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Abstract Background The biomechanics of the hindfoot in ankle osteoarthritis (OA) are not yet fully understood. Here, we aimed to identify hindfoot motion in a gait analysis using a multi-segment foot model (MFM) according to ankle OA stage and the presence of subtalar compensation defined by hindfoot alignment. Methods We retrospectively reviewed the medical records, plain radiographs, and gait MFM data of 54 ankles admitted to our hospital for the treatment of advanced ankle OA. Spatiotemporal gait parameters and three-dimensional motions of the hindfoot segment were analyzed according to sex, age, body mass index, Takakura classification, and the presence of subtalar compensation. Twenty ankles were categorized as compensated group, and 34 ankles as decompensated group. Results No spatiotemporal gait parameters differed significantly according to the presence of subtalar compensation or ankle OA stage. Only normalized step width differed significantly (P = 0.028). Average hindfoot motion (decompensation vs. compensation) did not differ significantly between the sagittal and transverse planes. Graphing of the coronal movement of the hindfoot revealed collapsed curves in both groups that differed significantly. Compared with Takakura stages 3a, 3b, and 4, cases of more advanced stage 3b had a smaller sagittal range of motion than those of stage 3a (P = 0.028). Coronal movement of the hindfoot in cases of Takakura stage 3a/3b/4 showed a relatively flat pattern. Conclusions The spatiotemporal parameters were not affected by the hindfoot alignment resulting from subtalar compensation. The sagittal range of hindfoot motion decreased in patients with advanced ankle OA. Once disrupted, the coronal movement of the subtalar joint in ankle OA did not change regardless of ankle OA stage or hindfoot compensation state.

Purpose: T1 high grade (T1HG) bladder cancer (BC) is a type of non-muscle invasive BC (NMIBC) that is recognized as an aggressive subtype with a heightened propensity for progression. Current risk stratification methods for NMIBC rely on clinicopathological indicators; however, these approaches do not adequately capture the aggressive nature of T1HG BC. Thus, new, more accurate biomarkers for T1HG risk stratification are needed. Here, we enrolled three different patient cohorts and investigated expression of collagen type VI alpha 1 (COL6A1), a key component of the extracellular matrix, at different stages and grades of BC, with a specific focus on T1HG BC. Materials and Methods: Samples from 298 BC patients were subjected to RNA sequencing and real-time polymerase chain reaction. Results: We found that T1HG BC and muscle invasive BC (MIBC) exhibited comparable expression of COL6A1, which was significantly higher than that by other NMIBC subtypes. In particular, T1HG patients who later progressed to MIBC had considerably higher expression of COL6A1 than Ta, T1 low grade patients, and patients that did not progress, highlighting the aggressive nature and higher risk of progression associated with T1HG BC. Moreover, Cox and Kaplan–Meier survival analyses revealed a significant association between elevated expression of COL6A1 and poor progression-free survival of T1HG BC patients (multivariate Cox hazard ratio, 16.812; 95% confidence interval, 3.283–86.095; p=0.001 and p=0.0002 [log-rank test]). Conclusions: These findings suggest that COL6A1 may be a promising biomarker for risk stratification of T1HG BC, offering valuable insight into disease prognosis and guidance of personalized treatment decisions.

Category: Ankle Arthritis; Other Introduction/Purpose: It is unknown whether perioperative bisphosphonate (BP) use reduces revision rates in total ankle replacement arthroplasty (TAR) although its effect has been demonstrated to be effective in reducing revision rates in total knee or hip replacement arthroplasty. Therefore, the purpose of this study was 1) to investigate whether there is a relationship between the use of BP and the revision rate of TAR, and (2) to determine the effect of BP medication period on the revision rate of TAR. Our hypothesis was that the use of BP would lower the revision rate of TAR. Methods: We reviewed National Health Insurance Service data based on national health insurance service claim data and health care utilization, health screening, socio-demographic variables, medication history, operation codes, and mortality data for 50 million Koreans. From 2002 to 2014, 6391 of 7300 patients who underwent TAR were BP non-users, while 909 patients were BP users. The revision rate according to BP medication and co-morbidities was investigated. The Kaplan-Meier estimate and extended Cox proportional hazard model were also used. Results: The revision rate of TAR was 7.9% for BP users and 9.5% for BP non-users, which showed no significant difference (p=0.251). Implant survival over time decreased constantly. Adjusted hazard ratio for hypertension was 1.242 (p=0.017), while other co-morbidities such as diabetes had no effect on revision rate of TAR. Conclusion: We found that the perioperative BP use do not reduce the revision rate of TAR. Co-morbidities except hypertension did not affect the revision rate of TAR. More research regarding various factor affecting revision of TAR could be warranted.

