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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). 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. 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. 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. [ABSTRACT FROM AUTHOR]

Introduction: Traditional Chinese Medicine (TCM) has a broad application in healthcare, with Danshen being a notable herb used in Eastern medicine for cancer treatment. This study aims to explore the relationship between Danshen use and cardiovascular risks among bladder cancer patients. Methods: Patients were selected based on a confirmed diagnosis of bladder cancer with specific inclusion and exclusion criteria to control for certain comorbidities and treatments. Utilizing Taiwan’s National Health Insurance data from 2003 to 2013, this retrospective, population-based study identified three groups: 525 patients treated with Danshen, 6,419 patients not treated with TCM, and 4,356 patients treated with TCM but not with Danshen. The Cox proportional hazard model was employed to estimate the risks of Major Adverse Cardiovascular Events (MACE) and mortality while accounting for various confounders. Results: The overall incidence of MACEs was significantly lower in the Danshen group (5%) compared to the TCM (8.1%) and non-TCM (9.9%) groups (p < 0.001). The Cox model revealed that bladder cancer patients treated with Danshen had the lowest risk of MACE (adjusted hazard ratio, 0.56; 95% confidence interval, 0.38–0.84) and all-cause mortality (adjusted hazard ratio, 0.60; 95% confidence interval, 0.44–0.82). Discussion: The findings suggest that Danshen reduces the risk of MACE and allcause mortality in bladder cancer patients, highlighting its potential benefits. This underpins the necessity for further research to substantiate the cardiovascular benefits of Danshen in bladder cancer patients and potentially broaden its application in oncology healthcare. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate the association between single-nucleotide polymorphisms (SNPs) in mir146a and mir196a and bladder cancer (BLCA) risk in Taiwan. The genotypes of mir146a rs2910164 and mir196a rs11614913 were determined in 375 BLCA patients and 375 healthy controls using PCR-RFLP methodology, and their associations with BLCA risk were evaluated. The study also measured the serum expression level of mir146a using quantitative RT-PCR. The results showed that the distributions of CC, CG and GG genotypes of mir146a rs2910164 were 31.7%, 45.6% and 22.7% in the control group, and 21.9%, 44.3% and 33.8% in the case group, respectively. In logistic regression analyses, the heterozygous variant genotype CG carriers showed a marginally significant association with increased BLCA risk (OR = 1.41, 95% CI = 0.99–2.01), while the homozygous variant genotype GG carriers had a 2.17-fold increased risk of BLCA (OR = 2.17, 95%CI = 1.46–3.21). Moreover, carriers of the GG/CG genotypes had significantly higher serum levels of mir146a than those with the CC genotype (p < 0.0001), indicating a genotype–phenotype correlation. In contrast, mir196a rs11614913 was not associated with BLCA risk. Therefore, the genotypes of mir146a rs2910164 may serve as a useful biomarker for predicting the risk of BLCA. [ABSTRACT FROM AUTHOR]

Particulate matter and volatile organic compounds, including total hydrocarbons (THCs), are major ambient air pollutants. Primary nonmethane hydrocarbons (NMHCs) originate from vehicle emissions. The association between air pollution and urinary bladder cancer (UBC) is debatable. We investigated whether long-term exposure to ambient hydrocarbons increases UBC risk among people aged ≥ 20 years in Taiwan. Linkage dataset research with longitudinal design was conducted among 589,135 initially cancer-free individuals during 2000–2013; 12 airborne pollutants were identified. Several Cox models considering potential confounders were employed. The study outcomes were invasive or in situ UBC incidence over time. The targeted pollutant concentration was divided into three tertiles: T1/T2/T3. The mean age of individuals at risk was 42.5 (SD 15.7), and 50.5% of the individuals were men. The mean daily average over 10 years of airborne THC concentration was 2.25 ppm (SD 0.13), and NMHC was 0.29 ppm (SD 0.09). Both pollutants show long-term monotonic downward trend over time using the Mann–Kendall test. There was a dose-dependent increase in UBC at follow-up. UBC incidence per 100,000 enrollees according to T1/T2/T3 exposure to THC was 60.9, 221.2, and 651.8, respectively; it was 170.0/349.5/426.7 per 100,000 enrollees, corresponding to T1/T2/T3 exposure to NMHC, respectively. Without controlling for confounding air pollutants, the adjusted hazard ratio (adj.HR) was 1.83 (95% CI 1.75–1.91) per 0.13-ppm increase in THC; after controlling for PM2.5, adj.HR was even higher at 2.09 (95% CI 1.99–2.19). The adj.HR was 1.37 (95% CI 1.32–1.43) per 0.09-ppm increase in ambient NMHC concentration. After controlling for SO2 and CH4, the adj.HR was 1.10 (95% CI 1.06–1.15). Sensitivity analyses showed that UBC development risk was not sex-specific or influenced by diabetes status. Long-term exposure to THC and NMHC may be a risk factor for UBC development. Acknowledging pollutant sources can inform risk management strategies. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objectives: To determine the earliest noticeable manifestation and diagnosis in patients diagnosed with tuberculosis (TB) epididymitis/epididymo-orchitis incidentally and to analyze their responses to surgical and medical treatment.Methods: Patients who underwent surgery for the preliminary impression of chronic epididymitis/epididymo-orchitis or epididymal/testicular tumor from 2000 to 2019 were included in the study. The clinical presentations, laboratory data, radiological examinations, and operative findings were analyzed retrospectively. The outcomes were assessed by the responses to anti-TB chemotherapy and post treatment radiographic evaluations.Results: All of our 25 patients with a mean age of 60.6 years were diagnosed incidentally with TB epididymitis (48.0%) and TB epididymo-orchitis (52.0%) according to the histopathological findings from their surgeries. The presence of a palpable scrotal mass (76.0%), was the major presentation. Nineteen (76.0%) patients had undergone complete chemotherapy after the surgery and 15 (78.9%) patients showed complete recovery. Four (21.1%) patients had unfavorable outcomes, 3 had TB autonephrectomies and 1 required re-surgery years after complete chemotherapy. Of the 3 (12.0%) patients who did not receive chemotherapy after their surgeries, 1 had a TB relapse in the spine and lung and 1 developed bladder cancer years later.Conclusion: Tuberculosis epididymitis/epididymo-orchitis is difficult to diagnose. However, some clinical clues can assist including aged patients, extragenital TB histories, poor responses to antibiotic treatment and scrotal skin lesion. Complete anti-TB chemotherapy is mandatory even after the total removal of TB lesion. Supplemental surgical interventions can be considered when the symptoms are not relieved after chemotherapy. Lifespan follow-up is recommended due to high relapse rate. [ABSTRACT FROM AUTHOR]

In Taiwan, the incidence of upper-tract urothelial carcinomas (UTUCs) is higher than in western countries (20%-31% vs. 5%-10%), as is bilateral disease. The standard management for high-grade UTUC is radical nephroureterectomy with bladder cuff excision and regional lymphadenectomy. The challenges in managing bilateral UTUCs are how to retain renal function and avoid permanent hemodialysis. We present two cases of developed bilateral highgrade renal pelvis urothelial carcinoma, cT3N0M0 stage III, that revealed excellent results in tumor regression after three cycles of half-dose pembrolizumab. One case received unilateral retroperitoneal laparoscopic nephroureterectomy with bladder cuff excision; thereafter, renal function has been good until now, and the remaining right kidney has been free of tumor recurrence in the 3 years of follow-up. The other patient, however, expired from an immune-related adverse event (irAE) 22 days after the third cycle of pembrolizumab, although tumor remission was evident also. Neoadjuvant pembrolizumab alone could be a potential strategy in positive of selected biomarkers for high-grade bilateral UTUC with remaining neglectable nephrotoxicity and may avoid permanent hemodialysis. [ABSTRACT FROM AUTHOR]

