Age related trends in the utilization of neoadjuvant chemotherapy for muscle invasive bladder cancer.

PURPOSE: The current standard of care for muscle invasive bladder cancer (MIBC) is neoadjuvant chemotherapy (NAC) followed by radical cystectomy (RC). Previous research has shown under-utilization of NAC for treatment of MIBC, especially among the elderly. Our aim was to stratify NAC use by decade of life and analyze trends in use over time along with recording pathologic downstaging and perioperative outcomes. MATERIALS AND METHODS: The National Cancer Database was queried for patients with cT2-4NanyM0 MIBC treated with RC from 2010 to 2016 with urothelial carcinoma. Nineteen thousand nine hundred fifty seven patients met criteria for analysis. We retrospectively analyzed trends in use of NAC, readmission rate, mortality rate, and pathologic downstaging with NAC all stratified by decade of life. RESULTS: Of the 19,957 patients treated with RC for MIBC, only 30.9% underwent NAC. There was a statistically significant increase in NAC use across all age groups from 2010 to 2016. Receipt of NAC was associated with decreased age on univariate analysis (P < 0.001) and on logistic regression (OR: 0.617 for age 70-79, OR: 0.221 for age ≥80 vs. age <60; P < 0.001). Patients receiving NAC were more likely to exhibit pathologic downstaging at time of RC (OR: 3.907; P < 0.001), and this trend held for each age group examined. Among patients receiving NAC, the risk of 30 and 90-day mortality was associated with increasing age; however, age was not associated with 30-day readmission for those receiving NAC. CONCLUSION: Rates of NAC use prior to RC have increased among all age groups with the lowest utilization rate among the elderly. NAC use was associated with greater pathologic downstaging in all age groups. These data show a promising trend in the uptake of the gold standard for treatment of MIBC; however, the underlying etiology of differing rates of NAC utilization remains to be determined.

Association between cigarette smoke exposure and urinary bladder cancer in Scottish terriers in a cohort study.

Canine urothelial carcinoma (UC) initially responds favorably to treatment, but is ultimately lethal in most cases. Research to identify modifiable risk factors to prevent the cancer is essential. The high breed-associated risk for UC, e.g. 20-fold higher in Scottish terriers, can facilitate this research. The objective was to identify environmental and host factors associated with UC in a cohort of Scottish terriers. Information was obtained through dog owner questionnaires for 120 Scottish terriers ≥ 6 years old participating in a bladder cancer screening study, with comparisons made between dogs that did or did not develop UC during the 3 years of screening. Univariable models were constructed, and variables with P < 0.20 were included when building the multivariable model, and then removed using a backward stepwise procedure. P < 0.05 was considered statistically significant. Urine cotinine concentrations were measured by liquid chromatography-mass spectrometry to further investigate potential cigarette smoke exposure. Biopsy-confirmed UC which was found in 32 of 120 dogs, was significantly associated with the dogs living in a household with cigarette smokers (odds ratio [OR], 6.34; 95 % confidence intervals [CI], 1.16-34.69; P = 0.033), living within a mile of a marsh or wetland (OR, 21.23; 95 % CI, 3.64-123.69; P = 0.001), and history of previous bladder infections (OR, 3.87; 95 % CI, 1.0-14.98; P = 0.050). UC was diagnosed in 18 of 51 dogs (35.3 %) with quantifiable cotinine concentrations, and six of 40 dogs (15.0 %) without quantifiable cotinine concentrations in their urine (P = 0.0165). In conclusion, the main modifiable risk factor for UC in this cohort of dogs was exposure to second-hand tobacco smoke.

The clinical impact of ureteroscopy for upper tract urothelial carcinoma: A multicenter study.