Category: Hindfoot; Ankle Arthritis Introduction/Purpose: Although intramedullary nailing is a popular method for tibiotalocalcaneal (TTC) arthrodesis, nonunion is one of the most commonly reported complications. The purpose of this study was to evaluate the fusion rate, improvement in functional outcomes, and occurrence of complications in TTC arthrodesis using retrograde intramedullary nailing with partial fibulectomy and onlay bone graft technique. Methods: We retrospectively reviewed 26 consecutive patients who underwent TTC arthrodesis using the proposed technique. For radiographic outcomes, the union rate, alignment, and any related complications were assessed. Functional outcomes were evaluated using the American Orthopedic Foot and Ankle Society hindfoot scale, Foot and Ankle Outcome Score, and visual analog scale, preoperatively and at the final follow-up. Results: The mean follow-up period was 38.2 months. For the tibiotalar joint, the union rate was 80.8% six months postoperatively, while all the cases achieved complete bony union at twelve months postoperatively and at the final follow-up. However, for the subtalar joint, the union rate was 26.9% at six months postoperatively, which gradually increased to 73.1% at 12 months postoperatively, and 80.8% at the final follow-up without revision surgery. A subgroup analysis showed there was a trend of higher subtalar fusion rate when an additional screw for the subtalar joint fixation was placed (86.7% vs. 54.5%). The functional outcomes significantly improved at the final follow-up. A few minor complications occurred, including surgical site infection, irritational symptoms, and metal failure; however, these eventually resolved. Conclusion: Our technique of TTC arthrodesis with partial fibulectomy and onlay bone grafting demonstrated reliable radiographic and satisfactory functional outcomes including patients with previous failed hindfoot surgery. In addition, it is considered safe, as minimal complications occur postoperatively. We believe that our method of TTC arthrodesis provides a good option where both the tibiotalar and subtalar joints need to be fused.

Background: We aimed to evaluate the current status of first-line treatment options for prostate cancer in patients aged ≥75 years in Korea. Materials and methods: The study included 873 patients diagnosed with biopsy-proven prostate cancer at 5 institutions in Korea from January 2009 to December 2018. Inclusion criteria were aged ≥75 years at diagnosis, prostate biopsy with ≥12 cores, and follow-up period ≥1 year. Clinical data were retrospectively collected from electronic medical records. Results: Primary treatment for prostate cancer in patients aged ≥75 years included androgen deprivation therapy (ADT) (n = 614), radical prostatectomy (RP) (n = 114), and radiation therapy (n = 62). Among patients with RP, nine patients received ADT before RP. The RP group was younger with better Eastern Cooperative Oncology Group Performance Status (ECOG PS), lower initial prostate-specific antigen (PSA), Gleason score (GS), max percent positive cores, less positive cores, and less advanced clinical Tumor Node Metastasis (TNM) stage compared with the ADT group. Multivariate analysis showed that age, ECOG PS, and PSA were independent prognostic factors for RP. When the ADT group was classified by therapeutic regimens, the most common therapeutic regimen was maximal androgen blockade (MAB) (n = 571), and leuprolide + bicalutamide (n = 330) was the most common MAB regimen. Multivariate analysis for secondary treatment showed that age, ECOG PS, GS, and clinical N1 or M1 stage were independent predictive factors. Enzalutamide was the most preferred treatment for tertiary treatment. Conclusion: In patients with prostate cancer aged ≥75 years, the most common treatment option was MAB, and the leuprolide + bicalutamide was the most common MAB regimen. Age, ECOG PS, and PSA are the useful indicators of surgical treatment, which increased during the study period. Younger patients with high GS and advanced clinical stage were more likely to undergo secondary treatment.

Background: Prostate-specific antigen (PSA) is a marker of prostate cancer (PCa), although its efficacy as a diagnostic marker remains controversial. A high false-positive rate leads to repeat biopsy in approximately 70% of patients, which may not be necessary. Epigenetic biomarkers of field cancerization have been investigated widely as promising tools for the diagnosis of patients with suspected tumors. In the current study, we examined the diagnostic value of two microRNA (miRNA) candidates, hsv1-miR-H18 and hsv2-miR-H9, using formalin-fixed paraffin-embedded (FFPE) tissues from patients with PCa or benign prostate hyperplasia (BPH) (as controls) to determine the usefulness of these markers for detecting the presence of cancer. Methods: Expression of hsv1-miR-H18 and hsv2-miR-H9 in 201 FFPE tissues, including 52 primary tumors, 73 surrounding noncancerous tissues, and 90 BPH nontumor controls was examined by real-time PCR. Results: Expression of hsv1-miR-H18 and hsv2-miR-H9 was significantly higher in primary tumors from PCa patients than in BPH controls (P

Purpose: Tumor microRNAs (miRNAs) are released to biofluids directly or indirectly. Although urinary miRNAs are promising non-invasive biomarkers for the diagnosis of prostate cancer (PCa), their clinical application is challenging for technical reasons. We examined the efficacy of urinary hsv2-miR-H9 to hsa-miR-3659 ratio as a non-invasive diagnostic biomarker of PCa. Materials and Methods: The expression of urinary miRNAs was quantified by real-time PCR in 116 samples from 53 patients with benign prostatic hyperplasia (BPH) and 63 patients with PCa. The miRNA expression ratio was calculated using an upregulated miRNA (hsv2-miR-H9) as the numerator and a downregulated miRNA (hsa-miR-3659) as the denominator. Results: The urinary miR-H9 to miR-3659 ratio was significantly higher in PCa than in BPH controls (p

