Comprehensive Analysis and Characterization of the GATA Gene Family, with Emphasis on the GATA6 Transcription Factor in Poplar.

GATA transcription factors are ubiquitously present in eukaryotic organisms and play a crucial role in multiple biological processes, such as plant growth, stress response, and hormone signaling. However, the study of GATA factors in poplar is currently limited to a small number of proteins, despite their evident functional importance. In this investigation, we utilized the most recent genome annotation and stringent criteria to identify 38 GATA transcription factor genes in poplar. Subsequently, we conducted a comprehensive analysis of this gene family, encompassing phylogenetic classification, protein characterization, analysis of promoter cis-acting elements, and determination of chromosomal location. Our examination of gene duplication events indicated that both tandem and segmental duplications have contributed to the expansion of the GATA gene family in poplar, with segmental duplication potentially being a major driving force. By performing collinearity analysis of genes across six different species, we identified 74 pairs of co-linear genes, which provide valuable insights for predicting gene functions from a comparative genomics perspective. Furthermore, through the analysis of gene expression patterns, we identified five GATA genes that exhibited differential expression in leaf-stem-root tissues and eight genes that were responsive to salt stress. Of particular interest was GATA6, which displayed strong induction by salt stress and overlapped between the two gene sets. We discovered that GATA6 encodes a nuclear-localized protein with transcription activation activity, which is continuously induced by salt stress in leaf and root tissues. Moreover, we constructed a co-expression network centered around GATA6, suggesting the potential involvement of these genes in the growth, development, and response to abiotic stress processes in poplar through cell transport systems and protein modification mechanisms, such as vesicle-mediated transport, intracellular transport, ubiquitination, and deubiquitination. This research provides a foundation for further exploration of the functions and mechanisms of GATA transcription factors in poplar.

Construction of a rAAV-SaCas9 system expressing eGFP and its application to improve muscle mass.

An ideal rAAV gene editing system not only effectively edits genes at specific site, but also prevents the spread of the virus from occurring off-target or carcinogenic risks. This is important for gene editing research at specific site in vivo. We report a single rAAV containing SaCas9 and guide RNAs under the control of subtle EF1a and tRNA promoters. The capacity of rAAV was compressed, and the editing efficiency was similar to that of the classical Cas9 system in vitro and in vivo. And we inserted the sequence of the green fluorescent protein eGFP into rAAV. The number of cells infected with the rAAV and the region in which the rAAV spreads were known by the fluorescent expression of eGFP in cells. In addition, we demonstrated that myostatin gene in the thigh muscles of C57BL/10 mice was knocked out by the rAAV9-SaCas9 system to make muscle mass increased obviously. The protein eGFP into rAAV has significant implications for our indirect analysis of the editing efficiency of SaCas9 in the genome of the target tissue and reduces the harm caused by off-target editing and prevents other tissue mutations. The rAAV system has substantial potential in improving muscle mass and preventing muscle atrophy.

Baicalin prevents tumor necrosis factor-α-induced apoptosis and dysfunction of pancreatic ß-cell line Min6 via upregulation of miR-205.

Baicalin (BAI), one major flavonoid from Scutellaria baicalensis, possesses anticancer and anti-inflammatory properties. However, the effect of BAI on diabetes mellitus has not been investigated. This study explored the antidiabetic effect of BAI on pancreatic ß-cell line Min6. Min6 cells were treated with tumor necrosis factor-α (TNF-α) to mimic ß-cell destruction in type 1 diabetes mellitus. The effects of BAI on viability and apoptosis of Min6 cells were analyzed by the cell counting kit-8 assay and Annexin V-fluoresceine isothiocyanate/propidium iodide staining method. The insulin secretion of Min6 cells was determined using radioimmunoassay. Expression of apoptosis-associated proteins and inducible nitric oxide synthase (iNOS), and activation of phosphatidylinositol 3'-kinase/protein kinase B (PI3K/AKT) and nuclear factor ΚB (NF-κB) pathways were analyzed by Western blot analysis. Relative microRNA-205 (miR-205) expression was determined by quantitative real time polymerase chain reaction. TNF-α treatment inhibited cell growth and insulin secretion, but promoted iNOS expression. All of these effects were reversed by BAI treatment. BAI promoted viability; suppressed apoptosis; regulated caspase-3, B-cell lymphoma 2 and Bcl-2-associated X protein; decreased iNOS level; and increased insulin production. BAI protected Min6 cells by upregulating miR-205. Besides, the Min6 cell-protective effect of BAI was PI3K/AKT pathway and NF-κB pathway dependent. BAI activated the PI3K/AKT pathway and inhibited the NF-κB pathway by regulating miR-205. In conclusion, BAI protected Min6 cells from TNF-α-induced injury by upregulating miR-205, which acts, at least in part, via activation of the PI3K/AKT pathway and inactivation of the NF-κB pathway.

