Hyun Ho Han

Transvesicoscopic Ureteral Reimplantation in Children with Bilateral Vesicoureteral Reflux: Surgical Technique and Results

OBJECTIVES To report our initial experience with transvesicoscopic cross-trigonal ureteral reimplantation (TVUR), describing stepwise the surgical procedure and determining critical aspects of this surgery in the actual surgical field. SUBJECTS AND METHODS Between September 2008 and April 2010, 48 patients with bilateral vesicoureteral reflux (VUR) underwent TVUR. To identify the critical aspects affecting the surgical difficulty, we divided our TVUR procedure into four steps: TVUR set-up, mobilization of ureters, creation of submucosal tunnels, and ureterovesical anastomosis. To evaluate the evolution of our TVUR, we analyzed changes in the operative time and complications versus increase in surgeon experience (dividing our cases into three groups: the first third, the second third, and the last third). Changes in operative time for all four steps of TVUR were analyzed separately, as well as change in overall operative time. RESULTS Of a total of 48 cases, 45 patients underwent TVUR successfully except for 3 cases of open conversion. Among the 45 cases, the mean overall operative time was 155.6 min. In 1 patient, proximal migration of the ureteral catheter occurred. No other perioperative complications were observed. The mean postoperative hospital stay was 1.6 days. The VUR resolution rate was 96.4%. Upon analysis of our results by step, Step 4 (ureterovesical anastomosis) required the largest portion of the overall operative time in most cases. During the early period of our TVUR, we encountered several technical difficulties. However, the operative times for all four steps were stabilized with increasing number of cases, without deteriorating surgical outcomes. CONCLUSIONS Our report demonstrates that TVUR might potentially be a safe and effective alternative to open ureteral reimplantation in children with VUR, with a shorter learning curve than expected.

Differential diagnosis of complex renal cysts based on lesion size along with the Bosniak renal cyst classification.

Purpose To identify size criteria for complex cystic renal masses that can distinguish renal cell carcinoma from benign cysts supplementing the Bosniak classification. Materials and Methods We reviewed the records of 97 patients who underwent surgery for complex cystic renal masses from January 2001 to April 2010. The pathological results were compared with the lesion sizes measured by preoperative computed tomography and other radiological features (contrast enhancement, irregularities of cyst walls and septa, and calcification) were also obtained for categorization according to the Bosniak renal cyst classification. Results Malignancy was significantly associated with cyst size (>2 cm), male gender, and younger patient age (<50 years). According to the Bosniak classification, there was no category I cyst, and all 8 category II cysts were benign. However, 3 of 18 (17%) category IIF cysts, 21 of 39 (54%) category III cysts, and 29 of 32 (90%) category IV cysts were malignant. All category IIF cysts were benign in patients older than 50 years of age. Conclusion Many complex cystic renal masses smaller than 2 cm were benign. We suggest that lesion size should be taken into account when formulating treatment plans for complex cystic renal masses.

Factors associated with continuing medical therapy after transurethral resection of prostate.

OBJECTIVE To report the clinical characteristics of patients who have persistent lower urinary tract symptoms (LUTS) after surgery for benign prostatic hyperplasia (BPH) and continue their medical therapy postoperatively. MATERIALS AND METHODS We retrospectively studied 372 patients who underwent transurethral resection of prostate for LUTS/BPH in 8 institutions to determine the differences between patients who continued LUTS/BPH medications for >3 months after surgery and those who did not. Preoperative, intraoperative, and postoperative clinical parameters were assessed. The Student t test and chi square test were used to compare each parameter between patient groups. Multivariate logistic regression analysis was performed to identify risk factors for persistent LUTS and continuing medical therapy after surgery. RESULTS There were 205 patients (55.1%) who continued their LUTS/BPH medications for >3 months postoperatively. They reported poorer International Prostate Symptom Scores and uroflowmetry results after surgery. Multivariate analysis showed that age >70 years (odds ratio [OR], 2.474; P = .001), history of diabetes (OR, 1.949; P = .040), history of cerebrovascular accident (OR, 5.932; P = .001), any previous LUTS/BPH medication use (OR, 5.384; P = <0.001), and previous antimuscarinic drug use (OR, 2.962; P = .016) were significantly associated with symptom persistency and continuing medical therapy. CONCLUSION Many patients have persistent voiding dysfunction after surgical treatment for LUTS/BPH. Older age, history of diabetes, history of cerebrovascular accidents, and preoperative antimuscarinic drug uses are possible risk factors.

