The intracellular distribution of inorganic carbon fixing enzymes does not support the presence of a C4 pathway in the diatom Phaeodactylum tricornutum.

Diatoms are unicellular algae and important primary producers. The process of carbon fixation in diatoms is very efficient even though the availability of dissolved CO2 in sea water is very low. The operation of a carbon concentrating mechanism (CCM) also makes the more abundant bicarbonate accessible for photosynthetic carbon fixation. Diatoms possess carbonic anhydrases as well as metabolic enzymes potentially involved in C4 pathways; however, the question as to whether a C4 pathway plays a general role in diatoms is not yet solved. While genome analyses indicate that the diatom Phaeodactylum tricornutum possesses all the enzymes required to operate a C4 pathway, silencing of the pyruvate orthophosphate dikinase (PPDK) in a genetically transformed cell line does not lead to reduced photosynthetic carbon fixation. In this study, we have determined the intracellular location of all enzymes potentially involved in C4-like carbon fixing pathways in P. tricornutum by expression of the respective proteins fused to green fluorescent protein (GFP), followed by fluorescence microscopy. Furthermore, we compared the results to known pathways and locations of enzymes in higher plants performing C3 or C4 photosynthesis. This approach revealed that the intracellular distribution of the investigated enzymes is quite different from the one observed in higher plants. In particular, the apparent lack of a plastidic decarboxylase in P. tricornutum indicates that this diatom does not perform a C4-like CCM.

No clinical significance of the time interval between biopsy and robotic-assisted radical prostatectomy for patients with clinically localized prostate cancer on biochemical recurrence: a propensity score matching analysis.

PURPOSE: To investigate the impact of the time interval (TI) between prostate biopsy and robot-assisted radical prostatectomy (RARP) on the risk of biochemical recurrence (BCR). METHODS: We retrospectively reviewed the medical records of 793 consecutive patients who were treated with RARP at our institution. Patients were divided into three groups, according to TI, to compare BCR-free survival (BCRFS) rates: Group 1 (n = 196), TI < 3 months; Group 2 (n = 513), 3 ≤ TI < 6 months; Group 3 (n = 84), TI ≥ 6 months. Eighty-three patients with TI ≥ 6 months were matched with an equal number of patients with TI < 6 months based on propensity scores by using four preoperative factors: prostate-specific antigen (PSA), primary (pGS) and secondary (sGS) Gleason score and positive prostate biopsy. RESULTS: The 5-year BCRFS rates for TI Groups 1, 2, and 3 were 76%, 80.7% and 82.6% (P = 0.99), respectively. The multivariate analysis revealed that PSA, pGS, sGS and a positive prostate biopsy were independent preoperative risk factors for BCR. The propensity adjusted 5-year BCRFS for patients with TI ≥ 6 months was 84.0%. This was not worse than that of patients with TI < 6 months (71.0%, P = 0.18). CONCLUSIONS: In our cohorts, a delay in the time from biopsy to RARP did not significantly affect recurrence. Therefore, hasty treatment decisions are unnecessary for at least 6 months after diagnosis of early prostate cancer.

Impact of Surgeon and Hospital Volume on the Safety of Robot-Assisted Radical Prostatectomy: A Multi-Institutional Study Based on a National Database.

INTRODUCTION: We aimed to perform a multi-institutional study using a national database led by the Japanese Society of Endourology to investigate the effect of surgeon or hospital volume on the safety of robot-assisted radical prostatectomy (RARP). MATERIALS AND METHODS: Clinical data of 3,214 patients who underwent RARP for the treatment of clinically localized prostate cancer between April 2012 and March 2013 in Japan were evaluated. Surgical outcomes and all intra- and perioperative complications were collected. RESULTS: The intraoperative complication rate was 0.56%. In a total number of 241 patients, 261 perioperative complications were observed. The following percentages of patients presented the Clavien-graded complications: 7.2%, grades 1-2; 0.84%, grade 3; and 0.093%, grade 4a. No cases of multiple organ dysfunction or death (grades 4b and 5) were found. Multivariable logistic regression analysis showed that the hospital volume (OR 3.6; p = 0.010) for intraoperative complications and surgeon volume (OR 0.19; p < 0.0001) and extended lymph node discectomy (OR 3.9; p < 0.0001) for perioperative complications were significant independent risk factors. CONCLUSIONS: Hospital volume for intraoperative complications and surgeon volume and extended lymph node dissection for perioperative complications were significantly associated with increased risk of each complication in RARP.