BACKGROUND: With the development of kidney-sparing surgery and neoadjuvant chemotherapy, ureteroscopic biopsy (URSBx) has become important for the management of upper tract urothelial carcinoma (UTUC). METHODS: We retrospectively analyzed data from 744 patients with UTUC who underwent radical nephroureterectomy (RNU), stratified into no ureteroscopy (URS), URS alone, and URSBx groups. Intravesical recurrence-free survival (IVRFS) was examined using the Kaplan-Meier method. We conducted Cox regression analyses to identify risk factors for IVR. We investigated differences between clinical and pathological staging to assess the ability to predict the pathological tumor stage and grade of RNU specimens. RESULTS: Kaplan-Meier curves and multivariate Cox regression revealed significantly more IVR and inferior IVRFS in patients who underwent URS and URSBx. Superficial, but not invasive, bladder cancer recurrence was more frequent in the URS and URSBx groups than in the no URS group. Clinical and pathological staging agreed for 55 (32.4%) patients. Downstaging occurred for 48 (28.2%) patients and clinical understaging occurred for 67 (39.4%) patients. Upstaging to muscle-invasive disease occurred for 39 (35.8%) of 109 patients with ≤cT1 disease. Clinical and pathological grading were similar for 72 (42.3%) patients. Downgrading occurred for 5 (2.9%) patients, and clinical undergrading occurred for 93 (54.7%) patients. CONCLUSION: URS and URSBx instrumentation will be risk factors for superficial, but not invasive, bladder cancer recurrence. Clinical understaging/undergrading and upstaging to muscle-invasive disease occurred for a large proportion of patients with UTUC who underwent RNU. These data emphasize the challenges involved in accurate UTUC staging and grading.

High grade urothelial carcinoma in kidney transplant patients with a history of BK viremia - Just a coincidence?

INTRODUCTION: Kidney transplant recipients (KTR) have a three-to-four-fold increased risk of developing urothelial carcinoma (UC) compared to the general population. BK polyoma virus (BKV) infection is known to affect approximately 15% of KTR. In vitro models support a potential pathogenic role for BKV in the development of UC. We describe a series of UC in kidney transplant recipients. METHODS: Electronic patient records were searched to identify KTR with UC who had undergone kidney only or simultaneous kidney and pancreas transplantation in a single UK center between 2009 and 2015. Where available, stored pathological samples were retrieved, re-examined and stained for SV40 as a marker of BKV using standard staining protocols for kidney biopsy samples. RESULTS: Fourteen KTR had developed UC post-transplant. Of these, 10 KTR had a history of BKV infection post-transplant. Six of these 10 KTR developed a rare micropapillary tumor subtype of UC which is typically only found in <1% of UC cases. All six micropapillary tumor samples stained positive for SV40, including samples from metastases. Three tumor samples were available from the four KTR with no history of BKV infection and were not micropapillary subtype and were negative for SV40. Three micropapillary tumors from immunocompetent patients were examined as controls and were negative for SV40. CONCLUSIONS: These findings would support a pathogenic role for BK virus in the development of rare micropapillary subtype urothelial tumors in the kidney transplant population.

External beam radiotherapy combination is a risk factor for bladder cancer in patients with prostate cancer treated with brachytherapy.

PURPOSE: To investigate the risk of bladder cancer (BCa) in patients treated with brachytherapy for prostate cancer (PCa). METHODS: We retrospectively analyzed 583 patients with PCa who underwent brachytherapy with or without external beam radiotherapy (EBRT). We analyzed the disease-free survival (DFS) of BCa in patients with PCa who underwent brachytherapy with or without EBRT. We performed multivariate Cox regression analyses of DFS using age, EBRT, and Brinkman index (BI) score (number of cigarettes smoked per day × number of years smoking) ≥ 200 as variables for BCa after brachytherapy. RESULTS: Fourteen patients (2.4%) developed BCa after brachytherapy with or without EBRT. The percentage of high-grade urothelial carcinoma (UC) was 63.6%. A total of 85.7% of patients had non-muscle invasive BCa, and 14.3% of patients had muscle invasive BCa. DFS was longer in brachytherapy monotherapy than in combination therapy (brachytherapy + EBRT). Multivariate Cox regression analysis showed that a BI score ≥ 200 (Hazard Ratio (HR 8.61; 95% Confidence Interval (CI) 1.12-65.98) and EBRT combination (HR 3.29; 95% CI 1.03-10.52) were significantly associated with BCa development in patients with PCa treated with brachytherapy. Furthermore, patients with BI score ≥ 200 and EBRT combination had a significantly higher risk of BCa compared with patients with BI score < 200 (HR Log-rank test P = 0.010). CONCLUSION: Most cases of BCa after brachytherapy with or without EBRT are high grade and invasive. We hypothesized that the EBRT combination might be a risk factor for BCa in patients with PCa who underwent brachytherapy.

De novo upper tract urothelial carcinoma after renal transplantation: a single-center experience in China.

