UTUC) is a less common disease in Western countries but has a high level of prevalence in Asian populations. Compared to bladder cancer, unique etiologic and genomic factors are involved in UTUC. Fibroblast growth factor receptor 3 (FGFR3) up-regulation has been proposed as a promising target for bladder cancer therapy. In this study, we aimed to profile the expression of FGFR3 in Asian and Caucasian UTUC tissues and to evaluate the in vitro therapeutic efficacy of small interference RNA (siRNA)-mediated FGFR3 silencing in UTUC treatment. The FGFR3 expression levels in renal pelvis tissues and microarray sections from Asian and Caucasian patients with UTUC, respectively, were measured via immunohistochemistry. The BFTC-909 and UM-UC-14 UTUC cell lines were used to examine the effects of FGFR3 silencing on proliferation, migration, epithelial-mesenchymal transition (EMT) marker expression, and signaling machinery. FGFR3 expression increased as the TNM stage increased in both Asian and Caucasian UTUC tumors, and no statistical difference was identified between the two groups. In vitro studies demonstrated that FGFR3 siRNA delivery significantly inhibited proliferation and migration and suppressed the expression of EMT markers and transcription factors in UTUC cells. Mechanistically, FGFR3 silencing alleviated the constitutive expression of RAS and the phosphorylation of MAPK signaling mediators, including ERK1/2 and JNK1/2. FGFR3 silencing elicited an apoptosis-inducing effect similar to that of FGFR inhibition. Conclusion: siRNA-targeted FGFR3 expression may impede the expansion and invasion of UTUC cells by alleviating the RAS/MAPK signaling pathway. The genetic interference of FGFR3 expression via siRNA in UTUC cells may constitute a useful therapeutic strategy.

Unusual presentation of upper urinary tract urothelial carcinoma in Taiwan: Direct comparison from Taiwan-Japan UTUC Collaboration Cohort.

OBJECTIVES: To carry out a comparison of upper urinary tract urothelial carcinoma characteristics and behavior between patients in Taiwan and Japan. METHODS: A Taiwan urinary tract urothelial carcinoma cohort was obtained from Kaohsiung Chang Gung Memorial Hospital, and a Japan urinary tract urothelial carcinoma cohort from Hirosaki University Hospital. The inclusion criteria were urinary tract urothelial carcinoma patients who underwent radical nephroureterectomy. Those who received perioperative chemotherapy were excluded. Finally, 765 patients in the Taiwan cohort and 325 in the Japan cohort were analyzed. The end-point of this study was to study the natural course of urinary tract urothelial carcinoma within 5 years between these two groups. RESULTS: The main finding was that urinary tract urothelial carcinoma patients in Taiwan were younger (P < 0.001), more were women (P < 0.001), with low-stage disease (P < 0.001), with more chronic kidney disease (P < 0.001), with less smoking history (P < 0.001), with more bladder cancer history (P = 0.002), with more multifocal (P < 0.001) and less high-grade disease (P = 0.015), as well as less lymphovascular invasion (P < 0.001) and more squamous differentiation (P < 0.001). However, the multivariate Cox regression analysis showed no racial difference in oncologic outcome, such as intravesical recurrence, systemic recurrence or cancer-specific death in primary and propensity-matched cohorts. Bladder cancer history was found to be the most important factor predicting intravesical recurrences, whereas stage was strongly associated with systemic recurrence and cancer specific mortality. CONCLUSIONS: The clinical characteristics of urinary tract urothelial carcinoma in Taiwan are significantly different from those of urinary tract urothelial carcinoma in Japan. However, there is no racial difference in stage-specific oncologic outcome after standard nephroureterectomy.

Tract creation using plasma vaporization versus metal dilatation in percutaneous nephrolithotomy: A propensity score-matched analysis.

