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Even with advances in perioperative medical care, anesthetic management, and surgical techniques, radical cystectomy (RC) which remains the gold standard therapy for the treatment of muscle-invasive bladder cancer, yet is still associated with a high morbidity rate as well as a prolonged length of hospitalization (LOH). Recently, there has been a great deal of interest in developing multimodal and multidisciplinary strategies that might aid in the acceleration postoperative convalescence by decreasing variance in perioperative care for patients having complex operations. Many patient series have shown that Enhanced Recovery After Surgery (ERAS) protocols can improve outcomes in patients having RC by reducing the incidence of gastrointestinal complications and the LOH without increasing readmissions or overall morbidity. Many studies are going to evaluate and incorporate scientific data in ERAS program to modify as many of the variables leading to RC morbidity, as well as to enhance how patients are cared for before and after operation. In this review, we offer a summary of the preoperative, intraoperative, and postoperative key components of undergoing an ERAS protocol for patients undergoing RC, as well as future research prospects.

Radical cystectomy (RC) is the gold standard treatment option for muscle invasive bladder cancer (MIBC). However, up to 25% of patients who undergo RC show metastatic lymph node deposits during the procedure. In such cases, the 5-year survival rate is reported to be 25%–30%. Pelvic lymph node dissection (PLND) can also provide useful prognostic information, including data regarding the disease burden, lymph node density, and extracapsular extension of metastatic lymph nodes. Accordingly, the National Comprehensive Cancer Network guidelines recommend that PLND that includes the common iliac lymph node should be performed at the time of RC to allow reliable staging of MIBC. In addition to its diagnostic role, many studies have reported the potential therapeutic role of PLND. Data from clinical trials indicate a substantial oncological advantage in PLND cohorts compared to non-PLND cohorts, regardless of pathological nodal status, as a result of removal of metastatic and micrometastatic tumor cells nested in lymph nodes. As such, despite the diagnostic and therapeutic role of PLND in MIBC, the optimal PLND template remains controversial. Currently, extended PLND (E-PLND) is recommended for diagnostic purposes, however, E-PLND did not show therapeutic effectiveness in some recent preliminary randomized controlled trials. In this review, we will discuss the appropriate range of PLND for RC in terms of its diagnostic and therapeutic importance, and propose an appropriate range of PLNDs based on the evidence and randomized trials so far.

In the surgical oncology field, the change from a past radical surgery to an organ preserving surgery is a big trend. In muscle-invasive bladder cancer treatment, neoadjuvant chemotherapy (NAC) followed by radical cystectomy (RC) is the standard of care for muscle-invasive bladder cancer (MIBC) patients eligible for cisplatin. There is a growing interest in bladder preserving strategies after NAC because good oncologic outcome has been reported for pathologic complete response (pCR) patients after NAC, and many studies have continued to discuss whether bladder preservation treatment is possible for these patients. However, in actual clinical practice, decision-making should be determined according to clinical staging and there is a gap that cannot be ignored between clinical complete response (cCR) and pCR. Currently, there is a lack in a uniform approach to post-NAC restaging of MIBC and a standardized cCR definition. In this review, we clarify the gap between cCR and pCR at the current situation and focus on emerging strategies in bladder preservation in selected patients with MIBC who achieve cCR following NAC.

BACKGROUND: Limited data compare first-line carboplatin-based chemotherapy and immune checkpoint blockade in cisplatin-ineligible metastatic urothelial carcinoma (mUC) patients. The primary evidence guiding treatment decisions was a recent Food and Drug Administration/European Medicines Agency safety alert based on emerging data from two ongoing phase III trials, reporting shorter survival in programmed death-ligand 1 (PD-L1) negative patients receiving immunotherapy. Final results from these trials are unknown. OBJECTIVE: To compare survival in cisplatin-ineligible mUC patients receiving first-line immunotherapy versus carboplatin-based chemotherapy. DESIGN, SETTING, AND PARTICIPANTS: We conducted a retrospective cohort study of 2,017 mUC patients receiving first-line carboplatin-based chemotherapy (n=1,530) or immunotherapy (n=487) from January 1, 2011 to May 18, 2018 using the Flatiron Health electronic health record-derived database. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary outcome was overall survival (OS), comparing 12- and 36-month OS, and hazard ratios before and after 12 months. Propensity score-based inverse probability of treatment weighting (IPTW) was used to address confounding in Kaplan-Meier and Cox regression model estimates of comparative effectiveness. RESULTS AND LIMITATIONS: IPTW-adjusted OS rates in the immunotherapy group were lower at 12 months (39.6% [95% CI 34.0-45.3%] versus 46.1% [95% CI 43.4-48.8%]) but higher at 36 months (28.3% [95% CI 21.8-34.7%] versus 13.3% [95% CI 11.1-15.5%]) relative to the chemotherapy group. Immunotherapy treatment demonstrated inferior OS during the first 12 months relative to carboplatin-based chemotherapy (IPTW-adjusted HR 1.37, 95% CI 1.15-1.62), but superior OS beyond 12 months (IPTW-adjusted HR 0.50, 95% CI 0.30-0.85). Limitations include retrospective design and potential unmeasured confounding. CONCLUSIONS: In the setting of mUC, clinicians and patients should carefully consider how to balance the short-term benefit of chemotherapy against the long-term benefit of immunotherapy. PATIENT SUMMARY: To determine the optimal first-line therapy for metastatic bladder cancer patients who are unfit for cisplatin, we compared carboplatin-based chemotherapy versus immunotherapy using real-world data. Survival in the first year of treatment was lower with immunotherapy relative to chemotherapy, but for patients surviving beyond the first year, immunotherapy was superior.