Clinical significance of preoperative renal function and gross hematuria for intravesical recurrence after radical nephroureterectomy for upper tract urothelial carcinoma.

OBJECTIVES: To investigate the predictive values of perioperative factors and to develop a nomogram for intravesical recurrence after radical nephroureterectomy in patients with upper urinary tract urothelial carcinoma. METHODS: A retrospective analysis of 144 patients who underwent radical nephroureterectomy from 1996 to 2014 was carried out. The actuarial probabilities of the intravesical recurrence-free survival rate were calculated using the Kaplan-Meier method. Prognostic indicators for intravesical recurrence were identified using competing-risks regression analyses. RESULTS: Intravesical recurrence occurred in 63 patients during the follow-up period. The intravesical recurrence-free survival rates at 1, 3, and 5 years were 65.7%, 50.6% and 47.1%, respectively. In univariate analysis, the presence of gross hematuria (P = 0.028) and the preoperative serum creatinine level (P = 0.033) were significantly associated with intravesical recurrence. In multivariate analysis, the presence of gross hematuria (subdistribution hazard ratio 2.03, 95% CI 1.145-3.496; P = 0.013) and the preoperative serum creatinine level (subdistribution hazard ratio 3.15, 95% CI 1.161-3.534; P = 0.021) were independent predictors for intravesical recurrence after radical nephroureterectomy. Accordingly, a nomogram based on the model was developed. The concordance index of this model was 0.632. CONCLUSION: The presence of gross hematuria and preoperative serum creatinine levels seem to be independent predictors for intravesical recurrence after radical nephroureterectomy. Our nomogram developed based on these factors might aid in appropriate patient selection for clinical trials of novel therapeutic interventions, including administration of intravesical chemotherapy.

Sarcopenia as a Novel Preoperative Prognostic Predictor for Survival in Patients with Bladder Cancer Undergoing Radical Cystectomy.

PURPOSE: To investigate the prognostic significance of sarcopenia on long-term outcomes in patients with bladder cancer after radical cystectomy (RC). METHODS: We retrospectively reviewed 136 patients undergoing RC for urothelial carcinoma at our institution. Prognostic impact of the preoperative clinical, laboratory, and radiologic parameters were evaluated by Cox proportional hazard model analyses, and a nomogram was developed to predict cancer-specific survival (CSS) after RC. RESULTS: The mean follow-up was 46.7 months. Patients with sarcopenia had a significantly shorter CSS than those without sarcopenia. On univariate Cox analysis, clinical T stage, histology of transurethral resection of bladder tumor (TURBT) specimen, pretreatment hemoglobin, pretreatment neutrophil-to-lymphocyte ratio (NLR), pretreatment serum C-reactive protein level, pretreatment serum albumin level, presence of hydronephrosis, and presence of sarcopenia were associated with significantly worse CSS. On multivariate Cox stepwise analysis, sarcopenia (hazard rate [HR] = 2.3, p = 0.015), clinical T stage (cT4: HR = 5.3; p = 0.0096), presence of hydronephrosis (HR = 2.0; p = 0.033), histology of TURBT specimen (HR = 2.2, p = 0.044), and NLR (HR = 1.3; p = 0.0048) were significant independent predictors of an unfavorable prognosis Based on the results of the multivariate analysis, we developed a nomogram to predict 1-, 3-, and 5-year CSS after RC. CONCLUSIONS: Sarcopenia, clinical T stage, presence of hydronephrosis, histology of TURBT specimen, and NLR are novel preoperative prognostic factors even after adjustment for other known preoperative predictors in patients undergoing RC for bladder cancer.