Epidemiology of prostate cancer in South Korea

Background Prostate cancer (PCa) is the second most frequently diagnosed cancer in male. In South Korea, PCa incidence has increased significantly, while its mortality rate has decreased steadily. To optimize the distribution of public medical resources, it is essential to analyze the contemporary epidemiology of PCa. Methods National population data from the National Health Insurance Statistical Yearbook and the annual report of national cancer registration and statistics in Korea were assessed. From the data, the incidence, prevalence, and mortality rates of PCa were calculated. The data were presented with reference to other types of cancers occurring in various countries from different continents. Results From 2007 to 2013, PCa incidence doubled (from 5,516 per year to 10,855 per year), while its prevalence in Korean men tripled (from 18,830 to 51,411) during the same period. The mortality rate increased slightly, from 4.2 in 2000 to 5.9 in 2007 and 6.0 in 2013 (per 100,000, age adjusted). PCa incidence increased significantly faster in men aged < 70 years than in the older age group. Conclusion PCa prevalence in South Korea has increased significantly, mainly due to the rise in its incidence. As the country is facing major changes, including westernization of dietary habits and rapid population aging, its prevalence would continue to increase in near future.

MicroRNA alteration and putative target genes in high-grade prostatic intraepithelial neoplasia and prostate cancer: STAT3 and ZEB1 are upregulated during prostate carcinogenesis

We aimed to identify alteration of cancer‐related miRNAs in HGPIN and PCa, and to investigate the clinical implications of HGPIN as a precancerous lesion of PCa.

Daily use of sildenafil 50mg at night effectively ameliorates nocturia in patients with lower urinary tract symptoms associated with benign prostatic hyperplasia: an exploratory multicenter, double-blind, randomized, placebo-controlled study

Abstract Purpose: To compare the efficacy and safety of sildenafil 25 mg qd, 25 mg bid or 50 mg qd – on treating lower urinary tract symptoms with benign prostatic hyperplasia (LUTS/BPH). Materials and methods: Men aged > 45 years with LUTS/BPH were randomly assigned to receive sildenafil 25 mg qd (n = 42), bid (n = 41), 50 mg qd (n = 38) or placebo (n = 41) for 8 weeks. Changes from baseline in International Prostate Symptom Score (I-PSS), maximum urinary flow rate (Qmax) and postvoid residual urine volume (PVR) were assessed at week 4 and week 8. Results: Sildenafil 25 mg qd (-7.3 ± 5.8) and 25 mg bid (-7.0 ± 5.7) exhibited significant improvements of I-PSS compared to placebo (-5.2 ± 6.4) (p = 0.020, 0.025, respectively). In particular, voiding domain was more affected than storage domain. Only sildenafil 50 mg qd improved nocturia significantly (versus placebo, p = 0.027). Quality of life score was improved in all treatment groups. Qmax and PVR did not change significantly in all groups. All regimens were well tolerated. Conclusions: Sildenafil 25 mg qd, 25 mg bid and 50 mg qd are safe and effective to improve LUTS/BPH in long term, along with coexisting ED. In particular, nocturia is most well-controlled by 50 mg qd.

Transcriptome-wide analysis of compression-induced microRNA expression alteration in breast cancer for mining therapeutic targets

Tumor growth–generated mechanical compression may increase or decrease expression of microRNAs, leading to tumor progression. However, little is known about whether mechanical compression induces aberrant expression of microRNAs in cancer and stromal cells. To investigate the relationship between compression and microRNA expression, microRNA array analysis was performed with breast cancer cell lines and cancer-associated fibroblasts (CAFs) exposed to different compressive conditions. In our study, mechanical compression induced alteration of microRNA expression level in breast cancer cells and CAFs. The alteration was greater in the breast cancer cells than CAFs. Mechanical compression mainly induced upregulation of microRNAs rather than downregulation. In a parallel mRNA array analysis, more than 25% of downregulated target genes were functionally involved in tumor suppression (apoptosis, cell adhesion, and cell cycle arrest), whereas generally less than 15% were associated with tumor progression (epithelial-mesenchymal transition, migration, invasion, and angiogenesis). Of all cells examined, MDA-MB-231 cells showed the largest number of compression-upregulated microRNAs. miR-4769-5p and miR-4446-3p were upregulated by compression in both MDA-MB-231 cells and CAFs. Our results suggest that mechanical compression induces changes in microRNA expression level, which contribute to tumor progression. In addition, miR-4769-5p and miR-4446-3p may be potential therapeutic targets for incurable cancers, such as triple negative breast cancer, in that this would reduce or prevent downregulation of tumor-suppressing genes in both the tumor and its microenvironment simultaneously.