Clear cell papillary renal cell carcinoma (ccpRCC) was recently established as a distinct type of epithelial neoplasm by the International Society of Urological Pathology Vancouver Classification of Renal Neoplasia. Here, we report a case of partial nephrectomy for a ccpRCC detected during the routine follow-up of a previously treated liposarcoma in a 70-year-old male patient. The patient was referred to the urology department for a right-sided renal mass (size: 2 cm) detected during routine annual imaging follow-up for a malignant right inguinal fibrous histocytoma and liposarcoma that had been diagnosed 6 and 4 years earlier, respectively, and treated with surgery and adjuvant radiation therapy. Following partial nephrectomy, the renal mass was pathologically diagnosed as ccpRCC, and immunohistochemistry revealed carbonic anhydrase 9 (CA9) expression. No recurrences or metastases were detected on follow-up imaging for 6 months. This is the first report of partial nephrectomy for incidentally discovered CA9-positive ccpRCC.

Objective: Often a sick or an anxious person can experience pain or anxiety relief if another person holds his or her hand. In this study, we conducted investigations to determine whether hand-holding during cystoscopy decreases patient anxiety, pain, and dissatisfaction while at the same time increasing patient comfort and tolerance during the procedure. Patients and Methods: Eighty-six male patients who underwent flexible cystoscopy between November 2015 and March 2017 were randomized as follows: hand-holding (group I, n = 43) or non-hand-holding (group II, n = 43) during the procedure. Before flexible cystoscopy, lidocaine gel was instilled in the urethra. Patients’ anxiety levels were quantified using the State-Trait Anxiety Inventory. A visual analog scale (0–10) was used for self-assessment of satisfaction, discomfort, and willingness to undergo repeat cystoscopy. Results: Demographic characteristics, mean age, procedure duration, procedure indications, and preprocedural analyses did not differ significantly between the 2 groups. In group I, the postprocedural mean anxiety level, pain score, heart rate, and systolic blood pressure were significantly lower compared with those in group II (p = 0.009, p = 0.003, p = 0.022, and p = 0.014, respectively). In group I, postprocedural mean satisfaction score were higher, and patients were more likely to undergo a repeat cystoscopy, compared with those in group II (p = 0.001 and p = 0.004, respectively). Conclusions: Hand-holding during cystoscopy significantly reduced patients’ feelings of anxiety, pain, discomfort, and dissatisfaction. Hand-holding served as a simple, inexpensive, and effective adjunct to sedation during cystoscopy.

PURPOSE Secondary primary cancers (SPCs) commonly arise in patients with renal cell carcinoma (RCC). We designed the present study to estimate the SPC incidence in Korean patients with RCC. MATERIALS AND METHODS The study cohort was population-based and consisted of 40,347 individuals from the Korean Central Cancer Registry who were diagnosed with primary renal cancer between 1993 and 2013. Standardized incidence ratios (SIRs) for SPCs were estimated for different ages at diagnosis, latencies, diagnostic periods, and treatments. RESULTS For patients with primary RCC, the risk of developing a SPC was higher than the risk of developing cancer in the general population (SIR, 1.13; 95% confidence interval, 1.08 to 1.18). Most cancer types showed higher incidences in patients with RCC than in the general population. However, the relative incidence of gastric cancer as an SPC varied by age. Gastric cancer incidence was elevated in young patients (< 30 years) with RCC, but reduced in older (≥ 30) patients with RCC. Patients with advanced RCC died prematurely, regardless of SPC development. In contrast, those with early-stage RCC survived for longer periods, although SPC development affected their post-RCC survival. After SPC development, women had better survival than men. CONCLUSION In Korean patients with primary RCC, the incidence of SPC was 13% higher than the incidence of cancer in the general population. These findings may play important roles in the conduct of follow-up evaluations and education for patients with RCC.

In the present study we examined the effect of the Prognostic Nutritional Index (PNI) on the overall survival (OS) and progression-free survival (PFS) of patients with metastatic renal cell carcinoma (RCC) treated with targeted therapy.The study included 125 patients with metastatic RCC. Pretreatment PNI was calculated as 10 × serum albumin (g/dL) + 0.005 × total lymphocyte count (per mmThe median follow-up time was 45.3 months (interquartile range, 23.7-77.3 months). Decreased PNI was significantly associated with older female patients, poor Eastern Cooperative Oncology Group performance status, types of initial drug, and increased Memorial Sloan Kettering Cancer Center (MSKCC) and Heng risk score (P .05). An increase in the PNI of 1 unit was associated with a 10% decrease in the risk of death from RCC (hazard ratio, 0.90; P .001). In the multivariable analysis, the PNI was an independent prognostic factor for OS (P .001). In intermediate-risk patients according to MSKCC and Heng risk criteria, OS was better in the high PNI group than in the low PNI group (P = .0136 and P = .0009, respectively).PNI is an independent prognostic factor in patients with metastatic RCC treated with targeted therapy. When used as an adjunct, it increases the prognostic accuracy of established factors and could be a valuable tool for tailoring surveillance, patient counseling, and clinical trial design.