Category: Hindfoot; Ankle; Ankle Arthritis Introduction/Purpose: We do not yet fully understand how the subtalar joint position is related to the varus osteoarthritic ankle joint. The purposes of this study were 1) to investigate the coronal orientation of the calcaneus relative to the talus according to the ankle osteoarthritis stage, talar tilt (TT), and 2) to determine if there is a TT threshold at which apparent subtalar compensation begins to fade. Methods: We retrospectively reviewed 132 ankles that underwent WBCT for varus ankle osteoarthritis. The TT, subtalar inclination angle (SIA), and calcaneal inclination angle (CIA) were measured using WBCT. Ankles were divided into 5 groups according to Takakura stage and 2 groups according to the apparent compensation status of the subtalar joint and compared the index of the inclination of the subtalar joint relative to the ankle (SIA) or the index of the inclination of the calcaneus relative to the ankle (CIA). Additionally, we explored the relationship between SIA or CIA and the TT. Results: Apparent subtalar compensation (SIA and CIA) was significantly lower in Takakura stages 3b and 4. The SIA and CIA significantly differed according to the apparent compensation status (p

Purpose: We aimed to determine the influence of nutritional status on urinary metabolic abnormalities and stone recurrence in patients with urolithiasis. Materials and Methods: We analyzed data for 464 stone-formers and 464 propensity-score-matched control patients that had been collected between 2003 and 2015. Nutritional status was evaluated by use of the Controlling Nutritional Status (CONUT) score, and patients were placed into two CONUT score categories (0–1 and ≥2). Serum and 24-hour urinary metabolites were evaluated in 464 stone-formers. Kaplan–Meier and multivariate Cox regression analyses were performed to assess the influence of nutritional status on stone recurrence. Stone recurrence was defined as radiographic appearance of new stones during the follow-up period. Results: Stone-formers showed a higher prevalence of poor nutrition (CONUT score ≥2) than did the propensity-score-matched control patients (p

Purpose: Few studies have demonstrated the clinical significance of pretreatment serum albumin and globulin in prostate cancer (PCa). This study evaluated the association between the pretreatment albumin to globulin ratio (AGR) and clinicopathologic characteristics of nonmetastatic PCa in a large multicenter setting in Korea. Materials and Methods: This study involved 742 patients with nonmetastatic PCa who underwent radical prostatectomy (RP) in seven institutions between January 2011 and December 2012. The AGR was calculated as follows: albumin/(total protein−albumin). Patients were divided into low and high AGR groups by a cutoff value from a receiver operating characteristic curve analysis. Results: The best cutoff for the AGR was set at 1.53. The area under the curve of the AGR was 0.624 (95% confidence interval, 0.557–0.671; p

Purpose: P21-activated kinase 4 (PAK4), a serine/threonine kinase that regulates a number of fundamental cellular processes, has been suggested as a prognostic factor for various human tumors. The aim of the present study was to evaluate the clinical implications of phospho-Ser474 PAK4 (pPAK4S474), an activated form of PAK4, in surgically treated renal cell carcinoma (RCC). Materials and Methods: Samples from 131 patients with surgically treated RCC were immunostained to detect PAK4 and pPAK4S474. Expression of PAK4 and pPAK4S474 was compared with clinicopathological characteristics and survival after nephrectomy. Results: PAK4 and pPAK4S474 were expressed predominantly in the nucleus. Overall, 57.3% (75/131) and 24.4% (29/119) of specimens exhibited high expression of pPAK4S474 and PAK4, respectively. High expression of pPAK4S474 was associated with adverse pathologic characteristics, including advanced tumor stage and grade (p=0.036 and p=0.002, respectively), whereas this association was not significant for PAK4 expression (each p>0.05). Kaplan-Meier estimates showed that high expression of pPAK4S474 was associated with shorter recurrence-free survival in a subgroup with localized RCC and with cancer-specific survival in the total RCC cohort (log-rank test: p=0.001 and p=0.005, respectively), whereas PAK4 expression was not. Multivariate Cox regression analysis identified that high pPAK4S474 expression was an independent predictor of recurrence in the subgroup with localized RCC. Conclusions: pPAK4S474 may be a more accurate prognostic factor than total PAK4 in RCC patients. This marker would be useful for identifying patients with pathologically localized disease who may require further interventions.

Purpose: MicroRNAs (miRNAs) are small non-coding RNAs and are involved in the development, proliferation, and pathogenesis of prostate cancer (PCa). Urinary miRNAs are promising non-invasive biomarkers for PCa diagnosis because of their stability in urine. Here, we evaluated the diagnostic value of urinary miR-1913 to miR-3659 ratio in PCa patients and benign prostate hyperplasia (BPH) controls. Materials and Methods: Candidate miRNAs were identified from urinary microarray data and tested by real-time PCR. The urinary miR-1913 to miR-3659 expression ratio was selected and tested in 83 urine samples (44 PCa and 39 BPH) to confirm its validity as a non-invasive diagnostic biomarker for PCa. Results: The expression ratio of urinary miR-1913 to miR-3659 was significantly higher in PCa than in BPH (p=0.002) and showed a higher area under the receiver operating characteristic curve than prostate-specific antigen (PSA; 0.821 vs. 0.518) in patients within the PSA gray zone (tPSA: 3–10 ng/mL), with sensitivity of 75.0% and specificity of 78.6% (p=0.003). Conclusions: The urinary miR-1913 to miR-3659 expression ratio was increased in PCa and may serve as a useful supplemental biomarker to PSA for the diagnosis of PCa, particularly in patients within the PSA gray zone.