BACKGROUND: Long-term prognosis and risk factors of de novo upper tract urothelial carcinoma after renal transplantation were rarely studied. Thus, the aim of this study was to investigate the clinical features, risk factors, and long-term prognosis of de novo upper tract urothelial carcinoma after renal transplantation, especially the impact of aristolochic acid on tumor, using a large sample. METHODS: 106 patients were enrolled in retrospective study. The endpoints included overall survival, cancer-specific survival, bladder or contralateral upper tract recurrence-free survival. Patients were grouped according to aristolochic acid exposure. Survival analysis was performed using Kaplan-Meier curve. Log-rank test was used to compare the difference. Multivariable cox regression was conducted to evaluate the prognostic significance. RESULTS: Median time from transplantation to development of upper tract urothelial carcinoma was 91.5 months. Cancer-specific survival rate at 1, 5, 10 years was 89.2%, 73.2%, 61.6%. Tumor staging (≥ T2), lymph node status (N +) were independent risk factors for cancer-specific death. Contralateral upper tract recurrence-free survival rate at 1, 3, 5 years was 80.4%, 68.5%, 50.9%. Aristolochic acid exposure was independent risk factor for contralateral upper tract recurrence. The patients exposed to aristolochic acid had more multifocal tumors and higher incidence of contralateral upper tract recurrence. CONCLUSION: Both higher tumor staging and positive lymph node status were associated with a worse cancer-specific survival in patients with post-transplant de novo upper tract urothelial carcinoma, which highlighted the importance of early diagnosis. Aristolochic acid was associated with multifocality of tumors and higher incidence of contralateral upper tract recurrence. Thus, prophylactic contralateral resection was suggested for post-transplant upper tract urothelial carcinoma, especially for patients with aristolochic acid exposure.

Identification of prognostic and therapeutic value of CC chemokines in Urothelial bladder cancer: evidence from comprehensive bioinformatic analysis.

BACKGROUND: Urothelial bladder cancer (BC) is one of the most prevalent malignancies with high mortality and high recurrence rate. Angiogenesis, tumor growth and metastasis of multiple cancers are partly modulated by CC chemokines. However, we know little about the function of distinct CC chemokines in BC. METHODS: ONCOMINE, Gene Expression Profiling Interactive Analysis (GEPIA), Kaplan-Meier plotter, cBioPortal, GeneMANIA, and TIMER were used for analyzing differential expression, prognostic value, protein-protein interaction, genetic alteration and immune cell infiltration of CC chemokines in BC patients based on bioinformatics. RESULTS: The results showed that transcriptional levels of CCL2/3/4/5/14/19/21/23 in BC patients were significantly reduced. A significant relation was observed between the expression of CCL2/11/14/18/19/21/23/24/26 and the pathological stage of BC patients. BC patients with high expression levels of CCL1, CCL2, CCL3, CCL4, CCL5, CCL8, CCL13, CCL15, CCL17, CCL18, CCL19, CCL22, CCL25, CCL27 were associated with a significantly better prognosis. Moreover, we found that differentially expressed CC chemokines are primarily correlated with cytokine activity, chemokines receptor binding, chemotaxis, immune cell migration. Further, there were significant correlations among the expression of CC chemokines and the infiltration of several types of immune cells (B cells, CD8+ T cells, CD4+ T cells, macrophages, neutrophils, and dendritic cells). CONCLUSIONS: This study is an analysis to the potential role of CC chemokines in the therapeutic targets and prognostic biomarkers of BC, which gives a novel insight into the relationship between CC chemokines and BC.

Management of Urological Malignancy in Heart and Lung Transplant Recipients: An Irish National Cohort Study.

OBJECTIVES: Following the first hearttransplantin Ireland in 1985, there have been almost 700 deceased donor heart and lung transplants carried out in Ireland at a single institution. In this retrospective study, our aim was to assess the incidence and management of urological malignancies arising in this national cohort. MATERIALS AND METHODS: Our retrospective analysis included all heart and lung transplant recipients identified as having a urological malignancy. Primary outcome variables included incidence, management, and clinical outcomes following cancer diagnosis. RESULTS: A total of 28 patients (4.1%) had radiologically or histologically confirmed urological malignancies. Fourteen patientswere diagnosedwith prostate cancer, with 13 who underwent radical treatment. Eight renal cell carcinomas were diagnosed in heart transplant recipients, with 5 who underwent nephrectomies. Two bladder cancers and 1 uppertract urothelial carcinoma were diagnosed and managed with endoscopic resection, radiotherapy, and nephroureterectomy, respectively. Two patients were diagnosed with penile squamous cell carcinoma and managed with radical surgery and lymph node dissection/sampling, with 1 patient receiving adjuvant chemoradiotherapy. CONCLUSIONS: Urological malignancies are not common in heart and lung transplant recipients; however, standard management options can be safely used, including radical surgery. Prospective monitoring of these patients and potential considerations for screening should be maintained.