Purpose We evaluated the impact of benign prostatic hyperplasia (BPH) and prostatitis on the risk of prostate cancer (PCa) in patients using nationally representative data of the Korean population from the National Health Insurance Service. Materials and methods A total of 5,580,495 Korean men, aged >20 years, who had undergone health screening in 2009 were followed-up for 9 years until 2017. Multivariate adjusted Cox regression analysis was conducted to determine the hazard ratio (HR) and 95% confidence interval (CI) for the association between BPH and/or prostatitis and PCa. The HR for PCa according to the presence of BPH and/or prostatitis was stratified by a combination of BPH and prostatitis in multivariable-adjusted models. Results The HR for PCa significantly increased in patients with BPH and prostatitis than in patients without BPH and prostatitis (adjusted HR, 1.626; 95% CI, 1.567-1.688 and adjusted HR, 1.557; 95% CI, 1.500-1.618, respectively). In particular, for the combination of BPH and prostatitis, the adjusted HR was 1.856 (95% CI, 1.743-1.976), which was the highest when a diagnosis of both BPH and prostatitis was made. Conclusions BPH and/or prostatitis are associated with an increased incidence for PCa in Korean patients, which is likely associated with similar effects to prostate-specific antigen (PSA) screening, so care must be taken in the interpretation. However, if follow-up survival studies demonstrate differences between the two groups (BPH and prostatitis vs. general), it could be one of the evidence for the introduction of PSA screening in Korea.

Background Docetaxel is the preferred chemotherapeutic agent for hormone-refractory prostate cancer (PC) patients. However, patients eventually develop docetaxel resistance, and no effective treatment options are available for them. Objective We aimed to establish docetaxel resistance in castration-resistant prostate cancer (CRPC) cell lines (DU145/TXR, PC-3/TXR, and CWR22/TXR) and characterized transcriptional changes upon acquiring resistance to the docetaxel. Methods Human PC cells (DU145, PC-3, CWR22) and all docetaxel-resistant cells were maintained in Roswell Park Memorial Institute Medium (RPMI) 1640 media supplemented with 10% fetal bovine serum and 1% penicillin/streptomycin. ABCB1 was detected by using both parental and docetaxel-resistant CRPCs prepared for flow cytometry. For the evaluation of tumor-suppressive effects under each chemotherapeutic agent, subcutaneous xenografts of DU145 or DU145/TXR were implanted at the mouse flank. Results The P-glycoprotein-encoding gene ABCB1 was distinctively upregulated in the resistant cells, and its overexpression played an essential role in docetaxel resistance in CRPC. When tested for the cytotoxicity of gemcitabine, another option for chemotherapy, the docetaxel-resistant cells were shown to become sensitive to the drug, implying additional phenotypic transformation in the docetaxel-resistant cells. Studies using xenograft animal models demonstrated that the growth of tumors composed of both docetaxel-sensitive and docetaxel-resistant cells was deterred most profoundly when docetaxel and gemcitabine were administered together. Conclusion This study suggests that when a drug develops therapeutic resistance, sensitivity tests could be another option, ultimately providing insight into a novel alternative clinical strategy.

Purpose. This study aimed to evaluate the statuses of P16INK4A expression and human papillomavirus (HPV) infection among patients with penile cancer at a single Korean institution. Patients and Methods. Fourteen patients with penile cancer at our center were retrospectively identified and their clinicopathological data were analyzed. The patients’ HPV and P16INK4A expression status (a known tumor suppressor protein) were tested using genotyping with a DNA chip assay and immunohistochemical staining, respectively. The results regarding HPV status were compared to those from another Asian study. Results. The mean age at diagnosis was 60 years (range: 34–86 years). The median tumor size was 3.0 cm (range: 0.6–4.7 cm). Ten tumors were located on the penile glans. Five patients tested positive for HPV DNA (5/14, 36%) and all cases involved HPV type 16 (5/5, 100%). Positive expression of P16INK4A was observed in 6 cases (6/14, 43%). Among the HPV positive cases, 80% of cases (4/5) were also positive for P16INK4A. The prevalence of HPV infection in our study (36%) was higher than in a previous Asian study (23%). Conclusions. This is the first study to evaluate the prevalence of HPV infection and P16INK4A expression among patients with penile cancer at a single Korean institution. The prevalence of HPV (36%) was slightly higher than the results from a previous Asian study. Additional multi-center studies are needed to better understand penile cancer in Korea and to identify biomarkers that can determine high-risk cases and predict their prognosis.