Impact of a preoperatively estimated prostate volume using transrectal ultrasonography on surgical and oncological outcomes in a single surgeon's experience with robot-assisted radical prostatectomy.

BACKGROUND: To assess the impact of preoperatively estimated prostate volume (PV) using transrectal ultrasonography (TRUS) on surgical and oncological outcomes in robot-assisted radical prostatectomy (RARP). METHODS: We analyzed the experience of a single surgeon at our hospital who performed 436 RARPs without neoadjuvant hormone therapy between August 2006 and December 2013. Patients were divided into three groups according to their preoperative PV calculated using TRUS (PV ≤ 20 cm(3): group 1, n = 61; 20 < PV < 50 cm(3): group 2, n = 303; PV ≥ 50 cm(3): group 3, n = 72). RESULTS: Blood loss was significantly higher in group 3 than in group 1 and group 2. In stage pT2 patients, the rate of positive surgical margin (PSM) was significantly lower in group 3 than in group 1. In addition, perioperative complications significantly increased with increasing PV, while the extraprostatic extension (EPE) rate significantly decreased with increasing PV. The preoperative biopsy Gleason score, prostate-specific antigen (PSA) density, and clinical T2 stage were inversely correlated with increasing PV. Biochemical recurrence-free survival after RARP was significantly lower in group 1 than in groups 2 and 3. CONCLUSIONS: A large prostate size was significantly associated with increased blood loss and a higher rate of perioperative complications. A small prostate size was associated with a higher PSM rate, PSA density, Gleason score, EPE rate, and biochemical recurrence rate. These results suggest that RARP was technically challenging in patients with large prostates, whereas small prostates were associated with unfavorable oncological outcomes.

Is scintigraphy necessary to detect migration of 125I seeds after brachytherapy for early prostate cancer?

BACKGROUND: We investigated whether scintigraphy was superior to radiography for detecting migrated seeds after brachytherapy for prostate cancer. METHODS: We studied 57 patients with early prostate cancer who were treated with free (125)I transperineal brachytherapy. Scintigraphy was used to detect seed migration on postoperative day (POD) 1, radiography was used on POD 2, and both tests were used on POD 30. RESULTS: The total number of implanted seeds in this study was 3,753 in 57 patients. Overall, there were 19 seed migrations in 12 patients. On POD 1, there were 4 seed migrations in 4 patients that were detected by scintigraphy. On POD 2, there were 10 seed migrations in 9 patients that were detected by radiography. On POD 30, 17 seed migrations were detected in 10 patients by radiography and 18 seeds migrations were detected by scintigraphy. However, 1 seed migration which was located outside of the detectable range of radiography was detected only by scintigraphy. CONCLUSIONS: Both scintigraphy and radiography have similar abilities to detect migrated seeds 1 month after (125)I brachytherapy for prostate cancer. While both tests have advantages and disadvantages, it is reasonable to only use radiography if scintigraphy is not available.

Preoperative predictive factors and further risk stratification of biochemical recurrence in clinically localized high-risk prostate cancer.

BACKGROUND: To identify preoperative predictive factors for biochemical recurrence (BCR) and to further stratify its risk in high-risk localized prostate cancer patients receiving radical prostatectomy (RP). METHODS: Subjects included 195 high-risk prostate cancer patients undergoing RP from 2000 to 2012. RP consisted of retropubic radical prostatectomy and robot-assisted radical prostatectomy, involving 84 cases and 111 cases, respectively. BCR was defined as a prostate serum antigen (PSA) level ≥0.2 ng/mL. BCR-free survival (BCRFS) was calculated using the Kaplan-Meier method. Preoperative predictors of BCR were assessed with Cox's proportional hazard regression analysis. RESULTS: Eighty-nine patients (45.6 %) experienced recurrence. BCRFS rates 3 and 5 years after RP were 58 and 50 %, respectively. Prostate volume, transition zone volume, and Gleason score were not significantly associated with BCR. Patients with higher preoperative PSA, PSA density (PSAD), PSA density of the transition zone, percentage of positive cores (PPC), and PPC from the dominant side showed significantly lower BCRFS. The PPC from the dominant side and PSAD were significant independent prognostic factors for BCR. Using these variables, the hazard ratio of BCR could be calculated and patients stratified into three risk groups. The 5-year BCRFS rates for Groups 1, 2, and 3 were 64.9 %, 48.1 %, and 21.3 %, respectively. CONCLUSIONS: Patients with high-risk localized prostate cancer as currently defined do not have uniformly poor prognosis after RP. PPC from the dominant side and PSAD are significant predictors of BCR. These factors can identify high-risk patients with very poor prognosis.