Bladder cancer is the most common malignancy involving the urinary system, resulting in ∼18,000 deaths each year. It is the 6th most common cancer in the United States, with non-muscle invasive bladder cancer (NMIBC) representing approximately 80% of bladder cancer diagnoses. With the current Bacillus Calmette-Guérin (BCG) shortage and limited effective alternative therapies, there remains a significant unmet need for treatment options for patients with NMIBC. TARA-002 is a lyophilized biological preparation for instillation containing cells of Streptococcus pyogenes (Group A, type 3) Su strain treated with benzylpenicillin and is being developed for the treatment of high-grade NMIBC. TARA-002 is manufactured using the same master cell bank as OK-432, which is approved in Japan and Taiwan for the treatment of several oncology indications. The dose for the Phase 1b/2 study is 40 KE, which is based on the recommended Phase 2 dose (RP2D) established in the Phase 1a study. ADVANCED-2 (NCT05951179) is a Phase 1b/2, dose-expansion, open-label study of intravesical instillation of TARA-002 in adults ≥18 years with CIS NMIBC (±Ta/T1). The purpose of this study is to assess the safety and anti-tumor activity of TARA‑002, at the established RP2D, in the treatment of subjects with CIS (±Ta/T1) with active disease. The key inclusion and exclusion criteria are summarized in Table 1. The study includes ∼102 subjects enrolled in 2 cohorts based on prior BCG experience (Figure 1). Cohort A includes 27 subjects with CIS (±Ta/T1) who are unable to obtain intravesical BCG or have not received it for 24 months prior to CIS diagnosis. Cohort B includes 75 subjects with CIS (±Ta/T1) BCG unresponsive after completion of adequate BCG therapy. The study duration per subject is 6 months for Cohort A and 24 months for Cohort B. Phase 1b/2 is currently open for enrollment. Results: Conclusions: [ABSTRACT FROM AUTHOR]

Objectives: To assess temporal patterns and regional differences in the incidence rate, and factors associated with survival of urinary tract urothelial carcinoma. Methods: The medical records of 8830 patients with new diagnoses of urinary tract urothelial carcinoma in the years 2001–2010 were retrieved from Taiwan National databases. Temporal trends, regional disparity and related survival factors were evaluated using the Cochran–Armitage trend test, local Moran's I statistic and log‐rank test, respectively. Results: The annual urinary tract urothelial carcinoma incidence rates (standardized by age) were steady at approximately 3.14–3.41 per 100 000 person‐years. Notably, women had a significantly higher annual urinary tract urothelial carcinoma incidence than men in most of the years studied (range of female‐to‐male annual standardized rate ratio: 2.08–3.25), and diabetes prevalence in urinary tract urothelial carcinoma increased significantly from 12.3% to 23.4% per year over the 10 years. High urinary tract urothelial carcinoma incidence cluster areas other than the latest endemic area of "blackfoot disease" were newly identified by local Moran's I statistic (P < 0.05). Furthermore, older age, male sex, end‐stage kidney disease and more advanced tumor grade were associated with lower 5‐year overall survival probabilities in the 2001–2015 cohort. Conclusions: The incidence and survival of urinary tract urothelial carcinoma over the decade 2001–2010 were different according to population and regional features. Various urinary tract urothelial carcinoma screening, prevention, treatment and care plans should be developed depending on age, sex, comorbidity and area of residence. [ABSTRACT FROM AUTHOR]

Ingested arsenic is carcinogenic to the human urinary tract, but uncertainties remain regarding the dose-response relationship. To assess dose-response relationships between arsenic ingestion and urinary cancers, we evaluated the associations between the arsenic level in drinking water and mortality of cancers of the bladder, kidney, and prostate in Taiwan. We utilized the 1971-2000 Taiwan death registry data and calculated the age-standardized mortality rates (ASMRs) using the 1976 world standard population as the reference group. We used the data from a 1974-1976 census survey of wells on the arsenic levels in drinking water conducted by the government to assess exposure levels, which had been divided into three categories: below 0.05 ppm, 0.05-0.35 ppm, and above 0.35 ppm. The data were analyzed using multiple linear regression models and geographical information system. We found no increase in ASMR for all, or any, of the urinary cancers at exposure levels of 0.05-0.35 ppm arsenic, but at exposure levels > 0.35 ppm arsenic was associated with increased ASMR in both males and females for bladder cancer, kidney cancer, and all urinary cancers combined. There was no increased ASMR associated with prostate cancer observed for either exposure category., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Aim: There is very little literature reporting the association of matrix metalloproteinase-1 (MMP1) with personal susceptibility to bladder cancer. In the current study, we carried out the first examination of the contribution of MMP1 rs1799750 to bladder cancer risk in Taiwanese. Materials and Methods: A total of 375 bladder cancer cases and 375 healthy controls were genotyped for MMP1 rs1799750 via polymerase chain reaction-restriction fragment length polymorphism methodology and this was evaluated for association with clinicopathological factors. Results: The frequencies of MMP1 rs1799750 2G/2G, 1G/2G, and 1G/1G genotypes were 35.7%, 44.8% and 19.5% in the group with bladder cancer and 32.5%, 46.4%, and 21.1% in the healthy control group (p for trend=0.6362). The odds ratios (ORs) for bladder cancer risk after adjusting for age and gender for those carrying 1G/2G and 1G/1G genotypes at MMP1 rs1799750 were 0.88 (95% CI=0.62-1.24, p=0.4357) and 0.83 (95% CI=0.61-1.26, p=0.3990), respectively, compared with the wild-type 2G/2G genotype. In allelic frequency analysis, the adjusted OR for those carrying the 1G allele at MMP1 rs1799750 was 0.87 (95% CI=0.71-1.23, p=0.3479) [ABSTRACT FROM AUTHOR]

[Display omitted] • This study scrutinizes the correlation between arsenic mitigation via tap water supply system installation in Blackfoot disease-endemic regions of Taiwan and the reduction in incidence rates of six arsenic-related cancers from 1995 to 2019. • Utilizing the Taiwan Cancer Registry dataset and employing random-effects age-period-cohort models and stabilized kriging method, the analysis reveals a consistent higher incidence of these cancers in Blackfoot disease-endemic areas, with a noticeable narrowing of incidence rates gap post-arsenic mitigation (initiated around 1960). • Notably, three cancers - small and squamous cell lung cancer, Bowen's disease, and urothelial bladder cancer showed a sharp decline to null excess incidence rates for individuals born post-mitigation, contrasting with a more gradual decline observed in upper tract urothelial carcinoma. • Spatiotemporal analysis identifies high incidence rate clusters in core Blackfoot disease-endemic townships, dissipating primarily post-1960 birth cohort, alongside other identified clusters in non-endemic regions. • The study substantiates the positive impact of arsenic mitigation on reducing the burden of arsenic-related cancers, albeit at varying rates across different cancer types, shedding light on the significance of environmental interventions in public health enhancement. • The findings also allude to the potential influence of other factors such as tobacco control and aristolochic acid prohibition in the observed cancer incidence trends, emphasizing a multifaceted approach in cancer prevention and control. Epidemiological evidence has demonstrated an association between arsenic in drinking water and increased cancer incidence. This population-based study investigates the impact of a tap water supply system installation in Blackfoot disease-endemic regions of Taiwan on cancer incidence. By using the Taiwan Cancer Registry dataset, we enrolled patients aged 40–84 diagnosed with arsenic-related cancers, including hepatocellular carcinoma, small and squamous cell lung cancer, Bowen's disease, basal and squamous cell skin cancer, urothelial bladder cancer, and upper tract urothelial carcinoma between 1995 and 2019. Random-effects age-period-cohort models were used to estimate the cancer incidence data, and a stabilized kriging method was employed to interpolate incidence rates to more precise spatiotemporal units. The results showed that the age-standardized incidence rates of all six types of studied cancers were consistently higher in Blackfoot disease-endemic areas than those in other areas from 1995 to 2019. However, the gap in incidence rates between Blackfoot disease-endemic areas and the remaining regions began to narrow approximately after the 1960 birth cohort when the tap water supply system installation commenced. For small and squamous cell lung cancer, Bowen's disease, and urothelial bladder cancer, the excess incidence rates sharply declined to null for those born after the year of arsenic mitigation. For upper tract urothelial carcinoma, the excess incidence rates decreased more gradually for those born after the year of arsenic mitigation. For hepatocellular carcinoma and basal and squamous cell skin cancer, the excess incidence rates remained constant. Spatiotemporal clusters of high incidence rates were identified in the core townships of Blackfoot disease-endemic areas. These clusters began to dissipate mainly after the 1960 birth cohort. Arsenic mitigation from drinking water in Taiwan is associated with a reduced burden of small and squamous cell lung cancers, Bowen's disease, urothelial bladder cancer, and upper tract urothelial carcinoma. [ABSTRACT FROM AUTHOR]