ZHX3 promotes the progression of urothelial carcinoma of the bladder via repressing of RGS2 and is a novel substrate of TRIM21.

Clinically, patients with urothelial carcinoma of the bladder (UCB) with tumor metastasis are incurable. To find new therapeutic strategies, the mechanisms underlying UCB invasion and metastasis should be further investigated. In this study, zinc finger and homeobox 3 (ZHX3) was first screened as a critical oncogenic factor associated with poor prognosis in a UCB dataset from The Cancer Genome Atlas (TCGA). These results were also confirmed in a large cohort of clinical UCB clinical samples. Next, we found that ZHX3 could promote the migration and invasion capacities of UCB cells both in vitro and in vivo. Mechanistically, coimmunoprecipitation (coIP) and mass spectrometry (MS) analysis indicated that ZHX3 was a target of tripartite motif 21 (TRIM21), which mediates its ubiquitination, and subsequent degradation. Notably, RNA-seq analysis showed that ZHX3 repressed the expression of regulator of G protein signaling 2 (RGS2). Generally, our results suggest that ZHX3 plays an oncogenic role in UCB pathogenesis and might serve as a novel therapeutic target for UCB.

Experience of a tertiary referral center in managing bladder cancer in conjunction with neurogenic bladder.

STUDY DESIGN: Case series. OBJECTIVES: The aim of this study was to present our experience with the management of bladder cancer (BCa) in individuals followed for neurogenic bladder (NB). SETTING: An Italian tertiary referral center for NB. METHODS: We retrospectively collected all pre-operative, intra-operative, and post-operative data of our NB cases with BCa, diagnosed from 2004 to 2019. RESULTS: We included ten cases: eight with acquired spinal cord injury (SCI) and two with myelomeningocele (MMC). Considering individuals with acquired SCI, the median age at BCa diagnosis and time since SCI were 53 and 34 years, respectively. One out of seven cases had positive urine cytology. All cases underwent a radical cystectomy, diagnosing squamous cell carcinoma (SCC) and transitional cell carcinoma in 60 and 40% cases, respectively. Surgical-related complications occurred after 90% procedures. Three out of eight individuals with acquired SCI died 2, 12, and 80 months after the diagnosis. Both individuals with MMC presented no evidence of disease after 24 and 27 months. CONCLUSIONS: BCa in individuals with NB proved to be associated with a diagnosis at an advanced stage and a high rate of surgical complications. In this population we advocate annual genitourinary ultrasound exam and urine cytology, and cystoscopy in all cases of macrohematuria. Considering the low accuracy of urine cytology and the difficult-to-interpret inflamed bladder walls at cystoscopy in NB, a patient-tailored follow-up schedule based on specific risk factors (e.g., smoking status, indwelling urinary catheter) is mandatory to diagnose and treat BCa at an early stage.

CT Findings of Upper Urinary Tract Lesions in IgG4-Related Disease: Comparison With Urothelial Carcinoma.

OBJECTIVE. IgG4-related disease is characterized by extensive infiltration of IgG4-positive plasma cells and fibrosis in various organs. The objective of this study is to investigate CT findings of IgG4-related lesions involving the upper urinary tract and compare them with those of urothelial carcinomas. MATERIALS AND METHODS. This study reviewed pretreatment CT images of 13 consecutive patients with IgG4-related disease with upper urinary tract lesions and 80 consecutive patients with urothelial carcinomas. The findings assessed were laterality, location, growth pattern, margins, internal structure, presence of calcification and lipid component, enhancement pattern, and extraurinary findings. RESULTS. Bilaterality (p < 0.0001), an extramural growth pattern (p < 0.0001), a greater number of affected segments (p = 0.04), and a gradual dynamic enhancement pattern (p < 0.001) were significantly more frequent in patients with IgG4-related disease. With regard to extraurinary findings, paraaortic fat stranding (p = 0.03), presacral fat stranding (p < 0.001), fat stranding of the pelvic walls (p < 0.001), and aortic involvement (p < 0.001) were seen more frequently in patients with IgG4-related disease; on the other hand, there was no statistically significant difference in terms of frequency of pancreatic involvement. Hydronephrosis and renal involvement were seen more frequently in patients with urothelial carcinoma, although the difference was not statistically significant. CONCLUSION. CT findings suggestive of IgG4-related upper urinary tract lesions in comparison with urothelial carcinoma are bilateral and have a longer urinary tract involvement and exhibit an extramural growth pattern, ill-defined margins, a gradual enhancement pattern, aortic involvement, and fat stranding in the paraaortic, presacral, or pelvic wall areas.