Prediction of renal function after nephroureterectomy in patients with upper tract urothelial carcinoma.

OBJECTIVE: The estimated glomerular filtration rate is significantly decreased after nephroureterectomy. Deteriorating renal function likely affects the eligibility for cisplatin-based chemotherapy in patients with upper tract urothelial carcinoma. The present study was undertaken to identify preoperative factors for the prediction of postoperative renal function and develop a prediction model. METHODS: Between June 1996 and January 2014, 110 patients who underwent radical nephroureterectomy at our institution were analyzed in this study. The estimated glomerular filtration rate was calculated using the Modification of Diet in Renal Disease study equation. Univariate linear regression analyses were performed to investigate the correlation between postoperative estimated glomerular filtration rate and preoperative variables. A stepwise multivariate linear regression analysis was performed to identify independent predictors of postoperative estimated glomerular filtration rate. RESULTS: Comparison of preoperative and postoperative estimated glomerular filtration rate for each patient showed a median difference of 13.1 ml/min/1.73 m(2). The postoperative estimated glomerular filtration rate was significantly lower than the preoperative estimated glomerular filtration rate (P < 0.001). On univariate analysis, age and preoperative estimated glomerular filtration rate were significantly correlated with postoperative estimated glomerular filtration rate. On multivariate analysis, age, preoperative estimated glomerular filtration rate and the presence of hydronephrosis were independent predictive factors of postoperative estimated glomerular filtration rate. The predicted postoperative estimated glomerular filtration rate, which was calculated using these independent factors, showed a significant correlation with the observed postoperative estimated glomerular filtration rate (correlation coefficient = 0.7533). CONCLUSIONS: Age, preoperative estimated glomerular filtration rate and the presence of hydronephrosis were independent predictors of postoperative estimated glomerular filtration rate in patients with upper tract urothelial carcinoma treated with radical nephroureterectomy. The predicted postoperative estimated glomerular filtration rate based on these factors may be useful for choosing alternative management strategies such as neoadjuvant chemotherapy for patients with upper tract urothelial carcinoma.

Prognostic value of preoperative pyuria in patients with non-muscle-invasive bladder cancer.

OBJECTIVES: To investigate the prognostic value of preoperative pyuria in patients with non-muscle-invasive bladder cancer. METHODS: We retrospectively reviewed data from 237 patients diagnosed with non-muscle-invasive bladder cancer. Pyuria was defined as urine containing ≥5 white blood cells per high power field. The association between clinicopathological factors and recurrence was assessed by Cox univariate and multivariate analyses. RESULTS: Preoperative pyuria was found in 116 (49.0%) patients. Pyuria was significantly associated with advanced age, positive cytology, multiple tumors, large tumor size, non-papillary tumors, T1 tumors and high-grade tumors. In univariate analysis of the entire patient population, pyuria, positive urine cytology, multiple tumors, pT1 tumors and no bacillus Calmette-Guérin were significantly associated with recurrence. Multivariate analysis showed that pyuria was an independent predictor of recurrence (hazard ratio 3.332, 95% confidence interval 2.052-5.410; P < 0.001), along with positive urine cytology, multiple tumors and no bacillus Calmette-Guérin therapy. Subanalysis of the patients who underwent bacillus Calmette-Guérin therapy also showed that pyuria was an independent predictor of recurrence (hazard ratio 2.062, 95% confidence interval 1.085-3.918, P = 0.027). The 2-year recurrence-free survival rate for patients with pyuria was significantly lower than for patients without pyuria (65.5% vs 80.7%; P = 0.027). CONCLUSIONS: Preoperative pyuria seems to be significantly associated with recurrence in patients with non-muscle-invasive bladder cancer, and it might be a useful predictor for recurrence after bacillus Calmette-Guérin therapy.

