Electronic Documentation of Intraoperative Observation of Cystoscopic Procedures Using the cMDX Information System.

PURPOSE: Accurate documentation of lesions during transurethral resection of bladder tumors (TURBT) is essential for precise diagnosis, treatment planning, and follow-up care. However, optimizing schematic documentation techniques for bladder lesions has received limited attention. MATERIALS AND METHODS: This prospective observational study used a cMDX-based documentation system that facilitates graphical representation, a lesion-specific questionnaire, and heatmap analysis with a posterization effect. We designed a graphical scheme for bladder covering bladder landmarks to visualize anatomic features and to document the lesion location. The lesion-specific questionnaire was integrated for comprehensive lesion characterization. Finally, spatial analyses were applied to investigate the anatomic distribution patterns of bladder lesions. RESULTS: A total of 97 TURBT cases conducted between 2021 and 2023 were included, identifying 176 lesions. The lesions were distributed in different bladder areas with varying frequencies. The distribution pattern, sorted by frequency, was observed in the following areas: posterior, trigone, lateral right and anterior, and lateral left and dome. Suspicious levels were assigned to the lesions, mostly categorized either as indeterminate or moderate. Lesion size analysis revealed that most lesions fell between 5 and 29 mm. CONCLUSION: The study highlights the potential of schematic documentation techniques for informed decision making, quality assessment, primary research, and secondary data utilization of intraoperative data in the context of TURBT. Integrating cMDX and heatmap analysis provides valuable insights into lesion distribution and characteristics.

Critical evaluation of artificial intelligence as a digital twin of pathologists for prostate cancer pathology.

Prostate cancer pathology plays a crucial role in clinical management but is time-consuming. Artificial intelligence (AI) shows promise in detecting prostate cancer and grading patterns. We tested an AI-based digital twin of a pathologist, vPatho, on 2603 histological images of prostate tissue stained with hematoxylin and eosin. We analyzed various factors influencing tumor grade discordance between the vPatho system and six human pathologists. Our results demonstrated that vPatho achieved comparable performance in prostate cancer detection and tumor volume estimation, as reported in the literature. The concordance levels between vPatho and human pathologists were examined. Notably, moderate to substantial agreement was observed in identifying complementary histological features such as ductal, cribriform, nerve, blood vessel, and lymphocyte infiltration. However, concordance in tumor grading decreased when applied to prostatectomy specimens (κ = 0.44) compared to biopsy cores (κ = 0.70). Adjusting the decision threshold for the secondary Gleason pattern from 5 to 10% improved the concordance level between pathologists and vPatho for tumor grading on prostatectomy specimens (κ from 0.44 to 0.64). Potential causes of grade discordance included the vertical extent of tumors toward the prostate boundary and the proportions of slides with prostate cancer. Gleason pattern 4 was particularly associated with this population. Notably, the grade according to vPatho was not specific to any of the six pathologists involved in routine clinical grading. In conclusion, our study highlights the potential utility of AI in developing a digital twin for a pathologist. This approach can help uncover limitations in AI adoption and the practical application of the current grading system for prostate cancer pathology.

Artificial Intelligence Reveals Distinct Prognostic Subgroups of Muscle-Invasive Bladder Cancer on Histology Images.

Muscle-invasive bladder cancer (MIBC) is a highly heterogeneous and costly disease with significant morbidity and mortality. Understanding tumor histopathology leads to tailored therapies and improved outcomes. In this study, we employed a weakly supervised learning and neural architecture search to develop a data-driven scoring system. This system aimed to capture prognostic histopathological patterns observed in H&E-stained whole-slide images. We constructed and externally validated our scoring system using multi-institutional datasets with 653 whole-slide images. Additionally, we explored the association between our scoring system, seven histopathological features, and 126 molecular signatures. Through our analysis, we identified two distinct risk groups with varying prognoses, reflecting inherent differences in histopathological and molecular subtypes. The adjusted hazard ratio for overall mortality was 1.46 (95% CI 1.05-2.02; z: 2.23; p = 0.03), thus identifying two prognostic subgroups in high-grade MIBC. Furthermore, we observed an association between our novel digital biomarker and the squamous phenotype, subtypes of miRNA, mRNA, long non-coding RNA, DNA hypomethylation, and several gene mutations, including FGFR3 in MIBC. Our findings underscore the risk of confounding bias when reducing the complex biological and clinical behavior of tumors to a single mutation. Histopathological changes can only be fully captured through comprehensive multi-omics profiles. The introduction of our scoring system has the potential to enhance daily clinical decision making for MIBC. It facilitates shared decision making by offering comprehensive and precise risk stratification, treatment planning, and cost-effective preselection for expensive molecular characterization.