Purpose: To assess the association of tumor architecture with cancer recurrence, metastasis, and cancer-specific survival (CSS) in patients treated with radical nephroureterectomy (RNU) for upper urinary tract urothelial carcinoma (UTUC) in Taiwan. Materials and Methods: Data were collected from 857 patients treated with RNU between January 2005 and August 2016 in our hospital. Pathologic slides were reviewed by genitourinary pathologists. Propensity score weighting was performed for data analysis. Results: Sessile growth pattern was observed in 212 patients (24.7%). Tumor architecture exhibited a significant association with bladder cancer history, chronic kidney disease (CKD), tumor stage, lymph node status, histological grade, lymphovascular invasion, concomitant carcinoma in situ , and the variant type [standardized mean difference (SMD) > 0.1 for all variables before weighting]. In the propensity score analysis, 424 papillary and sessile tumor architecture were analyzed to balance the baseline characteristics between the groups. Tumor architecture was an independent predictor of metastatic disease and CSS (p = 0.033 and p = 0.002, respectively). However, the associations of tumor architecture with bladder and contralateral recurrence were nonsignificant (p = 0.956 and p = 0.844, respectively). Conclusions: Tumor architecture of UTUC after RNU is associated with established features of aggressive disease and predictors of metastasis and CSS. Assessment of tumor architecture may help identify patients who could benefit from close follow-up or early administration of systemic therapy after RNU. Tumor architecture should be included in UTUC staging after further confirmation. [ABSTRACT FROM AUTHOR]

Background: Intravesical bacillus Calmette-Guerin (BCG) therapy is the treatment of choice for patients with T1 or high-grade superficial bladder cancer or those with carcinoma in situ after transurethral resection. A personal history of tuberculosis infection has been viewed as a relative contraindication for BCG therapy, because it may increase the risk of complications or decrease the treatment effectiveness. We determined the safety and efficacy of intravesical BCG treatment for patients with prior tuberculosis infection by analyzing the data obtained from the National Health Insurance Research Database in Taiwan.Methods: We included patients who were newly diagnosed with bladder cancer from 2000 to 2009 and who received adjuvant intravesical BCG therapy within 3 months after the surgery. We excluded those who developed upper urinary tract cancer during the study period. Disease recurrence, disease progression, and major adverse effects were compared between patients with and without a prior diagnosis of tuberculosis infection until December 31, 2011.Results: Among the 3915 patients included, 187 (4.8%) had been previously diagnosed with tuberculosis infection. The proportion of men (84.0% versus 76.9%) and older patients was higher in the group with a prior tuberculosis infection than in those without a prior tuberculosis infection. Significant differences in disease recurrence (20.3% versus 22.8%; hazard ratio [HR], 0.87; 95% confidence interval [CI], 0.63-1.21, p = 0.404) or disease progression (10.2% versus 12.8%, HR, 0.74; 95% CI, 0.46-1.17, p = 0.191) were not observed between the two groups. None of the patients with a prior tuberculosis infection had severe urinary tract infections, whereas four (0.1%) patients without such an infection developed severe urinary tract infections.Conclusion: A prior tuberculosis infection did not affect the treatment efficacy or safety of intravesical BCG treatment. The efficacy and safety of intravesical BCG therapy are comparable between bladder cancer patients with and without prior tuberculosis infections. [ABSTRACT FROM AUTHOR]

Background: Urothelial cancer (UC) includes carcinomas of the bladder, ureters, and renal pelvis. New treatments and biomarkers of UC emerged in this decade. To identify the key information in a vast amount of literature can be challenging. In this study, we use text mining to explore UC publications to identify important information that may lead to new research directions.Method: We used topic modeling to analyze the titles and abstracts of 29,883 articles of UC from Pubmed, Web of Science, and Embase in Mar 2020. We applied latent Dirichlet allocation modeling to extract 15 topics and conducted trend analysis. Gene ontology term enrichment analysis and Kyoto encyclopedia of genes and genomes pathway analysis were performed to identify UC related pathways.Results: There was a growing trend regarding UC treatment especially immune checkpoint therapy but not the staging of UC. The risk factors of UC carried in different countries such as cigarette smoking in the United State and aristolochic acid in Taiwan and China. GMCSF, IL-5, Syndecan-1, ErbB receptor, integrin, c-Met, and TRAIL signaling pathways are the most relevant biological pathway associated with UC.Conclusions: The risk factors of UC may be dependent on the countries and GMCSF, IL-5, Syndecan-1, ErbB receptor, integrin, c-Met, and TRAIL signaling pathways are the most relevant biological pathway associated with UC. These findings may provide further UC research directions. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the treatment pattern of non‐muscle invasive bladder cancer patients among urologists in Japan, Korea and Taiwan, with emphasis on compliance with important treatment guidelines. Methods: A Web‐based questionnaire survey was conceived by representative members of each country's urological oncology society and was open from June 2016 to February 2017 to each society's members. Descriptive statistics and multinomial logistic regression analysis were used. Results: A total of 2334 urologists were invited and 701 responded to the survey with a response rate of 30.0%. Instruments used during transurethral resection of bladder cancer varied significantly between countries and depended on their availability. The re‐transurethral resection rate for pT1 or high‐grade disease >50% of the time was significantly higher in Japan than in the other two countries, but the collective rate was just 49%. The frequency of intravesical therapy in intermediate‐ to high‐risk disease was generally consistent across countries. However, the choice of agent between chemotherapy and bacillus Calmette–Guérin was significantly different between countries. Maintenance bacillus Calmette–Guérin was used <10% of the time by 45% of respondents, the most important reasons being fear of side‐effects, followed by a lack of efficacy and shortage of drug supply. Conclusions: There are significant differences between Japan, Korea and Taiwan in the management of intermediate‐ to high‐risk non‐muscle invasive bladder cancer. The results of this survey can serve as the basis for joint efforts to develop common clinical guidelines. [ABSTRACT FROM AUTHOR]