Estrogen Receptor Status Predicts Late-Onset Skeletal Recurrence in Breast Cancer Patients.

AbstractEstrogen receptor-positive (ER+) breast cancer (BCa) often recurs after long latency, and is known to favor bone as a metastatic site. We hypothesized that skeletal recurrence of ER+ BCa follows a different chronological pattern from that of nonskeletal recurrence.We retrospectively evaluated 434 matched pairs of ER+ and ER− female patients who underwent surgery for clinically localized BCa between 2005 and 2009. Patient age, tumor size, lymph node involvement, and adjuvant treatment biases were adjusted by the propensity score method. We conducted competing risk analysis to determine the prognostic significance of ER expression status on the risk of overall recurrence and late recurrence (after 3 years). We also compared chronological patterns of ER+ and ER− tumor recurrence, stratified by the first metastatic site (skeletal vs nonskeletal).After 3 postoperative years, ER+ tumor had a significantly higher risk of overall distant recurrence than ER− tumor (P = 0.02). When further stratified by first site of metastasis, only late skeletal recurrence was significantly associated with ER status (P = 0.029). In multivariate analysis, ER and lymph node involvement status were significant prognostic factors for late skeletal recurrence, with adjusted hazard ratios of 5.2 (95% CI = 1.2–22.4, P = 0.025) and 5.2 (1.7–16.3, P = 0.005), respectively. For nonskeletal distant recurrence, tumor size (>2 cm) was the only significant risk factor with adjusted hazard ratio of 2.8 (1.4–5.7, P = 0.005). Annual hazard of skeletal recurrence events of ER+ tumors continued to exist up to 10 years, while annual hazard of nonskeletal recurrences decreased after peaking at 5 years. ER− tumor recurrences exhibited similar annual hazard patterns across skeletal and nonskeletal sites.ER expression and lymph node involvement status were strong predictors of BCa late-onset (>3 years) recurrences, especially in skeletal sites. Therefore, skeletal system surveillance is mandatory for long-term follow-up of this subpopulation.

Mechanical compression induces VEGFA overexpression in breast cancer via DNMT3A-dependent miR-9 downregulation

Tumor growth generates mechanical compression, which may trigger mechanotransduction in cancer and stromal cells and promote tumor progression. However, very little is known about how compression stimulates signal transduction and contributes to tumor progression. In the present study, we demonstrated that compression enhances a tumor progression phenotype using an in vitro compression model, and validated the results from the in vitro model with high- and low-compressed breast cancer tissues. Mechanical compression induced miR-9 downregulation by DNMT3A-dependent promoter methylation in the MDA-MB-231 and BT-474 breast cancer cell lines and in cancer-associated fibroblasts. The overexpression of miR-9 target genes (LAMC2, ITGA6, and EIF4E) was induced by miR-9 downregulation, which eventually enhanced vascular endothelial growth factors production. Demethylation and decompression could reverse compression-induced miR-9 downregulation and following overexpression of miR-9 target genes and VEGFA.

Nodal metastasis signatures in breast cancer

Although the molecular taxonomy of invasive breast cancer is based on heterogeneous histologic types, pathologic nodal (pN) stage remains one of the most important independent prognostic factors. Although node-positive number (NPN) has been widely as an accepted staging algorithm of pN stage, the node-positive ratio (NPR) in totally resected axillary nodes has been considered as another reasonable indicator. We aimed to identify signatures to play a predictive role in nodal metastasis for analytic validation between the primary breast cancers with positive node metastasis and those with negative node metastasis. We validated expression profiles of surrogate candidates extracted from the prior 2D MALDI-TOF data for invasive breast cancer using fluorescence/silver in situ hybridization (FISH/SISH) and immunohistochemistry (IHC) in 151 primary breast cancers accompanied with 102 metastatic nodal tissues. Cox proportional hazards regression analyses indicated that event factors (recurrence or metastasis) were significantly more frequent in cases with CCDN1, c-myc gene amplification, IgHA2 low expression. CCDN1 gene amplification (OR: 5.702, p=0.0006), IgHA2 low expression (OR: 0.16, p=0.0184) remained significant factors for events on multivariate analyses. WDR+/ERK++ was significantly detected in higher pN stage (averaging 6.5 regional nodes or 43% of NPR), while seldom found in pN0-1. In conclusion, both overexpression of WDR1 and p-ERK in the primary breast cancer could play a role in the nodal signature over pN2-3.