OBJECTIVES: To share our 10-year experience of tract creation by using plasma vaporization compared with metal dilatation in percutaneous nephrolithotomy. METHODS: We retrospectively reviewed the medical records of 230 patients who had undergone 244 percutaneous nephrolithotomy procedures at Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan, from January 2007 to December 2016, and divided the patients into the plasma (n = 130) and metal (n = 114) groups. All patients underwent percutaneous nephrolithotomy by either a bipolar resectoscope mounted with a plasma vaporization button electrode or metal dilatation for tract creation. Propensity score matching was applied to reduce selection bias. Perioperative and postoperative data analysis included procedure time, length of hospital stay, blood transfusion rate, any early and late complications, stone-free rate, renal function, and time of need for pain control. RESULTS: Before propensity score matching, there were significantly shorter hospital stay (2.6 vs 3.8 days, P < 0.01), less operating time (66.1 vs 108.1 min, P < 0.01) and no blood transfusion rate (0 vs 4 [3.5%], P = 0.031) in the plasma vaporization group. After propensity score matching, there was no statistically significant difference in the patients' baseline characteristics. There were significantly shorter hospital stay (odds ratio 0.46, 95% confidence interval 0.32-0.66; P < 0.001) and shorter average operating time (odds ratio 0.98, 95% confidence interval 0.97-0.99, P < 0.001) in the plasma vaporization group. CONCLUSIONS: In comparison with metal dilatation, the plasma vaporization technique is a safe and effective method for creating the nephrostomy tract for percutaneous nephrolithotomy, based on shorter postoperative stay, less operating time, zero blood transfusion rate, acceptable stone-free rate and no major complications.

Primary whole-gland ablation for localized prostate cancer with high-intensity focused ultrasound: The important predictors of biochemical recurrence.

OBJECTIVES: To identify predictive factors of biochemical recurrence for patients undergoing high-intensity focused ultrasound treatment for localized prostate cancer. METHODS: We retrospectively identified patients receiving whole-gland prostate ablation with high-intensity focused ultrasound for localized prostate cancer from 2009 to 2015. All the patients received pre-high-intensity focused ultrasound radical transurethral resection of the prostate. We included perioperative parameters as follows: age, preoperative prostate volume, stage of operation, initial prostate-specific antigen, T stage, postoperative prostate-specific antigen nadir, Gleason score, time to prostate-specific antigen nadir and the presence of prostate-specific antigen biochemical recurrence. Multivariable Cox regression and Kaplan-Meier analysis were used for investigating predictors of recurrence, and receiver operating characteristic analysis was used for the cut-off values of prostate-specific antigen nadir. RESULTS: Among 182 patients, 26.9% had prostate-specific antigen biochemical recurrence after high-intensity focused ultrasound during the median follow-up period of 32.21 months. Gleason score ≥7 (Gleason score 7, hazard ratio 2.877, P = 0.027), stage ≥T2b (T2b, hazard ratio 3.16, P = 0.027) and prostate-specific antigen nadir (hazard ratio 1.11, P < 0.001) were statistically significant, whereas there was no significance in prostate volume and initial prostate-specific antigen. We posit that a cut-off level of prostate-specific antigen nadir 0.43 ng/mL might be considered as an independent predictive factor for prostate-specific antigen biochemical recurrence in high-intensity focused ultrasound patients in multivariate analysis (P < 0.001, hazard ratio 7.39, 95% confidence interval 3.56-15.37), and created a new nadir-related prediction model for biochemical recurrence prediction. CONCLUSIONS: Postoperative prostate-specific antigen nadir of 0.43 ng/mL can be considered an important predictive factor for biochemical recurrence in primary whole-prostate gland high-intensity focused ultrasound treatment, and the nadir-related prediction model might provide a reference for early salvage treatment. Furthermore, Gleason score ≥7, stage ≥T2b might be associated with unfavorable outcomes, although prostate volume and higher initial prostate-specific antigen appear not to be associated with biochemical recurrence for the high-intensity focused ultrasound treatment.

MiR-30a-5p Inhibits Epithelial-to-Mesenchymal Transition and Upregulates Expression of Tight Junction Protein Claudin-5 in Human Upper Tract Urothelial Carcinoma Cells.