Studies have shown a high risk of tumor development within a bladder diverticulum (BD). We were interested in the relationship between BD and the development of bladder cancer. Herein, we attempted to investigate whether there exists an association between documented BD and subsequent risk of bladder cancer. We identified 10,662 hospitalized urology patients, including 2,134 documented BD patients (study cohort) and 8,528 non-BD subjects (comparison cohort) from Taiwan's National Health Insurance database. Only urology patients were enrolled in the study to minimize selection bias. The two cohorts were frequency-matched 1:4 by age, sex and index-year. Patients with less than one year of follow-up were excluded to avoid inverting cause and effect. Risks of developing bladder cancer were estimated using the Cox proportional hazard regression model. There was an increased bladder cancer risk in the documented BD patients. The incidence of bladder cancer in documented BD patients was 2.60-fold higher than that in the comparison group, and the overall risk-factor-adjusted hazard ratio was 2.63 (95% CI, 1.74–3.97). Moreover, stratified analysis by sex also showed that documented BD patients were at higher risk of subsequent bladder cancer than the comparison cohort. The effect of BD on the risk of bladder cancer was higher in males than in females and was more profound in patients without comorbidities than in those with comorbidities. In this population-based longitudinal study, urology patients with documented BD might have an elevated risk of subsequent bladder cancer. Based on the limitations of the retrospective study design, further studies are required. [ABSTRACT FROM AUTHOR]

Background Urothelial carcinoma (UC) is derived from the urothelium of the urinary tract, and includes cancers of the bladder, renal pelvis and ureter. The aim of this study was to investigate the clinical and demographic features among patients with bladder cancer and urothelial carcinoma of the upper urinary tract (UTUC) in Taiwan. Methods The present study recruited a total of 736 histopathologically confirmed UC cases, which consisted of 470 bladder cancer and 266 UTUC between September 1998 and December 2009. Clinical and demographic features were collected by an interview utilizing a structured questionnaire, and supplemented by medical chart review. This study was approved by institutional review boards of the collaborating hospitals. The multivariate Cox proportional hazards model was performed to investigate prognostic factors for disease-free survival (DFS) and overall survival (OS). All statistical analyses were performed using the Statistical Analysis Software for Windows, version 9.1 (SAS Institute, Cary, NC, USA). Results UTUC patients had higher proportions of advanced clinical stage (T2–4) and poor cell differentiation (G3). Bladder cancer patients with advanced clinical stages (T2–3 and T4) had increased risks of poorer OS (hazard ratio, HR = 1.7 and 3.9, respectively). UTUC patients with the advanced clinical stage (T4) had a significantly greater risk of poorer OS (HR = 8.7). Bladder cancer patients with a high grade (G2–3) had a significantly increased risk of poorer OS (HR = 3.8). Conclusion Based on the limited parameters and heterogeneous data, the present study merely observed that bladder cancer and UTUC patients with the higher tumor stage have a significant increased risk of poor overall survival. Therefore, the causal mechanisms of UC prognosis remained to be further explored in a larger population. [ABSTRACT FROM AUTHOR]

PurposeThis study used the a nationwide population-based retrospective cohort study with the claims data from the Taiwan National Health Insurance Research Database to investigate the risk of urothelial carcinoma (UC) for hemodialysis (HD) patients.MethodsThe study population consisted of 2689 patients with end-stage renal disease (ESRD) newly diagnosed in 2000–2002 and underwent maintenance HD. Then, 21,449 reference patients were collected without HD randomly selected and matched with sex and age. The exclusion criteria were previous long-term analgesics and Chinese medication usage. Incidence density rates of UC in upper urinary tract (UTUC) and bladder (UBUC) were estimated for both cohorts by the end of 2012. Hazard ratios (HRs) of UC were measured in association with HD, covariates, and comorbidity.ResultsThe incidence of UC was significantly higher in the HD cohort than in the reference cohort for both UT (21.8 vs. 0.65 per 10,000 person-years) and UB (17.7 vs. 3.55 per 10,000 person-years). The multivariate Cox proportional hazard regression analysis showed that the HRs of UTUC in HD cohort was 33.3 (95% CI = 15.9–69.5) and 5.14 for UBUC (95% CI = 3.24–8.15). The risk increased further for HD patients with comorbidity of hematuria, urinary tract infection (UTI) or hydronephrosis.ConclusionPatients with ESRD on HD are at a high risk of developing UC, especially UTUC in Taiwan. They will be paid more frequent to check urine analysis, urine cytology, and upper urinary tract survey. [ABSTRACT FROM PUBLISHER]

Abstract: Objective: To examine the analytic role of arsenic exposure on cancer mortality among the low-dose (well water arsenic level <150μg/L) villages in the Blackfoot-disease (BFD) endemic area of southwest Taiwan and with respect to the southwest regional data. Method: Poisson analyses of the bladder and lung cancer deaths with respect to arsenic exposure (μg/kg/day) for the low-dose (<150μg/L) villages with exposure defined by the village median, mean, or maximum and with or without regional data. Results: Use of the village median well water arsenic level as the exposure metric introduced misclassification bias by including villages with levels >500μg/L, but use of the village mean or the maximum did not. Poisson analyses using mean or maximum arsenic levels showed significant negative cancer slope factors for models of bladder cancers and of bladder and lung cancers combined. Inclusion of the southwest Taiwan regional data did not change the findings when the model contained an explanatory variable for non-arsenic differences. A positive slope could only be generated by including the comparison population as a separate data point with the assumption of zero arsenic exposure from drinking water and eliminating the variable for non-arsenic risk factors. Conclusion: The cancer rates are higher among the low-dose (<150μg/L) villages in the BFD area than in the southwest Taiwan region. However, among the low-dose villages in the BFD area, cancer risks suggest a negative association with well water arsenic levels. Positive differences from regional data seem attributable to non-arsenic ecological factors. [Copyright &y& Elsevier]

Background: Diabetic patients have a higher risk of bladder cancer and benign prostatic hyperplasia (BPH). Theoretically, BPH patients may have an increased risk of bladder cancer because residual urine in the bladder surely increases the contact time between urinary excreted carcinogens and the urothelium. However, whether BPH increases bladder cancer risk in patients with type 2 diabetes has not been studied. Methods: The reimbursement databases of all Taiwanese diabetic patients under oral anti-diabetic agents or insulin from 1996 to 2009 were retrieved from the National Health Insurance. An entry date was set at 1 January 2006 and a total of 547584 men with type 2 diabetes were followed up for bladder cancer incidence until the end of 2009. Incidences of bladder cancer for BPH by status and by duration were calculated and adjusted hazard ratios (95% confidence intervals) were estimated by Cox regression. The effects of diabetes duration and medications used for diabetic control in relation with bladder cancer risk were also evaluated by Cox regression in BPH men. Results: The incidences were 258.77 and 69.34 per 100,000 person-years for patients with and without BPH, respectively, adjusted hazard ratio 1.794 (1.572, 2.047). For BPH patients, those who underwent surgical procedures for BPH had a higher incidence than those who did not (355.45 vs. 250.09 per 100,000 person-years), respective adjusted hazard ratios: 2.459 (1.946, 3.109) and 1.709 (1.492, 1.958). The significantly higher risk could be demonstrated for BPH of any duration: respective adjusted hazard ratios 1.750 (1.430, 1.605), 1.844 (1.543, 2.203), 2.011 (1.680, 2.406) and 1.605 (1.341, 1.921) for BPH <1, 1-3, 3-5 and ⩾5 years versus patients without BPH. Sensitivity analyses for patients aged ⩾60 years and after excluding BPH patients with surgical procedures or without surgical procedures, respectively, yielded similar results. In BPH men, diabetes duration was not significantly related with bladder cancer; but metformin was consistently associated with a significantly lower risk, with adjusted hazard ratio of 0.719 (0.590, 0.875) for all ages and 0.742 (0.604, 0.912) for age ⩾60 years. Conclusions: BPH is a significant risk factor for bladder cancer in men with type 2 diabetes. Metformin may protect against bladder cancer in BPH men. [ABSTRACT FROM AUTHOR]