Does muscle invasive bladder cancer following pelvic radiotherapy portend worse prognosis? A seer-based study.

BACKGROUND: Although emerging evidence demonstrates increased risk of secondary bladder cancer following pelvic radiotherapy, the aggressiveness of these tumors is not well-characterized. MATERIALS AND METHODS: A search of the Surveillance, Epidemiology, and End Results (SEER) 18 Database, identified 25,734 patients diagnosed with bladder cancer following definitive therapy for previous pelvic malignancy. Kaplan-Meier curve analyses were utilized to determine overall survival with significance set at p<0.05. RESULTS: Of the 25,734 patients, 11,376 (44.2%) received radiation treatment for their first cancer. Overall survival of bladder cancer was found to be 80%, 69.5%, and 49.2% at 1,2 and 5 years, respectively. There was no significant survival difference between groups whose first cancer was treated with or without radiation (p=0.8). A survival advantage was seen for the bladder cancer patients not treated with radiation for cervical (p=0.004), uterine (p=0.0006), and vaginal cancers (p<0.0001). Bladder cancer patients treated with radiation for prostate cancer showed a survival advantage (p=0.002). The average time to second cancer diagnosis was 6.5±6.1 years. Patients treated with radiation for first primary cancer showed a longer time to second cancer (7.2±6.0 years) compared to those treated without radiation (5.9±6.0 years) (p<0.01). CONCLUSION: Patients with prior history of female cancers treated without radiation demonstrated significant survival advantage in second primary bladder cancer. A small significant survival advantage was seen in bladder cancer patients previously treated for prostate cancer with radiation. This data suggests that second primary bladder cancer following pelvic radiotherapy has similar biologic aggressiveness to urothelial carcinoma developing without a history of radiotherapy. MICROABSTRACT: The overall survival of 25,734 patients diagnosed with bladder cancer following definitive therapy for a previous pelvic malignancy was 49.2% at 5 years. There was no significant survival difference between groups whose first cancer was treated with or without radiation. Second primary bladder cancer following pelvic radiotherapy has similar biologic aggressiveness to urothelial carcinoma developing without a history of radiotherapy.

Traumatic spinal cord injury confers bladder cancer risk to patients managed without permanent urinary catheterization: lessons from a comparison of clinical data with the national database.

PURPOSE: Life expectancy for people with traumatic spinal cord injury (SCI) is increasing due to advances in treatment methods and in neuro-urology. Thus, developing urinary bladder cancer (UBC) is gaining importance. METHODS: Single-centre retrospective evaluation of consecutive in- and out-patient data with spinal cord injury between January 1st, 1998 and December 31st, 2018 was carried out and data were compared with UBC data of the German population from the German Centre for Cancer Registry Data at Robert Koch Institute. RESULTS: A total of 37 (4 female, 33 male) out of 7004 patients with SCI were diagnosed with histologically proven UBC (median follow-up 85 months). Median age at UBC diagnosis was 54.0 years (general population: 74 years). The SCI patients had significantly (p < 0.0001, each) more frequent muscle-invasive tumors (81% ≥ T2) and unfavorable grading (76% G3), compared to the general population. Median survival was 13 months for transitional cell carcinoma (n = 31) and 4 months for squamous cell carcinoma (n = 5) (p = 0.0039), resp. The median survival of the 24 cystectomized patients was 15.0 months. Long-term suprapubic or indwelling catheterization was found in only eight patients for a total of only 5.09% (median 15.5 months) of the latency of all patients. No significant differences for T category and grading were observed between the bladder emptying methods intermittent catheterisation and catheter-free voiding. CONCLUSION: The results indicate that in patients with SCI bladder management even without permanent catheterization represents a considerable risk for the development of UBC.