Purpose We aimed to evaluate the efficacy and safety of the use of docetaxel plus androgen deprivation therapy (ADT) for metastatic hormone-sensitive prostate cancer (mHSPC) in Korean patients. Materials and methods This study was conducted retrospectively. In total, 61 Korean patients with mHSPC who used docetaxel plus ADT were identified from medical records. Patients received docetaxel plus ADT at a dose of 75 mg/m2 every 3 weeks for 6 cycles. We evaluated prostate-specific antigen (PSA) response, PSA progression, progression to castration-resistant prostate cancer (CRPC), clinical progression, and adverse events. Results Most of the patients had high volume disease (98.3%) and 83.6% had a Gleason score of 8 or higher. The median PSA level at the start of ADT was 131.4 ng/mL. The percentage of patients whose PSA levels decreased to less than 0.2 ng/mL at 3, 6, and 12 months were 28.3%, 41.0%, and 45.0%, respectively. During a median of 12.0 months after treatment, PSA progression occurred in 13.3% of patients. Clinical progression and progression to CRPC were observed in 15.1% and 14.8%, respectively. Neutropenia grade ≥3 and febrile neutropenia occurred in 63.5% and 11.5%, respectively. Conclusions Comparing our findings with those of the prior chemohormonal therapy versus androgen ablation randomized trial for extensive disease in prostate cancer (CHAARTED) study, in Korean patients, the use of docetaxel plus ADT for mHSPC showed similar results for early oncologic outcomes including PSA response and time to clinical progression. However, we observed a higher rate of adverse events, which should be considered seriously.

Background For the expanding population of bladder cancer survivors in Korea, the development of subsequent cancers is a significant concern. Here, we provide the second primary cancer incidence rates and types in Korean patients with bladder cancer. Methods Using population-based data from the Korea Central Cancer Registry from 1993 to 2013, we studied the standardized incidence ratios among 48,875 individuals with an initial diagnosis of bladder cancer. Standardized incidence ratios for second primary cancers were evaluated according to age at diagnosis, latency, diagnostic year, and treatment. Results Over the same period, the overall risk of a second primary cancer was reduced by 6% in patients with bladder cancer compared with the development of a new malignancy in the general population (standardized incidence ratio = 0.94; 95% CI, 0.91–0.97, p

The aim of this study was to identify factors that can be used to predict severe neutropenia (grade 3 or higher) in patients with advanced urothelial cancer after cisplatin-based systemic chemotherapy.The study examined 79 Korean patients with advanced urothelial cancer who were treated with several cycles of cisplatin-based systemic chemotherapy from May 2006 to May 2015. Risk factors for neutropenia (grade 3 or higher) and for the occurrence of neutropenia (grade 3 or higher) during the first cycle of chemotherapy were examined.Thirty-six out of the 79 patients (45.6%) developed neutropenia at grade 3 or higher during the first cycle of cisplatin-based systemic chemotherapy: 18 (22.7%) of these experienced grade 3 neutropenia and 18 (22.7%) experienced grade 4. Multivariate analysis identified pretreatment neutrophil counts (P = .001) as the only significant factor predictive for severe neutropenia.The pretreatment neutrophil count was found to be the factor that poses a significant and independent risk in development of severe neutropenia induced by applying cisplatin-based systemic chemotherapy to patients with advanced urothelial cancer.

Objective The aim of this study was to predict the discriminating prognostic power of the neutrophil-to-lymphocyte ratio for overall survival in patients with metastatic renal cell carcinoma and to make a new model using the neutrophil-to-lymphocyte ratio. Methods From 2007 to 2014, 190 patients with metastatic renal cell carcinoma treated with either systemic immunotherapy or/and vascular endothelial growth factor-targeted therapy were enroled. A multivariable proportional hazard model was developed to investigate the effects of the neutrophil-to-lymphocyte ratio as predictive prognostic factors for overall survival. This new model was incorporated into the current Heng risk model to validate a modified prognostic classification for overall survival. Results In multivariable analysis, a high neutrophil-to-lymphocyte ratio [hazard ratio (HR) = 1.65] was a significant independent predictor of shorter overall survival (P = 0.005). Additional neutrophil-to-lymphocyte ratio markers improved the discriminating power of the Heng risk classification, as compared to the existing classification model (C-statistic: 0.7198 vs. 0.6943, P = 0.008). The reclassification of patient prognostic categories using the new model showed a total overall net improvement of 61.4% (P < 0.001). Conclusion The neutrophil-to-lymphocyte ratio was a significant prognostic factor of overall survival in metastatic renal cell carcinoma patients treated with systemic therapy. Adding the neutrophil-to-lymphocyte ratio to the Heng model significantly improved the discriminatory power of risk prediction in metastatic renal cell carcinoma.