Abstract Background Recent reports show that the pre-operative or post-operative skeletal mass index (sarcopenia) affects survival rates for various cancers; however, the link between prostate cancer survival and sarcopenia is unclear. Therefore, this study examined the effect of the pre-operative internal obturator muscle (IOM) mass index on biochemical recurrence (BCR) of prostate cancer (PCa) patients who underwent radical prostatectomy. Methods In total, 222 patients, who underwent open, laparoscopic, or robot-assisted radical prostatectomy at seven centers in 2011 and were followed up for 5 years, were enrolled. BCR was examined in the context of pre-operative IOM mass index and BMI. Results The mean age of the patients was 67.82 ± 6.23 years, and the mean pre-operative prostate-specific antigen (PSA) level was 11.61 ± 13.22 ng/ml. There was no significant difference in baseline characteristics between the low and high IOM mass index groups (p > 0.05). Age, pre-op PSA level, ECE, and T-stage were associated with BCR (p = 0.049, p 0.05). Conclusions Pre-operative IOM mass index was not associated with BCR; however, long-term follow-up is necessary to evaluate cancer-specific and overall survival of PCa patients.

Purpose: Basal metabolic rate (BMR) is an indicator of overall body metabolism and may portend unique aberrations in urine physico-chemistry and stone recurrence. The present study examined the effect of predicted BMR on 24 hours urinary metabolic profiles and stone recurrence in obese stone patients. Materials and Methods: Data from 308 obese patients (body mass index [BMI] ≥30 kg/m2) diagnosed with urinary stone disease between 2003 and 2015 were analyzed retrospectively. BMR was calculated using the Harris–Benedict equation, and patients were classified into two predicted BMR categories (

Microbes play different roles in metabolism, local or systemic inflammation, and immunity, and the human microbiome in tumor microenvironment (TME) is important for modulating the response to immunotherapy in cancer patients. Renal cell carcinoma (RCC) is an immunogenic tumor, and immunotherapy is the backbone of its treatment. Correlations between the microbiome and responsiveness to immune checkpoint inhibitors have been reported. This review summarizes the recent therapeutic strategies for RCC and the effects of TME on the systemic therapy of RCC. The current understanding and advances in microbiome research and the relationship between the microbiome and the response to immunotherapy for RCC are also discussed. Improving our understanding of the role of the microbiome in RCC treatment will facilitate the development of microbiome targeting therapies to modify the tumor microbiome and improve treatment outcomes.

Background: The present study investigated the association of serum parathyroid hormone (PTH), vitamin D, and calcium levels with prostate cancer (CaP). Methods: The study population consisted of an experimental group [459 patients including 216 patients with CaP and 243 patients with benign prostate hyperplasia (BPH)] and a prostatectomy group (47 patients who underwent radical prostatectomy). Patients with serum creatinine levels >1.4 mg/dl, parathyroid disease, and/or PTH levels 20 ng/ml), Gleason score (≤7 or ≥8), and stage (≤T3 or ≥ T4), there was no significant difference in PTH levels between the two groups. Mean postoperative PTH levels (26.93 ± 13.58 pg/ml) were significantly lower than preoperative PTH levels (36.71 ± 21.04 pg/ml) in the same patients who underwent radical prostatectomy. Conclusion: Serum PTH levels were higher in patients with CaP than in patients with BPH and decreased significantly after radical prostatectomy. The present results suggest an association between serum PTH and CaP. Further large cohort studies are necessary to validate the present data.

Purpose: The aim of this study was to identify a noninvasive urinary marker for prostate cancer (PCa) diagnosis and to validate the clinical performance of this novel urinary mRNA signature using the droplet digital polymerase chain reaction (ddPCR) approach. Materials and Methods: A gene expression microarray (HT-12, Illumina Inc., USA) was used to identify genes differentially expressed between 16 PCa and 8 benign prostatic hyperplasia (BPH) tissues; ddPCR (QX200; Bio-Rad Laboratories, USA) was carried out to quantify the expression of selected genes in urine. The urinary molecular PCa risk score (UMPCaRS) was calculated by using the sum of three upregulated genes as the numerator and the sum of three downregulated genes as the denominator. The diagnostic utility of the UMPCaRS was validated by using a screening set (10 PCa and 10 BPH samples) and a validation set (131 PCa and 105 BPH samples). Results: Three upregulated genes (PDLIM5, GDF-15, THBS4) and three downregulated genes (UPK1A, SSTR3, NPFFR2) were selected from the microarray and subjected to ddPCR. The UMPCaRS for PCa in the screening and validation sets was significantly higher than that for BPH. For the validation set, the diagnostic accuracy of the UMPCaRS was comparable with that of prostate-specific antigen (PSA). Importantly, in the “PSA gray zone” (3–10 ng/mL), the AUC for the UMPCaRS was 0.843 and that for PSA was 0.628 (p

To evaluate the utility of different risk assessments in non-muscle-invasive bladder cancer (NMIBC) patients, a total of 178 NMIBC patients from Chungbuk National University Hospital (CBNUH) were enrolled, and the predictive value of the molecular signature-based subtype predictor (MSP888) and risk calculators based on clinicopathological factors (EORTC, CUETO and 2021 EAU risk scores) was compared. Of the 178 patients, 49 were newly analyzed by the RNA-sequencing, and their MSP888 subtype was evaluated. The ability of the EORTC, MSP888 and two molecular subtyping systems of bladder cancer (Lund and UROMOL subtypes) to predict progression of 460 NMIBC patients from the UROMOL project was assessed. Cox regression analyses showed that the MSP888 was an independent predictor of NMIBC progression in the CBNUH cohort (p = 0.043). Particularly in patients without an intravesical BCG immunotherapy, MSP888 significantly linked with risk of disease recurrence and progression (both p < 0.05). However, the EORTC, CUETO and 2021 EAU risk scores showed disappointing results with respect to estimating the NMIBC prognosis. In the UROMOL cohort, the MSP888, Lund and UROMOL subtypes demonstrated a similar capacity to predict NMIBC progression (all p < 0.05). Conclusively, the MSP888 is favorable for stratifying patients to facilitate optimal treatment.