Avoidance of androgen deprivation therapy in radiorecurrent prostate cancer as a clinically meaningful endpoint for salvage cryoablation.

BACKGROUND: To investigate the ability of salvage cryoablation of the prostate (SCAP) to delay the need for androgen deprivation therapy (ADT) in local recurrence after radiation therapy to the prostate using the Cryo-On-Line Database (COLD) registry. METHODS: The COLD registry is comprised of a combination of retrospectively and prospectively collected data on patients undergoing primary and SCAP. Patients with local recurrence after radiation therapy were identified. Kaplan-Meier analysis was used to calculate ADT-free survival. RESULTS: We identified 898 patients that have undergone SCAP in the COLD registry. Overall, the calculated 5-year ADT-free survival probability was 0.713. When stratified by D'Amico risk group, 264 high-risk patients (71.9%), 234 intermediate-risk (86.7%),and 228 low-risk (87.7%) were free of ADT post-SCAP. This correlates with a 5-year ADT-free survival of 60.7, 73.9, and 82.4%, respectively. Patients with post-SCAP PSA nadir of <0.2 ng/mL had a 5 year ADT-free survival of 87.1% compared to 48.7% with a PSA nadir ≥0.2 ng/mL. Pre-operative ADT use or full versus partial gland SCAP did not have an effect on ADT use post-operatively. In 118 (55.4%) of patients with post-operative biochemical recurrence, ADT was not used. CONCLUSION: For patients with local recurrence after radiation, SCAP is an option that provides a high chance of avoiding or delaying ADT. The potential to delay ADT and its associated side effects should be a part of counseling sessions with the patient when discussing treatment options for locally recurrent prostate cancer after radiation. Avoidance of ADT is more clinically relevant than PSA elevation.

Predicting Prostate Cancer Recurrence After Radical Prostatectomy.

BACKGROUND: Prostate cancer prognosis is variable, and management decisions involve balancing patients' risks of recurrence and recurrence-free death. Moreover, the roles of body mass index (BMI) and race in risk of recurrence are controversial [1,2]. To address these issues, we developed and cross-validated RAPS (Risks After Prostate Surgery), a personal prediction model for biochemical recurrence (BCR) within 10 years of radical prostatectomy (RP) that includes BMI and race as possible predictors, and recurrence-free death as a competing risk. METHODS: RAPS uses a patient's risk factors at surgery to assign him a recurrence probability based on statistical learning methods applied to a cohort of 1,276 patients undergoing RP at the University of Pennsylvania. We compared the performance of RAPS to that of an existing model with respect to calibration (by comparing observed and predicted outcomes), and discrimination (using the area under the receiver operating characteristic curve (AUC)). RESULTS: RAPS' cross-validated BCR predictions provided better calibration than those of an existing model that underestimated patients' risks. Discrimination was similar for the two models, with BCR AUCs of 0.793, 95% confidence interval (0.766-0.820) for RAPS, and 0.780 (0.745-0.815) for the existing model. RAPS' most important BCR predictors were tumor grade, preoperative prostate-specific antigen (PSA) level and BMI; race was less important [3]. RAPS' predictions can be obtained online at https://predict.shinyapps.io/raps. CONCLUSION: RAPS' cross-validated BCR predictions were better calibrated than those of an existing model, and BMI information contributed substantially to these predictions. RAPS predictions for recurrence-free death were limited by lack of co-morbidity data; however the model provides a simple framework for extension to include such data. Its use and extension should facilitate decision strategies for post-RP prostate cancer management. Prostate 77:291-298, 2017. © 2016 Wiley Periodicals, Inc.