Background. Renal transplantation has been regarded as the treatment of choice for end-stage renal disease. Renal transplantation increases the risk of cancers due to long-term immunosuppression. The types of post-transplantation malignancies may vary among different geographic regions and ethnic populations. To date, large population-based studies of post-transplantation malignancies in Asian renal transplant recipients (RTRs) have rarely been reported. Methods. To investigate the patterns of post-transplantation malignancies in Chinese RTRs, we performed a nationwide population-based cohort study between 1997 and 2008 based on data from the National Health Insurance Database in Taiwan. Patterns of cancer incidence in RTRs were compared with those of the general population using standardized incidence ratios (SIRs). Results. Among the 4716 RTRs (2475 males and 2241 females; mean age 44.1 ± 12.4 years) and 22 556 person-years of observation, 320 post-transplant cancers were diagnosed. The SIR of all cancers was 3.75 (95% confidence interval 3.36–4.18). Women had a higher risk than men for the development of malignancies (SIR 5.04 for women and SIR 2.88 for men). Renal, bladder and liver cancers were the most common cancers, with SIRs of 44.29, 42.89 and 5.07, respectively. When stratified by age, RTRs of young age at transplant (<20 years) had the highest risk of post-transplantation malignancies. Conclusions. This study demonstrates different patterns of malignancies after renal transplantation in Chinese RTRs, with higher incidences of kidney and bladder cancers. Physicians should be more vigilant in examining RTRs for post-transplantation malignancies especially in younger patients. [ABSTRACT FROM AUTHOR]

Introduction: p53 codon 72 polymorphism has been reported to be associated with bladder cancer incidence, progression and prognosis, but the association is still under debate. A tentative model was constructed to evaluate the association between p53 codon 72 polymorphism and bladder cancer. Subjects and Methods: In this study, a total of 554 participants were enrolled. The genotyping was carried out using PCR-RFLP and DNA direct sequencing. Results: The genotype distribution of p53 codon 72 polymorphism was significantly different between bladder cancer patients and controls (p = 0.039). In logistic regression, diagnostic age and genotype Pro/Pro were the risk factors for developing an invasive tumor. A 4.526-fold risk was estimated for the patients with Pro/Pro genotype as opposed to non-Pro/Pro genotype to develop invasive tumors. However, the extent of p53 codon 72 polymorphism did not predict bladder cancer prognosis. Conclusions: A conceptual mode was constructed; in addition, the moderating and mediating analysis was also carried out in a structural equation model to resolve possible confounding effects. Taken together, p53 codon 72 polymorphism may be associated with bladder cancer incidence and progression, but not prognosis. Further study is needed to evaluate the usefulness of the constructed model in risk assessment. Copyright © 2011 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

The article focuses on an ecological study concerning the associations between arsenic in drinking water, and incidence of bladder cancer in 243 townships in Taiwan. Three methods, including direct, indirect, and variable, were used in the study. The background, methods, results, and conclusions of the study, are discussed.

Study Type – Diagnosis (case series) Level of Evidence 4 OBJECTIVES To investigate the cytogenetic marker detected by fluorescence in situ hybridization (FISH; UroVysionTM, Vysis, Inc., Abbott Laboratories, Des Plaines, IL, USA) in the diagnosis of bladder cancer and upper tract urothelial carcinoma (UC) in Taiwanese patients, as FISH has been used in Western countries for detecting UC, but there are limited results in Asian populations. PATIENTS AND METHODS We analysed polyploidy of chromosome 3, 7, 17 and aneuploidy of chromosome 21, using uroepithelial cells collected at the first void or by instrumental extraction of urine, for bladder cancer, and shedding cells from the upper tract flushed by normal saline via ureteric catheterization or ureterorenoscopy. The criteria for positive tumour cells included three or more positive staining in two or more chromosomes showing polyploidy or <50% staining of the chromosome 9p21. RESULTS In all, 32 patients with bladder UC and 12 with upper tract UC were assessed. The overall sensitivity for bladder cancer by UroVysion was 96.8%. The sensitivity of the cytology test was 36% for UC of the bladder. The sensitivity for UroVysion in upper tract UC was 12/12 but the specificity was three of nine. CONCLUSIONS This preliminary report shows that UroVysion was a sensitive screening method for UC of the bladder and upper urinary tract. [ABSTRACT FROM AUTHOR]

Primary cancers of the ureter and renal pelvis are rare tumours, >90% of which are transitional cell carcinomas. Only ≈5% of urothelial tumours arise in the upper urinary tract (UUT). Many environmental factors contribute to the development of these cancers. Some are similar to bladder cancer-associated factors (tobacco, occupational exposure), while others are more specific to carcinogenesis of the UUT (phenacetine, Balkan endemic nephropathy [BEN], Chinese herb nephropathy or association with Blackfoot disease [BFD]). This review discusses the environmental factors involved in UUT carcinoma. Tobacco and occupational exposure remain the principal exogenous risk factors for developing these tumours. Conversely, carcinogenesis of UUT tumours resulting from phenacetine consumption has almost disappeared. Although the incidence of BEN is also on the decline, roles for aristolochic acid and the consumption of Chinese herbs in the physiopathology and induction of this nephropathy, respectively, have proposed. In Taiwan, the association of this tumour type with BFD and arsenic exposure remains unclear to date. As some genetic polymorphisms are associated with an increased risk of cancer or faster disease progression, there is variability in interindividual susceptibility to the development of UUT carcinoma when exposed to the aforementioned risk factors Cytosolic sulfotransferases (SULTs) catalyse the detoxification of many environmental chemicals but also in the bioactivation of dietary and other mutagens. Polymorphism of the SULT gene, is thought to confer susceptibility to upper tract tumours. [ABSTRACT FROM AUTHOR]

Purpose: We compared clinicopathological characteristics and outcomes in patients with bladder cancer who were exposed to graded arsenic levels in drinking water. Materials and Methods: From 1993 through 2006, 977 patients with bladder cancer in Taiwan were studied retrospectively. Patients were from 3 areas, including the core zone (arsenic related blackfoot disease endemic area with a well water arsenic level of 350 to 1,100 ng/ml), zone 1 (a well water arsenic level of 350 ng/ml or greater but not a blackfoot disease endemic area) and zone 2 (a well water arsenic level of less than 350 ng/ml). Clinicopathological characteristics and survival outcome were compared among the groups. Results: Of these patients 81 (8.3%), 246 (25.2%) and 650 (66.5%) lived in the core zone, and zones 1 and 2, respectively. More high grade and high stage tumors were observed in core zone patients than in those in zones 1 and 2, including high grade in 48.7% vs 41.4% and 39.2% of patients, advanced disease in 39.5% vs 31.0% and 18.5% and nodal metastasis in 8.6% vs 3.3% and 3.4%, respectively. Median overall and cancer specific survival in core zone patients was significantly shorter than in patients in zones 1 and 2, including 69 vs 119 and 113-month overall survival and for the 75th percentile of cancer specific survival 34.5 vs 119 and 113 months, respectively. On multivariate analysis with adjustment for tumor grade and stage the zonal difference was not a significant factor for overall or cancer specific survival. Conclusions: Patients with arsenic related bladder cancer may have decreased overall and cancer specific survival because they have more unfavorable tumor phenotypes than patients in other areas in Taiwan. [Copyright &y& Elsevier]