Bladder cancer is a common global cancer with a high percentage of metastases and high mortality rate. Thus, it is necessary to identify new biomarkers that can be helpful in diagnosis. Pyruvate dehydrogenase kinase 4 (PDK4) belongs to the PDK family and plays an important role in glucose utilization in living organisms. In the present study, we evaluated the role of PDK4 in bladder cancer and its related protein changes. First, we observed elevated PDK4 expression in high-grade bladder cancers. To screen for changes in PDK4-related proteins in bladder cancer, we performed a comparative proteomic analysis using PDK4 knockdown cells. In bladder cancer cell lines, PDK4 silencing resulted in a lower rate of cell migration and invasion. In addition, a PDK4 knockdown xenograft model showed reduced bladder cancer growth in nude mice. Based on our results, PDK4 plays a critical role in the metastasis and growth of bladder cancer cells through changes in ERK, SRC, and JNK.

Abstract Background A complete enumeration study was conducted to evaluate trends in national practice patterns and direct medical costs for prostate cancer (PCa) in Korea over a 10-year retrospective period using data from the Korean National Health Insurance Service. Methods Reimbursement records for 874,924 patients diagnosed between 2002 and 2014 with primary PCa according to the International Classification of Disease (ICD) 10th revision code C61 were accessed. To assess direct medical costs for patients newly diagnosed after 2005, data from 68,596 patients managed between January 2005 and 31 December 2014 were evaluated. Results From 2005 to 2014, the total number of PCa patients showed a 2.6-fold increase. Surgery and androgen deprivation therapy were the most common first-line treatment, alone or within the context of combined therapy. Surgery as a monotherapy was performed in 23.5% of patients in 2005, and in 39.4% of patients in 2014. From 2008, the rate of robot-assisted RP rose sharply, showing a similar rate to open RP in 2014. Average total treatment costs in the 12 months post-diagnosis were around 10 million Korean won. Average annual treatment costs thereafter were around 5 million Korean won. Out-of-pocket expenditure was highest in the first year post-diagnosis, and ranged from 12 to 17% thereafter. Conclusions Between 2005 and 2014, a substantial change was observed in the national practice pattern for PCa in Korea. The present data provide a reliable overview of treatment patterns and medical costs for PCa in Korea.

Purpose: To analyze trends over a period of 28 years in the clinical, operative, and pathologic characteristics of patients with a renal mass who underwent surgical resection in Korea. Materials and Methods: Consecutive patients (n=6,231) with a renal mass who underwent surgical resection at eight Korean institutions between 1988 and 2015 were reviewed. Patients were assigned to one of three groups according to the date of surgery: group 1, 1988–1999; group 2, 2000–2009; and group 3, 2010–2015. Results: Age at the time of surgery, body mass index, smoking status, incidence of diabetes and hypertension, and the number of incidentally identified renal masses increased significantly over time. The proportion of patients undergoing partial nephrectomy (PN) or minimally invasive surgery (MIS) increased sharply during the last two time periods. From 2010, the rate of robot-assisted nephrectomy rose sharply, occurring in 37.8% of MIS cases. Benign pathology was identified in 1.8% and 5.2% of cases in the middle and last periods, respectively; angiomyolipoma was the most common pathology. In later years, tumors were more often localized, although tumor grade increased. Sub-group analysis of small renal masses ≤4 cm revealed similar trends in operative and pathologic characteristics over time. Conclusions: Between 1988 and 2015, there was a substantial change in the clinical, operative, and histological characteristics of patients who underwent resection of a renal mass in Korea. The most notable changes were stage migration towards localized disease and widespread use of PN and MIS.

Purpose: To determine the role of metabolic syndrome (MetS) as a risk factor for acquired premature ejaculation (PE) after considering the various risk factors, such as lower urinary tract symptoms, erectile dysfunction, hypogonadism, and prostatitis. Materials and Methods: From January 2012 to January 2017, records of 1,029 men were analyzed. We performed multivari-ate analysis to identify risk factors for PE, including the covariate of age, marital status, International Prostate Symptom Score, International Index of Erectile Function (IIEF) score, National Institutes of Health-Chronic Prostatitis Symptom Index (NIH-CPSI) score, serum testosterone levels, and all components of MetS. Acquired PE was defined as self-reported intravaginal ejacula-tion latency time ≤3 minutes, and MetS was diagnosed using the modified National Cholesterol Education Program Adult Treatment Panel III criteria. Results: Of 1,029 men, 74 subjects (7.2%) had acquired PE and 111 (10.8%) had MetS. Multivariate analysis showed that the IIEF overall satisfaction score (odds ratio [OR]=0.67, p

