Takashi Iguchi

Prognostic factors and risk stratification in patients with castration-resistant prostate cancer receiving docetaxel-based chemotherapy

BackgroundWhile novel drugs have been developed, docetaxel remains one of the standard initial systemic therapies for castration-resistant prostate cancer (CRPC) patients. Despite the excellent anti-tumor effect of docetaxel, its severe adverse effects sometimes distress patients. Therefore, it would be very helpful to predict the efficacy of docetaxel before treatment. The aims of this study were to evaluate the potential value of patient characteristics in predicting overall survival (OS) and to develop a risk classification for CRPC patients treated with docetaxel-based chemotherapy.MethodsThis study included 79 patients with CRPC treated with docetaxel. The variables, including patient characteristics at diagnosis and at the start of chemotherapy, were retrospectively collected. Prognostic factors predicting OS were analyzed using the Cox proportional hazard model. Risk stratification for overall survival was determined based on the results of multivariate analysis.ResultsPSA response ≥50 % was observed in 55 (69.6 %) of all patients, and the median OS was 22.5 months. The multivariate analysis showed that age, serum PSA level at the start of chemotherapy, and Hb were independent prognostic factors for OS. In addition, ECOG performance status (PS) and the CRP-to-albumin ratio were not significant but were considered possible predictors for OS. Risk stratification according to the number of these risk factors could effectively stratify CRPC patients treated with docetaxel in terms of OS.ConclusionsAge, serum PSA level at the start of chemotherapy, and Hb were identified as independent prognostic factors of OS. ECOG PS and the CRP-to-albumin ratio were not significant, but were considered possible predictors for OS in Japanese CRPC patients treated with docetaxel. Risk stratification based on these factors could be helpful for estimating overall survival.

Recurrent stone‐forming patients have high visceral fat ratio based on computed tomography images compared to first‐time stone‐forming patients

To compare various fat parameters based on computed tomography images between recurrent stone‐forming patients and patients forming stones for the first time.

MP88-20 DNAJB8 EXPRESSION IS ASSOCIATED WITH RECURRENCE OF RENAL CELL CARCINOMA

interfering RNAs (siRNAs) to examine the effects of GNMT knockdown on cell proliferation and the cell cycle. In addition, the expression of GNMT protein in UC and RCC tissues was evaluated. METHODS: We performed western blotting analysis using lysates from normal urothelial and kidney cells and a panel of UC and RCC cell lines to examine GNMT expression levels and to evaluate the induction of apoptosis in response to GNMT knockdown. GNMT expression in normal and cancer tissue specimens was examined by immunohistochemistry. RESULTS: GNMT expression was upregulated in RCC cell lines, especially the high-grade SKR1 RCC cell line. Inversely, GNMT expression among urothelial cells was upregulated in especially the normal urothelial cells (KT4). Immunohistochemical analysis revealed that GNMT protein was expressed in the cytoplasm of UC and RCC cells. siRNA-mediated knockdown of GNMT had only a modest effect on the proliferation of cancer and normal cells, but dramatically inhibited the proliferation of SKR1 and KK47 (high grade UC) cells. Furthermore, while GNMT knockdown led to only a slight increase in the G1 fraction of HEK293 and KT4 cells, it induced a prominent increase in the sub-G1 fraction of SKR1 and KK47 cells, indicating cellular death. To investigate the mechanism of cellular death caused by GNMT knockdown, western blotting analysis was performed to determine the presence of cleaved PARP, a degradation product of the caspase cascade, which serves as a marker of apoptosis. As the results, GNMT knockdown induced PARP cleavage. CONCLUSIONS: This is the first investigation to suggest that GNMT plays an important role in promoting cell growth in UC and RCC, especially high grade UC and RCC, via the regulation of apoptosis. The modulation of GNMT expression or function may therefore provide a strategy for the development of novel therapeutics for UC and RCC.

