ProsTAV, a novel blood-based test for biopsy decision management in significant prostate cancer.

BACKGROUND: Current pathways in early diagnosis of prostate cancer (PCa) can lead to unnecessary biopsy procedures. Here, we used telomere analysis to develop and evaluate ProsTAV®, a risk model for significant PCa (Gleason score >6), with the objective of improving the PCa diagnosis pathway. METHODS: This retrospective, multicentric study analyzed telomeres from patients with serum PSA 3-10 ng/mL. High-throughput quantitative fluorescence in-situ hybridization was used to evaluate telomere-associated variables (TAVs) in peripheral blood mononucleated cells. ProsTAV® was developed by multivariate logistics regression based on three clinical variables and six TAVs. The predictive capacity and accuracy of ProsTAV® were summarized by receiver operating characteristic (ROC) curves and its clinical benefit with decision curves analysis. RESULTS: Telomeres from 1043 patients were analyzed. The median age of the patients was 63 years, with a median PSA of 5.2 ng/mL and a percentage of significant PCa of 23.9%. A total of 874 patients were selected for model training and 169 patients for model validation. The area under the ROC curve of ProsTAV® was 0.71 (95% confidence interval [CI], 0.62-0.79), with a sensitivity of 0.90 (95% CI, 0.88-1.0) and specificity of 0.33 (95% CI, 0.24-0.40). The positive predictive value was 0.29 (95% CI, 0.21-0.37) and the negative predictive value was 0.91 (95% CI, 0.83-0.99). ProsTAV® would make it possible to avoid 33% of biopsies. CONCLUSIONS: ProsTAV®, a predictive model based on telomere analysis through TAV, could be used to increase the prediction capacity of significant PCa in patients with PSA between 3 and 10 ng/mL.

Glomerular hyperfiltration is an independent predictor of postoperative outcomes: A NSQIP multi-specialty surgical cohort analysis.

AIM: While high estimated glomerular filtration rate (eGFR) has been associated with increased overall mortality, its effect on postoperative outcomes is relatively understudied. We sought to investigate the association between high eGFR and 30-day postoperative outcomes using a multi-specialty surgical cohort. METHODS: Using the National Surgical Quality Improvement Program database, we selected adult for whom eGFR could be calculated using the 2021 Chronic Kidney Disease Epidemiology Collaboration equation. Based on sex-specific distributions of eGFR stratified by age quintiles, we classified patients into low (<5th percentile), normal (5-95th percentile) and high eGFR (>95th percentile). The primary outcome was a composite of any 30-day major adverse outcomes, including: death, reoperation, cardiac arrest, myocardial infarction and stroke. Secondary outcomes included 30-day infectious complications, venous thromboembolism (VTE), bleeding requiring transfusion, prolonged length of stay and unplanned readmission. After matching for demographic differences, comorbidity burden and operative characteristics, logistic regression models were used to evaluate the association between extremes of eGFR and the outcomes of interest. RESULTS: Of 1 668 447 patients, 84 115 (5.07%) had a high eGFR. High eGFR was not associated with major adverse outcomes (odds ratio [OR] 1.00 [95% confidence interval (CI): 0.97, 1.03]); however, it was associated with reoperation (OR 1.04 [95% CI: 1.00,1.08]), infectious complications (OR 1.14 [95% CI: 1.11, 1.16]), VTE (OR 1.15 [95% CI: 1.09, 1.22]) and prolonged length of stay (OR 1.19 [95% CI: 1.16, 1.21]). CONCLUSION: Our findings support an association between high eGFR and adverse 30-day postoperative outcomes.

Enhanced Succinate Oxidation with Mitochondrial Complex II Reactive Oxygen Species Generation in Human Prostate Cancer.

The transformation of prostatic epithelial cells to prostate cancer (PCa) has been characterized as a transition from citrate secretion to citrate oxidation, from which one would anticipate enhanced mitochondrial complex I (CI) respiratory flux. Molecular mechanisms for this transformation are attributed to declining mitochondrial zinc concentrations. The unique metabolic properties of PCa cells have become a hot research area. Several publications have provided indirect evidence based on investigations using pre-clinical models, established cell lines, and fixed or frozen tissue bank samples. However, confirmatory respiratory analysis on fresh human tissue has been hampered by multiple difficulties. Thus, few mitochondrial respiratory assessments of freshly procured human PCa tissue have been published on this question. Our objective is to document relative mitochondrial CI and complex II (CII) convergent electron flow to the Q-junction and to identify electron transport system (ETS) alterations in fresh PCa tissue. The results document a CII succinate: quinone oxidoreductase (SQR) dominant succinate oxidative flux model in the fresh non-malignant prostate tissue, which is enhanced in malignant tissue. CI NADH: ubiquinone oxidoreductase activity is impaired rather than predominant in high-grade malignant fresh prostate tissue. Given these novel findings, succinate and CII are promising targets for treating and preventing PCa.