Efficient Augmented Intelligence Framework for Bladder Lesion Detection.

PURPOSE: Development of intelligence systems for bladder lesion detection is cost intensive. An efficient strategy to develop such intelligence solutions is needed. MATERIALS AND METHODS: We used four deep learning models (ConvNeXt, PlexusNet, MobileNet, and SwinTransformer) covering a variety of model complexity and efficacy. We trained these models on a previously published educational cystoscopy atlas (n = 312 images) to estimate the ratio between normal and cancer scores and externally validated on cystoscopy videos from 68 cases, with region of interest (ROI) pathologically confirmed to be benign and cancerous bladder lesions (ie, ROI). The performance measurement included specificity and sensitivity at frame level, frame sequence (block) level, and ROI level for each case. RESULTS: Specificity was comparable between four models at frame (range, 30.0%-44.8%) and block levels (56%-67%). Although sensitivity at the frame level (range, 81.4%-88.1%) differed between the models, sensitivity at the block level (100%) and ROI level (100%) was comparable between these models. MobileNet and PlexusNet were computationally more efficient for real-time ROI detection than ConvNeXt and SwinTransformer. CONCLUSION: Educational cystoscopy atlas and efficient models facilitate the development of real-time intelligence system for bladder lesion detection.

Tumor detection under cystoscopy with transformer-augmented deep learning algorithm.

Objective.Accurate tumor detection is critical in cystoscopy to improve bladder cancer resection and decrease recurrence. Advanced deep learning algorithms hold the potential to improve the performance of standard white-light cystoscopy (WLC) in a noninvasive and cost-effective fashion. The purpose of this work is to develop a cost-effective, transformer-augmented deep learning algorithm for accurate detection of bladder tumors in WLC and to assess its performance on archived patient data.Approach.'CystoNet-T', a deep learning-based bladder tumor detector, was developed with a transformer-augmented pyramidal CNN architecture to improve automated tumor detection of WLC. CystoNet-T incorporated the self-attention mechanism by attaching transformer encoder modules to the pyramidal layers of the feature pyramid network (FPN), and obtained multi-scale activation maps with global features aggregation. Features resulting from context augmentation served as the input to a region-based detector to produce tumor detection predictions. The training set was constructed by 510 WLC frames that were obtained from cystoscopy video sequences acquired from 54 patients. The test set was constructed based on 101 images obtained from WLC sequences of 13 patients.Main results.CystoNet-T was evaluated on the test set with 96.4 F1 and 91.4 AP (Average Precision). This result improved the benchmark of Faster R-CNN and YOLO by 7.3 points in F1 and 3.8 points in AP. The improvement is attributed to the strong ability of global attention of CystoNet-T and better feature learning of the pyramids architecture throughout the training. The model was found to be particularly effective in highlighting the foreground information for precise localization of the true positives while favorably avoiding false alarmsSignificance.We have developed a deep learning algorithm that accurately detects bladder tumors in WLC. Transformer-augmented AI framework promises to aid in clinical decision-making for improved bladder cancer diagnosis and therapeutic guidance.

Real-time Detection of Bladder Cancer Using Augmented Cystoscopy with Deep Learning: a Pilot Study.