Prediction of biochemical recurrence after robot-assisted radical prostatectomy: analysis of 784 Japanese patients.

OBJECTIVES: To examine biochemical recurrence after robot-assisted radical prostatectomy in Japanese patients, and to develop a risk stratification model for biochemical recurrence. METHODS: The study cohort consisted of 784 patients with localized prostate cancer who underwent robot-assisted radical prostatectomy without neoadjuvant or adjuvant endocrine therapy. The relationships of biochemical recurrence with perioperative findings were evaluated. The prognostic factors for biochemical recurrence-free survival were evaluated using Cox proportional hazard model analyses. RESULTS: During the follow-up period, 80 patients showed biochemical recurrence. The biochemical recurrence-free survival rates at 1, 3, and 5 years were 92.2%, 85.2% and 80.1%, respectively. In univariate analysis, the prostate-specific antigen level, prostate-specific antigen density, biopsy Gleason score, percent positive core, pathological T stage, pathological Gleason score, lymphovascular invasion, perineural invasion and positive surgical margin were significantly associated with biochemical recurrence. In multivariate analysis, prostate-specific antigen density ≥0.4 (P = 0.0011), pathological T stage ≥3a (P = 0.002), pathological Gleason score ≥8 (P = 0.007) and positive surgical margin (P < 0.0001) were independent predictors of biochemical recurrence. The patients were stratified into three risk groups according to these factors. The 5-year biochemical recurrence-free survival rate was 89.4% in the low-risk group, 65.6% in the intermediate-risk group and 30.3% in the high-risk group. CONCLUSIONS: The prostate-specific antigen density, pathological T stage, pathological Gleason score and positive surgical margin were independent prognostic factors for biochemical recurrence. The risk stratification model developed using these four factors could help clinicians identify patients with a poor prognosis who might be good candidates for clinical trials of alternative management strategies.

Prognostic implication of infiltrative growth pattern and establishment of novel risk stratification model for survival in patients with upper urinary tract urothelial carcinoma.

PURPOSE: To investigate the prognostic significance of infiltrative growth pattern (INF) and to develop a novel risk stratification model for disease-specific survival (DSS) in patients with upper urinary tract urothelial carcinoma (UTUC). METHODS: This study included 113 patients with UTUC treated with radical nephroureterectomy. Pathological features, including INF, were compared with DSS. INF was classified into 3 patterns (INFa, INFb, and INFc). The prognostic factors of DSS were evaluated with univariate and multivariate Cox proportional hazard model analyses. A risk stratification model based on the relative risks of DSS was then established. RESULT: Univariate analysis revealed that patients with high-grade tumor, pathological T stage ≥T3, a non-expanding infiltration pattern (INF ≥b), sessile-type carcinoma, the presence of lymphovascular invasion and positive lymph node involvement showed significantly lower survival rates than their respective counterparts. In the multivariate analysis, high grade tumor, positive lymph node involvement and INF ≥b were independent predictors for DSS (p < 0.05). The patients were stratified into 3 risk groups. The 5-year DSS rates were 94.4 % in the low-risk group, 67.5 % in the intermediate-risk group and 20.5 % in the high-risk group. CONCLUSION: In addition to lymph node involvement and pathological tumor grade, INF is a novel independent prognostic factor in patients with UTUC treated with radical nephroureterectomy. Our risk stratification model developed using these 3 factors may help clinicians identify patients with a poor prognosis who might be good candidates for clinical trials of innovative therapies.

Clinical variables for predicting metastatic renal cell carcinoma patients who might not benefit from cytoreductive nephrectomy: neutrophil-to-lymphocyte ratio and performance status.