Neuropeptide Y nerve paracrine regulation of prostate cancer oncogenesis and therapy resistance.

BACKGROUND: Nerves are key factors in prostate cancer (PCa) progression. Here, we propose that neuropeptide Y (NPY) nerves are key regulators of cancer-nerve interaction. METHODS: We used in vitro models for NPY inhibition studies and subsequent metabolomics, apoptotic and migration assays, and nuclear transcription factor-κB (NF-κB) translocation studies. Human naïve and radiated PCa tissues were used for NPY nerve density biomarker studies. Tissues derived from a Botox denervation clinical trial were used to corroborate metabolomic changes in humans. RESULTS: Cancer cells increase NPY positive nerves in vitro and in preneoplastic human tissues. NPY-specific inhibition resulted in increased cancer apoptosis, decreased motility, and energetic metabolic pathway changes. A comparison of metabolomic response in NPY-inhibited cells with the transcriptome response in human PCa patients treated with Botox showed shared 13 pathways, including the tricarboxylic acid cycle. We identified that NF-κB is a potential NPY downstream mediator. Using in vitro models and tissues derived from a previous human chemical denervation study, we show that Botox specifically, but not exclusively, inhibits NPY in cancer. Quantification of NPY nerves is independently predictive of PCa-specific death. Finally, NPY nerves might be involved in radiation therapy (RT) resistance, as radiation-induced apoptosis is reduced when PCa cells are cocultured with dorsal root ganglia/nerves and NPY positive nerves are increased in prostates of patients that failed RT. CONCLUSION: These data suggest that targeting the NPY neural microenvironment may represent a therapeutic approach for the treatment of PCa and resistance through the regulation of multiple oncogenic mechanisms.

Relation between surgeon age and postoperative outcomes: a population-based cohort study.

BACKGROUND: Aging may detrimentally affect cognitive and motor function. However, age is also associated with experience, and how these factors interplay and affect outcomes following surgery is unclear. We sought to evaluate the effect of surgeon age on postoperative outcomes in patients undergoing common surgical procedures. METHODS: We performed a retrospective cohort study of patients undergoing 1 of 25 common surgical procedures in Ontario, Canada, from 2007 to 2015. We evaluated the association between surgeon age and a composite outcome of death, readmission and complications. We used generalized estimating equations for analysis, accounting for relevant patient-, procedure-, surgeon- and hospital-level factors. RESULTS: We found 1 159 676 eligible patients who were treated by 3314 surgeons and ranged in age from 27 to 81 years. Modelled as a continuous variable, a 10-year increase in surgeon age was associated with a 5% relative decreased odds of the composite outcome (adjusted odds ratio [OR] 0.95, 95% confidence interval [CI] 0.92 to 0.98, p = 0.002). Considered dichotomously, patients receiving treatment from surgeons who were older than 65 years of age had a 7% lower odds of adverse outcomes (adjusted OR 0.93, 95% CI 0.88-0.97, p = 0.03; crude absolute difference = 3.1%). INTERPRETATION: We found that increasing surgeon age was associated with decreasing rates of postoperative death, readmission and complications in a nearly linear fashion after accounting for patient-, procedure-, surgeon- and hospital-level factors. Further evaluation of the mechanisms underlying these findings may help to improve patient safety and outcomes, and inform policy about maintenance of certification and retirement age for surgeons.

Seminal vesicle invasion combined with extraprostatic extension is associated with higher frequency of biochemical recurrence and lymph node metastasis than seminal vesicle invasion alone: Proposal for further pT3 prostate cancer subclassification.