BACKGROUND: Detection of bladder tumors under white light cystoscopy (WLC) is challenging yet impactful on treatment outcomes. Artificial intelligence (AI) holds the potential to improve tumor detection; however, its application in the real-time setting remains unexplored. AI has been applied to previously recorded images for post hoc analysis. In this study, we evaluate the feasibility of real-time AI integration during clinic cystoscopy and transurethral resection of bladder tumor (TURBT) on live, streaming video. METHODS: Patients undergoing clinic flexible cystoscopy and TURBT were prospectively enrolled. A real-time alert device system (real-time CystoNet) was developed and integrated with standard cystoscopy towers. Streaming videos were processed in real time to display alert boxes in sync with live cystoscopy. The per-frame diagnostic accuracy was measured. RESULTS AND LIMITATIONS: Real-time CystoNet was successfully integrated in the operating room during TURBT and clinic cystoscopy in 50 consecutive patients. There were 55 procedures that met the inclusion criteria for analysis including 21 clinic cystoscopies and 34 TURBTs. For clinic cystoscopy, real-time CystoNet achieved per-frame tumor specificity of 98.8% with a median error rate of 3.6% (range: 0 - 47%) frames per cystoscopy. For TURBT, the per-frame tumor sensitivity was 52.9% and the per-frame tumor specificity was 95.4% with an error rate of 16.7% for cases with pathologically confirmed bladder cancers. CONCLUSIONS: The current pilot study demonstrates the feasibility of using a real-time AI system (real-time CystoNet) during cystoscopy and TURBT to generate active feedback to the surgeon. Further optimization of CystoNet for real-time cystoscopy dynamics may allow for clinically useful AI-augmented cystoscopy.

Conceptual framework and documentation standards of cystoscopic media content for artificial intelligence.

BACKGROUND: The clinical documentation of cystoscopy includes visual and textual materials. However, the secondary use of visual cystoscopic data for educational and research purposes remains limited due to inefficient data management in routine clinical practice. METHODS: A conceptual framework was designed to document cystoscopy in a standardized manner with three major sections: data management, annotation management, and utilization management. A Swiss-cheese model was proposed for quality control and root cause analyses. We defined the infrastructure required to implement the framework with respect to FAIR (findable, accessible, interoperable, reusable) principles. We applied two scenarios exemplifying data sharing for research and educational projects to ensure compliance with FAIR principles. RESULTS: The framework was successfully implemented while following FAIR principles. The cystoscopy atlas produced from the framework could be presented in an educational web portal; a total of 68 full-length qualitative videos and corresponding annotation data were sharable for artificial intelligence projects covering frame classification and segmentation problems at case, lesion, and frame levels. CONCLUSION: Our study shows that the proposed framework facilitates the storage of visual documentation in a standardized manner and enables FAIR data for education and artificial intelligence research.

PlexusNet: A neural network architectural concept for medical image classification.

State-of-the-art (SOTA) convolutional neural network models have been widely adapted in medical imaging and applied to address different clinical problems. However, the complexity and scale of such models may not be justified in medical imaging and subject to the available resource budget. Further increasing the number of representative feature maps for the classification task decreases the model explainability. The current data normalization practice is fixed prior to model development and discounting the specification of the data domain. Acknowledging these issues, the current work proposed a new scalable model family called PlexusNet; the block architecture and model scaling by the network's depth, width, and branch regulate PlexusNet's architecture. The efficient computation costs outlined the dimensions of PlexusNet scaling and design. PlexusNet includes a new learnable data normalization algorithm for better data generalization. We applied a simple yet effective neural architecture search to design PlexusNet tailored to five clinical classification problems that achieve a performance noninferior to the SOTA models ResNet-18 and EfficientNet B0/1. It also does so with lower parameter capacity and representative feature maps in ten-fold ranges than the smallest SOTA models with comparable performance. The visualization of representative features revealed distinguishable clusters associated with categories based on latent features generated by PlexusNet. The package and source code are at https://github.com/oeminaga/PlexusNet.git.

Conceptual Framework and Documentation Standards of Cystoscopic Media Content for Artificial Intelligence.

