The current stratification model may represent a useful tool for clinicians treating patients with ureteral obstruction due to advanced cancer.

ObjectivesTo identify risk factors and develop a model for predicting recurrence of upper urinary tract urothelial carcinoma (UTUC) in the bladder in patients without a history of bladder cancer after radical nephroureterectomy (RNU). Patients and MethodsWe retrospectively reviewed 754 patients with UTUC without prior or concurrent bladder cancer or distant metastasis at 13 institutions in Japan. Univariate and multivariate Fine and Gray competing risks proportional hazards models were used to examine the cumulative incidence of bladder recurrence of UTUC. A risk stratification model and a nomogram were constructed. Two prediction models were compared using the concordance index (c-index) focusing on predictive accuracy and decision-curve analysis, which indicate whether a model is appropriate for decision-making and determining subsequent patient prognosis. ResultsThe cumulative incidence rates of bladder UTUC recurrence at 1 and 5 years were 15 and 29%, respectively; the median time to bladder UTUC recurrence was 10 months.Multivariate analysis showed that papillary tumour architecture, absence of lymphovascular invasion and higher pathological T stage were both predictive factors for bladder cancer recurrence. The predictive accuracy of the risk stratification model and the nomogram for bladder cancer recurrence were not different (c-index: 0.60 and 0.62). According to the decision-curve analysis, the risk stratification was an acceptable model because the net benefit of the risk stratification was equivalent to that of the nomogram. The overall cumulative incidence rates of bladder cancer 5 years after RNU were 10, 26 and 44% in the low-, intermediate-and high-risk groups, respectively. ConclusionsWe identified risk factors and developed a risk stratification model for UTUC recurrence in the bladder after RNU. This model could be used to provide both an individualised strategy to prevent recurrence and a risk-stratified surveillance protocol. Keywordsupper tract urothelial carcinoma, radical nephroureterectomy, bladder recurrence

Abbreviations & Acronyms CI = confidence interval CSS = cancer-specific survival DUx = distal ureterectomy EAU = European Association of Urology eGFR = estimated glomerular filtration rate HR = hazard ratio NCCN = National Comprehensive Cancer Network NUx = nephroureterectomy RFS = recurrence-free survival UC = urothelial carcinoma UUT-UC = upper urinary tract urothelial carcinoma Objectives: To investigate the oncological and functional outcome of distal ureterectomy compared with nephroureterectomy in the management of distal ureteral urothelial carcinoma. Methods: Using a database including upper urinary tract urothelial carcinoma patients (n = 1329), 282 patients were identified with urothelial carcinoma localized in the distal ureter on clinical evaluation. To adjust for potential baseline differences between groups, 43 patients undergoing distal ureterectomy were matched with 86 patients undergoing nephroureterectomy using propensity scoring. Cox regression models tested the effect of surgery type on recurrence-free survival and cancer-specific survival. Estimated glomerular filtration rate was measured before and after surgery. Results: The median follow-up period was 50 months. There were no significant differences in 5-year recurrence-free survival and cancer-specific survival rates between the distal ureterectomy and nephroureterectomy groups (P = 0.22 and P = 0.70, respectively). Multivariate analysis showed that surgery type was not associated with recurrence-free survival and cancer-specific survival (P = 0.90 and P = 0.28, respectively). In the subanalysis, recurrence-free survival and cancer-specific survival in the distal ureterectomy group were equivalent to those of the nephroureterectomy group in both pTa-1 and pT2-4 patients. Renal function was better preserved in the distal ureterectomy group than in the nephroureterectomy group (rate of change in estimated glomerular filtration rate 2% vs −20%; P < 0.001). Conclusions:The oncological outcome of distal ureterectomy is comparable with that of nephroureterectomy in distal ureteral urothelial carcinoma patients, and distal ureterectomy provides better preservation of renal function. Distal ureterectomy would be feasible for carefully selected patients with distal ureteral urothelial carcinoma.