The standard management for patients with muscle-invasive bladder cancer (MIBC) involves radical cystectomy and pelvic lymph node dissection. Although this treatment may be curative, a large proportion of patients will develop recurrence and will ultimately die because of metastatic disease. Prospective randomized clinical trials have revealed a survival advantage for patients who receive neoadjuvant chemotherapy (NAC) before radical cystectomy, and this concept has been confirmed using meta-analysis. Moreover, cisplatin-based combination NAC has consistently provided a survival benefit of 5%, and pathological downstaging is used as a surrogate endpoint for evaluating its efficacy. The efficacy of NAC for MIBC has primarily been established for regimens with methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC), which provide complete response rates (pT0) as high as 38%. Dose-dense MVAC is preferred over standard MVAC, and gemcitabine/cisplatin is a reasonable alternative to standard MVAC for NAC.

In a previous report, 3-aminopropyl functionalized magnesium phyllosilicate (aminoclay) improved adenovirus transduction efficiency by shielding the negative surface charges of adenovirus particles. The present study analyzed the physicochemical characterization of the electrostatic complex of adenoviruses with aminoclay and explored whether it could be utilized for enhancing tumor suppressive activity in the bladder. As a result of aminoclay-adenovirus nanobiohybridization, its transduction was enhanced in a dose-dependent manner, increasing transgene expression in bladder cancer cells and in in vivo animal models. Physicochemical studies demonstrated that positively charged aminoclay led to the neutralization of negative surface charges of adenoviruses, protection of adenoviruses from neutralizing antibodies and lowered transepithelial electrical resistance (TEER). As expected from the physicochemical properties, the aminoclay enabled tumor-targeting adenoviruses to be more potent in killing bladder cancer cells and suppressing tumor growth in orthotopic bladder tumors, suggesting that aminoclay would be an efficient, versatile and biocompatible delivery carrier for intravesical instillation of adenoviruses.

PURPOSE The use of prostate-specific antigen as a biomarker for prostate cancer (PC) has been controversial and is, therefore, not used by many countries in their national health screening programs. The biological characteristics of PC in East Asians including Koreans and Japanese are different from those in the Western populations. Potential lifestyle risk factors for PC were evaluated with the aim of developing a risk prediction model. Materials and Methods A total of 1,179,172 Korean men who were cancer free from 1996 to 1997, had taken a physical examination, and completed a lifestyle questionnaire, were enrolled in our study to predict their risk for PC for the next eight years, using the Cox proportional hazards model. The model's performance was evaluated using the C-statistic and Hosmer‒Lemeshow type chi-square statistics. RESULTS The risk prediction model studied age, height, body mass index, glucose levels, family history of cancer, the frequency of meat consumption, alcohol consumption, smoking status, and physical activity, which were all significant risk factors in a univariate analysis. The model performed very well (C statistic, 0.887; 95% confidence interval, 0.879 to 0.895) and estimated an elevated PC risk in patients who did not consume alcohol or smoke, compared to heavy alcohol consumers (hazard ratio [HR], 0.78) and current smokers (HR, 0.73) (p < 0.001). CONCLUSION This model can be used for identifying Korean and other East Asian men who are at a high risk for developing PC, as well as for cancer screening and developing preventive health strategies.

Objective To characterize the clinical and metabolic abnormalities of patients presenting with multiple stones and determine their risk of new stone formation. Materials and Methods This retrospective case-controlled study consisted of 911 patients who had ureter stones for the first time and 107 age- and sex-matched patients without stones. The patients were classified into 2 groups: those with a single ureter stone (n = 690) and those with 1 or more additional stones somewhere in the ureter or kidney (n = 221). All patients underwent 24-hour urinary metabolic evaluation. The 240 patients (26.3%) who were followed for >12 months (median follow-up, 35.0 months) were included in recurrence analyses. Stone recurrence was defined as “new stone formation,” namely, the radiographic appearance of stones that had not been present in previous examinations. Results The multiple-stone group had significantly lower urinary citrate excretion than the single-stone (P = .011) and control (P = .003) groups. Compared with the single-stone group, it also had a higher incidence of hypocitraturia (P = .011) and stone recurrence (27 of 84 [32.1%] vs 29 of 156 [18.6%] patients; P = .025). Multivariate Cox regression analyses revealed that stone multiplicity (hazard ratio, 2.343; 95% confidence interval, 1.302-4.220; P = .005) was an independent predictor of recurrent stone formation. Kaplan-Meier curves showed identical results. Conclusion The patients with multiple stones had distinct metabolic characteristics, particularly hypocitraturia and a significantly higher risk of recurrence than patients with 1 stone. Patients with multiple stones, even if it is their first stone episode, should undergo metabolic evaluation and possibly also potassium citrate therapy to prevent future stones.

The aim of this study was to determine predictive factors for neutropenia after docetaxel-based systemic chemotherapy in patients with castration-resistant prostate cancer (CRPC). The study included 40 Korean CRPC patients who were treated with several cycles of docetaxel plus prednisolone from May 2005 to May 2012. Patients were evaluated for neutropenia risk factors and for the incidence of neutropenia. In this study, nine out of forty patients (22.5%) developed neutropenia during the first cycle of docetaxel-based systemic chemotherapy. Four experienced grade 2, three grade 3, and one grade 4 neutropenia. Multivariate analysis showed that pretreatment white blood cell (WBC) count (p=0.042), pretreatment neutrophil count (p=0.015), pretreatment serum creatinine level (p=0.027), and pretreatment serum albumin level (p=0.017) were significant predictive factors for neutropenia. In conclusion, pretreatment WBC counts, neutrophil counts, serum creatinine levels, and serum albumin levels proved to be significant independent risk factors for the development of neutropenia induced by docetaxel-based systemic chemotherapy in patients with CRPC.