BACKGROUND: Cytoreductive nephrectomy (CN) plays an important role in the multimodal treatment of metastatic renal cell carcinoma (RCC). However, certain patients experience rapid progression of the carcinoma following CN. This study aimed to investigate the value of neutrophil-to-lymphocyte ratio (NLR) in the selection of patients for CN. METHODS: Records corresponding to 73 patients with metastatic RCC were retrospectively reviewed. Forty-eight patients underwent CN, and their overall survival (OS) and preoperative variables were analyzed. The OS of patients who did not undergo CN was used as a reference. RESULTS: Univariate analysis showed that symptomatic tumors, Eastern Cooperative Oncology Group Performance Status (ECOG-PS) ≥ 1, hemoglobin level <12 g/dl, neutrophil count ≥ 5500/µL, C-reactive protein level ≥ 2.0 mg/dl, and NLR ≥ 4.0 were significantly associated with poor outcomes in patients who underwent cytoreductive nephrectomy. The median OS of patients with NLR ≥ 4.0 was 10.2 months, which was significantly shorter than that of patients with NLR <4.0 (36.5 months) (P = 0.0020). Multivariate analysis showed that NLR and ECOG-PS were independent predictors of OS in patients treated with CN. The OS of CN patients with NLR ≥ 4.0 and ECOG-PS ≥1 was similar to that of patients who did not undergo CN (8.4 vs. 6.1 months, P = 0.939). CONCLUSIONS: Preoperative NLR elevation is significantly associated with poor outcomes in patients with metastatic RCC who underwent CN. Patients with NLR ≥4.0 and ECOG-PS ≥ 1 might not benefit from immediate CN after initial diagnosis.

Factors predicting incisional surgical site infection in patients undergoing open radical cystectomy for bladder cancer.

BACKGROUND: The risk factors of incisional surgical site infection (iSSI) after open radical cystectomy (ORC) have not been fully investigated. The aim of the present study is to examine factors correlated with iSSI development after ORC with intestinal urinary diversion. METHODS: A total of 178 patients who had undergone ORC with intestinal urinary diversion between 2003 and 2012 at our institution were included in this retrospective study. Correlations between different perioperative factors and iSSI development were determined using univariate and multivariate logistic regression analyses. RESULTS: iSSI was observed in 53 patients (29.8 %). In the univariate analysis, age, diabetes mellitus, thickness of subcutaneous fat (TSF), and allogeneic transfusion were significant predictors of iSSI development. Although subcutaneous closed-suction drainage (SCSD) was not a significant factor in univariate analysis, SCSD, age, and TSF were all finally identified as independent predictors of iSSI development (P = 0.020, P < 0.001, and P = 0.022, respectively). Further analyses demonstrated that SCSD was frequently used in patients with relatively thick subcutaneous fat tissue and that SCSD significantly decreased iSSI development in these patients. CONCLUSIONS: Advanced patient age, thick subcutaneous fat tissue, and the absence of SCSD were significantly associated with iSSI development in bladder cancer patients who underwent ORC with intestinal urinary diversion. SCSD may be a useful procedure for iSSI prevention, especially in patients with relatively thick subcutaneous fat tissue.

Preoperative prognostic factors for biochemical recurrence after robot-assisted radical prostatectomy in Japan.

PURPOSE: We investigated oncological outcomes in Japanese patients who underwent robot-assisted radical prostatectomy (RARP). MATERIALS AND METHODS: This study included 389 patients who underwent RARP at a single institution with a follow-up period of at least 1 year. Preoperative findings were compared with biochemical recurrence (BCR). Predictors of BCR-free survival (BCRFS) were evaluated by univariate and multivariate Cox proportional hazard model analyses, and a risk stratification model based on the relative risks of BCR was established. RESULTS: Fifty incidences of BCR were noted during a median follow-up period of 28.7 months (range, 12.1-80.0 months). The BCRFS rate for the entire cohort at the median follow-up time was 85.9 %; the 1-, 3-, and 5-year estimates were 91.0, 85.1, and 81.1 %, respectively. From univariate analyses, prostate-specific antigen (PSA), PSA density, biopsy Gleason score, and percent positive core were significantly associated with BCR. Multivariate analysis showed that PSA [hazard ratio (HR), 2.75; p = 0.001], percent positive core (HR, 2.22; p = 0.001), and biopsy Gleason score (HR, 2.61; p = 0.007) were independent predictors of BCR. CONCLUSION: This study at a single Japanese center demonstrates that RARP provides a satisfactory BCRFS rate. This report provides a framework with which to estimate oncological outcomes in patients who underwent RARP for localized prostate cancer. Our results support the increased use of RARP for the treatment of localized prostate cancer in Japan.