Clinicopathologic Characterization of Post-Renal Transplantation BK Polyomavirus-Associated Urothelial CarcinomaSingle Institutional Experience.

OBJECTIVES: To review rare cases of BK polyomavirus (BKPyV) associated urologic carcinomas in kidney transplant recipients at one institution and in the literature. METHODS: We describe the clinicopathologic features of BKPyV-associated urologic carcinomas in a single-institution cohort. RESULTS: Among 4,772 kidney recipients during 1994 to 2014, 26 (0.5%) and 26 (0.5%) developed posttransplantation urothelial carcinomas (UCs) and renal cell carcinomas (RCCs), respectively, as of 2017. Six (27%) UCs but none of the RCCs expressed large T antigen (TAg). TAg-expressing UCs were high grade with p16 and p53 overexpression (P < .05 compared to TAg-negative UCs). Tumor genome sequencing revealed BKPyV integration and a lack of pathogenic mutations in 50 cancer-relevant genes. Compared to TAg-negative UCs, TAg-expressing UCs more frequently presented at advanced stages (50% T3-T4) with lymph node involvement (50%) and higher UC-specific mortality (50%). CONCLUSIONS: Post-renal transplantation BKPyV-associated UCs are aggressive and genetically distinct from most non-BKPyV-related UCs.

PTRF independently predicts progression and survival in multiracial upper tract urothelial carcinoma following radical nephroureterectomy.

OBJECTIVES: Polymerase I and transcript release factor (PTRF) has been implicated in cancer biology but its role in upper tract urothelial carcinoma (UTUC) is unknown. From a pilot transcriptome, we identified PTRF was significantly upregulated in high stage UTUC. Bladder cancer transcriptome from The Cancer Genome Atlas (TCGA) supported our finding and high PTRF level also predicted poor survival. We, therefore, investigated the correlation of PTRF with patients' clinicopathologic characteristics and outcomes in a multiracial UTUC cohort. MATERIALS AND METHODS: By immunohistochemical staining, PTRF expression was determined using H-score. PTRF expression of 575 UTUCs from 8 institutions, including 118 Asians and 457 Caucasians, was compared with various clinicopathologic parameters. Human urothelial cancer cell lines were used to evaluate the level of PTRF protein and mRNA expression, and PTRF transcript level was assessed in fresh samples from 12 cases of the cohort. The impact of PTRF expression on disease progression, cancer-specific death and overall mortality was also examined. RESULTS: High PTRF expression was significantly associated with multifocality (P = 0.023), high pathologic tumor stage (P < 0.00001), nonurothelial differentiation (P = 0.035), lymphovascular invasion (P = 0.003) and lymph node metastasis (P = 0.031). PTRF mRNA expression was also markedly increased in advanced stage UTUC (P = 0.0003). High PTRF expressing patients had consistently worse outcomes than patients with low PTRF expression regardless of demographic variation (all P < 0.005). In multivariate analysis, high PTRF expression was an independent predictor for progression-free survival (hazard ratio [HR] 1.70, 95% confidence interval [CI] 1.07-2.69, P = 0.025), cancer-specific survival (HR 2.09, 95% CI 1.28-3.42, P = 0.003), and overall survival (HR 2.04, 95% CI 1.33-3.14, P = 0.001). CONCLUSIONS: Results indicate that PTRF is a predictive biomarker for progression and survival and an independent prognosticator of UTUC. Elevated PTRF could probably propel clinically aggressive disease and serve as a potential therapeutic target for UTUC.

Preventive Role of mTOR Inhibitor in Post-Kidney Transplant Urothelial Carcinoma.