To validate the Memorial Sloan-Kettering Cancer Center (MSKCC) and Heng models with metastatic renal cell carcinoma treated with sunitinib, and to investigate prognostic factors in these patients. This study included 106 patients with metastatic renal cell carcinoma who were treated with sunitinib from April 2007 to July 2012 including 35 patients who received systemic treatment before sunitinib and 71 that were naive to systemic treatment. Patients were evaluated using the MSKCC and Heng models, and the significance of several prognostic factors were evaluated. The application of the MSKCC and Heng risk criteria resulted in stratification into 3 groups (favorable, intermediate, and poor risk) with distinctly different overall survival (OS) curves (P

Purpose: Patients with bladder pain syndrome/interstitial cystitis (BPS/IC) can have pain as a main symptom and overactive bladder (OAB) symptoms that are directly or indirectly related to a major mechanism that causes pain. The primary purpose of this study is firstly to identify the prevalence rate of OAB symptoms in patients with BPS/IC, secondly to identify changes in OAB symptoms after low-dose triple therapy, and thirdly to build a theoretical foundation to improve quality of life for patients. Methods: Patients who met the inclusion criteria of BPS/IC through basic tests including the O’Leary-Sant symptom index, overactive bladder symptom score (OABSS), and visual analog scale (VAS) were identified. Treatment-based changes in OAB symptoms were identified using the IC Symptom Index and IC Problem Index (ICSI/ICPI), OABSS, and VAS before, and 4 and 12 weeks after low-dose triple therapy. Results: The patients consisted of 3 men and 20 women, and their mean age was 61.9 years (41.0–83.2 years). Comparing values before treatment, and 4 and 12 weeks after treatment (baseline vs. 4 weeks to baseline vs. 12 weeks), the rates of improvement were as follows: ICSI, 44.2% to 63.7%; ICPI, 46.9% to 59.4%; OABSS, 34.3% to 58.2%; and VAS, 53.6% to 75.0%, which showed statistically significant differences (P0.05). Conclusions: Low-dose triple therapy in BPS/IC results in a clear decrease in OAB symptoms in the first 4 weeks after treatment, and additional treatment for 8 weeks had a partial effect with varied statistical significances depending on the questionnaires.

// Ho Kyung Seo 1, 2 , Seung-Phil Shin 2 , Na-Rae Jung 2 , Whi-An Kwon 3 , Kyung-Chae Jeong 4 and Sang-Jin Lee 2 1 Center for Prostate Cancer, Hospital, National Cancer Center, Goyang, Gyeonggi-do, Korea 2 Genitourinary Cancer Branch, Research Institute, National Cancer Center, Goyang, Gyeonggi-do, Korea 3 Department of Urology, School of Medicine, Institute of Wonkwang Medical Science, Wonkwang University, Wonkwang University Sanbon Hospital, Gunpo, Gyeonggi-do, Korea 4 Biomolecular Function Research Branch, Research Institute, National Cancer Center, Goyang, Gyeonggi-do, Korea Correspondence to: Sang-Jin Lee, email: leesj@ncc.re.kr Ho Kyung Seo, email: seohk@ncc.re.kr Keywords: bladder cancer, c-myc, orthotopic bladder cancer model, MBT-2 Received: April 20, 2016 Accepted: June 17, 2016 Published: July 22, 2016 ABSTRACT To properly evaluate the biological effects of immunotherapy, it is critical to utilize a model of cancer in immune-competent mice. Currently, MBT-2 is the most common murine bladder cancer cell line used in orthotopic bladder cancer models, even though this cell type often has an inappropriate genetic mutation landscape. In these models, after tumors are detected with in vivo imaging, the mouse usually dies within two to three weeks due to post-renal azotemia caused by the rapidly growing mass. This event prohibits the evaluation of tumor behavior upon intravesical drug treatment. We explored whether an shRNA-induced decrease in the expression of the c-myc oncogene in MBT-2 cells could slow down their in vitro proliferation and in vivo tumor growth. We transduced MBT-2 cells with shRNA lentiviruses that bound c-myc, established MBT2.cMYCshRNA and confirmed the retardation of the growth of tumors implanted in C3H/He mice. Accordingly, this study suggests that this novel orthotopic bladder cancer model in immune-competent mice may be more appropriate for the analysis of the effects of the intravesical instillation of immunotherapeutic agents.