The involvement of microRNAs (miRNAs) in cancer development and their potential as prognostic biomarkers are becoming increasingly known. However, the signature of miRNAs and their regulatory roles in tumorigenesis of upper tract urothelial carcinoma (UTUC) remain to be elucidated. This study aimed to profile the miRNA expression pattern in UTUC tumor tissues and identify candidate miRNAs with prognostic and/or therapeutic functions. METHODS AND RESULTS: We collected 22 UTUC tissue and adjacent normal tissues samples from patients who underwent nephroureterectomy. The miRNAs signatures of three selected UTUC samples using next-generation sequencing showed that miR-30a-5p was significantly downregulated in UTUC tumors compared to adjacent normal tissues. The differentially-expressed miRNAs were specifically validated by quantitative real-time polymerase chain reaction. In addition, the miRNA expression signatures were analyzed with the transcriptome profile characterized by microarray. Further in vitro studies indicated that overexpression of miR-30a-5p significantly suppressed proliferation, migration, and epithelial-to-mesenchymal transition (EMT) in cultured BFTC-909 UTUC cells. As a potential target gene of miR-30a-5p in the tight junction pathway suggested by the pathway enrichment analysis, the reduced expression of tight junction protein claudin-5 in UTUC cells was demonstrated to be upregulated by miR-30a-5p genetic delivery. CONCLUSIONS: Taken together, our findings demonstrated that miR-30a-5p inhibits proliferation, metastasis, and EMT, and upregulates the expression of tight junction claudin-5 in UTUC cells. Thus, miR-30a-5p may provide a promising therapeutic strategy for UTUC treatment.

Predictors of prostate-specific antigen biochemical recurrence in patients undergoing primary whole-gland prostate cryoablation.

PURPOSE: Cryoablation has been proven as a less invasive, safe, and effective treatment for localized prostate cancer. We attempted to identify the predictors of biochemical recurrence after prostate cryoablation for localized prostate cancer in this study. METHODS: We reviewed 114 patients who underwent primary whole-gland prostate cryoablation for localized prostate cancer from October 2008 to March 2013. The perioperative parameters included age >70 years, initial prostate-specific antigen (PSA), preoperative prostate volume, Gleason score, T stage, D'Amico risk group, postoperative PSA nadir, time to PSA nadir, and PSA biochemical recurrence, defined by Phoenix definition (nadir plus 2 ng/mL). Receiver operating characteristic (ROC) analysis was used for the best cutoff value of PSA nadir for PSA biochemical recurrence. The parameters were analyzed in binary logistic regression and Kaplan-Meier analysis for PSA biochemical recurrence. RESULTS: A total of 31.6 % (N = 36) patients had PSA biochemical recurrence during the median follow-up of 34.87 ± 16.49 months. ROC analysis revealed that the best cutoff value for biochemical recurrence prediction was when the PSA nadir = 0.3 ng/mL. On multivariate analysis and Kaplan-Meier analysis, the D'Amico high-risk group [hazard ratio (HR) 6.552; p = 0.014], PSA nadir >0.3 ng/mL (HR 34.062; p < 0.001), and time to PSA nadir <3 months (HR 4.144; p = 0.021) were statistically significant for PSA biochemical recurrence. CONCLUSIONS: The D'Amico high-risk group, postoperative PSA nadir >0.3 ng/mL, and time to PSA nadir <3 months predict biochemical recurrence in primary whole-gland prostate cryoablation.

The role of laparoscopy-assisted renal autotransplantation in the treatment of primary ureteral tumor.