Prediction of non-biochemical recurrence rate after radical prostatectomy in a Japanese cohort: development of a postoperative nomogram.

OBJECTIVE: To develop a nomogram based on postoperative factors and prostate-specific antigen levels to predict the non-biochemical recurrence rate after radical prostatectomy ina Japanese cohort. METHODS: A total of 606 Japanese patients with T1-3N0M0 prostate cancer who underwent radical prostatectomy and pelvic lymph node dissection at Tokyo Medical University hospital from 2000 to 2010 were studied. A nomogram was constructed based on Cox hazard regression analysis evaluating the prognostic significance of serum prostate-specific antigen and pathological factors in the radical prostatectomy specimens. The discriminating ability of the nomogram was assessed by the concordance index (C-index), and the predicted and actual outcomes were compared with a bootstrapped calibration plot. RESULTS: With a mean follow up of 60.0 months, a total of 187 patients (30.9%) experienced biochemical recurrence, with a 5-year non-biochemical recurrence rate of 72.3%. Based on a Cox hazard regression model, a nomogram was constructed to predict non-biochemical recurrence using serum prostate-specific antigen level and pathological features in radical prostatectomy specimens. The concordance index was 0.77, and the calibration plots appeared to be accurate. CONCLUSIONS: The postoperative nomogram described here can provide valuable information regarding the need for adjuvant/salvage radiation or hormonal therapy in patients after radical prostatectomy.

[Robot-assisted surgery-the current state of radical prostatectomy].

Minimally invasive surgeries such as laparoscopic surgery and robot-assisted surgery have become validated treatment modalities and hold a prominent position in clinical practice. Robot-assisted radical prostatectomy(RARP)is a relatively new procedure. Because this technique does not require the urologist to overcome a steep and long learning curve, a dramatic increase in the number of RARP surgeries was observed in recent years and RARP has rapidly gained acceptance in the Japanese urological community after its introduction in Japan in 2006. Robot-assisted surgery that combines optical magnification, three-dimensional vision, and instruments with 7 degrees of freedom allows surgeons to perform meticulous, precise, and accurate movements. In summary, for the previously mentioned reasons, RARP is considered to be an effective procedure for improving intraoperative blood loss, the transfusion and complication rates, as well as the recovery of urinary continence and potency rates. In this article, we briefly describe the evolution of this minimally invasive technique. In addition, we present the current state of RARP and a critical evaluation of the learning curves associated with performing RARP as well as published oncological, continence, and potency outcomes.

Hiding in plain view: genetic profiling reveals decades old cross contamination of bladder cancer cell line KU7 with HeLa.

PURPOSE: KU7 is a popular urothelial carcinoma cell line that was isolated from the bladder of a patient at Keio University in 1980. It has subsequently been widely used in laboratories around the world. We describe how routine cell line authentication revealed that KU7 was cross contaminated almost 30 years ago with HeLa, a cervical carcinoma cell line. MATERIALS AND METHODS: Presumed KU7 clones dating from 1984 to 1999 were provided by M.D. Anderson Cancer Center, Vancouver Prostate Centre, Kyoto University, Tokyo Medical University and Keio University. HeLa was obtained from ATCC. Genomic DNA was isolated and short tandem repeat analysis was performed at the M.D. Anderson Cancer Center Characterized Cell Line Core Facility, Johns Hopkins University Fragment Analysis Facility and RIKEN BioResource Center, Ibaraki, Japan. Comparative genomic hybridization was performed on a platform (Agilent Technologies, Santa Clara, California) at Vancouver Prostate Centre. RESULTS: The short tandem repeat profile of all KU7 clones was an exact match with that of HeLa. Comparative genomic hybridization of all samples revealed an abundance of shared chromosomal aberrations. Slight differences in some genomic areas were explained by genomic drift in different KU7 clones separated by many years. CONCLUSIONS: Our analysis identified that cross contamination of KU7 with HeLa occurred before 1984 at the source institution. All KU7 clones in the urological literature should be considered HeLa and experimental results should be viewed in this light. Our results emphasize the need to authenticate cell lines in oncological research.