In contrast to Western counties, the incidence of urothelial carcinoma (UC) remains mar-edly elevated in Taiwan. Regulatory T cells (Tregs) play a crucial role in limiting immune responses within the tumor microenvironment. To elucidate the relationship between immune checkpoints in the tumor immune microenvironment and UC progression, we utilize the Gene Expression Omnibus (GEO) to analyze a microarray obtained from 308 patients with UC. We observed that the expression level of CD276 or TIM-3 was positively correlated with late-stage UC and poor prognosis. Patients with simultaneously high CD276 and TIM-3 expression in tumors have significantly reduced both univariate and multivariate survival, indicating that mRNA levels of these immune checkpoints could be independent prognostic biomarkers for UC overall survival and recurrence. Our cohort study showed rare CD8+ cytotoxic T-cells and Tregs infiltration during early-stage UC-known as cold tumors. Approximately 30% of late-stage tumors exhibited highly infiltrated cytotoxic T cells with high PD-1 and FOXP3 expression, which implied that cytotoxic T cells were inhibited in the advanced UC microenvironment. Collectively, our findings provide a better prognosis prediction by combined immune checkpoint biomarkers and a basis for early-stage UC standard treatment to convert cold tumors into hot tumors, followed by immune checkpoint therapy. [ABSTRACT FROM AUTHOR]

To investigate the relationship between petrochemical air pollution and risk of death due to bladder cancer, studies were conducted using a matched cancer case-control model based upon deaths that occurred in Taiwan from 1995 through 2005. Data on all eligible bladder cancer deaths were obtained from the Bureau of Vital Statistics of the Taiwan Provincial Department of Health. The control group consisted of individuals who died from causes other than neoplasms or diseases associated with genitourinary problems. The controls were pair matched to the cases by gender, year of birth, and year of death. Each matched control was selected randomly from the set of possible controls for each case. The proportion of a municipality's total population employed in the petrochemical industry in a municipality was used as an indicator of a resident's exposure to air emissions from the petrochemical industry. The subjects were divided into three levels (≤25th percentile; 25th-50th percentile; >50th percentile). Subjects who lived in the group of municipalities characterized by the high levels of petrochemical air pollution had a significantly higher risk of death attributed to bladder cancer than subjects in the group that lived in municipalities with the lowest petrochemical air pollution levels, after controlling for possible confounders. The findings of this study warrant further investigation of the role of petrochemical air pollution in the etiology of bladder cancer. [ABSTRACT FROM AUTHOR]

Abstract: Ingested inorganic arsenic is strongly associated with a wide spectrum of adverse health outcomes. We propose a bioaccumulation and the Weibull model-based epidemiological framework to accurately estimate the reference arsenic intake guideline for tilapia consumption and tilapia-cultured water arsenic concentration based on bioaccumulations of tilapia and gender/age/cancer-specific epidemiological data from the arseniasis-endemic area in Taiwan. Our results show a positive relationship between arsenic exposure and age/gender- and cancer-specific cumulative incidence ratio using Weibull dose–response model. Based on male bladder cancer with an excess lifetime cancer risk of 10−4, we estimate the reference tilapia inorganic arsenic guideline value to be 0.084μgg−1 dry wt based on the suggested daily consumption rate of 120gd−1. Our findings show that consumption of tilapia in a blackfoot disease (BFD)-endemic area poses no significant cancer risk (excess cancer risks ranging from 3.4×10−5 to 9.3×10−5), implying that people in BFD-endemic areas are not readily associated with higher fatalities for bladder cancer exposed from tilapia consumption. We are confident that our model can be easily adapted for other aquaculture species, and encourage risk managers to use the model to evaluate the potential population-level long-term low-dose cancer risks. We conclude that, by integrating the bioaccumulation concept and epidemiological investigation of humans exposed to arsenic, we can provide a scientific basis for risk analysis to enhance risk management strategies. [Copyright &y& Elsevier]

The objective of this study was to evaluate whether exposure to disinfection by-products (DBP) is associated with bladder cancer. A matched case-control study was used to investigate the relationship between the risk of death from bladder cancer and exposure to total trihalomethanes (TTHM) in drinking water in 65 municipalities in Taiwan. All bladder cancer deaths of the 65 municipalities from 1996 through 2005 were obtained from the Bureau of Vital Statistics of the Taiwan Provincial Department of Health. Controls were deaths from other causes and were pair-matched to the cases by gender, year of birth,and year of death. Each matched control was selected randomly from the set of possible controls for each cancer case. Data on TTHM levels in drinking water in study municipalities were collected from the Taiwan Environmental Protection Administration. The municipality of residence for cancer cases and controls was assumed to be the source of the subject's TTHM exposure via drinking water. The adjusted odds ratios for bladder cancer death for those with high TTHM concentrations in their drinking water were 1.8 (1.18-2.74) and 2.11 (1.43-3.11) compared to the lowest group. The results of this study show that there was a significant positive correlation between the concentration of TTHM in drinking water and risk of death from bladder cancer. [ABSTRACT FROM AUTHOR]

The relationship between nitrate levels in drinking water and bladder cancer development is controversial. A matched cancer case-control with nitrate ecology study was used to investigate the association between bladder cancer mortality occurrence and nitrate exposure from Taiwan drinking water. All bladder cancer deaths of Taiwan residents from 1999 through 2003 were obtained from the Bureau of Vital Statistics of the Taiwan Provincial Department of Health. Controls were deaths from other causes and were pair-matched to the cases by gender, year of birth,and year of death. Each matched control was selected randomly from the set of possible controls for each cancer case. Data on nitrate-nitrogen (NO3-N) levels in drinking water throughout Taiwan were collected from Taiwan Water Supply Corporation (TWSC). The municipality of residence for cancer cases and controls was assumed to be the source of the subject's nitrate exposure via drinking water. The adjusted odds ratios for bladder cancer death for those with high nitrate levels in their drinking water were 1.76 (1.28-2.42) and 1.96 (1.41-2.72) as compared to the lowest tertile. The results of the present study show that there was a significant positive relationship between the levels of nitrate in drinking water and risk of death from bladder cancer. [ABSTRACT FROM AUTHOR]

A database of cancer mortality and arsenic concentrations in village wells in an arseniasis-endemic area of southwestern Taiwan has been the predominant source of information for risk assessments of U. S. Environmental Protection Agency and two National Research Council reports on arsenic and drinking water. A limitation of the data, however, is that exposure is ecological, that is, cancer mortality cannot be matched with arsenic exposure on an individual basis, just grouped by village. The resultant potential for bias is examined by comparing dose-response analyses of villages divided into two groups, those with well concentrations in a narrow range and the remainder. The narrow range group suggests a flat or downward change in risk in the low dose range, whereas the other group indicates increasing risk. More disturbingly, however, the dose-response data are highly dispersed for both groups and the dose-response curve predicts background bladder/lung cancer levels much higher than a southwestern Taiwan comparison population. This may be due to a large variability between villages of the study area in bladder/lung cancer not directly attributable to arsenic. Including the comparison population in the dose-response analysis artificially anchors the dose-response curve at a background level inconsistent with the study population and likely just biases the slope factor upward. [ABSTRACT FROM AUTHOR]

Quantitative analysis for the risk of human cancer from the ingestion of inorganic arsenic has been based on the reported cancer mortality experience in the blackfoot disease (BFD)-endemic area of southwest Taiwan. Linear regression analysis shows that arsenic as the sole etiologic factor accounts for only 21% of the variance in the village standardized mortality ratios for bladder and lung cancer. A previous study had reported the influence of confounders (township, BFD prevalence, and artesian well dependency) qualitatively, but they have not been introduced into a quantitative assessment. In this six-township study, only three townships (2, 4, and 6) showed a significant positive dose-response relationship with arsenic exposure. The other three townships (0, 3, and 5) demonstrated significant bladder and lung cancer risks that were independent of arsenic exposure. The data for bladder and lung cancer mortality for townships 2, 4, and 6 fit an inverse linear regression model (p < 0.001) with an estimated threshold at 151 μg/L (95% confidence interval, 42 to 229 μg/L). Such a model is consistent with epidemiologic and toxicologic literature for bladder cancer. Exploration of the southwest Taiwan cancer mortality data set has clarified the dose-response relationship with arsenic exposure by separating out township as a confounding factor. [ABSTRACT FROM AUTHOR]