BACKGROUND: To evaluate the effect and safety of laparoscopy-assisted renal autotransplantation treatment for primary ureteral cancer (PUC). METHODS: Medical records of patients undergoing hand-assisted retroperitoneoscopic nephroureterectomy­extracorporeal total ureterectomy­renal autotransplantation­pyelocystostomy (Lap AutoTx) were analyzed. Demographic, intraoperative, and postoperative data were assessed. RESULTS: Fifteen patients diagnosed with PUC underwent this novel approach. Three kidneys were abandoned owing to the detection of residual cancer on the renal pelvic junction, surgeon's judgment on three severe atherosclerotic arteries, and palpable pelvic lymph nodes proven to be evidence of metastatic disease by frozen section analysis. Twelve patients (mean ± SD age 67.5 ± 7.5 years) were treated with Lap AutoTx for PUC successfully. No perioperative mortality occurred. One patient with solitary kidney experienced delayed graft function that required short-term hemodialysis. Three recurrent superficial diseases in three patients were treated with transurethral resection. The mean ± SD follow-up duration was 12.1 ± 6.7 months (range 3­24 months). The renal pelvicaliceal system was easily examined by flexible cystoscopy. CONCLUSIONS: Lap AutoTx is less invasive compared with the traditional two-incisional manner and can be performed safely even among elderly patients. Compared with other currently used therapies, this novel treatment can be used to successfully treat PUC with the added advantages of total resection of the ureteral lesion, preservation of the renal function, and simplification of follow-up procedures.Primary ureteral cancer (PUC) is an aggressive disease and has a poor prognosis.1 Studies have shown high prevalence and invasiveness of PUC in Taiwan.2,3 Nephroureterectomy with excision of the bladder cuff is still believed to be the gold standard treatment for PUC.4 Most PUC occurs among individuals aged more than 60 years, and most of these patients are also at high risk of chronic kidney disease (CKD).5,6 Nephroureterectomy not only results in excessive loss of renal function, but also puts the patient at risk of CKD, which contributes to the progression of end-stage renal disease requiring dialysis. In addition, diminished renal function after nephroureterectomy compromises the possible use of adjuvant chemotherapy for advanced disease.Endoscopic surgery (ES) and segmental resection (SR) can be used for renal preservation in PUC cases, but there still are limitations to these approaches, and indefinite invasive ureteroscopy is required during follow-up. Only a few studies have focused on renal autotransplantation (AutoTx) after extracorporeal total ureterectomy (ETU) for PUC. This type of treatment possesses advantages of total resection of malignant ureteral lesions, preservation of renal function, and simplification of follow-up protocols. In two reported case series, all cases involved surgery performed with the traditional 2-incision approach, and only a few cases involved pure PUC.7,8 We have reported that hand-assisted retroperitoneoscopic nephroureterectomy (HARNU) for the treatment of PUC is less invasive and results in better functional outcomes with fewer complications and comparable oncologic control compared with open nephroureterectomy.9 In this study, we report our experience of this treatment combined with ETU and AutoTx for pure PUC.

Subclassification of upper urinary tract urothelial carcinoma by the neutrophil-to-lymphocyte ratio (NLR) improves prediction of oncological outcome.

OBJECTIVE: To examine the potential role of the neutrophil-to-lymphocyte ratio (NLR) for subclassification of localised upper urinary tract urothelial carcinoma (UUT-UC). PATIENTS AND METHODS: From 2004 to 2010, 234 patients with localised UUT-UC underwent radical nephroureterectomy (RNU). NLRs were only obtained under afebrile conditions before RNU. Patients that underwent neoadjuvant or adjuvant chemotherapy were excluded. The prognostic impact of the NLR was assessed using the log-rank test and multivariate analyses. RESULTS: Only advanced pathological stage (>T2) and a NLR of >3 were independently associated with metastasis (P < 0.001 and P = 0.02, respectively) and cancer-specific mortality (P = 0.002 and P = 0.006, respectively). The use of a NLR of >3 further identified a poor prognostic group, especially in patients with T3 UUT-UC for metastasis-free survival and cancer-specific survival (log-rank test, both P < 0.001). CONCLUSIONS: For localised UUT-UC, pathological stage and preoperative NLR independently predict systemic recurrence and cancer-specific death after RNU. Using the NLR for subclassification of T3 UUT-UC seems to further identify a poor prognostic group and may help with clinical decisions about treatment intervention in clinical practice.

Oncological impact of endoscopic bladder cuff management during nephroureterectomy varies according to upper urinary tract tumor location.

OBJECTIVES: To compare the oncological outcome between extravesical excision and transurethral excision for bladder cuff management in patients undergoing nephroureterectomy with upper urinary tract urothelial cancer. METHODS: From January 2005 to December 2010, 396 patients were enrolled in the present retrospective study. Nephroureterectomy was carried out either by endoscopic or extravesical bladder cuff excision. The oncological outcome between these two procedures was analyzed in patients with different tumor locations. RESULTS: The average age of the patients was 66.41 ± 10.52 years, and the median follow-up duration was 40.65 ± 23.84 months. For upper urinary tract urothelial cancer management, extravesical bladder cuff excision was carried out in 240 patients, whereas the endoscopic method was carried out in 156 patients. Previous bladder cancer is still the most independent predictor for bladder recurrence (P < 0.001). In addition, endoscopic bladder cuff management for low ureteral tumor was also independently associated with more bladder tumor recurrence (P = 0.017). Non-organ confined pathological stage still independently predicted metastasis (P < 0.001) and cancer-specific death (P < 0.001). CONCLUSIONS: There are similar oncological outcomes after nephroureterectomy combined with extravesical or endoscopic bladder cuff management for patients with upper urinary tract urothelial cancer above the low ureter. However, there is a higher incidence of bladder tumor recurrence for the low ureteral tumor after nephroureterectomy with endoscopic bladder cuff excision.