Summary: Background: Little is known about the preoperative predictive factors that could identify subsets of favorable patients who can be possibly cured with robot-assisted radical prostatectomy (RARP) alone in locally advanced prostate cancer (LAPCa). Our study was designed to identify clinical predictors of pathologic organ-confined disease (pOCD) in RARP setting. Methods: Between 2007 and 2013, clinicopathological and oncological data from 273 consecutive men undergoing robot-assisted RP with extended PLND for clinically LAPCa were reviewed in a single-institution, retrospectively. After exclusion of patients who received neoadjuvant hormone treatment before surgery, 186 subjects satisfied the final inclusion criteria. Results: Fourty-three patients (23.1% of total cohort) with preoperative clinically LAPCa patients were down-staged to pOCD following RARP. Preoperative prostate-specific antigen (PSA) level, preoperative PSAD, positive core percent, maximal tumor volume in any core, and biopsy Gleason score were significantly associated with down-staging into pOCD following RARP. Multivariate logistic regression analysis revealed that lower preoperative PSA (≤10 ng/mL) and maximal tumor volume in any core (≤70%) were independent predictors of pOCD following RARP. Conclusions: Approximately 23% of preoperative clinically LAPCa patients were down-staged to pOCD following RARP. Preoperative PSA and maximal tumor volume in any biopsy core might be useful clinical predictors of pOCD in clinically LAPCa patients in RARP setting. Keywords: Robotics, Prostatic neoplasms, Prostatectomy, Treatment outcome

Category: Basic Sciences/Biologics; Other Introduction/Purpose: Stair walking is one of common activities of daily living. It is more demanding than level walking and can aggravate discomfort of the foot, such as Morton’s neuroma, plantar fasciitis, Achilles tendinitis, pressure related-ulcer, and etc. Therefore, analysis of increased pressure in specific plantar area at stair walking can be used as a risk assessment of foot discomfort and basic data in the clinical field. The purpose of this study is to analyze plantar pressure distribution and pressure patterns during gait cycle at stair walking compared to level walking. Methods: Fourty healthy male adults were recruited. Radiologic measurements and gait analysis were performed to check participants’ normality, and 35 healthy males with 20-28 years old were included. They performed level walking (18 meters walkway), stair (26 steps stair, height:16.7cm, depth:29.8cm) ascending, and descending in same type of running shoes. Measurements of in-shoe plantar pressure including peak pressure, pressure-time integral (PTI) were done by Pedar-X system. The sole was masked in 7 segments (hallux, 2nd-5th toes, medial forefoot, central forefoot, lateral forefoot, midfoot, heel region) to analyze properly. Percentages were assigned in relation to the size for each mask segment. Statistical analysis was performed using repeated measure ANOVA, and Bonferroni post hoc test was done. Results: PP in all regions except for the midfoot were higher during level walking than stair walking. During stair descent, PP in all the regions except for the midfoot were generally lower than other types of walking, but it was the highest in the midfoot region. PTI in the medial and central forefoot was higher during stair descent than level walking. PTI in the central and lateral forefoot, and the midfoot was higher when stair ascending than level walking. PTI in the heel region was the highest during level walking, followed by stair ascent, stair descent. Conclusion: The risk of aggravation of discomfort in the midfoot area increases when stair descending. The medial region of forefoot bear high pressure load during stair descent, and the lateral region of forefoot and the midfoot region bear high pressure load during stair ascent. This is the first study to show plantar pressure patterns during level and stair walking in the large healthy gender-controlled population. We recommend that patients with pressure related foot lesions in the forefoot or midfoot avoid stair walking.

The transfibular approach is a common procedure for tibiotalar fusion. However, this technique has several concerns: inadequate stability to resist rotational and shearing forces, a fibula is suboptimal for bone grafting, and an onlay fibular graft that might prevent impacting and cause distraction. We present a modified transfibular technique using partial fibular resection and onlay bone graft, which may address these potential problems. This study aimed to evaluate whether the ankle joint is well fused with neutral alignment and functionally improved at the final follow-up. For this study, 27 consecutive patients (mean age, 68.5 years; range, 58-83) who underwent tibiotalar fusion with a follow-up period of >1 year were retrospectively included. A modified transfibular lateral approach was performed, in which the distal anterior half fibula was resected and fixed as an onlay graft to achieve fusion between the tibia, fibula, talus, and fibular onlay graft simultaneously. Radiographic outcomes were assessed using computed tomography at 4 months after operation and serial follow-up radiographs. Functional outcomes were assessed using the American Orthopedic Foot and Ankle Society hindfoot scale and Foot and Ankle Outcome Score. The mean follow-up period was 17.3 (range, 12-32) months. Four months after operation, complete union was achieved in 13 patients, near-complete union in 8 patients, and partial union in the remaining 6 patients. At the final follow-up, all the patients achieved complete union and maintained neutral ankle alignment. The functional outcome showed a significant increase between the preoperative and postoperative periods. One minor complication occurred, in which medial side ankle pain was relieved after screw removal. This modified technique is safe and effective, and has several merits, including saving the soft tissue of the anterior ankle, saving the course of the peroneal tendons by leaving the posterior half of the fibula, resected fibula serving as a good bone stock, and reducing the likelihood of valgus deformity after fibulectomy.