The 8th edition of the American Joint Committee on Cancer (AJCC) TNM staging system subdivides prostatic pT3 tumors into pT3a, which includes cases with extraprostatic extension (EPE) and pT3b, which is defined by the presence of seminal vesicle invasion (SVI) with or without EPE. Yet, it is not established whether combined SVI and EPE impart a worse prognosis compared to SVI alone. We studied a cohort of 69 prostatectomy patients with SVI with or without EPE. Patient age at the time of radical prostatectomy was documented and Gleason score and presence or absence of EPE and/or SVI were determined. Biochemical recurrence (BCR) was defined as a PSA rise >0.2 ng/mL. The frequency of BCR was 33.9% in cases with combined EPE and SVI versus 12.5% in cases with SVI alone (relative risk = 2.71). An additional cohort of 88 patients also showed a higher frequency of lymph node metastasis of 29% in patients with combined SVI and EPE at the time of radical prostatectomy versus a 10% frequency of lymph node metastasis in patients with SVI alone (relative risk = 2.9). Based on our data, we propose further subdividing pT3 prostate cancers into three groups: EPE alone (pT3a), SVI alone (pT3b), and combined EPE and SVI (pT3c). This classification system would more accurately identify patients with pT3 prostate cancer who are more likely to experience worse outcomes and provide clinicians with additional information to aid in follow-up and postoperative treatment decisions.

Influence of the neural microenvironment on prostate cancer.

BACKGROUND: Nerves are key factors in prostate cancer (PCa), but the functional role of innervation in prostate cancer is poorly understood. PCa induced neurogenesis and perineural invasion (PNI), are associated with aggressive disease. METHOD: We denervated rodent prostates chemically and physically, before orthotopically implanting cancer cells. We also performed a human neoadjuvant clinical trial using botulinum toxin type A (Botox) and saline in the same patient, before prostatectomy. RESULT: Bilateral denervation resulted in reduced tumor incidence and size in mice. Botox treatment in humans resulted in increased apoptosis of cancer cells in the Botox treated side. A similar denervation gene array profile was identified in tumors arising in denervated rodent prostates, in spinal cord injury patients and in the Botox treated side of patients. Denervation induced exhibited a signature gene profile, indicating translation and bioenergetic shutdown. Nerves also regulate basic cellular functions of non-neoplastic epithelial cells. CONCLUSION: Nerves play a role in the homeostasis of normal epithelial tissues and are involved in prostate cancer tumor survival. This study confirms that interactions between human cancer and nerves are essential to disease progression. This work may make a major impact in general cancer treatment strategies, as nerve/cancer interactions are likely important in other cancers as well. Targeting the neural microenvironment may represent a therapeutic approach for the treatment of human prostate cancer.

Neuronal Trans-Differentiation in Prostate Cancer Cells.

BACKGROUND: Neuroendocrine (NE) differentiation in prostate cancer (PCa) is an aggressive phenotype associated with therapy resistance. The complete phenotype of these cells is poorly understood. Clinical classification is based predominantly on the expression of standard NE markers. METHODS: We analyzed the phenotype of NE carcinoma of the prostate utilizing in vitro methods, in silico, and immunohistochemical analyses of human disease. RESULTS: LNCaP cells, subjected to a variety of stressors (0.1% [v/v] fetal bovine serum, cyclic AMP) induced a reproducible phenotype consistent with neuronal trans-differentiation. Cells developed long cytoplasmic processes resembling neurons. As expected, serum deprived cells had decreased expression in androgen receptor and prostate specific antigen. A significant increase in neuronal markers also was observed. Gene array analysis demonstrated that LNCaP cells subjected to low serum or cAMP showed statistically significant manifestation of a human brain gene expression signature. In an in silico experiment using human data, we identified that only hormone resistant metastatic prostate cancer showed enrichment of the "brain profile." Gene ontology analysis demonstrated categories involved in neuronal differentiation. Three neuronal markers were validated in a large human tissue cohort. CONCLUSION: This study proposes that the later stages of PCa evolution involves neuronal trans-differentiation, which would enable PCa cells to acquire independence from the neural axis, critical in primary tumors. Prostate 76:1312-1325, 2016. © 2016 Wiley Periodicals, Inc.

Performance of robotic simulated skills tasks is positively associated with clinical robotic surgical performance.