Diagnostic ureteroscopy independently correlates with intravesical recurrence after nephroureterectomy for upper urinary tract urothelial carcinoma.

BACKGROUND: Little is known about the effects of diagnostic ureteroscopy on intravesical recurrence after nephroureterectomy. METHODS: This study was designed to determine the effect of diagnostic ureteroscopy on intravesical recurrence after nephroureterectomy. From 2004 to 2010, 446 patients underwent nephroureterectomy for upper urinary tract cancer at our tertiary medical center. We included 115 patients who underwent preoperative diagnostic ureteroscopy and 281 patients who did not. This study analyzed the impact of the reported risk factors and diagnostic ureteroscopy for intravesical recurrence after nephroureterectomy by multivariate Cox regression model. RESULTS: The rates of metastasis and cancer-specific mortality did not differ significantly between the two groups. Diagnostic ureteroscopy was associated with a higher incidence of intravesical recurrence in patients with (p=0.02) and without (p=0.016) a previous history of bladder cancer. Ureter tumor biopsy (p=0.272) and ureter involvement (p=0.743) were not associated with the rate of intravesical recurrence in this study. Multivariate Cox regression analysis showed that only bladder cancer history (p<0.001), multifocal tumor (p=0.05), and diagnostic ureteroscopy (p=0.05) were independently associated with intravesical recurrence. CONCLUSIONS: Diagnostic ureteroscopy for upper urinary tract cancer was not associated with metastasis and cancer-specific mortality. However, ureteroscopy was associated with an increased incidence of intravesical tumor recurrence. Methods of prevention should be considered to decrease intravesical recurrence and avoid repeated surgical interventions or the development of advanced bladder disease in patients at risk.

Severity of hydronephrosis correlates with tumour invasiveness and urinary bladder recurrence of ureteric cancer.

OBJECTIVES: To explore the prognostic role of hydronephrosis grade in patients with pure ureteric cancer. PATIENTS AND METHODS: The study included 162 patients with pure ureteric cancer who were treated between January 2005 and December 2010 at a single tertiary referral centre. The association between hydronephrosis grade with pathological findings and oncological outcomes was assessed using multivariate Cox regression analysis. RESULTS: Hydronephrosis grade >2 was independently associated with non-organ-confined ureteric cancer (P = 0.003). Hydronephrosis grade <2 was highly prevalent in organ-confined disease. Hydronephrosis grade >2 and bladder cancer history independently predict bladder cancer recurrence (P = 0.021 and P = 0.002, respectively) Hydronephrosis of grade >2 was found to be associated with local and distant recurrence only in univariate analysis; non-organ-confined pathology independently predicted local and distant oncological failure (P ≤ 0.001 and P = 0.002, respectively). CONCLUSIONS: Hydronephrosis grade >2 is associated with non-organ-confined ureteric cancer and with bladder cancer recurrence. Non-organ-confined pathology is still the most important predictor for local and distant oncological failure.

Treatment outcomes with radium-223 in docetaxel-naïve versus docetaxel-treated metastatic castration-resistant prostate cancer patients: Real-world evidence from Taiwan.