Resveratrol, which is a polyphenol found in grapes, peanuts, and other plants, has health benefits for various chronic diseases. The aim of the present study was to examine the effect of resveratrol on cataract formation in diabetic rats. Male Wistar rats (7-week-old) were treated with streptozotocin, and the streptozotocin-treated animals were administered 5% D-glucose in drinking water to promote the formation of cataracts by inducing severe hyperglycemia. Resveratrol supplementation (10 or 30 mg/kg/d) in drinking water was initiated immediately after induction of diabetes was confirmed. The full lens images of the horizontal plane were captured with the digital camera system which we developed. Cataract formation was assessed by an observer-based scoring method and by quantitative analysis of digital images of the lens. Cataracts at the peripheral region of the lens were detected 2 weeks after induction of hyperglycemia and progressed depending on the length of the diabetic period. The majority of them developed severe cataracts after 9 weeks of hyperglycemia. Resveratrol did not prevent the appearance of diabetic cataracts but significantly delayed the progression of cataracts compared with controls. The contents of sorbitol and protein carbonyls in lenses of diabetic rats were higher than those of control rats. Resveratrol suppressed the increase in protein carbonyls, but not of sorbitol, in diabetic lenses. These results suggest that resveratrol delays the progression of diabetic cataracts partially through attenuation of oxidative damage to lens proteins. Resveratrol may be beneficial in preventing the progression of diabetic cataracts.

Germ cell tumors (GCTs) are thought to arise from primordial germ cells (PGCs) that undergo epigenetic reprogramming: erasure of the somatic imprint in the genital ridge, and re-establishment of the sex-specific imprint at gametogenesis in the developing gonad. Previous studies suggested that GCTs show epigenetic patterns reflecting the reprogramming process of PGCs; however, epigenetic alterations of imprinted genes and their relationship with the methylation status of tumor suppressor genes (TSGs) have not been comprehensively studied. We analyzed the methylation status of the H19 and SNRPN differential methylated regions (DMRs) and the promoter region of 17 TSGs, and the expression status of H19, IGF2 and SNRPN in 45 GCTs, and found that 25 and 20 were in the normal and abnormal reprogramming pathways, respectively, defined on the basis of the methylation status of the two DMRs and the anatomical tumor site. The methylation pattern of the H19 and SNRPN DMRs was total erasure in seminomas, mostly physiological in teratomas, and various in yolk sac tumors. There were no correlations between the methylation status of the H19 DMR and mono-or biallelic expression of H19 or IGF2. Furthermore, we found that yolk sac tumors had a higher number of methylated TSGs than seminomas (P < 0.001) teratomas (P = 0.004) or other childhood tumors. While TSG methylation was known to have prognostic implications in various cancers, it did not affect the outcomes of patients with yolk sac tumor, suggesting that mechanisms of TSG methylation may be different between yolk sac tumor and other cancers. (Cancer Sci 2009; 100: 698-708) C hildhood germ-cell tumor (GCT) is a rare malignant neoplasm of the gonad or the extra-gonadal site, occurring at an incidence of 2.4 per million children and representing approximately 1% of cancers diagnosed in persons younger than 15 years.(1) In contrast, testicular GCT in men between the ages 20-40 is the most common cancer with an incidence of 8-10 per 100 000 in some European countries.(2) GCT is a unique tumor, thought to arise from primordial germ cells (PGCs) that undergo epigenetic reprogramming.(3) Genomic imprinting is the phenomenon that the paternal and maternal sets of chromosomes have different functionality in mammals, due to parental-specific epigenetic modification of the genome. This modification in mouse PGCs starts with imprint erasure on embryonic day 10.5 and is completed with imprint reestablishment at gametogenesis. (4)(5)(6) The H19 gene is located in 11p15.5 and encodes non-coding RNA, and the gene SNRPN (small nuclear ribonucleoprotein associated polypeptide N) located in 15q11-13 and encodes SmN, a protein involved in spliceosomes. (7,8) In normal tissues, while paternal H19 is not expressed due to methylation of the H19 differentially methylated region (DMR), maternal H19 is expressed due to the unmethylation of H19 DMR. Likewise, while paternal SNRPN is expressed due to the unmethylation of SNRPN DMR, maternal SNRPN is not expressed due to the methylation of SNRPN DMR. It...