The Black–Foot Disease (BFD) endemic area of SW Taiwan has historically been the principal data source for assessing cancer risks from arsenic in drinking water in the United States, most recently in a 42–village ecological study. The data showed a discontinuity for bladder cancer risk at about 400 µg/L. A proposed explanation was that the arsenic–dependent bladder cancer risk was found only for those villages that were dependent on water from the artesian well aquifer (As > 350 µg/L and co–contamination with humic acids) and not for those villages receiving water from the shallow aquifer (As et al. 2004).The U.S. data excluded the SW Taiwan slope estimate derived from the artesian well–dependent subpopulation but were consistent with the slope estimate derived from the subpopulation using shallow aquifer water. Both the SW Taiwan data in the absence of high arsenic levels ( [ABSTRACT FROM AUTHOR]

Background: Either sodium-glucose cotransporter-2 (SGLT-2) inhibitors or pioglitazone (Pio) has doubtful issues of bladder cancer, especially for the combination therapy with these two drugs. Our study aimed to investigate the risk of bladder cancer under combination therapy of SGLT-2 inhibitors and Pio. Materials and Methods: We included 97,024 patients with type 2 diabetes mellitus (T2DM) in the Chang Gung Research Database in Taiwan from 1 January 2016 to 31 December 2019. The primary outcome was newly diagnosed bladder cancer after combination therapy with SGLT-2 inhibitors and Pio. Group 1 received both study drugs, group 2 received SGLT-2 inhibitors, group 3 received Pio, and group 4 received non-study drugs (the reference group). The secondary outcome in each group was all-cause mortality. Results: In group 1, no newly diagnosed bladder cancer was detected after a mean 2.8-year follow-up and all-cause mortality decreased significantly (adjusted hazard ratio (AHR), 0.70; 95% confidence interval (CI), 0.54–0.92) in comparison to the reference group (group 4). In group 2 and group 3, no trend of increased bladder cancer was observed (group 2: AHR 0.49, 95% CI 0.05–4.94; group 3: AHR 0.48, 95% CI 0.15–1.58) and it still reduced all-cause mortality (group 2: AHR 0.83, 95% CI 0.70–0.99; group 3: AHR 0.90, 95% CI 0.83–0.99). Conclusions: In T2DM patients without previous or active bladder cancer, the combination therapy of SGLT-2 inhibitors and Pio was not associated with newly diagnosed bladder cancer and had lower all-cause mortality. [ABSTRACT FROM AUTHOR]

Simple Summary: Several lymph node-related prognosticators have been reported in bladder cancer patients with lymph node involvement who undergo radical cystectomy. However, the role of extranodal extension (ENE) remains debatable for outcome prediction. The aim of our study is to investigate the association between ENE and prognosis in Taiwanese patients with pathological nodal bladder cancer who were treated with radical cystectomy using a nationwide database. Our study concluded that ENE significantly reduced OS and CSS among the pathological nodal bladder cancer patients. After the identification of pathological nodal disease, adjuvant chemotherapy was associated with better survival outcomes in the patients with ENE. Background: Several lymph node-related prognosticators were reported in bladder cancer patients with lymph node involvement and receiving radical cystectomy. However, extranodal extension (ENE) remained a debate to predict outcomes. Methods: A retrospective analysis of 1303 bladder cancer patients receiving radical cystectomy and bilateral pelvic lymph node dissection were identified in the National Taiwan Cancer Registry database from 2011 to 2017. Based on the 304 patients with lymph node involvement, the presence of ENE and major clinical information were recorded and calculated. The overall survival (OS) and cancer-specific survival (CSS) were estimated with Kaplan–Meier analysis and compared using the log-rank test. Hazard ratios (HR) and the associated 95% confidence intervals were calculated in the univariate and stepwise multivariable models. Results: In the multivariable analysis, ENE significantly reduced OS (HR = 1.74, 95% CI 1.09–2.78) and CSS (HR = 1.69, 95% CI 1.01–2.83) more than non-ENE. In contrast, adjuvant chemotherapy was significantly associated with better OS and CSS upon the identification of pathological nodal disease. Conclusions: Reduced OS and CSS outcomes were observed in the pathological nodal bladder cancer patients with ENE compared with those without ENE. After the identification of pathological nodal disease, adjuvant chemotherapy was associated with better survival outcomes. [ABSTRACT FROM AUTHOR]

Arsenic is a well-established human carcinogen and is considered a health risk worldwide, especially where groundwater is consumed as drinking water. In 2018, bladder and kidney cancers were the 14th and 17th leading causes of global cancer mortality, respectively. Our aim was to investigate the association between arsenic exposure, DNA damage, and the incidence of bladder and kidney cancers. A total of 788 participants aged ≥40 years were enrolled in a prospective cohort study in Taiwan between 1991 and 1994, with follow-up between 2011 and 2014. Well-water and first-morning spot urine samples were collected between 1991 and 1994 to estimate arsenic exposure, and the baseline urinary levels of 8-Oxo-2′-deoxyguanosine (8-OHdG) and N7-methylguanine (N7-MeG) were quantified to assess DNA lesions. The Cox proportional hazard model was used to estimate the effects of arsenic exposure and DNA adduct levels on the risk of bladder or kidney cancer. Urinary arsenic species were associated with significantly increased 8-OHdG and N7-MeG after adjusting for age, sex, and cigarette smoking. Only non-statistically significant mediation effects of 8-OHdG were observed. In a fully adjusted Cox model, participants with arsenic exposure and urinary 8-OHdG levels higher than the median had a higher risk of bladder cancer (HR = 4.60, confidence interval: 1.43–14.85). Overall, the combined effects of high cumulative arsenic exposure from artesian well-water and advanced DNA damage predicted the risk of bladder cancer. • The subjects were followed for two decades in an arseniasis endemic area of northeastern Taiwan. • The urinary 8-OHdG and N7-MeG positively associated with cumulative well arsenic exposure. • Arsenic exposure and 8-OHdG have joint effects on risk of kidney/bladder cancer. [ABSTRACT FROM AUTHOR]

We sought to examine the effect of tumor location on the prognosis of patients with upper tract urothelial carcinoma (UTUC) treated with radical nephroureterectomy (RNU). This retrospective study came from the Taiwan UTUC Collaboration Group, which consisted of 2658 patients at 15 institutions in Taiwan from 1988 to 2019. Patients with kidney-sparing management, both renal pelvic and ureteral tumors, as well as patients lacking complete data were excluded; the remaining 1436 patients were divided into two groups: renal pelvic tumor (RPT) and ureteral tumor (UT), with 842 and 594 patients, respectively. RPT was associated with more aggressive pathological features, including higher pathological T stage (p < 0.001) and the presence of lymphovascular invasion (p = 0.002), whereas patients with UT often had synchronous bladder tumor (p < 0.001), and were more likely to bear multiple lesions (p = 0.001). Our multivariate analysis revealed that UT was a worse prognostic factor compared with RPT (overall survival: HR 1.408, 95% CI 1.121–1.767, p = 0.003; cancer-specific survival: HR 1.562, 95% CI 1.169–2.085, p = 0.003; disease-free survival: HR 1.363, 95% CI 1.095–1.697, p = 0.006; bladder-recurrence-free survival: HR 1.411, 95% CI 1.141–1.747, p = 0.002, respectively). Based on our findings, UT appeared to be more malignant and had a worse prognosis than RPT. [ABSTRACT FROM AUTHOR]