Bladder failure is a condition or a collection of symptoms in which the bladder is unable to evacuate the urine completely due to inadequate detrusor contraction [1]. This hidden condition that does not usually lead to complaints is common in the elderly, and its incidence increases inevitably with aging. Moreover, there is a lack of basic research into the underlying causes of this disease, along with a lack of unified terminology and related definitions and acceptable diagnostic criteria. The biggest burden to us, clinicians, is the necessity of requiring incapable elderly patients to perform painful clean intermittent catheterization several times a day. It is urgent that we restart by coming to a consensus on the terminology of this disease. In cases of heart failure, there seems to be no other currently used terminology for that condition, which might be the first important step towards the current achievements in treating heart failure. This may be the key to the possible differences in the academic content and achievements in the fields of heart failure and bladder failure. The term “bladder failure” still remains surrounded by ambiguity with a lack of accepted terminology [2]. In our opinion, the terminology for any disease should be simple and easily recognizable by the patients as well as physicians. Although “bladder failure” may give the impression of an all-or-nothing event, giving the condition a name may be the first step toward an expansion in the development of bladder failure research. The heart and bladder are harder-working organs than any others in the body, continuously pumping blood or urine out. The failure of these organs may have similar underlying mechanistic causes and pathogenesis. In this issue of International Neurourology Journal, Marquez et al. [3] introduces a close relationship between the heart and mitochondrial function in the regulation of cellular energetics and metabolism, and describes the beneficial effect of targeting mitochondrial biogenesis in failing hearts. Furthermore, although there are currently no pharmacologic agents that directly affect mitochondrial biogenesis in heart failure, this article shows current advances in the development of heart failure therapies, including mitochondrial biogenesis, mitochondrial oxidative stress, and mitochondrial pore transition proteins. A similar relationship between the bladder and mitochondrial function was described previously in a study of bladder failure [4,5]. However, researchers in the field of bladder failure seem to have much work to do in the future.

Aim of this study was to evaluate HRQoL of patients affected by NMIBC underwent intravesical instillations of Bacillus Calmette-Gu erin (BCG) or Mytomicin C (MMC) with a short-term follow-up. METHODS: From December 2011 to December 2014 we recruited 108 consecutive patients in a single academic center with a first-time diagnosis of NMIBC at intermediate or high risk. The median age was 73 years (38-94) and 55.3% (N 57) patients underwent BCG and 44.7% (N 46) patients underwent MMC after TURBT respectively. The assessment of HRQoL was performed using two questionnaires from EORTC: QLQ-C30 and QLQ-BLS24 specific for NMIBC. Patients self-completed the questionnaires in three different times: T0 (before intravesical instillation), T1 (after intravesical instillation), T2 (at three months after last instillation). The above analysis was stratified by gender, age (?70 years and >70 years), tumour degree risk (intermediate and high risk) and type of intravesical therapy (MMC and BCG). Wilcoxon two sample test was used to verify differences. Statistical significance was achieved if pvalue was 1⁄40.05 (two-sides). RESULTS: Treatment was well tolerated in both groups of patients underwent intravesical instillations of BCG and MMC respectively. Grade I and II side effects, as CTCAE classification, were reported by 46.6% of patients at T1 and 47.5% at T2. 5 patients dropped out of the study (3 lost in follow-up and 2 developed side effects of BCG). At T1 we founded a drop in QoL, with reference to Physical, Role, Emotional and Social functioning domains and a worsening of urinary bladder symptoms with a generally decrease of Global Quality of Life Score. The sexual sphere was affected by adjuvant therapy with persistence or worsening of sexual disorders. At T2 patients showed a progressive return to baseline QoL, in particular in the Social and clinical symptoms domains. Male gender, age>70 years, high-risk tumours and BCG seem to be the factors that worsening HRQoL of these patients. CONCLUSIONS: Intravesical instillations seem to modify the HRQoL of these patients with a return at 3 months to baseline conditions.

Objectives: We investigated the outcomes of paclitaxel and cisplatin chemotherapy as an optional regimen for patients with metastatic urothelial carcinoma after failure of two consecutive platinum-based regimens. Methods: We retrospectively analyzed the data of 21 patients who had evidence of disease progression after two consecutive platinum-based regimens, gemcitabine and cisplatin (GC course), and methotrexate, vinblastine, doxorubicin and cisplatin (M-VAC course) as first-line and second-line treatments. As third-line chemotherapy, patients received paclitaxel (175 mg/m2) and cisplatin (70 mg/m2) every 3 weeks until disease progression. Results: Complete remission occurred in one patient (4.8%), partial remission occurred in three patients (14.3%) and stable disease occurred in five patients (23.8%). The overall response rate was 19.0% and the overall disease control rate, including stable disease, was 42.9%. The median progression-free survival (PFS) was 3 months (95% CI 3.0–5.0). The median overall survival was 9 months (95% CI 7.0–15.0). Grade 3 to 4 neutropenia appeared in 85.7% of patients. No life-threatening complications were observed. Conclusions: Paclitaxel and cisplatin chemotherapy could be an optional regimen for patients with metastatic urothelial carcinoma after the failure of two consecutive standard platinum-based regimens.