Association of glucagon-like peptide-1 receptor agonist use and rates of acute myocardial infarction, stroke and overall mortality in patients with type 2 diabetes mellitus in a large integrated health system.

AIMS: To assess the potential impact of glucagon-like peptide-1 receptor agonist (GLP-1RA) exposure on cardiovascular disease (CVD) and mortality outcomes in patients with type 2 diabetes (T2D), using a large retrospective cohort. RESEARCH DESIGN AND METHODS: Patients who had T2D between 2005 and 2014 (N = 105 862) were identified from the electronic health record system at Cleveland Clinic using a validated electronic phenotype. A time-dependent, Cox, multiple regression analysis was used to assess the association between GLP-1RA exposure and risk of acute myocardial infarction (AMI), stroke/cerebrovascular accident (CVA), and overall mortality, as well as the composite of all three outcomes. The findings were further evaluated by assessing the effect of GLP-1RAs on the same variables in patients with and without prior CVD. The model adjusted for differences in demographic information, hypertension, laboratory/vital signs, history of outcomes, and T2D medications. RESULTS: There were significantly lower rates of AMI (hazard ratio [HR] 0.80, 95% confidence interval [CI] 0.65 to 0.99; P = .045), CVA (HR 0.82, 95% CI 0.74 to 0.91, P < .001), overall mortality (HR 0.48, 95% CI 0.41 to 0.57; P < .001), and the composite outcome (HR 0.82, 95% CI 0.74 to 0.91; P < .002) during the consolidated time that patients were exposed to GLP-1RAs compared to corresponding rates during intervals without GLP-1RA exposure. GLP-1RA treatment was associated with a significant decrease in CVA, mortality, and the composite outcome in patients with and without established CVD, not significantly affecting AMI in these subgroups. CONCLUSIONS: GLP-1RA exposure was found to be associated with a reduction in the risk of cardiovascular events observed and overall mortality among patients with T2D with and without established CVD, after adjusting for potential confounders.

Validation of the Kattan Nomogram for Prostate Cancer Recurrence After Radical Prostatectomy.

BACKGROUND: The Kattan postoperative radical prostatectomy (RP) nomogram is used to predict biochemical recurrence-free progression (BCRFP) after RP. However, external validation among contemporary patients using modern outcome definitions is limited. METHODS: A total of 1,931 patients who underwent RP at Roswell Park Cancer Institute (RPCI) between 1993 and 2014 (median follow-up, 47 months; range, 0-244 months) were assessed for NCCN-defined biochemical failure (BF) and RPCI-defined treatment failure (TF). Actual rates of biochemical failure-free survival (BFS; defined as 1 - BF) and treatment failure-free survival (TFS; defined as 1 - TF) were compared with Kattan BCRFP nomogram predictions. RESULTS: The Kattan BCRFP nomogram predictions at 5 and 10 years were predictive of BFS (area under the receiver operating characteristic curve [AUC], 0.772) and TFS (AUC, 0.774). The Kattan BCRFP nomogram tended to underestimate BFS and TFS compared with actual outcomes. The Kattan 5-year BCRFP predictions consistently overestimated actual 5-year BFS outcomes among subgroups of high- and intermediate-risk patients with at least 5-year outcomes. CONCLUSIONS: The Kattan BCRFP nomogram is a robust predictor of NCCN-defined BF in a large sample of patients with RP with substantial follow-up and modern, standardized failure definitions.

A pretreatment nomogram for prediction of biochemical failure after primary cryoablation of the prostate.