MP55-18 PREDICTING URETEROSOCPIC LITHOTRIPSY OUTCOME BY THREE-DIMENTIONAL MEAN STONE DENSITY

CONCLUSIONS: The clinical outcomes of the new-generation SMP in patients with moderate size renal stone were comparable when compared with the first-generation SMP. New-generation SMP system using an irrigation-suction sheath improved intra-operative irrigation, a more efficient hydrodynamic mechanism for retrieval of fragments. This may account for the shorter operative time than the first-generation SMP system demonstrated in this study.

Three-dimensional mean stone density measurement is superior for predicting extracorporeal shock wave lithotripsy success

The objective of the present study was to investigate the usefulness of three‐dimensional images of stones to measure mean stone density for predicting the outcome of shock wave lithotripsy.

MP64-14 SIMPLE PROGNOSTIC MODEL FOR HIGH-RISK PROSTATE CANCER AFTER RADICAL PROSTATECTOMY

Patients were categorized into three risk groups: 1) men with N1 disease (N1), 2) men without N0, but who had either pT3 stage, RP Gleason score 8, lymphovascular invasion or tertiary Gleason 5 pattern (N0 high-risk [HR]) and 3) men with no high-risk features at RP (N0IR). Decipher scores were obtained from 263 RP specimens and 25 matching biopsy specimens. Fisher’s exact test was used to compare the difference in patient risk groups. Logistic regression analysis was used to evaluate performance of Decipher for prediction of LNI. Discrimination of the Partin tables ( 2%) and combined model of Partin tables ( 2%) and Decipher (>0.6) was assessed using c-index. Concordance of biopsy and RP Decipher (lowand intermediatevs high-risk) was also assessed. RESULTS: Of the 263 men, 42 (16.0%), 98 (37.2%) and 123 (46.8%) men were categorized as N1, N0HR and N0IR risk groups, respectively. Partin tables classified 34/42 (81%) N1, 70/98 (71%) N0HR and 66/123 (54%) N0IR men as high clinical risk ( 2%) for LNI (p1⁄40.0012). Decipher classified 23/42 (55%) N1, 34/98 (35%) N0HR and 35/123 (29%) N0IR as high genomic risk (>0.6) for metastasis (p1⁄40.013). After adjusting for Partin Tables, Decipher high genomic risk had an odds ratio of 2.3 (95% CI 1.2-4.5) as a predictor of LNI (p1⁄40.02). Addition of Decipher to Partin Tables improved the c-index from 0.60 (95%CI 0.530.67) to 0.66 (95%CI 0.57-0.75). The concordance of Decipher risk groups between matched Biopsy and RP specimens was 84%. CONCLUSIONS: Decipher may be an important adjunct tool to improve preoperative staging that may be useful for prioritizing intermediate risk patients to ePLND. Further investigation of Decipher biopsy specimens is required to validate these findings.

MP62-02 VARIATION COEFFICIENT OF STONE DENSITY: A NOVEL PREDICTOR OF TREATMENT OUTCOME FOLLOWING EXTRACORPOREAL SHOCKWAVE LITHOTRIPSY.

