Y.D. Choi

Analysis of fluorescence in situ hybridization, mtDNA quantification, and mtDNA sequence for the detection of early bladder cancer

We designed this study to test the sensitivities of cytology, the nuclear matrix protein 22 (NMP22) assay, and fluorescence in situ hybridization (FISH) in the early detection of urothelial carcinoma, and to identify mtDNA alterations in urinary epithelial cells. We collected 41 urine samples and 26 corresponding peripheral blood samples from patients with clinically suspected urothelial carcinoma. The FISH and NMP22 assays detected 92.1% of the cancers, and cytology detected 60.5%. In the low-grade group, NMP22 and FISH analyses were more sensitive than cytology, but in the high-grade group, all three methods showed approximately 90% sensitivity. Overall, the FISH and NMP22, or FISH and cytology assays combined detected 97.4% of cancers, while cytology with NMP22 detected 92.1%. In the low-grade group, the sensitivity of the three methods combined was above 80%, but in high-grade group, the combined sensitivity was approximately 100%. In the mtDNA control region, we detected characteristic heteroplasmic mtDNA substitution mutations in 1 patient and a mtDNA length heteroplasmic mutation in 303 polyC or 16184 poly C in 20 patients. Overall, urothelial carcinoma-specific mtDNA mutations were observed in 20 of the 26 patients (76.9%). The average mtDNA copy numbers in urine samples and corresponding peripheral blood samples (83.45 +/- 60.36 and 39.0 +/- 24.38, respectively) (mean +/- standard deviation [SD]) differed significantly (P < 0.001). The mtDNA copy numbers in the urine samples from patients with high-grade and low-grade tumors (81.83 +/- 67.78 and 86.49 +/- 46.69, respectively) did not differ significantly (P = 0.589). In conclusion, the FISH assay showed the highest sensitivity for detecting low-grade urothelial carcinoma, and mtDNA copy numbers in urine samples were higher than those in the corresponding peripheral blood samples. The frequency of mtDNA mutations in the D-loop region in patients with cancer was approximately 80% in our study. This report further supports the significance of genetic alteration in urothelial carcinoma and the clinical utility of the FISH, mtDNA quantitation polymerase chain reaction, mtDNA sequencing, and capillary electrophoresis for this purpose.

A multi-institutional study on histopathological characteristics of surgically treated renal tumors: The importance of tumor size

Purpose The incidence of accidentally detected small renal tumors is increasing throughout the world. In this multi-institutional study performed in Korea, histopathological characteristics of contemporarily surgically removed renal tumors were reviewed with emphasis on tumor size. Materials and Methods Between January 1995 and May 2005, 1,702 patients with a mean age of 55 years underwent surgical treatment at 14 training hospitals in Korea for radiologically suspected malignant renal tumors. Clinicopathological factors and patient survival were analyzed. Results Of the 1,702 tumors, 91.7% were malignant and 8.3% were benign. The percentage of benign tumors was significantly greater among those ≤ 4 cm (13.2%) than those > 4 cm (4.5%) (p < 0.001). Among renal cell carcinoma patients, the percentage of tumors ≤ classed as stage ≥ T3 was significantly less among tumors 4 cm (5.2%) than those > 4 cm (26.8%) (p < 0.001). The percentage of tumors classed as Fuhrmans nuclear grades ≥ 3 was also significantly less among tumors ≤ 4 cm (27.3%) than tumors > 4 cm (50.9%) (p < 0.001). The 5-year cancer-specific survival rate was 82.7%, and T stage (p < 0.001), N stage (p < 0.001), M stage (p = 0.025), and Fuhrmans nuclear (p < 0.001) grade were the only independent predictors of cancer-specific survival. Conclusion In renal tumors, small tumor size is prognostic for favorable postsurgical histopathologies such as benign tumors, low T stages, and low Fuhrmans nuclear grades. Our observations are expected to facilitate urologists to adopt function-preserving approach in the planning of surgery for small renal tumors with favorable predicted outcomes.

462 Computed tomography-based novel prediction model for the outcome of SWL in proximal ureteral stone

INTRODUCTION AND OBJECTIVES: Variations in morphology and internal structure of urinary calculi may cause differences in stone fragility. Stone heterogeneity index (SHI), a proxy of such variations, was defined as the standard deviation of a Hounsfield unit (HU) on noncontrast computed tomography (NCCT). As shown in Fig. 1, because the composition of urinary stones can vary even though they have a similar MSD, we postulated that a heterogeneous stone may be more fragile than a homogeneous stone. Herein, we defined the stone heterogeneity index (SHI) as the standard deviation of stone density on NCCT, and investigated whether SHI can be a novel predictor for SWL outcomes in patients with ureteral stones. METHODS: Medical records were obtained from the consecutive database of 1,519 patients who underwent the first session of SWL for urinary stones between Nov 2005 and Dec 2013. Ultimately, 604 patients with radiopaque ureteral stones were eligible for this study. Stone related variables including stone size, mean stone density (MSD), skin-to-stone distance, and SHI were obtained on NCCT. Patients were classified into the low and high SHI groups using mean SHI and compared. RESULTS: One-session success rate in the high SHI group was better than in the low SHI group (74.3% vs. 63.9%, P1⁄40.008). Multivariate logistic regression analyses revealed that smaller stone size (Odds ratio [OR] 0.889, 95% Confidence Interval [CI]: 0.841-0.937, P<0.001), lower MSD (OR 0.995, 95% CI: 0.994-0.996, P<0.001), and higher SHI (OR 1.011, 95% CI: 1.008-1.014, P<0.001) were independent predictors of one-session success. Similarly, stone size, MSD, and SHI also had an independent impact on one-session stone-free status (Table 1). CONCLUSIONS: The radiologic heterogeneity of urinary stones or SHI was an independent predictor for SWL success in patients with ureteral calculi and a useful clinical parameter for stone fragility.