BACKGROUND: To create a predictive nomogram for biochemical failure following primary whole-gland cryoablation of the prostate for localized prostate cancer (LPCa). METHODS: We retrospectively analyzed 2,242 patients from the Cryo On-Line Database (COLD) who were treatment naive and had undergone primary whole gland cryoablation of the prostate for biopsy-confirmed LPCa. Kaplan-Meier (KM) curves estimating 5 year biochemical progression-free survival (bPFS) were generated. Multivariable Cox proportional hazards analysis (CoxPH) was performed in order to construct the nomogram. The nomogram was internally validated using the bootstrap technique. RESULTS: Overall, the KM estimated 5 year bPFS was 72.8%. Stratified by D'Amico risk, The KM estimated 5 year bPFS was 82.6%, 71.1%, and 57.8% for low-, intermediate-, and high-risk groups, respectively. Statistically significant predictors of biochemical outcomes from CoxPH analysis were pre-treatment prostate specific antigen (PTPSA) (P < 0.001), total prostate volume (P = 0.004), clinical stage (P = 0.034), and Gleason score (0.004). A nomogram for predicted 5 year biochemical progression free probability was constructed with a concordance index of 0.652. An online risk calculator was also generated. CONCLUSIONS: To the best of our knowledge, this is the first predictive nomogram for biochemical outcomes after primary whole gland cryoablation of the prostate using socio-demographic, pretreatment, clinical, and prostate biopsy data. Our nomogram and online risk calculator can guide both patients and urologists for shared decision making regarding definitive treatment options.

Gleason Upgrading with Time in a Large Prostate Cancer Active Surveillance Cohort.

PURPOSE: We report the percentage of patients on active surveillance who had disease pathologically upgraded and factors that predict for upgrading on surveillance biopsies. MATERIALS AND METHODS: Patients in our active surveillance database with at least 1 repeat prostate biopsy were included. Histological upgrading was defined as any increase in primary or secondary Gleason grade on repeat biopsy. Multivariate analysis was used to determine baseline and dynamic factors associated with Gleason upgrading. This information was used to develop a nomogram to predict for upgrading or treatment in patients electing for active surveillance. RESULTS: Of 862 patients in our cohort 592 had 2 or more biopsies. Median followup was 6.4 years. Of the patients 20% were intermediate risk, 0.3% were high risk and all others were low risk. During active surveillance 31.3% of cases were upgraded. On multivariate analysis clinical stage T2, higher prostate specific antigen and higher percentage of cores involved with disease at the time of diagnosis predicted for upgrading. A total of 27 cases (15% of those upgraded) were Gleason 8 or higher at upgrading, and 62% of all 114 upgraded cases went on to have active treatment. The nomogram incorporated clinical stage, age, prostate specific antigen, core positivity and Gleason score. The concordance index was 0.61. CONCLUSIONS: In this large re-biopsy cohort with medium-term followup, most cases have not been pathologically upgraded to date. A model predicting for upgrading or radical treatment was developed which could be useful in counseling patients considering active surveillance for prostate cancer.

Postoperative Nomogram for Predicting Cancer-Specific Mortality in Medullary Thyroid Cancer.

BACKGROUND: Medullary thyroid cancer (MTC) is a rare thyroid cancer accounting for 5 % of all thyroid malignancies. The purpose of our study was to design a predictive nomogram for cancer-specific mortality (CSM) utilizing clinical, pathological, and biochemical variables in patients with MTC. METHODS: MTC patients managed entirely at Memorial Sloan-Kettering Cancer Center between 1986 and 2010 were identified. Patient, tumor, and treatment characteristics were recorded, and variables predictive of CSM were identified by univariable analyses. A multivariable competing risk model was then built to predict the 10-year cancer specific mortality of MTC. All predictors of interest were added in the starting full model before selection, including age, gender, pre- and postoperative serum calcitonin, pre- and postoperative CEA, RET mutation status, perivascular invasion, margin status, pathologic T status, pathologic N status, and M status. Stepdown method was used in model selection to choose predictive variables. RESULTS: Of 249 MTC patients, 22.5 % (56/249) died from MTC, whereas 6.4 % (16/249) died secondary to other causes. Mean follow-up period was 87 ± 67 months. The seven variables with the highest predictive accuracy for cancer specific mortality included age, gender, postoperative calcitonin, perivascular invasion, pathologic T status, pathologic N status, and M status. These variables were used to create the final nomogram. Discrimination from the final nomogram was measured at 0.77 with appropriate calibration. CONCLUSIONS: We describe the first nomogram that estimates cause-specific mortality in individual patients with MTC. This predictive nomogram will facilitate patient counseling in terms of prognosis and subsequent clinical follow up.