Clinical significance of preoperative peripheral blood neutrophil count in patients with non-metastatic upper urinary tract carcinoma.

PURPOSE: Preoperative elevation of markers of systemic inflammation is associated with a poor outcome in several cancers. The purpose of this study was to evaluate the prognostic significance of preoperative systemic inflammatory markers in patients with non-metastatic upper urinary tract cancer (UUTC). METHODS: The records of 84 patients with non-metastatic UUTC who had undergone nephroureterectomy were reviewed, and the associations between preoperative clinical variables and recurrence-free survival (RFS) were analyzed by univariate and multivariate analyses. RESULTS: Clinical tumor stage, neutrophil count, and neutrophil-to-lymphocyte ratio were significantly associated with RFS in univariate analysis. Multivariate analysis showed that clinical T stage (hazard ratio [HR], 3.009; 95 % confidence interval [CI], 1.149-9.321; p = 0.024) and neutrophil count (HR, 3.521; 95 % CI, 1.423-9.108; p = 0.007) were independent predictors of RFS. The 3-year RFS in patients with a neutrophil count <4,000/µL was significantly higher than that in patients with a neutrophil count ≥ 4,000/µL (82.9 vs. 51.0 %, p = 0.004). Based on clinical T stage (T2 or less vs. T3 or greater) and neutrophil count (<4,000 vs. ≥ 4,000/µL), patients were stratified into 3 groups: low, intermediate, and high risk groups. RFS rates were significantly different between the 3 groups (p = 0.0005). CONCLUSIONS: Preoperative neutrophil count was an independent predictor of RFS in patients with non-metastatic UUTC. Stratification of patients based on neutrophil count and clinical T stage may be valuable for preoperative patient counseling and identifying patients with poor prognosis who may be candidates for neoadjuvant chemotherapy.

Association of legumain expression pattern with prostate cancer invasiveness and aggressiveness.

OBJECTIVES: To investigate the clinical implication of legumain, an asparaginyl endopeptidase that is highly expressed in several types of cancer, expression in prostate cancer. METHODS: Legumain expression in prostate cancer cell lines was determined by real-time reverse transcriptase PCR and Western blot. Furthermore, legumain expression in 88 prostatectomy specimens was evaluated by immunohistochemistry. The association between legumain expression and clinicopathological factors was analyzed. RESULTS: Legumain expression was confirmed at the mRNA and protein levels in all the cells. Although all the cancer tissues were positive for legumain, 2 staining patterns were observed in the cytoplasm: diffuse cytoplasmic and vesicular positivity. The rates of Gleason score ≥8, extracapsular extension, and perineural invasion in the group with vesicular staining were significantly higher than those in the diffuse cytoplasmic group (p < 0.05). The maximum size of the tumor with vesicular staining was significantly greater than that of the tumor with diffuse cytoplasmic staining (p = 0.0302). The 5-year biochemical recurrence-free rate in the patients with vesicular legumain staining was 53.2%; this rate was significantly lower than that (78.8%) in the patients with diffuse cytoplasmic staining (p = 0.0269). CONCLUSIONS: Tumors that showed a vesicular staining pattern of legumain had the potential of being highly invasive and aggressive in patients with prostate cancer who were treated with radical prostatectomy. This suggests that legumain might contribute to the invasiveness and aggressiveness of prostate cancer.