BACKGROUND: The clinical documentation of cystoscopy includes visual and textual materials. However, the secondary use of visual cystoscopic data for educational and research purposes remains limited due to inefficient data management in routine clinical practice. METHODS: A conceptual framework was designed to document cystoscopy in a standardized manner with three major sections: data management, annotation management, and utilization management. A Swiss-cheese model was proposed for quality control and root cause analyses. We defined the infrastructure required to implement the framework with respect to FAIR (findable, accessible, interoperable, re-usable) principles. We applied two scenarios exemplifying data sharing for research and educational projects to ensure the compliance with FAIR principles. RESULTS: The framework was successfully implemented while following FAIR principles. The cystoscopy atlas produced from the framework could be presented in an educational web portal; a total of 68 full-length qualitative videos and corresponding annotation data were sharable for artificial intelligence projects covering frame classification and segmentation problems at case, lesion and frame levels. CONCLUSION: Our study shows that the proposed framework facilitates the storage of the visual documentation in a standardized manner and enables FAIR data for education and artificial intelligence research.

An Efficient Framework for Video Documentation of Bladder Lesions for Cystoscopy: A Proof-of-Concept Study.

Processing full-length cystoscopy videos is challenging for documentation and research purposes. We therefore designed a surgeon-guided framework to extract short video clips with bladder lesions for more efficient content navigation and extraction. Screenshots of bladder lesions were captured during transurethral resection of bladder tumor, then manually labeled according to case identification, date, lesion location, imaging modality, and pathology. The framework used the screenshot to search for and extract a corresponding 10-seconds video clip. Each video clip included a one-second space holder with a QR barcode informing the video content. The success of the framework was measured by the secondary use of these short clips and the reduction of storage volume required for video materials. From 86 cases, the framework successfully generated 249 video clips from 230 screenshots, with 14 erroneous video clips from 8 screenshots excluded. The HIPPA-compliant barcodes provided information of video contents with a 100% data completeness. A web-based educational gallery was curated with various diagnostic categories and annotated frame sequences. Compared with the unedited videos, the informative short video clips reduced the storage volume by 99.5%. In conclusion, our framework expedites the generation of visual contents with surgeon's instruction for cystoscopy and potential incorporation of video data towards applications including clinical documentation, education, and research.

Artificial Intelligence-Based Prognostic Model for Urologic Cancers: A SEER-Based Study.

BACKGROUND: Prognostication is essential to determine the risk profile of patients with urologic cancers. METHODS: We utilized the SEER national cancer registry database with approximately 2 million patients diagnosed with urologic cancers (penile, testicular, prostate, bladder, ureter, and kidney). The cohort was randomly divided into the development set (90%) and the out-held test set (10%). Modeling algorithms and clinically relevant parameters were utilized for cancer-specific mortality prognosis. The model fitness for the survival estimation was assessed using the differences between the predicted and observed Kaplan-Meier estimates on the out-held test set. The overall concordance index (c-index) score estimated the discriminative accuracy of the survival model on the test set. A simulation study assessed the estimated minimum follow-up duration and time points with the risk stability. RESULTS: We achieved a well-calibrated prognostic model with an overall c-index score of 0.800 (95% CI: 0.795-0.805) on the representative out-held test set. The simulation study revealed that the suggestions for the follow-up duration covered the minimum duration and differed by the tumor dissemination stages and affected organs. Time points with a high likelihood for risk stability were identifiable. CONCLUSIONS: A personalized temporal survival estimation is feasible using artificial intelligence and has potential application in clinical settings, including surveillance management.

Specific spatial distribution patterns of tumor foci are associated with a low risk of biochemical recurrence in pT2pN0R0 prostate cancer.