OBJECTIVE: To compare user performance of four fundamental inanimate robotic skills tasks (FIRST) as well as eight da Vinci Skills Simulator (dVSS) virtual reality tasks with intra-operative performance (concurrent validity) during robot-assisted radical prostatectomy (RARP) and to show that a positive correlation exists between simulation and intra-operative performance. MATERIALS AND METHODS: A total of 21 urological surgeons with varying robotic experience were enrolled. Demographics were captured using a standardized questionnaire. User performance was assessed concurrently in simulated (FIRST exercises and dVSS tasks) and clinical environments (endopelvic dissection during RARP). Intra-operative robotic clinical performance was scored using the previously validated six-metric Global Evaluative Assessment of Robotic Skills (GEARS) tool. The relationship between simulator and clinical performance was evaluated using Spearman's rank correlation. RESULTS: Performance was assessed in 17 trainees and four expert robotic surgeons with a median (range) number of previous robotic cases (as primary surgeon) of 0 (0-55) and 117 (58-600), respectively (P = 0.001). Collectively, the overall FIRST (ρ = 0.833, P < 0.001) and dVSS (ρ = 0.805, P < 0.001) simulation scores correlated highly with GEARS performance score. Each individual FIRST and dVSS task score also demonstrated a significant correlation with intra-operative performance, with the exception of Energy Switcher 1 exercise (P = 0.063). CONCLUSIONS: This is the first study to show a significant relationship between simulated robotic performance and robotic clinical performance. Findings support implementation of these robotic training tools in a standardized robotic training curriculum.

A randomized, double-blind, solifenacin succinate versus placebo control, phase 4, multicenter study evaluating urinary continence after robotic assisted radical prostatectomy.

PURPOSE: Bladder dysfunction influences recovery of urinary continence after radical prostatectomy. We performed a multicenter, randomized, double-blind study evaluating solifenacin vs placebo on return to continence in patients who were still incontinent 7 to 21 days after catheter removal after robot-assisted radical prostatectomy. MATERIALS AND METHODS: A wireless personal digital assistant was given to patients the day of catheter removal. Encrypted answers were transmitted daily to dedicated servers. After a 7 to 21-day treatment-free washout period, patients requiring 2 to 10 pads per day for 7 consecutive days were randomized (1:1) to 5 mg solifenacin daily or placebo. The primary end point was time from first dose to continence defined as 0 pads per day or a dry security pad for 3 consecutive days. Secondary end points included proportion of patients continent at end of study, average change in pads per day number and quality of life assessments. RESULTS: A total of 1,086 screened patients recorded personal digital assistant information. Overall 640 patients were randomized to solifenacin vs placebo and 17 failed to take medication. There was no difference in time to continence (p=0.17). Continence was achieved by study end in 91 of 313 (29%) vs 66 of 309 (21%), respectively (p=0.04). Pads per day change from baseline was -3.2 and -2.9, respectively (p=0.03). Dry mouth was the only common adverse event seen in 6.1% and 0.6%, respectively. Constipation rates were similar. The overall rate of continence in the entire population from screening to end of study was 73%. CONCLUSIONS: There was no effect on primary outcome but some secondary end points benefited the solifenacin arm. The study provides level 1B clinical evidence for continence outcomes after robot-assisted radical prostatectomy.

Quantification of collagen content and stromal cellularity within reactive stroma is predictive of prostate cancer biochemical recurrence and specific death.

Semiquantitative reactive stromal grading has been shown to be a predictor of biochemical recurrence and prostate cancer (PCa) specific death. It has been extensively validated. In this study we tested novel technologies to introduce quantitative measures of host response, in particular collagen content and stromal cellularity. We use 3 large retrospective cohorts, the Baylor College of Medicine cohort, the Brady cohort and the Pound cohort. Slides were stained and digitized using image deconvolution and analyzed using image segmentation and image analyses. PicroSirius red stain histochemical stains were used for collagen quantification. Area of cancer and stroma were measured independently, without regard to quality of stroma. Cellularity, in each compartment, was measured using image deconvolution, image segmentation and image analysis. Two biomarkers were tested in 3 independent cohorts with two endpoints, biochemical recurrence and prostate cancer specific death. Stromal cellularity (qCollCell) and stromal collagen area (qCollArea) are independently predictive biochemical recurrence in the Hopkins Brady cohort, particularly in Gleason 6-7 patients. Multivariate analysis demonstrated that increased stroma cellularity (qCollCell) was a significant predictor of PCa specific death, when compared to an established model of PCa, in the Baylor cohort. Stromal collagen (qCollArea) independently predicts PCa-specific death in the Hopkins Pound cohort. The introduction of a computerized quantitative test of the host response increases the probability that this test will be reproducible in other cohorts. The ability to improve prediction of prostate cancer specific death might lie in the study of the host and its response.