Monocular-binocular feature fidelity induced index for stereoscopic image quality assessment.

Perceptual three-dimensional image quality assessment (3D-IQA) aims to use computational models to measure image quality in a way that is consistent with human visual perception. Unlike previous studies that directly extended the two-dimensional metrics to the three-dimensional (3D) case, the major technical innovation of this paper is to simulate monocular and binocular visual perception and propose a monocular-binocular feature fidelity induced index for 3D-IQA. To be more specific, in the training stage, we train monocular and binocular dictionaries from the training database, so that the latent response properties can be represented as a set of basis vectors. In the quality estimation stage, we compute monocular feature fidelity and binocular feature fidelity indexes based on the estimated sparse coefficient vectors and compute a global energy response similarity index by considering global energy changes. The final quality score is obtained by incorporating them. Experimental results on four 3D-IQA databases demonstrate that in comparison with the most relevant existing methods, the devised algorithm achieves high consistency alignment with subjective assessment.

Nomograms incorporating serum C-reactive protein effectively predict mortality before and after surgical treatment of renal cell carcinoma.

OBJECTIVES: To incorporate C-reactive protein into nomograms estimating survival in patients with renal cell carcinoma. METHODS: Patients undergoing surgery for renal cell carcinoma from 2005-2012 were studied retrospectively. Multivariable Cox proportional hazards regression and competing risks regression models including stage, grade, C-reactive protein levels and presence of metastatic disease were constructed. Outcomes analyzed include overall mortality overall mortality and renal cell carcinoma-specific mortality. RESULTS: The cohort included 516 patients with a mean follow up of 1.7 years (SD 1.4 years). One- and 3-year renal cell carcinoma-specific mortality was 8.8% and 13.5%, respectively. Four nomograms were generated using overall mortality and renal cell carcinoma-specific mortality as end-points, two each for pre- and postoperative counseling. The factor with the largest effect on all nomograms was preoperative C-reactive protein. Based on the internal validation with bootstrapping, the concordance indices for renal cell carcinoma-specific mortality in the preoperative nomogram, postoperative nomogram, and the Mayo Clinic stage, size, grade and necrosis score were 0.889, 0.893, and 0.832, respectively (P = 0.005 and 0.002 comparing with stage, size, grade and necrosis scores for preoperative or postoperative nomograms). For overall mortality, the preoperative nomogram, postoperative nomogram, and stage, size, grade and necrosis score showed concordance indices of 0.866, 0.897, and 0.828, respectively (P = 0.123 and 0.008 compared with stage, size, grade and necrosis score for preoperative or postoperative nomograms). CONCLUSIONS: We have generated nomograms incorporating serum C-reactive protein levels that effectively predict overall mortality and renal cell carcinoma specific mortality. Our findings warrant external validation.

Nomograms for preoperative prediction of prognosis in patients with oral cavity squamous cell carcinoma.