BACKGROUND: The previous attempts for pT2 substaging of prostate cancer (PCa) were insufficient in providing prognostic subgroups and the search for new prognostic parameters to subcategorize pT2 PCa is, therefore, needed. Therefore, the current study investigated the association between tumor distribution patterns and the biochemical recurrence (BCR)-free survival rate in pT2pN0R0 PCa. METHODS: Following radical prostatectomy, the anatomical distribution of PCa in 743 men with pT1-pT3pN0 disease was analyzed to determine 20 types of PCa distribution patterns. Then, 245 men with pT2pN0R0 PCa was considered for prognostic evaluation with a mean follow-up period of 60 months. The spatial distribution patterns of PCa were evaluated using a cMDX©-based map model of the prostate. An analysis including 552,049 comparison operations was performed to assist in the evaluation of the similarity levels of the distribution patterns. A k-mean cluster analysis was applied to determine groups with similar distribution patterns. A decision-tree analysis was performed to divide these groups according to frequency of BCR. The BCR-free survival rate was analyzed using Kaplan-Meier curves. Predictors of progression were investigated using a Cox proportional hazards model. RESULTS: BCR occurred in 8.2% of the 245 men with pT2pN0R0 PCa. The median time of recurrence was 60 months (interquartile range [IQR]: 42-77). In univariate and multivariate analyses, the prostate volume and the distribution patterns were independent predictors for BCR, whereas the sub-staging of pT2 tumors, Gleason grading, prostate-specific antigen (PSA) level, and relative tumor volume were not. In the patients with pT2pN0R0 disease, PCa distribution patterns with the apical involvement were significantly associated with the risk of BCR (P = 0.001). CONCLUSION: The spread tumor patterns with the apical involvement are associated with a high-risk of BCR in the pT2 tumor stage. The vertical tumor spread could be considered in developing improved prognostic pT2 sub-categories.

Current Trends in Artificial Intelligence Application for Endourology and Robotic Surgery.

With the advent of electronic medical records and digitalization of health care over the past 2 decades, artificial intelligence (AI) has emerged as an enabling tool to manage complex datasets and deliver streamlined data-driven patient care. AI algorithms have the ability to extract meaningful signal from complex datasets through an iterative process akin to human learning. Through advancements over the past decade in deep learning, AI-driven innovations have accelerated applications in health care. Herein, the authors explore the development of these emerging AI technologies, focusing on the application of AI to endourology and robotic surgery.

Combination possibility and deep learning model as clinical decision-aided approach for prostate cancer.

This study aims to introduce as proof of concept a combination model for classification of prostate cancer using deep learning approaches. We utilized patients with prostate cancer who underwent surgical treatment representing the various conditions of disease progression. All possible combinations of significant variables from logistic regression and correlation analyses were determined from study data sets. The combination possibility and deep learning model was developed to predict these combinations that represented clinically meaningful patient's subgroups. The observed relative frequencies of different tumor stages and Gleason score Gls changes from biopsy to prostatectomy were available for each group. Deep learning models and seven machine learning approaches were compared for the classification performance of Gleason score changes and pT2 stage. Deep models achieved the highest F1 scores by pT2 tumors (0.849) and Gls change (0.574). Combination possibility and deep learning model is a useful decision-aided tool for prostate cancer and to group patients with prostate cancer into clinically meaningful groups.

A prognostic score for overall survival in patients treated with abiraterone in the pre- and post-chemotherapy setting.

Background: Therapy resistance remains a serious dilemma in metastatic castration-resistant prostate cancer (mCRPC) with primary or secondary resistance frequently occurring against any given therapy. Available prognostic models for Abiraterone Acetate (AA) are specifically designed for either pre- or post-chemotherapy settings and mostly based on trial datasets not necessarily reflecting real-life. Results: A score of 0-2 (low-risk) is associated with an OS-probability of 80.0% (95%CI: 71.3-90.6) and 50.5% (95%CI: 38.7-66.0) after 1 and 2 years while a score of 3-4 (high risk) is associated with an OS-probability of 35.3% (95%CI: 22.3-55.8) and 5.7% (95%CI: 1.5-21.8), respectively. The bootstrapping survival analysis of the scoring-system revealed a median c-index of 0.80 (IQR: 0.79-0.82). Material and Methods: We developed a scoring-system using four real-life parameters 117 mCRPC patients treated with AA either pre- or post-chemotherapy. These parameters were evaluated using COX regression analysis. The scoring-system consists of binary-categorized parameters; when any of these exceeds the given cut-off, one point is added up to a final score ranging between 0-4 points. The final score was stratified by a median threshold of 2 into low- and high-risk groups. We evaluated the discriminative ability of our scoring-system using concordance probability (C-index) and Kaplan-Meier-analysis and applied a 100-times bootstrap for survival analysis. Conclusions: Our study introduces a novel prognostic scoring-system for OS of real-life mCRPC patients receiving AA treatment irrespective of the line of therapy. The scoring-system is simple and can be easily utilized based on PSA and LDH values, neutrophil to lymphocyte ratio, and ECOG performance status.