Because castration-resistant prostate cancer (CRPC) does not respond to androgen deprivation therapy and has a very poor prognosis, it is critical to identify a prognostic indicator for predicting high-risk patients who will develop CRPC. Here, we report a dataset of whole genomes from four pairs of primary prostate cancer (PC) and CRPC samples. The analysis of the paired PC and CRPC samples in the whole-genome data showed that the average number of somatic mutations per patients was 7,927 in CRPC tissues compared with primary PC tissues (range, 1,691 to 21,705). Our whole-genome sequencing data of primary PC and CRPC may be useful for understanding the genomic changes and molecular mechanisms that occur during the progression from PC to CRPC.

Purpose: This study aims to assess the predictive factors and treatment outcomes of Steinstrasse formation following shock wave lithotripsy (SWL) for ureter stone. Materials and Methods: The medical records of 1,418 ureter stone patients who underwent one-session SWL from November 2005 to May 2013 at our medical institute were retrospectively reviewed. Finally, 551 patients met inclusion criteria. Maximal length and location of stone, stone attenuation (Hounsfield units), and skin-to-stone distance (SSD) were determined on pretreatment non-contrast computed tomography. Results: Of 551 patients, 12 patients (2.2% of total cohort) developed Steinstrasse after one-session SWL. The Steinstrasse incidence was significantly associated with stone size, stone attenuation value, and SSD. Prophylactic ureter stenting was not a statistically significant predictor of Steinstrasse formation. After propensity-score matching, Steinstrasse group showed a significant shorter SSD compare to non-Steinstrasse group. Multivariate logistic regression and Bayesian analysis revealed that stone size, stone attenuation and SSD were significant predictor of Steinstrasse formation following SWL for ureter stone. The Steinstrasse resolved spontaneously in six patients and remaining six patients were treated by additional SWL. None of patients with Steinstrasse required ureteral stenting, percutaneous drainage, or consequent surgical intervention. Conclusions: Steinstrasse formation following SWL for ureter stone was rare event but nonnegligible. Large stone size, high stone attenuation and short SSD were significant predictors of Steinstrasse formation following SWL for ureter stone. Majority of patients with Steinstrasse formation could be treated conservatively in this clinical scenario.

Non-muscle-invasive bladder cancer (NMIBC) is a common disease with a high recurrence rate requiring lifetime surveillance. Although NMIBC is not life-threatening, it can progress to muscle-invasive bladder cancer (MIBC), a lethal form of the disease. The management of the two diseases differs, and patients with MIBC require aggressive treatments such as chemotherapy and radical cystectomy. NMIBC patients at a high risk of progression benefit from early immediate cystectomy. Thus, identifying concordant markers for accurate risk stratification is critical to predict the prognosis of NMIBC. Candidate genetic biomarkers associated with NMIBC prognosis were screened by RNA-sequencing of 24 tissue samples, including 16 NMIBC and eight normal controls, and by microarray analysis (GSE13507). Lastly, we selected and investigated a mitotic checkpoint serine/threonine kinase, BUB1, that regulates chromosome segregation during the cell cycle. BUB1 gene expression was tested in 86 NMIBC samples and 15 controls by real-time qPCR. The performance of BUB1 as a prognostic biomarker for NMIBC was validated in the internal Chungbuk cohort (GSE13507) and the external UROMOL cohort (E-MTAB-4321). BUB1 expression was higher in NMIBC patients than in normal controls (p < 0.05), and the overexpression of BUB1 was correlated with NMIBC progression (log-rank test, p = 0.007). In in vitro analyses, BUB1 promoted the proliferation of bladder cancer cells by accelerating the G2/M transition of the cell cycle. Conclusively, BUB1 modulates the G2/M transition to promote the proliferation of bladder cancer cells, suggesting that it could serve as a prognostic marker in NMIBC.

We present here a case of extensive necrotizing fasciitis during sorafenib treatment in a patient with HBV-related hepatocellular carcinoma. Despite emergent extensive surgical debridement, the patient's clinical status progressive worsened until interruption of sorafenib therapy. The patient was successfully treated with temporal interruption of sorafenib therapy. To our knowledge, this is the first case report of sorafenib-associated necrotizing fasciitis. Given the life-threatening nature of the infection and the necessity for urgent intervention, clinicians should be aware of this possible adverse effect of tyrosine kinase inhibitors. Keywords: Necrotizing fasciitis, Adverse drug reaction, Tyrosine kinase inhibitors, Hepatocellular carcinoma

Non-muscle-invasive bladder cancer (NMIBC) is clinically heterogeneous; thus, many patients fail to respond to treatment and relapse. Here, we identified a molecular signature that is both prognostic and predictive for NMIBC heterogeneity and responses to Bacillus Calmette-Guérin (BCG) therapy. Transcriptomic profiling of 948 NMIBC patients identified a signature-based subtype predictor, MSP888, along with three distinct molecular subtypes: DP.BCG+ (related to progression and response to BCG treatment), REC.BCG+ (related to recurrence and response to BCG treatment), and EP (equivocal prognosis). Patients with the DP.BCG+ subtype showed worse progression-free survival but responded to BCG treatment, whereas those with the REC.BCG+ subtype showed worse recurrence-free survival but responded to BCG treatment. Multivariate analyses revealed that MSP888 showed independent clinical utility for predicting NMIBC prognosis (each p = 0.001 for progression and recurrence, respectively). Comparative analysis of this classifier and previously established molecular subtypes (i.e., Lund taxonomy and UROMOL class) revealed that a great proportion of patients were similar between subtypes; however, the MSP888 predictor better differentiated biological activity or responsiveness to BCG treatment. Our data increase our understanding of the mechanisms underlying the poor prognosis of NMIBC and the effectiveness of BCG therapy, which should improve clinical practice and complement other diagnostic tools.