BACKGROUND: This study sought to develop prognostic tools that will accurately predict overall and cancer-related mortality and risk of recurrence in individual patients with oral cancer based on host and tumor characteristics. These tools would take into account numerous prognosticators beyond those covered by the traditional TNM (tumor-node-metastasis) staging system. METHODS: Demographic, host, and tumor characteristics of 1617 patients with cancer of the oral cavity, who were treated primarily with surgery at a single-institution tertiary care cancer center between 1985 and 2009, were reviewed from a preexisting database. Recurrent disease was recorded in 509 patients (456 locoregional and 116 distant); 328 patients died of cancer-related causes, and 542 died of other causes. The median follow-up was 42 months (range, 1-300 months). The following variables were analyzed as predictors of prognosis: age, sex, race, alcohol and tobacco use, oral cavity subsite, invasion of other structures, comorbidity, tumor size, and clinical nodal status. The stepdown method was used to select the statistically most influential predictors for inclusion in the final nomogram for each outcome of interest. RESULTS: The most influential predictors of both recurrence and cancer-specific mortality probability (CSMP) were tumor size, nodal status, subsite, and bone invasion. Nomograms were generated for prediction of overall survival (OS), CSMP, and locoregional recurrence-free probability (LRRFP). The nomograms were internally validated with an overfit-corrected predictive discrimination metric (concordance index) for OS of 67%, CSMP of 66%, and LRRFP of 60%. CONCLUSIONS: Nomograms have been developed that can reasonably estimate OS, CSMP, and LRRFP based on specific tumor and host characteristics in patients with oral cancer.

Urinary PCA3 as a predictor of prostate cancer in a cohort of 3,073 men undergoing initial prostate biopsy.

PURPOSE: PCA3 is a urinary marker that has shown promise in predicting the presence of prostate cancer in men undergoing repeat prostate biopsy. We studied PCA3 before initial prostate biopsy. MATERIALS AND METHODS: Records from a single organization were retrospectively reviewed. The predictive value of PCA3 was explored using nonparametric receiver operating characteristic curve analysis (ROC) and multivariable logistic regression analysis. RESULTS: A total of 3,073 men underwent PCA3 analysis before initial prostate biopsy sampling of 12 to 14 areas. Mean PCA3 was 27.2 and 52.5 for patients without and with cancer, respectively. Prostate cancer was identified in 1,341 (43.6%) men. Overall 54.5% had Gleason 6 disease and 45.5% had Gleason 7 or greater (high grade prostate cancer). Mean PCA3 was 47.5 and 58.5 for the patients with Gleason 6 and 7 or greater disease, respectively. On multivariable logistic analysis PCA3 was statistically significantly associated with prostate cancer and high grade prostate cancer after adjusting for prostate specific antigen (p<0.001 for both), free prostate specific antigen (p=0.04 and p=0.01, respectively), age (p<0.001 for both), family history (p<0.001 and p=0.59, respectively), abnormal digital rectal examination (p=0.31 and p<0.001, respectively), prostate volume (p<0.001 for both) and body mass index (p<0.001 for both). Using ROC analysis PCA3 outperformed prostate specific antigen in the prediction of prostate cancer (AUC 0.697 vs 0.599, p<0.01) but not for high grade prostate cancer (AUC 0.682 vs 0.679, p=0.702). CONCLUSIONS: PCA3 proved a useful tool in identifying patients at risk for prostate cancer before initial prostate biopsy. To our knowledge this is the largest PCA3 study in the initial biopsy population. These results suggest that further exploration of the value of PCA3 is warranted.

Postoperative nomograms predictive of survival after surgical management of malignant tumors of the major salivary glands.

OBJECTIVES: The objective of this study was to create a nomogram predictive of survival in salivary gland cancer. METHODS: Clinical, tumor, and treatment characteristics were collected for 301 patients who underwent surgery for salivary gland cancer between 1985 and 2009 at Memorial Sloan Kettering Cancer Centre. Factors predictive of overall survival (OS) and cancer-specific survival (CSS) were determined by univariate analysis. Cox risk regression was used to model OS data. Competing risks regression was used for cancer-specific death. Deaths from other causes were treated as competing risks for cancer-specific death. Predictive nomograms for OS and CSS were then created using stepdown method to select predictors of outcome. RESULTS: The median age was 62 (range 9-89) years. There were 156 (52%) males and 145 (48%) females. Five variables predictive for OS (age, clinical T4 stage, histological grade, perineural invasion, and tumor dimension) were used to generate a parsimonious model, and a nomogram was created to predict 10-year survival probability. The concordance index (CI) for this nomogram was 0.809. Five variables predictive for CSS (histological grade, perineural invasion, clinical T4 stage, positive nodal status, and status of margins) were used to generate a second nomogram predicting CSS. This nomogram had a CI of 0.856. Both nomograms were validated internally by assessing discrimination and calibration. CONCLUSIONS: We have developed the first nomograms to predict prognosis in an individual patient with salivary gland cancer.