Genomic analysis of benign prostatic hyperplasia implicates cellular re-landscaping in disease pathogenesis.

Benign prostatic hyperplasia (BPH) is the most common cause of lower urinary tract symptoms in men. Current treatments target prostate physiology rather than BPH pathophysiology and are only partially effective. Here, we applied next-generation sequencing to gain new insight into BPH. By RNAseq, we uncovered transcriptional heterogeneity among BPH cases, where a 65-gene BPH stromal signature correlated with symptom severity. Stromal signaling molecules BMP5 and CXCL13 were enriched in BPH while estrogen regulated pathways were depleted. Notably, BMP5 addition to cultured prostatic myofibroblasts altered their expression profile towards a BPH profile that included the BPH stromal signature. RNAseq also suggested an altered cellular milieu in BPH, which we verified by immunohistochemistry and single-cell RNAseq. In particular, BPH tissues exhibited enrichment of myofibroblast subsets, whilst depletion of neuroendocrine cells and an estrogen receptor (ESR1)-positive fibroblast cell type residing near epithelium. By whole-exome sequencing, we uncovered somatic single-nucleotide variants (SNVs) in BPH, of uncertain pathogenic significance but indicative of clonal cell expansions. Thus, genomic characterization of BPH has identified a clinically-relevant stromal signature and new candidate disease pathways (including a likely role for BMP5 signaling), and reveals BPH to be not merely a hyperplasia, but rather a fundamental re-landscaping of cell types.

The upregulation of hypoxia-related miRNA 210 in primary tumor of lymphogenic metastatic prostate cancer.

AIM: To show the association between the expression level of hsa-miR-210 (miR-210) and tumor progression in prostate cancer (PCa). METHODS: Quantitative PCR was performed to measure miR-210 on 55 subjects with different tumor stages; our results were then validated using three external datasets. ANOVA and Tukey's post hoc analysis were performed for comparative analyses between different tumor stages. Using the transcriptome data from The Cancer Genome Atlas for CaP, the gene expression analyses were performed on experimentally validated target genes of miR-210 identified in Tarbase and miRWalk datasets. RESULTS & CONCLUSION: miR-210 was significantly higher in N1 PCa compared with nonmetastatic PCa, whereas the metastatic tumor revealed a lower expression level of miR-210 than the primary tumor.

Diagnostic Classification of Cystoscopic Images Using Deep Convolutional Neural Networks.

PURPOSE: The recognition of cystoscopic findings remains challenging for young colleagues and depends on the examiner's skills. Computer-aided diagnosis tools using feature extraction and deep learning show promise as instruments to perform diagnostic classification. MATERIALS AND METHODS: Our study considered 479 patient cases that represented 44 urologic findings. Image color was linearly normalized and was equalized by applying contrast-limited adaptive histogram equalization. Because these findings can be viewed via cystoscopy from every possible angle and side, we ultimately generated images rotated in 10-degree grades and flipped them vertically or horizontally, which resulted in 18,681 images. After image preprocessing, we developed deep convolutional neural network (CNN) models (ResNet50, VGG-19, VGG-16, InceptionV3, and Xception) and evaluated these models using F1 scores. Furthermore, we proposed two CNN concepts: 90%-previous-layer filter size and harmonic-series filter size. A training set (60%), a validation set (10%), and a test set (30%) were randomly generated from the study data set. All models were trained on the training set, validated on the validation set, and evaluated on the test set. RESULTS: The Xception-based model achieved the highest F1 score (99.52%), followed by models that were based on ResNet50 (99.48%) and the harmonic-series concept (99.45%). All images with cancer lesions were correctly determined by these models. When the focus was on the images misclassified by the model with the best performance, 7.86% of images that showed bladder stones with indwelling catheter and 1.43% of images that showed bladder diverticulum were falsely classified. CONCLUSION: The results of this study show the potential of deep learning for the diagnostic classification of cystoscopic images. Future work will focus on integration of artificial intelligence-aided cystoscopy into clinical routines and possibly expansion to other clinical endoscopy applications.