Contemporary morbidity and mortality of open versus robotic cystectomy for bladder cancer: An analysis of the National Surgical Quality Improvement Program (NSQIP) procedure targeted cystectomy database.

OBJECTIVES: To evaluate the association between surgical modality (RARC vs. ORC) and the risk of 30-day complications. MATERIALS AND METHODS: We utilized the American College of Surgeons-National Surgical Quality Improvement Program (ACS-NSQIP) Cystectomy-Targeted database from 2019 to 2021. The primary outcome was a composite of major complications including 30-day mortality, reoperation, cardiac events, and stroke. Secondary outcomes included individual major and cystectomy-specific complications. Propensity score matching (PSM) was employed to minimize inherent differences within our cohort. We performed logistic regression to assess the association between outcomes of interest and operative modality. RESULTS: We found no difference between operative modality and the primary outcome, however, RARC was associated with a 70% lower risk of 30-day mortality (OR 0.30, 95% CI 0.13-0.70) and had favorable outcomes with respect to respiratory, deep venous thrombosis, wound complications, and length of stay. Limitations are related to residual confounding given the observational methodology. CONCLUSIONS: RARC was associated with reduced risk of multiple 30-day complications, including mortality, as well as organ system and cystectomy-specific outcomes. These data support the clinical benefit of increased adoption of RARC.

Capturing relationships between suturing sub-skills to improve automatic suturing assessment.

Suturing skill scores have demonstrated strong predictive capabilities for patient functional recovery. The suturing can be broken down into several substep components, including needle repositioning, needle entry angle, etc. Artificial intelligence (AI) systems have been explored to automate suturing skill scoring. Traditional approaches to skill assessment typically focus on evaluating individual sub-skills required for particular substeps in isolation. However, surgical procedures require the integration and coordination of multiple sub-skills to achieve successful outcomes. Significant associations among the technical sub-skill have been established by existing studies. In this paper, we propose a framework for joint skill assessment that takes into account the interconnected nature of sub-skills required in surgery. The prior known relationships among sub-skills are firstly identified. Our proposed AI system is then empowered by the prior known relationships to perform the suturing skill scoring for each sub-skill domain simultaneously. Our approach can effectively improve skill assessment performance through the prior known relationships among sub-skills. Through the proposed approach to joint skill assessment, we aspire to enhance the evaluation of surgical proficiency and ultimately improve patient outcomes in surgery.

Superstition in Surgery: A Population-Based Cohort Study to Assess the Association Between Surgery on Friday the 13th and Postoperative Outcomes.

Objective: We sought to examine whether the outcomes of patients who receive a surgical procedure on Friday the 13th differ from patients who receive surgery on flanking Fridays. Background: Numerous studies have demonstrated that increased anxiety from the provider or patient around the time of surgery can lead to worse outcomes. Superstitious patients often express significant concern and anxiety when undergoing a surgical procedure on Friday the 13th. Methods: A retrospective, population-based cohort study of 19,747 adults undergoing 1 of 25 common surgical procedures on Friday the 13th or flanking control Fridays (Friday the 6th and Friday the 20th) between January 1, 2007, and December 31, 2019, with 1 year of follow-up. The main outcomes included death, readmission, and complications at 30 days (short-term), 90 days (intermediate-term), and 1 year (long-term). Results: A total of 7,349 (37.2%) underwent surgery on Friday the 13th, and 12,398 (62.8%) underwent surgery on a flanking Friday during the study period. Patient characteristics were similar between the 2 groups. We found no evidence that patients receiving surgery on Friday the 13th group were more likely to experience the composite primary outcome at 30 days [adjusted odds ratio (aOR) = 1.02 (95% CI = 0.94-1.09)], 90 days [aOR = 0.97 (95% CI = 0.90-1.04)], and 1 year [aOR = 0.99 (95% CI = 0.94-1.04)] after surgery. Conclusion: Patients receiving surgery on Friday the 13th do not appear to fare worse than those treated on ordinary Fridays with respect to the composite outcome.