While radium (Ra)-223 is among the multiple, known life-prolonging treatments in bone-predominant metastatic castration-resistant prostate cancer (mCRPC), optimal treatment sequencing has not been determined, particularly in the Asia-Pacific context. Hence, we aimed to compare treatment outcomes of docetaxel-naïve and post-docetaxel mCRPC patients undergoing Ra-223 therapy in Taiwan. Using a single-center retrospective cohort design, we reviewed records of adult patients receiving Ra-223 for bone-metastatic mCRPC from 2018 to 2021. Patients were categorized into docetaxel-naïve or post-docetaxel groups based on history of docetaxel use preceding Ra-223. We compared the 2 groups in terms of all-cause death, 6-cycle treatment completion, and the following secondary outcomes: pain control, change in biochemical parameters (prostate-specific antigen, lactate dehydrogenase, alkaline phosphatase), biochemical response, and treatment-emergent adverse events. We performed total population sampling and a complete case analysis. We included 48 patients (25 docetaxel-naïve, 23 post-docetaxel) in the study. The mean follow-up duration was 12.4 months for the entire cohort. The docetaxel-naïve group exhibited a significantly lower all-cause mortality rate versus the post-docetaxel group (40.0% vs 78.3%, P = .02), as well as a significantly higher treatment completion rate (72.0% vs 26.1%, P < .01). We did not find significant differences in pain control, change in biochemical parameters, biochemical response, or hematologic treatment-emergent adverse events between the 2 groups. However, the docetaxel-naïve group had a numerically higher pain control rate, numerically greater improvements in alkaline phosphatase and prostate-specific antigen, and numerically lower rates of grade ≥ 3 neutropenia and grade ≥ 3 thrombocytopenia than the post-docetaxel group. Use of Ra-223 in docetaxel-naïve patients with mCRPC led to lower mortality and higher treatment completion than post-docetaxel use. Our study adds preliminary real-world evidence that Ra-223 may be used safely and effectively in earlier lines of treatment for bone-predominant mCRPC. Further large-scale, longer-term, and controlled studies are recommended.

The prognostic impact of lymphovascular invasion for upper urinary tract urothelial carcinoma: A propensity score-weighted analysis.

Lymphovascular invasion (LVI) predicts poor survival in patients with pathologically localized or locally advanced upper urinary tract urothelial carcinoma (UT-UC). However, LVI is associated with high tumor grade, tumor necrosis, advanced tumor stage, tumor location, concomitant carcinoma in situ, lymph node metastasis, and sessile tumor architecture. These factors might interfere with the analysis of the impact of LVI on oncological prognosis. To address this, this study aimed to clarify the relationship between LVI and patient prognosis in UT-UC using propensity score weighting. Data were collected from 789 patients with UT-UC treated with radical nephroureterectomy without chemotherapy. We evaluated the significance of LVI in predicting metastasis-free survival (MFS), cancer-specific survival (CSS), and overall survival (OS) using propensity score weighting. All weighted baseline characteristics included in the propensity score model were balanced between the LVI (+) and LVI (-) groups. The MFS, CSS, and OS were all significantly poorer in the LVI (+) group. For patients without LVI, the 5-year MFS, CSS, and OS rates were 65.3%, 73.1%, and 67.3%, respectively, whereas the corresponding rates were 50.2%, 63.8 %, and 54.6%, respectively, for patients with LVI. (all P < .001). For patients without LVI, the 10-year MFS, CSS, and OS rates were 61.5%, 69.6%, and 59.2%, respectively, whereas those for patients with LVI were 44.5%, 57.0%, and 42.7%, respectively (all P < .001). LVI is an important pathological feature that predicts metastasis development and worse survival outcome after radical surgery in UT-UC patients.

High-intensity diode laser in combination with bipolar transurethral resection of the prostate: a new strategy for the treatment of large prostates (>80 ml).

BACKGROUND AND OBJECTIVE: The ideal treatment of large prostates with symptomatic benign prostatic hyperplasia (BPH) remains controversial. We compare the efficacy and safety of monopolar transurethral resection of the prostate (TURP) with high-intensity diode laser in combination with bipolar TURP (DL + b-TURP) in the treatment of large prostates. MATERIALS AND METHODS: We retrospectively analyzed all patients with lower urinary tract symptoms (LUTS) secondary to BPH with prostates larger than 80 ml, undergoing monopolar TURP (n = 36) or DL + b-TURP (n = 37) between January 2008 and March 2010. The preoperative and follow-up functional parameters including International Prostate Symptom Score (IPSS), post-void residual urine (PVR), maximum flow rate (Q(max) ), quality of life score (QoLs), prostate size, and prostate-specific antigen (PSA) were assessed. The operative data, peri- and post-operative complications were also recorded. RESULTS: The demographic data were comparable between the two groups. Preoperative prostate volume was 110.8 ± 28.9 ml in the DL + b-TURP group and 103.7 ± 31.2 ml in the TURP group. TURP group had significantly shorter operative time; however, the catheterization time and hospital stay were in favor of the DL + b-TURP group (P < 0.001). The decrease in hemoglobin was statistically significantly greater in the TURP group. Late complications were also comparable. Both groups could achieve significant improvements in functional outcomes during the follow-up of 24 months. CONCLUSIONS: With regard to the operative safety and functional results, high-intensity diode laser combined with bipolar TURP is feasible for BPH treatment with large prostates.