Novel lincRNA SLINKY is a prognostic biomarker in kidney cancer.

Clear cell renal cell carcinomas (ccRCC) show a broad range of clinical behavior, and prognostic biomarkers are needed to stratify patients for appropriate management. We sought to determine whether long intergenic non-coding RNAs (lincRNAs) might predict patient survival. Candidate prognostic lincRNAs were identified by mining The Cancer Genome Atlas (TCGA) transcriptome (RNA-seq) data on 466 ccRCC cases (randomized into discovery and validation sets) annotated for ~21,000 lncRNAs. A previously uncharacterized lincRNA, SLINKY (Survival-predictive LINcRNA in KidneY cancer), was the top-ranked prognostic lincRNA, and validated in an independent University of Tokyo cohort (P=0.004). In multivariable analysis, SLINKY expression predicted overall survival independent of tumor stage and grade [TCGA HR=3.5 (CI, 2.2-5.7), P < 0.001; Tokyo HR=8.4 (CI, 1.8-40.2), P = 0.007], and by decision tree, ROC and decision curve analysis, added independent prognostic value. In ccRCC cell lines, SLINKY knockdown reduced cancer cell proliferation (with cell-cycle G1 arrest) and induced transcriptome changes enriched for cell proliferation and survival processes. Notably, the genes affected by SLINKY knockdown in cell lines were themselves prognostic and correlated with SLINKY expression in the ccRCC patient samples. From a screen for binding partners, we identified direct binding of SLINKY to Heterogeneous Nuclear Ribonucleoprotein K (HNRNPK), whose knockdown recapitulated SLINKY knockdown phenotypes. Thus, SLINKY is a robust prognostic biomarker in ccRCC, where it functions possibly together with HNRNPK in cancer cell proliferation.

Blind Biobanking of the Prostatectomy Specimen: Critical Evaluation of the Existing Techniques and Development of the New 4-Level Tissue Extraction Model With High Sampling Efficacy.

BACKGROUND: Fresh tissue is mandatory to perform high-quality translation studies. Several models for tissue extraction from prostatectomy specimens without guidance by frozen sections are already introduced. However, little is known about the sampling efficacy of these models, which should provide representative tissue in adequate volumes, account for multifocality and heterogeneity of tumor, not violate the routine final pathological examination, and perform quickly without frozen section-based histological control. The aim of the study was to evaluate the sampling efficacy of the existing tissue extraction models without guidance by frozen sections ("blind") and to develop an optimized model for tissue extraction. METHODS: Five hundred thirty-three electronic maps of the tumor distribution in prostates from a single-center cohort of the patients subjected to radical prostatectomy were used for analysis. Six available models were evaluated in silico for their sampling efficacy. Additionally, a novel model achieving the best sampling efficacy was developed. RESULTS: The available models showed high efficacies for sampling "any part" from the tumor (up to 100%), but were uniformly low in efficacy to sample all tumor foci from the specimens (with the best technique sampling only 51.6% of the all tumor foci). The novel 4-level extraction model achieved a sampling efficacy of 93.1% for all tumor foci. CONCLUSIONS: The existing "blind" tissue extraction models from prostatectomy specimens without frozen sections control are suitable to target tumor tissues but these tissues do not represent the whole tumor. The novel 4-level model provides the highest sampling efficacy and a promising potential for integration into routine. Prostate 77: 396-405, 2017. © 2016 Wiley Periodicals, Inc.