Background: A high incidence of upper urinary tract urothelial carcinoma has been reported in the southwestern area of Taiwan, where arsenic water contamination was considered the main cause. However, there is no definite proof to show a correlation between arsenic water contamination and upper urinary tract urothelial carcinoma. To investigate the clinical and epidemiological features of patients with upper urinary tract urothelial carcinoma between arsenic water endemic and non-endemic areas, we analyzed patients in terms of characteristics, stratified overall survival, disease-free survival, and cancer-specific survival. Methods: The records of a total of 1194 patients diagnosed with upper urinary tract urothelial carcinoma were retrospectively reviewed. Clinical data and current medical status were collected from the medical records. Statistical analyses were performed to determine the clinical variables and stratified survival curves between endemic and non-endemic groups. Results: Female predominance was revealed in both endemic and non-endemic groups (male:female ratio = 1:1.2–1.4). No statistical differences were found in histological types, staging, and tumor size between the two groups. Nonetheless, patients with characteristics of aging and having end-stage renal disease were outnumbered in the non-endemic group, while a higher prevalence of previous bladder tumors and more ureteral tumors were found in the endemic group. Adjusted stratified cumulative survival curves suggested a poorer prognosis in endemic patients, especially in disease-free survival of early stage disease. Conclusions: A higher mortality rate with more previous bladder cancer history and ureteral tumors was seen in patients with upper urinary tract urothelial carcinoma residing in the arsenic water contamination area. This may be attributed to the long-term carcinogenic effect of arsenic underground water.

Folic acid exerts both anti-inflammatory and antifibrotic effects. Glycine N-methyltransferase (GNMT), the major folic acid-binding protein in the liver, is a crucial enzyme that regulates the cellular methylation process by maintaining S-adenosylmethionine levels. However, as yet neither the therapeutic effects of folic acid in renal fibrosis nor whether GNMT is involved in these folic acid-associated mechanisms has been investigated. First, the expression of GNMT was examined in human kidneys with or without obstructive nephropathy. Later, wild-type and GNMT knockout (GNMT^−/−) mice were subjected to unilateral ureteral obstruction (UUO) and then treated with either folic acid or vehicle for 14 days. Renal tubular injury, inflammation, fibrosis, and autophagy were evaluated by histological analysis and Western blotting. We observed increased expression of GNMT in humans with obstructive nephropathy. Furthermore, UUO significantly increased the expression of GNMT in mice; in addition, it caused renal injury as well as the development of both hydronephrosis and tubular injury. These were all alleviated by folic acid treatment. In contrast, GNMT^−/− mice exhibited exacerbated UUO-induced renal injury, but the protective effect of folic acid was not observed in GNMT^−/− mice. We propose a novel role for folic acid in the treatment of renal fibrosis, which indicates that GNMT may be a therapeutic target.

Chen CH, et al. World J Mens Health. 2024 May;42:e59. https://doi.org/10.5534/wjmh.230344

The clinical efficacy of adjuvant chemotherapy in upper tract urothelial carcinoma (UTUC) is unclear. We aimed to assess the therapeutic outcomes of adjuvant chemotherapy in patients with advanced UTUC (pT3-T4) after radical nephroureterectomy (RNU). We retrospectively reviewed the data of 2108 patients from the Taiwan UTUC Collaboration Group between 1988 and 2018. Comprehensive clinical features, pathological characteristics, and survival outcomes were recorded. Univariate and multivariate Cox proportional hazards models were used to evaluate overall survival (OS), cancer-specific survival (CSS), and disease-free survival (DFS). Of the 533 patients with advanced UTUC included, 161 (30.2%) received adjuvant chemotherapy. In the multivariate analysis, adjuvant chemotherapy was significantly associated with a reduced risk of overall death (hazard ratio (HR), 0.599; 95% confidence interval (CI), 0.419–0.857; p = 0.005), cancer-specific mortality (HR, 0.598; 95% CI, 0.391–0.914; p = 0.018), and cancer recurrence (HR, 0.456; 95% CI, 0.310–0.673; p < 0.001). The Kaplan–Meier survival analysis revealed that patients receiving adjuvant chemotherapy had significantly better five-year OS (64% vs. 50%, p = 0.002), CSS (70% vs. 62%, p = 0.043), and DFS (60% vs. 48%, p = 0.002) rates compared to those who did not receive adjuvant chemotherapy. In conclusion, adjuvant chemotherapy after RNU had significant therapeutic benefits on OS, CSS, and DFS in advanced UTUC.

Background/Objectives: Radical nephroureterectomy (RNU) is the standard of care for high-risk upper tract urothelial carcinoma (UTUC) but causes permanent renal decline, often disqualifying patients from essential cisplatin-based adjuvant chemotherapy. Segmental ureteral resection (SUR) preserves renal function, but its safety in high-risk patients remains fiercely debated due to historical treatment selection biases and a lack of competing risk adjustments. We aimed to compare long-term oncological outcomes and postoperative renal function preservation between SUR and RNU for high-risk UTUC strictly localized to the ureter. Methods: Retrospective data from 859 patients (783 RNU, 76 SUR) with high-risk ureteral UTUC (high-grade or pathologic T2–T4) were analyzed from a 21-hospital nationwide database. Propensity score overlap weighting was implemented to achieve covariate balance. Overall survival (OS) was assessed via Cox proportional hazards regression, whereas cancer-specific survival (CSS), metastasis-free survival (MFS), and local recurrence-free survival (LRFS) were evaluated using multivariable Fine–Gray subdistribution hazard models to robustly account for the competing risk of non-cancer mortality. Results: Overlap weighting achieved excellent baseline comparability with an effective sample size of 429.5 patients per cohort. Weighted analyses demonstrated comparable long-term trajectories between SUR and RNU for OS (p = 0.62), CSS (hazard ratio [HR]: 0.94, p = 0.835), and MFS (HR: 0.88, p = 0.664). The Fine–Gray model confirmed that the surgical approach was not a significant independent predictor of local recurrence (HR: 0.74, p = 0.351). Crucially, the SUR group demonstrated a significantly lower renal function decline both at 1 month (−0.11 vs. −10.58 mL/min/1.73 m², p < 0.001) and through final clinical follow-up (−5.33 vs. −12.49 mL/min/1.73 m², p = 0.001). Conclusions: For meticulously selected patients with high-risk ureteral UTUC, SUR provides equivalent oncological control and survival outcomes to standard RNU. Crucially, this kidney-sparing approach significantly preserves postoperative renal function, safeguarding the physiological reserve required for patients to maintain eligibility for optimal subsequent systemic adjuvant therapies.