Purpose: Previously, we reported the presence of virus-encoded microRNAs (miRNAs) in the urine of prostate cancer (CaP) patients. In this study, we investigated the expression of two herpes virus-encoded miRNAs in prostate tissue. Methods: A total of 175 tissue samples from noncancerous benign prostatic hyperplasia (BPH), 248 tissue samples from patients with CaP and BPH, and 50 samples from noncancerous surrounding tissues from these same patients were analyzed for the expression of two herpes virus-encoded miRNAs by real-time polymerase chain reaction (PCR) and immunocytochemistry using nanoparticles as molecular beacons. Results: Real-time reverse transcription-PCR results revealed significantly higher expression of hsv1-miR-H18 and hsv2-miRH9- 5p in surrounding noncancerous and CaP tissues than that in BPH tissue (each comparison, P

This study was designed to identify clinical predictors of favorable pathology and biochemical recurrence (BCR) in patients with intermediate-risk prostate cancer (IRPCa). Between 2006 and 2012, clinicopathological and oncological data from 203 consecutive men undergoing robot-assisted radical prostatectomy (RARP) for IRPCa were reviewed in a single-institutional retrospective study. Favorable pathology was defined as Gleason score ≤6 and organ-confined cancer as detected by surgical pathology. Logistic regression analysis was used to determine predictive variables of favorable pathology, and the Kaplan-Meier and multivariate Cox regression model were used to estimate BCR-free survival after RARP. Overall, 38 patients (18.7%) had favorable pathology after RARP. Lower quartile prostate-specific antigen density (PSAD) was associated with favorable pathology compared to the highest quartile PSAD after adjusting for preoperative PSA, clinical stage and biopsy Gleason score (odds ratio, 5.42; 95% confidence interval, 1.01-28.97; P = 0.048). During a median 37.8 (interquartile range, 24.6-60.2) months of follow-up, 66 patients experienced BCR. There were significant differences with regard to BCR free survival by PSAD quartiles (log rank, P = 0.003). Using a multivariable Cox proportion hazard model, PSAD was found to be an independent predictor of BCR in patients with IRPCa after RARP (hazard ratio, 4.641; 95% confidence interval, 1.109-19.417; P = 0.036). The incorporation of the PSAD into risk assessments might provide additional prognostic information and identify some patients in whom active surveillance would be appropriate in patients with IRPCa.

Due to the rare occurrence of young-onset bladder cancer (YBC), its genomic characteristics remain largely unknown. Twenty-nine biopsy-proven YBC cases were collected using a nation-wide search for bladder cancer diagnosed at 20 years or younger. Whole exome sequencing and RNA sequencing were carried out in 21 and 11 cases, respectively, and compared with those of adult bladder cancer (ABC) cases obtained from public databases. Almost all YBCs were low grade, non-invasive papillary tumors. YBC had a low mutation burden and less complex copy number alterations. All cases harbored putative driver mutations. Mutations were most commonly found in HRAS (10 cases), with a preference for exon 5. FGFR3 gene fusions were noted with various partner genes (7 cases). The alterations on HRAS and FGFR3 occurred in a mutually exclusive manner. Others included KRAS mutations (2 cases), chromosomes 4p and 10q arm-level deletions (1 case), and ERCC2 mutation (1 case). There were no point mutations in TP53 and FGFR3. The gene expression profiles of YBC were similar to those of the ABC group with good prognosis. None of the YBCs and ABCs with YBC-like mutations showed progression to muscle-invasive tumors. Our results suggest that bladder cancer with YBC-like mutations represents an indolent bladder tumor, regardless of age.

Purpose: MicroRNAs (miRNAs) in biological fluids are potential biomarkers for the diagnosis and assessment of urological diseases such as benign prostatic hyperplasia (BPH) and prostate cancer (PCa). The aim of the study was to identify and validate urinary cell-free miRNAs that can segregate patients with PCa from those with BPH. Methods: In total, 1,052 urine, 150 serum, and 150 prostate tissue samples from patients with PCa or BPH were used in the study. A urine-based miRNA microarray analysis suggested the presence of differentially expressed urinary miRNAs in patients with PCa, and these were further validated in three independent PCa cohorts, using a quantitative reverse transcriptionpolymerase chain reaction analysis. Results: The expression levels of hsa-miR-615-3p, hsv1-miR-H18, hsv2-miR-H9-5p, and hsa-miR-4316 were significantly higher in urine samples of patients with PCa than in those of BPH controls. In particular, herpes simplex virus (hsv)-derived hsv1-miR-H18 and hsv2-miR-H9-5p showed better diagnostic performance than did the serum prostate-specific antigen (PSA) test for patients in the PSA gray zone. Furthermore, a combination of urinary hsv2-miR-H9-5p with serum PSA showed high sensitivity and specificity, providing a potential clinical benefit by reducing unnecessary biopsies. Conclusions: Our findings showed that hsv-encoded hsv1-miR-H18 and hsv2-miR-H9-5p are significantly associated with PCa and can facilitate early diagnosis of PCa for patients within the serum PSA gray zone.