Impact of international variation of prostate cancer on a predictive nomogram for biochemical recurrence in clinically localised prostate cancer.

OBJECTIVE: Prostate cancer (PCa) incidence has been rising rapidly in Korea with aggressive clinicopathologic features compared to those observed in Western countries. Our aim was to develop a predictive nomogram for BCR-free survival based on the characteristics of PCa in Korean men and compared its predictive accuracy to an established Western nomogram. METHODS: A nationwide multicenter study was designed involving 723 Korean men with clinically localised PCa that had undergone radical prostatectomy. The Cox proportional hazards model was applied to 549 cases from four heavy volume institutions to define prognostic factors and develops the Korean nomogram, which was subjected to internal validation, external validation using a separate cohort of 295 cases, and head-to-head comparison with the updated Kattan nomogram. RESULTS: During the mean follow-up period of 44.8 months, BCR occurred in 251 patients (35.4 %) with aggressive clinicopathologic features. Similar to Western cases, preoperative prostate-specific antigen (PSA), pathologic tumour stage (pT), and Gleason score (GS) were independent prognostic factors and used to develop the Korean nomogram in conjunction with age and surgical margin status. The Korean nomogram performed well for predicting BCR-free 5- and 10-year survival on internal validation. On external validation, the Korean nomogram showed better calibration than the updated Kattan nomogram. CONCLUSIONS: Preoperative PSA, pT, and GS were independent prognostic factor for BCR in clinically localised PCa in Korean men. The superior performance of the Korean nomogram for Korean PCa patients suggests that geographic variation in clinicopathologic factors should be considered in a predictive nomogram.

Long-term survival of extremely advanced prostate cancer patients diagnosed with prostate-specific antigen over 500 ng/ml.

OBJECTIVE: To investigate survival of hormone-naïve prostate cancer patients diagnosed with prostate-specific antigen ≥500 ng/ml, stratified according to the prostate-specific antigen level and type of therapy. METHODS: Data of prostate cancer patients with prostate-specific antigen ≥500 ng/ml diagnosed between 2001 and 2003 and receiving primary androgen deprivation therapy were extracted from the Japan Study Group of Prostate Cancer database. Cancer-specific survival and overall survival were assessed according to the prostate-specific antigen level (500-999, 1000-4999 and ≥5000 ng/ml) and type of therapy using Kaplan-Meier analyses and multivariate Cox proportional hazards models including age, Gleason score, oncological stage and comorbidity. RESULTS: The median follow-up was 27 months (interquartile range, 13-51) and a total of 1961 patients were included. Five-year cancer-specific and overall mortalities were 39.0 and 33.0%, respectively. There was a significant inverse relationship between overall survival and prostate-specific antigen magnitude among combination therapy patients, but not monotherapy patients (log-rank test, P = 0.034 and 0.558, respectively). The median overall survival in combination therapy patients with low-, intermediate- and high prostate-specific antigen and monotherapy patients with any prostate-specific antigen were 79, 59, 45 and 43 months, respectively. Multivariate analysis showed that combination therapy in patients with low- and intermediate prostate-specific antigen was significantly associated with a favorable overall survival compared with monotherapy (hazard ratios 0.66 and 0.75, respectively, both P < 0.001). Similar results were obtained for cancer-specific survival. CONCLUSIONS: There are major survival differences in extremely high prostate-specific antigen cases according to the prostate-specific antigen level and hormone therapy type and those patients would benefit notably from combination androgen blockade.

Factors affecting choice between ureterostomy, ileal conduit and continent reservoir after radical cystectomy: Japanese series.