INTRODUCTION AND OBJECTIVES: The mean stone density (MSD) and stone heterogeneity index (SHI), was defined as the mean of Hounsfield unit (HU) and the standard deviation of a HU on non-contrast computed tomography (NCCT), are already reported independent predictor of SWL outcomes. We investigated whether MSD-SHI ratio can be a significant predictor for SWL outcomes in patients with ureteral stones. METHODS: Medical records were obtained from a consecutive database of patients (n 1⁄4 1,824) who had undergone the first session of SWL between November 2005 and December 2014 in the Severance Hospital, Seoul, Korea. Ultimately, 700 patients with ureter calculi were eligible for the current analyses. Stone related variables including mean stone length (MSL), MSD, skin-to-stone distance (SSD), and SHI were obtained on NCCT. RESULTS: The mean age of total patients was 52.55 13.88 years. The distribution of ureteral stone locations was comprised of 573 cases of upper ureter stones (81.9%), 48 cases of mid-ureter stones (6.9%), and 79 cases of lower ureter stones (11.2%). The MSL was 9.12 3.89 mm, and the mean MSD and SHI were 707.04 272.10 HU and 244.90 110.16 HU, respectively. The mean SSD was 110.81 18.98 mm. The one-session success and onesession stone-free rates were 69.6%. The univariate logistic regression models revealed the following predictive factors of one-session success following SWL for ureteral stones: shorter MSL, lower MSD, higher SHI, and lower MSD-SHI ratio. The multivariate analyses also demonstrated that a shorter MSL, lower MSD, higher SHI, and lower MSD-SHI were independent predictors of one-session success after SWL for ureteral calculi. For one-session success rates, the AUC of ROC curves in total cohort were 0.725 for MSD, 0.661 for MSL, and 0.749 for MSD-SHI ratio and there were no significant differences between MSD and MSD-SHI ratio (P 1⁄4 0.348). In patients with upper 50% MSL, the AUC of ROC curves were 0.676 for MSD, 0.661 for MSL, and 0.764 for MSD-SHI ratio and there were significant differences between MSD and MSD-SHI ratio (P 1⁄4 0.011) (Fig. 1). CONCLUSIONS: MSL, MSD, SHI, and MSD-SHI were independent predictors of one-session success after SWL for ureteral calculi. MSD-SHI showed higher predictive value compared to MSD or MSL in patients with relatively large stone. Source of Funding: None

MP01-16 METABOLIC SYNDROME INCREASES THE RISK FOR CALCIUM OXALATE STONE FORMATION: RESULTS FROM A NATIONWIDE SURVEY ON UROLITHIASIS IN JAPAN

INTRODUCTION AND OBJECTIVES: Recent epidemiologic studies have shown an increased prevalence of kidney stones in patients with metabolic syndrome (MetS). We have reported that the clustering of MetS traits is associated with greater severity of kidney stone disease (Am J Kidney Dis 61: 923-929, 2013). The aim of the present study is to clarify which stone composition is associated with MetS. METHODS: We retrospectively analyzed detailed clinical data from 30,448 patients with urolithiasis enrolled in the 6th Nationwide Survey on Urolithiasis in Japan conducted in 2005. Patients with lower urinary tract stones, struvite stones, cystine stones, other types of rare stone composition, unknown stone composition, or hyperparathyroidism and those younger than 15 years were excluded. According to the types of stone composition, the severity of kidney stone disease, assessed by the number of existing stones (single/multiple) and number of stone episodes (first time/recurrent), and abnormalities in urine constituents were examined by the number of MetS traits (obesity, hypertension, dyslipidemia, and diabetes). RESULTS: A total of 4,440 patients included in the final analyses were classified into four groups: calcium oxalate (CaOx) (n1⁄43213), CaOx + calcium phosphate (CaP) (n1⁄4881), CaP (n1⁄4115), uric acid (UA) (n1⁄4191). The proportions of patients with recurrent and/or multiple stones significantly increased with the number of MetS traits only in patients with CaOx stone (P < 0.01, table 1). However, similar associations were not observed in patients with other stone compositions. In patients with CaOx stone, there was a significant and stepwise increase in the odds of recurrent and/or multiple stones after adjustment for age and sex. In patients with 3 or 4 MetS traits, the odds was 1.8-fold greater compared with patients with 0 traits (OR, 1.78; 95% CI, 1.292.42). In addition, the presence of MetS traits was associated with significantly increased odds of having hypercalciuria in patients with CaOx stone after adjustment for age and sex. CONCLUSIONS: In patients with CaOx stone, MetS trait clustering is associated with greater severity of the disease and increased urinary calcium excretion. These results suggest that CaOx stone disease should be regarded as a systemic disorder linked to MetS.