Petrochemical complexes and oil refineries are well known sources of a wide range of environmental pollutants. Consequently, the potential harmful health effects of living near these facilities is a topic of concern among the population living in the neighborhood. Anyhow, the number of studies carried out on this issue is rather limited and, in some cases, results are even slightly contradictory. The present Review was aimed at assessing whether living in the vicinity of petrochemical industries and oil refineries is associated with a higher incidence of cancer and cancer mortality. In this sense, up to 23 investigations were found in PubMed and Scopus databases. According to the type of cancer, leukemia and other hematological malignancies were reported as the main types of cancer for populations living in the neighborhood of petrochemical industries. This was concluded based on studies performed in Taiwan, Spain, United Kingdom, Italy and Nigeria. In contrast, no association was found in 4 different investigations conducted in Sweden, Finland and USA with the same purpose. Other scientific studies reported a high incidence of lung and bladder cancer in Taiwan, Italy and USA, as well as an excess mortality of bone, brain, liver, pleural, larynx and pancreas cancers in individuals living near petrochemical complexes from Taiwan, Spain, Italy, United Kingdom and USA. Thus, human exposure to certain carcinogenic pollutants emitted from petrochemical industries might increase the incidence of some cancers and cancer mortality. Anyway, since the limited number of investigations conducted until now, further studies are required in order to corroborate -in a more generalized way-this conclusion. • Living near petrochemical industries is associated with a higher incidence of cancer. • Leukemia and other hematological malignancies are the main kinds of cancer. • Carcinogenic pollutants from petrochemical industries can increase cancer mortality. [ABSTRACT FROM AUTHOR]

Background: Past studies suggest mixed associations between selective serotonin reuptake inhibitor (SSRI) prescription and carcinogenic risk. There is no epidemiological study reporting on the association between SSRI use and the incidence of bladder cancer. The aim of this study is to determine whether SSRI use influences the risk of bladder cancer. Methods: We conducted a nationwide retrospective cohort study by Taiwan's National Health Insurance Research Database from January 1, 1997 to December 31, 2013. 192,392 SSRI prescribed individuals were randomly matched 1 to 1 with 191,786 individuals who had never received any SSRIs by propensity scores match. The Cox Proportional Hazard models were conducted to examine the risk of bladder cancer between individuals prescribed SSRIs and individuals not prescribed SSRIs. Results: SSRIs were associated with significant reduced risk of bladder cancer with 0.5, 1, and 2 year induction periods (adjusted hazard ratio (aHR) = 0.86, 95% CI (confidence interval) = 0.76–0.98, aHR = 0.85, 95% CI = 0.75–0.97, and aHR = 0.77, 95% CI = 0.66–0.89). When examining the effect of specific SSRI, there was significantly lower risk of bladder cancer in individuals prescribed fluoxetine (6 month induction period: aHR = 0.78, 95% CI = 0.65–0.93; 1 year induction period: aHR = 0.78, 95% CI = 0.65–0.94; 2 year induction period: aHR = 0.73, 95% CI = 0.60–0.89), paroxetine (6 month induction period: aHR = 0.78, 95% CI = 0.61–0.99; 1 year induction period: aHR = 0.79, 95% CI = 0.61–1.01; 2 year induction period: aHR = 0.72, 95% CI = 0.54–0.95), and citalopram (6 month induction period: aHR = 0.74, 95% CI = 0.53–1.03; 1 year induction period: aHR = 0.70, 95% CI = 0.50–0.99; 2 year induction period: aHR = 0.60, 95% CI = 0.41–0.88). Conclusions: Individuals prescribed fluoxetine, paroxetine, or citalopram had a reduced risk of bladder cancer in this large, cross-national database. [ABSTRACT FROM AUTHOR]

Aim: To determine the incidence of adenocarcinoma of the prostate for patients undergoing radical cystoprostatectomy for bladder cancer in Taiwan. Methods: A total of 248 patients in Taiwan who were histologically confirmed for transitional cell carcinoma of the bladder underwent cystoprostatectomy. Histopathologic evaluation of the prostate specimens sectioned at 5 mm intervals was performed. Results: Of the 248 patients, 10 (4.03%) were found to have prostate cancer. Of the 10 cases of unsuspected prostate cancer, eight proved to be at stage T1 or T2, and two at T3 and T4, respectively. This rate of incidentally found prostate cancer amongst our bladder cancer patients appeared to be lower than that found in bladder cancer patients in similar studies in USA. Conclusion: Although the incidence of incidental prostate cancer in patients in Taiwan with bladder cancer is not high compared with that in Western countries, we suggest that digital rectal examination and prostate-specific antigen (PSA) are important screening tools for men with bladder cancer, especially for those aged 60 years and older in Taiwan. [ABSTRACT FROM AUTHOR]

Cancer treatment causes adverse effects that lead to refusal or discontinuation of treatment. The purposes of this study were to identify 1) the factors associated with and 2) the reasons for refusing and discontinuing treatment in patients with bladder cancer (BC). We conducted a retrospective cohort study in patients diagnosed with BC in Taiwan from 1 January 2014 to 30 June 2019 using a linked cancer registry database. Of the 1247 BC patients in the study cohort, 2.1% reported refusing treatment. Patients with less education and those diagnosed at cancer stage II-IV were more likely to refuse treatment. The major reason for refusing treatment was "patient or the family considered patient's poor physical condition (chronic disease or unstable systemic disease), difficulty in enduring any condition likely to cause physical discomfort from disease treatment". A total of 4.3% of BC patients reported discontinuing treatment. Patients not living in the northern region of Taiwan and those diagnosed at cancer stage II-IV were more likely to terminate treatment before completion. The major reason given for discontinuing treatment was inconvenient transportation. Sufficient social resources and supportive care can help BC patients cope with the physical and psychological burden of treatment.

Background: 5α-reductase inhibitors (5-ARIs) inhibit the pathway of converting the testosterone to dihydrotestosterone and are widely used in benign prostatic hyperplasia patients. Since androgen receptor activation may play a role in urothelial tumorigenesis, we conducted this retrospective cohort study to determine whether 5α-reductase inhibitors (5-ARIs) administration is associated with bladder cancer mortality, bladder cancer recurrence and upper tract urothelial carcinoma mortality, using the Taiwan National Health Insurance database., Methods: The data of this retrospective cohort study were sourced from the Longitudinal Health Insurance Database of Taiwan, compiled by the Taiwan National Health Insurance database from 1996 to 2010. It consists of 18,530 men with bladder cancer, of whom 474 were 5-ARIs recipients and 4384 men with upper tract urothelial carcinoma, of whom 109 were 5-ARIs recipients. Propensity Score Matching on the age and geographic data was done at the ratio of 1:10. We analyzed the odds ratios (OR) and 95% confidence interval (CI) of the risk of bladder cancer death, bladder cancer recurrence rate and upper tract urothelial carcinoma related death by the 5-ARIs administration., Results: Those who received 5-ARIs showed a lower risk of bladder cancer related death compared to nonusers in multivariable adjusted analysis (OR 0.835, 95% CI 0.71-0.98). However, there was no significant difference in the bladder cancer recurrence rate (OR 0.956, 95% CI 0.82-1.11) and upper tract urothelial carcinoma related mortality in multivariable adjusted analysis (OR 0.814, 95% CI 0.6-1.1)., Conclusions: Patients who receive 5-ARIs have lower bladder cancer related mortality compared to those who don't. 5-ARIs may prove to be a viable strategy to improve bladder cancer outcomes.