INTRODUCTION AND OBJECTIVES: Animal models have shown that oxalate is both absorbed and secreted within the intestine. Gastrointestinal oxalate absorption has been demonstrated in humans but there are limited data regarding secretion and the conformation of oxalate within the human alimentary tract. The objective of this study was to measure the amount and conformation of oxalate in the stomach and small intestine of adults undergoing upper G.I. endoscopy. METHODS: Eight adults undergoing endoscopy of the stomach or both the stomach and the small bowel participated in this study. None of the patients had end stage renal disease. All fasted for a minimum of 8 hours. Aspirates from fluid and material within these areas were obtained. Oxalate was measured by ion chromatography. The limit of detection of this technique is 1.5 micro-molar. A determination of the soluble and insoluble components of oxalate was made by centrifugation of the sample and subsequent acidification of the resultant pellet. RESULTS: Only one of eight gastric samples had detectable oxalate, 4.9 micro-molar. There was no insoluble oxalate in the gastric samples. In contrast, two of six small intestinal samples contained oxalate, 14.6 micro-molar and 130 micro-molar. All intestinal samples had no insoluble oxalate except the 130 micro-molar specimen, 58 micrograms per gram. CONCLUSIONS: These results demonstrate that there is no measurable oxalate secretion in the stomach in the fasted state in individuals who do not have end stage renal disease. Our results also indicate that in the majority there is no measurable oxalate secretion in the small intestine in the fasted state in subjects without end stage renal disease. While small intestinal oxalate secretion could have occurred in 2 of the subjects, this oxalate could also have emanated from residual food. Further studies are warranted including in patients with renal dysfunction.

ObjectiveThe sound of running water (SRW) has been effectively used for toilet training during toddlerhood. However, the effect of SRW on voiding functions in adult males with lower urinary tract symptoms (LUTS) has not been evaluated. To determine the effect of SRW on urination in male patients with LUTS, multiple voiding parameters of uroflowmetry with postvoid residual urine (PVR) were assessed according to the presence of SRW played by a mobile application.MethodsEighteen consecutive male patients with LUTS were prospectively enrolled between March and April 2014. Uroflowmetry with PVR measured by a bladder scan was randomly performed once weekly for two consecutive weeks with and without SRW in a completely sealed room after pre-checked bladder volume was scanned to be more than 150 cc. SRW was played with river water sounds amongst relaxed melodies from a smartphone mobile application.ResultsThe mean age of enrolled patients and their mean International Prostate Symptom Score (IPSS) were 58.9 ± 7.7 years (range: 46-70) and 13.1 ± 5.9, respectively. All patients had not been prescribed any medications, including alpha-blockers or anti-muscarinic agents, in the last 3 months. There was a significant increase in mean peak flow rate (PFR) with SRW in comparison to without SRW (15.7 mL/s vs. 12.3 mL/s, respectively, p = 0.0125). However, there were no differences in other uroflowmetric parameters, including PVR.ConclusionsThe study showed that SRW from a mobile phone application may be helpful in facilitating voiding functions by increasing PFR in male LUTS patients.

Objective: To determine whether listening to music during transrectal ultrasound (TRUS)-guided 12-core needle prostate biopsy decreases anxiety, pain and dissatisfaction among patients and results in a more comfortable and better tolerated procedure. Patients and Methods: 76 male patients who underwent TRUS-guided prostate biopsy between March 2013 and June 2014 were randomized into the following groups: no music (group I, n = 38) or classical music (group II, n = 38) during the procedure. Before TRUS-guided prostate biopsy, lidocaine gel was instilled into the rectum. Patient anxiety levels were quantified using the State-Trait Anxiety Inventory. A visual analog scale (0-10) was used for self-assessment of satisfaction, discomfort and willingness among patients to have a repeat TRUS-guided prostate biopsy. Results: Demographic characteristics, mean age, procedure duration and procedure indications did not differ statistically between the two groups. The mean anxiety level and mean pain score of group II were significantly lower than those of group I (p = 0.001 and p = 0.003, respectively). Group II also had a significantly higher mean satisfaction score than group I (p = 0.007). Before the procedure, heart rate and systolic blood pressure were similar in groups I and II; however, after the procedure, levels were lower in group II than in group I (heart rate, p = 0.014; systolic blood pressure, p = 0.011). Conclusion: Listening to music during TRUS-guided prostate biopsy significantly reduced patients' feelings of pain, discomfort and dissatisfaction. Music can serve as a simple, inexpensive and effective adjunct to sedation during TRUS-guided prostate biopsy. We recommend playing music during TRUS-guided prostate biopsy.

Objective To confirm the hypothesis that nuclear matrix protein 22 (NMP22) is overestimated in concentrated urine, we compared the NMP22 values measured at different dietary states. Methods We retrospectively reviewed 531 healthy subjects who had had abnormal urinary NMP22 values ≥10 U/mL at the first test and underwent a second NMP22 test within 2 weeks. The first NMP22 test was performed after overnight fasting, and the second was performed with no dietary restrictions. We compared the NMP22 values between the 2 measurements and investigated the relationship between the NMP22 value and urine specific gravity. Results At the second test, 504 subjects (94.9%) had a normal NMP22 value of