BACKGROUND: Little is known about the disparity of choices between three urinary diversions after radical cystectomy, focusing on patient and institutional factors. METHODS: We identified urothelial carcinoma patients who received radical cystectomy with cutaneous ureterostomy, ileal conduit or continent reservoir using the Japanese Diagnosis Procedure Combination database from 2007 to 2012. Data comprised age, sex, comorbidities (converted into the Charlson index), TNM classification (converted into oncological stage), hospitals' academic status, hospital volume, bed volume and geographical region. Multivariate ordinal logistic regression analyses fitted with the proportional odds model were performed to analyze factors affecting urinary diversion choices. For dependent variables, the three diversions were converted into an ordinal variable in order of complexity: cutaneous ureterostomy (reference), ileal conduit and continent reservoir. Geographical variations were also examined by multivariate logistic regression models. RESULTS: A total of 4790 patients (1131 cutaneous ureterostomies [23.6 %], 2970 ileal conduits [62.0 %] and 689 continent reservoirs [14.4 %]) were included. Ordinal logistic regression analyses showed that male sex, lower age, lower Charlson index, early tumor stage, higher hospital volume (≥3.4 cases/year) and larger bed volume (≥450 beds) were significantly associated with the preference of more complex urinary diversion. Significant geographical disparity was also found. CONCLUSION: Good patient condition and early oncological status, as well as institutional factors, including high hospital volume, large bed volume and specific geographical regions, are independently related to the likelihood of choosing complex diversions. Recognizing this disparity would help reinforce the need for clinical practice uniformity.

Estimating a time-dependent concordance index for survival prediction models with covariate dependent censoring.

Given a predictive marker and a time-to-event response variable, the proportion of concordant pairs in a data set is called concordance index. A specifically useful marker is the risk predicted by a survival regression model. This article extends the existing methodology for applications where the length of the follow-up period depends on the predictor variables. A class of inverse probability of censoring weighted estimators is discussed in which the estimates rely on a working model for the conditional censoring distribution. The estimators are consistent for a truncated concordance index if the working model is correctly specified and if the probability of being uncensored at the truncation time is positive. In this framework, all kinds of prediction models can be assessed, and time trends in the discrimination ability of a model can be captured by varying the truncation time point. For illustration, we re-analyze a study on risk prediction for prostate cancer patients. The effects of misspecification of the censoring model are studied in simulated data.

External validation of preoperative nomograms predicting biochemical recurrence after radical prostatectomy.

OBJECTIVE: Preoperative nomograms can accurately predict the rate of biochemical recurrence after radical prostatectomy. Although these nomograms were shown to be valid in several external validation cohorts of Caucasian patients, they have not been validated in non-Caucasian patients from Asian countries. We therefore validated these preoperative nomograms in a Japanese cohort, using different cutoff values of prostate-specific antigen concentrations for biochemical recurrence. METHODS: We analyzed 637 patients who underwent radical prostatectomy for clinically localized prostate cancer at the Tokyo Medical University Hospital between February 2000 and January 2011. We evaluated two prostate-specific antigen cutoff values for biochemical recurrence, 0.2 and 0.4 ng/ml. Using c-index and calibration plots, we validated the previously developed Kattan and Stephenson nomograms. RESULTS: Overall, the mean 5-year non-biochemical recurrence rate was 72 ± 4%. Using a prostate-specific antigen cutoff values of 0.2 and 0.4 ng/ml, the c-indices for the Kattan nomogram were 0.714 and 0.733. Similarly, using a prostate-specific antigen cutoff values of 0.2 and 0.4 ng/ml, the c-indices for the Stephenson nomograms were 0.717 and 0.671. The calibration plots showed that the predictive value of the Stephenson nomogram at a prostate-specific antigen cutoff of 0.2 ng/ml was close to the actual outcomes compared with other combinations of nomograms and prostate-specific antigen cutoff levels. CONCLUSIONS: Because the c-indices of both nomograms were generally high, these nomograms can be applied to our cohort. The addition of biopsy information did not markedly improve the c-index but resulted in good calibration, indicating that the Stephenson nomogram may be a better fit for our patient cohort.