The lowest level of tumor involvement is a significant prognostic factor for upper tract urothelial carcinoma after radical nephroureterectomy: A large retrospective cohort study.

Purpose: To evaluate the prognostic impact of the lowest level of tumor location for upper tract urothelial carcinoma (UTUC) treated with radical nephroureterectomy (RNU). Materials and methods: Data were collected from patients with UTUC treated with RNU (01/2005- 06/2020) at a single center in Taiwan. Patients were stratified by the lowest level of tumor location into three groups: renal pelvis only (RPO), above upper ureter (AUU), and below upper ureter (BUU). We compared characteristics between groups and examined the association of the lowest level of tumor involvement with intravesical recurrence (IVR), systemic metastasis (SM), and cancer-specific mortality (CSM). Results: Overall, 1239 patients (542 RPO, 260 AUU, 437 BUU) were enrolled. Concurrent bladder cancer, multifocality, tumor architecture, lymphovascular invasion, carcinoma in situ, and variant histology were significantly different across different tumor locations. BUU had worse five-year intravesical recurrence (IVR), systemic metastasis (SM) and cancer-specific mortality (CSM) (p < 0.001, p = 0.056 and p = 0.13, respectively). In multivariable models, the lowest level of tumor involvement was an independent predictor of IVR (AUU hazard ratio (HR) = 1.52, p = 0.007; BUU HR = 1.75, p < 0.001), but only BUU was an independent predictor of SM (HR = 1.61, p = < 0.001) and CSM (HR = 1.51, p = 0.008). Conclusion: The lowest level of tumor involvement in UTUC, especially BUU, was associated with a higher risk of IVR, SM and CSM. Assessment of the lowest level of tumor involvement after RNU may help identify patients who require more intensive follow-up.

MiR-26a-5p as a useful therapeutic target for upper tract urothelial carcinoma by regulating WNT5A/ß-catenin signaling.

The role of miRNAs in cancer and their possible function as therapeutic agents are interesting and needed further investigation. The miR-26a-5p had been demonstrated as a tumor suppressor in various cancers. However, the importance of miR-26a-5p regulation in upper tract urothelial carcinoma (UTUC) remains unclear. Here, we aimed to explore the miR-26a-5p expression in UTUC tissues and to identify its regulatory targets and signal network involved in UTUC tumorigenesis. The miR-26a-5p expression was validated by quantitative real-time polymerase chain reaction (qPCR) using renal pelvis tissue samples from 22 patients who were diagnosed with UTUC and 64 cases of renal pelvis tissue microarray using in situ hybridization staining. BFTC-909 UTUC cells were used to examine the effects of miR-26a-5p genetic delivery on proliferation, migration and expression of epithelial-to-mesenchymal transition (EMT) markers. MiR-26a-5p was significantly down-regulated in UTUC tumors compared to adjacent normal tissue and was decreased with histological grades. Moreover, restoration of miR-26a-5p showed inhibition effects on proliferation and migration of BFTC-909 cells. In addition, miR-26a-5p delivery regulated the EMT marker expression and inhibited WNT5A/ß-catenin signaling and expression of downstream molecules including NF-κB and MMP-9 in BFTC-909 cells. This study demonstrated that miR-26a-5p restoration may reverse EMT process and regulate WNT5A/ß-catenin signaling in UTUC cells. Further studies warranted to explore the potential roles in biomarkers for diagnostics and prognosis, as well as novel therapeutics targets for UTUC treatment.