BACKGROUND: There is little evidence about whether mammalian target of rapamycin (mTOR) inhibitor could prevent post-kidney transplant (KT) urothelial carcinoma (UC) or not. The aim of this study is to analyze the role of mTOR inhibitor add-on in tacrolimus-based kidney transplant recipients. METHOD: The data were obtained from the Kaohsiung Chang Gung Memorial Hospital using the Chang Gung Research Database and retrospectively reviewed from January 2000 to December 2015. Patients then were categorized into 2 groups: group FK (more than 2-year tacrolimus [FK] prescription) and group FK + mTOR inhibitor (more than 2-year tacrolimus plus at least 6-month continued sirolimus prescription). The primary end point is post-KT UC development. The secondary end point is mTOR inhibitor add-on effect on renal function deterioration episode. RESULTS: There were 140 patients with tacrolimus-based immunosuppressant (group FK) and 82 patients with tacrolimus-based and add-on mTOR inhibitor regimen (group FK + mTOR inhibitor). The follow-up duration, sex distribution, and combined mycophenolate mofetil rate are similar in both groups. Younger age, lower tacrolimus trough level, lower UC incidence, and longer KT-to-UC interval were observed. Short- to intermediate-term results revealed noninferior graft outcome by creatinine level or creatinine deterioration. CONCLUSIONS: In our preliminary result, mTOR inhibitor add-on in patients with tacrolimus-based regimen revealed less post-KT UC occurrence. In addition, noninferior graft outcome was also observed. In Taiwan, a high UC prevalence area, mTOR inhibitor add-on strategy can be considered as a preventive strategy for UC after KT.

Epithelial-to-mesenchymal transition: Event and core associates in bladder cancer.

Urothelial carcinoma of the bladder (UCB) shows different biological outcomes, diverse biological propensities for invading the muscularis as well as epithelial-to-mesenchymal transition (EMT), a dynamic key event during developmental processes, wound healing, and tissue repair. The EMT core molecules include EMT-activating transcription factors (EMT-ATFs), and a host of downstream effectors and target genes including extracellular inducers and growth factors. Here, we describe molecular regulatory determinants of mesenchymal-to-epithelial transition (MET) and more specifically EMT that allows a subset of urothelial cancer cells to gain mesenchymal traits with self-renewal potential. EMT accelerates tumor progression and poses a clinical challenge to anticancer therapies. Targeting the populations of tumor-initiating cells and those with a metastable phenotype provide the basis for the development of more reliable risk assessment of tumor progression and risk, and better treatment strategies of UCB.

Smoking Cessation and the Risk of Bladder Cancer among Postmenopausal Women.

Smoking is the strongest established risk factor for bladder cancer. Former smokers have a lower risk of bladder cancer compared with current smokers, but findings on the dose-response relationship between years after quitting and the risk of bladder cancer are inconsistent. A total of 143,279 postmenopausal women from the Women's Health Initiative Study were included. Cox proportional hazards regression models were applied for estimating age- and multivariable-adjusted HRs and their 95% confidence intervals (CI). There were 870 bladder cancer cases identified over an average of 14.8 years of follow-up. After adjusting for pack-years of smoking, bladder cancer risk among former smokers declined by 25% within the first 10 years of cessation and continued to decrease as cessation time increased but remained higher than never smokers after 30 years of quitting (HR, 1.92; 95% CI, 1.43-2.58). Smokers who quit smoking had a lower risk of bladder cancer compared with current smokers (HR, 0.61; 95% CI, 0.40-0.94). We conclude that among postmenopausal women, there is a significant reduction in the risk of bladder cancer after quitting smoking. In addition to primary prevention, smoking cessation is critical to prevent the incidence of bladder cancer in older women.

Recent advances in upper tract urothelial carcinomas: From bench to clinics.

Urothelial carcinoma in the upper tract is rare and often discussed separately. Many established risk factors were identified for the disease, including genetic and external risk factors. Radiographic survey, endoscopic examination and urine cytology remained the most important diagnostic modalities. In localized upper tract urothelial carcinomas, radical nephroureterectomy with bladder cuff excision are the gold standard for large, high-grade and suspected invasive tumors of the renal pelvis and proximal ureter, whereas kidney-sparing surgeries should be considered in patients with low-risk disease. Advances in technology have given endoscopic surgery an important role, not only in diagnosis, but also in treatment. Although platinum-based combination chemotherapy is efficacious in advanced or metastatic disease, current established chemotherapy regimens are toxic and lack a sustained response. Immune checkpoint inhibitors have led to a new era of treatment for advanced or metastatic urothelial carcinomas. The remarkable results achieved thus far show that immunotherapy will likely be the future treatment paradigm. The combination of immune checkpoint inhibitors and other agents is another inspiring avenue to explore that could benefit even more patients. With respect to the high incidence rate and different clinical appearance of upper tract urothelial carcinomas in Taiwan, a possible correlation exists between exposure to certain external risk factors, such as arsenic in drinking water and aristolochic acid in Chinese herbal medicine. As more gene sequencing differences between upper tract urothelial carcinomas and various disease causes are detailed, this has warranted the era of individualized screening and treatment for the disease.