Comparative real-world survival outcomes of muscle-invasive bladder cancer treated with bladder-only vs. whole-pelvis concurrent chemoradiation.

INTRODUCTION: Elective pelvic nodal irradiation for patients with muscle-invasive bladder cancer (MIBC) undergoing trimodal therapy (TMT ) is controversial. In patients with node-negative (N0) MIBC, the benefit of elective whole-pelvis concurrent chemoradiation (WP-CCR) compared to bladder-only (BO )-CCR has not been demonstrated. Using real-world data from the National Cancer Database (NCDB ), we sought to compare the overall survival (OS ) between BO-CCR and WP-CCR for MIBC. METHODS: Using the 2020 NCDB Participant User File, we identified cases of MIBC diagnosed between 2017 and 2019. We selected patients with clinical T2-T4aN0M0 disease receiving CCR as first-line treatment. CCR was defined as transurethral resection of bladder tumor followed by ≥40 Gy radiation to the bladder with concurrent single- or multiple-agent chemotherapy. Based on elective nodal irradiation status, patients were stratified as having received BO-CCR vs. WP-CCR. OS analysis was performed using summary three-month conditional landmark, inverse probability treatment weighting (IPTW)-adjusted Kaplan-Meier estimates, and Cox regression. RESULTS: A total of 604 patients receiving CCR for MIBC were identified: 367 (60.8%) BO-CCR and 237 (39.2%) WP-CCR. Before IPTW, the groups were imbalanced in terms of baseline characteristics. The median followup of the weighted population was 42.3 months (interquartile range 18.1-49.1 months). In IPTW-adjusted Cox proportional hazards regression analysis, WP-CCR was associated with a significant OS benefit compared to BO-CCR (adjusted hazard ratio 0.72, 95% confidence interval 0.54-0.96, p=0.026). CONCLUSIONS: In the setting of CCR for N0 MIBC, this retrospective NCDB analysis revealed that WP-CCR was associated with a benefit in OS compared to BO-CCR.

Testosterone replacement therapy in patients with prostate cancer after radical prostatectomy.

PURPOSE: Testosterone replacement therapy in men with prostate cancer is controversial, with concern that testosterone can stimulate cancer growth. We evaluated the safety and efficacy of testosterone in hypogonadal men with prostate cancer treated with radical prostatectomy. MATERIALS AND METHODS: We performed a review of 103 hypogonadal men with prostate cancer treated with testosterone after prostatectomy (treatment group) and 49 nonhypogonadal men with cancer treated with prostatectomy (reference group). There were 77 men with low/intermediate (nonhigh) risk cancer and 26 with high risk cancer included in the analysis. All men were treated with transdermal testosterone, and serum hormone, hemoglobin, hematocrit and prostate specific antigen were evaluated for more than 36 months. RESULTS: Median (IQR) patient age in the treatment group was 61.0 years (55.0-67.0), and initial laboratory results included testosterone 261.0 ng/dl (213.0-302.0), prostate specific antigen 0.004 ng/ml (0.002-0.007), hemoglobin 14.7 gm/dl (13.3-15.5) and hematocrit 45.2% (40.4-46.1). Median followup was 27.5 months, at which time a significant increase in testosterone was observed in the treatment group. A significant increase in prostate specific antigen was observed in the high risk and nonhigh risk treatment groups with no increase in the reference group. Overall 4 and 8 cases of cancer recurrence were observed in treatment and reference groups, respectively. CONCLUSIONS: Thus, testosterone therapy is effective and, while followed by an increase in prostate specific antigen, does not appear to increase cancer recurrence rates, even in men with high risk prostate cancer. However, given the retrospective nature of this and prior studies, testosterone therapy in men with history of prostate cancer should be performed with a vigorous surveillance protocol.

Which skills really matter? proving face, content, and construct validity for a commercial robotic simulator.