MP62-03 PREDICTING ESWL OUTCOME USING CLASSIFICATION AND REGRESSION TREE (CART) ANALYSIS

INTRODUCTION AND OBJECTIVES: Previous studies have developed various predictive models for stone-free rate following extracorporeal shock wave lithotripsy (ESWL). However, these models have several limitations such as difficulty in usage and lack of information derived from CT imaging. In this study, we sought to develop a user-friendly predictive model for ESWL outcome using the classification and regression tree (CART) analysis. METHODS: We retrospectively reviewed charts of 245 patients who underwent ESWL for upper urinary tract calculi between January 2008 and January 2016. To create the CART decision tree, predictor variables were entered into the software (R version 3.2.2) to classify patients who achieved stone-free after a first session of ESWL. Variables included age, sex, hydronephrosis, urinary drainage, stone location, stone volume, number of stones and three indices based on CT attenuation of the stone, i.e., mean stone density (MSD), standard deviation of stone density (SDSD) and variation coefficient of stone density (VCSD). Stone-free status was determined as absence or residual fragments <4mm using NCCT within three months after a first session of ESWL. RESULTS: Overall stone-free rate was 47.8%. In CART analysis, VCSD had the greatest variable importance (100%) followed by MSD (56.7%), stone volume (52.7%) and SDSD (49.3%). A total of five subgroups of patients with distinct stone-free rate were produced by three predictive variables (Figure). CONCLUSIONS: We have generated a first CART decision tree for ESWL outcome that included VCSD as a novel and most important factor, as well as previously reported predictors such as MSD and stone volume. This model provides clinician with practical bedside tool for predicting stone-free following ESWL.

PD21-10 ACTIVE STONE REMOVAL CAN PREVENT UROLITHIASIS-RELATED DEATHS IN PATIENTS WITH POOR PERFORMANCE STATUS.

INTRODUCTION AND OBJECTIVES: Post-operative imaging used to assess retrograde intra-renal surgery (RIRS) results affects stone-free rates (SFR). Imaging after RIRS may be unnecessary if surgeon0s endoscopic evaluation (EE) at the end of RIRS proved to be reliable. The objective of our study was to assess the reliability of surgeon0s EE at the end of RIRS. METHODS: We made a retrospective analysis on all consecutive RIRS performed for renal stones from January 2009 to August 2016 and included in a prospectively maintained database. RIRS were performed with fiber optics instruments in one-day surgery under spinal anesthesia. A ureteral access sheath was used, laser lithotripsy was performed and significant fragments extracted. Multiple stones, stones > 2 cm and staged procedures were included. Surgeons recorded their EE particularly about the presence of significant residual fragments (SRF). Residual fragments were considered clinically insignificant (CIRF) if 4 mm. Primary endpoint of our study was the ability of EE made by an expert surgeon to exclude the presence of SRF at US at 2-3 weeks. Chi-square and Fisher tests were used for statistical analysis. RESULTS: 294 RIRS were included. EE was available in 281 cases and US in 211. Mean stone size was 12.31 mm 4.87 mm (SD). In 68 cases (23.13%) stones were multiple. Post-operative US outcomes significantly differed from urologist0s EE in term of SRF, CIRF and SFR (p < 0.0001), independently from the number of RIRS performed per year by the surgeon (p < 0.001). 14% more patients were found stone-free (SFR 0U) at US compared to EE, 28% less were found to have CIRF and 14% more to have SRF. Table 1 shows how the concordance of EE and US outcomes varied in relation with surgeon0s expertise. In particular the difference in terms of SRF and CIRF decreased when EE was made by a surgeon performing 20 RIRS/ year. The absence of SRF assessed at EE by a surgeon performing 20 RIRS/year was confirmed at US in 92% of cases. The probability to diagnose at US SRF not assessed at EE increased to 36% when EE was made by surgeons performing < 20 RIRS/year (OR 1⁄4 6.4). CONCLUSIONS: Post-operative US outcomes significantly differed from urologist0s EE. EE underestimated SFR and overestimated CIRF. SRF were underestimated at EE, but an expert surgeon reliably predicted the absence of SRF.