The aim of this study was to establish permutation for cancer risk estimation in the urothelium. Twenty-six samples of normal control urothelium obtained from patients without urothelial carcinomas (C), 47 samples of non-cancerous urothelium without noticeable morphological changes obtained from patients with urothelial carcinomas (N), and 46 samples of the corresponding cancerous tissue (T) in the learning cohort and 64 N samples in the validation cohort, i.e. 183 tissue samples in total, were analyzed. Genome-wide DNA methylation analysis was performed using the Infinium HumanMethylation 450K BeadChip, and DNA methylation levels were verified using pyrosequencing and MassARRAY. Amplicon sequencing was performed using the GeneRead DNAseq Targeted Panels V2. Although N samples rarely showed genetic mutations or copy number alterations, they showed DNA methylation alterations at 2502 CpG sites compared to C samples, and such alterations were inherited by or strengthened in T samples, indicating that DNA methylation alterations may participate in field cancerization in the urothelium. Receiver operating characteristic curve analysis confirmed the feasibility of cancer risk estimation to identify urothelium at the precancerous stage by DNA methylation quantification. Cancer risk estimation permutation was established using a combination of two marker CpG loci on the HOXC4, TENM3 and TLR1 genes (sensitivity and specificity 96–100%). Among them, the diagnostic impact of 10 patterns of permutation was successfully validated in the validation cohort (sensitivity and specificity 94–98%). These data suggest that cancer risk estimation using procedures such as urine tests during health checkups might become applicable for clinical use.
The aim of this study was to develop a less invasive and accurate diagnostic system for upper urinary tract urothelial carcinoma (UTUC) based on genome-wide DNA methylation profiling. Genome-wide DNA methylation screening was performed using the Infinium HumanMethylation450 BeadChip, and DNA methylation quantification was verified using pyrosequencing. We analysed 26 samples of normal control urothelial tissue (C), an initial cohort of 62 samples (31 samples of non-cancerous urothelium [N] from UTUC patients and 31 samples of the corresponding UTUCs), a validation cohort of 82 samples (41 N and 41 UTUC samples), and 14 samples of urinary bladder urothelial carcinoma (BUC). In the initial cohort, we identified 2,448 CpG sites showing significant differences in DNA methylation levels between both C and UTUC and N and UTUC, but not showing differences between C and N. Among these CpG sites, 10 were located within CpG islands or their shores and shelves included in genomic domains where DNA methylation levels are stably controlled, allowing discrimination of UTUC even from BUC. Receiver operating characteristic curve analysis for discrimination of UTUC from N in these 10 CpG and neighbouring sites (37 diagnostic panels in total) yielded area under the curve values of 0.959–1.000, with a sensitivity and specificity of 86.6–100% and 93.5–100%, respectively. The diagnostic impact was successfully confirmed in the validation cohort. Our criteria were useful for diagnosis of UTUC, regardless of its clinicopathological features. Application of our criteria to voided urine samples will ultimately allow non-invasive DNA methylation diagnosis of UTUC.
Xanthogranulomatous cystitis (XC) is a rare benign chronic inflammatory disease of unknown etiology. Curative treatment of XC requires surgical resection, and most of reported cases were treated by partial cystectomy. Here we describe a case with XC that was treated using transurethral resection.
We report a case of nutcracker syndrome that developed after delivery. A 32-year-old woman visited our clinic complaining of gross hematuria 4 months after delivery. Urethrocystoscopic examination failed to show hematuria coming from the ureteral orifice; however, enhanced computed tomography revealed the compression of the left renal vein between the aorta and superior mesenteric artery. Therefore, we diagnosed her with nutcracker syndrome and conservatively observed her. The macrohematuria disappeared by itself after 1 month. This is the first report to describe a case of nutcracker syndrome that developed after delivery.
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