BACKGROUND: A novel computer simulator is now commercially available for robotic surgery using the da Vinci(®) System (Intuitive Surgical, Sunnyvale, CA). Initial investigations into its utility have been limited due to a lack of understanding of which of the many provided skills modules and metrics are useful for evaluation. In addition, construct validity testing has been done using medical students as a "novice" group-a clinically irrelevant cohort given the complexity of robotic surgery. This study systematically evaluated the simulator's skills tasks and metrics and established face, content, and construct validity using a relevant novice group. METHODS: Expert surgeons deconstructed the task of performing robotic surgery into eight separate skills. The content of the 33 modules provided by the da Vinci Skills Simulator (Intuitive Surgical, Sunnyvale, CA) was then evaluated for these deconstructed skills and 8 of the 33 determined to be unique. These eight tasks were used for evaluating the performance of 46 surgeons and trainees on the simulator (25 novices, 8 intermediate, and 13 experts). Novice surgeons were general surgery and urology residents or practicing surgeons with clinical experience in open and laparoscopic surgery but limited exposure to robotics. Performance was measured using 85 metrics across all eight tasks. RESULTS: Face and content validity were confirmed using global rating scales. Of the 85 metrics provided by the simulator, 11 were found to be unique, and these were used for further analysis. Experts performed significantly better than novices in all eight tasks and for nearly every metric. Intermediates were inconsistently better than novices, with only four tasks showing a significant difference in performance. Intermediate and expert performance did not differ significantly. CONCLUSION: This study systematically determined the important modules and metrics on the da Vinci Skills Simulator and used them to demonstrate face, content, and construct validity with clinically relevant novice, intermediate, and expert groups. These data will be used to develop proficiency-based training programs on the simulator and to investigate predictive validity.

A multi-institutional study using artificial intelligence to provide reliable and fair feedback to surgeons.

BACKGROUND: Surgeons who receive reliable feedback on their performance quickly master the skills necessary for surgery. Such performance-based feedback can be provided by a recently-developed artificial intelligence (AI) system that assesses a surgeon's skills based on a surgical video while simultaneously highlighting aspects of the video most pertinent to the assessment. However, it remains an open question whether these highlights, or explanations, are equally reliable for all surgeons. METHODS: Here, we systematically quantify the reliability of AI-based explanations on surgical videos from three hospitals across two continents by comparing them to explanations generated by humans experts. To improve the reliability of AI-based explanations, we propose the strategy of training with explanations -TWIX -which uses human explanations as supervision to explicitly teach an AI system to highlight important video frames. RESULTS: We show that while AI-based explanations often align with human explanations, they are not equally reliable for different sub-cohorts of surgeons (e.g., novices vs. experts), a phenomenon we refer to as an explanation bias. We also show that TWIX enhances the reliability of AI-based explanations, mitigates the explanation bias, and improves the performance of AI systems across hospitals. These findings extend to a training environment where medical students can be provided with feedback today. CONCLUSIONS: Our study informs the impending implementation of AI-augmented surgical training and surgeon credentialing programs, and contributes to the safe and fair democratization of surgery.

Surgeons aim to master skills necessary for surgery. One such skill is suturing which involves connecting objects together through a series of stitches. Mastering these surgical skills can be improved by providing surgeons with feedback on the quality of their performance. However, such feedback is often absent from surgical practice. Although performance-based feedback can be provided, in theory, by recently-developed artificial intelligence (AI) systems that use a computational model to assess a surgeon's skill, the reliability of this feedback remains unknown. Here, we compare AI-based feedback to that provided by human experts and demonstrate that they often overlap with one another. We also show that explicitly teaching an AI system to align with human feedback further improves the reliability of AI-based feedback on new videos of surgery. Our findings outline the potential of AI systems to support the training of surgeons by providing feedback that is reliable and focused on a particular skill, and guide programs that give surgeons qualifications by complementing skill assessments with explanations that increase the trustworthiness of such assessments.

A vision transformer for decoding surgeon activity from surgical videos.

The intraoperative activity of a surgeon has substantial impact on postoperative outcomes. However, for most surgical procedures, the details of intraoperative surgical actions, which can vary widely, are not well understood. Here we report a machine learning system leveraging a vision transformer and supervised contrastive learning for the decoding of elements of intraoperative surgical activity from videos commonly collected during robotic surgeries. The system accurately identified surgical steps, actions performed by the surgeon, the quality of these actions and the relative contribution of individual video frames to the decoding of the actions. Through extensive testing on data from three different hospitals located in two different continents, we show that the system generalizes across videos, surgeons, hospitals and surgical procedures, and that it can provide information on surgical gestures and skills from unannotated videos. Decoding intraoperative activity via accurate machine learning systems could be used to provide surgeons with feedback on their operating skills, and may allow for the identification of optimal surgical behaviour and for the study of relationships between intraoperative factors and postoperative outcomes.