Convergence of coronary artery disease genes onto endothelial cell programs.

Linking variants from genome-wide association studies (GWAS) to underlying mechanisms of disease remains a challenge1-3. For some diseases, a successful strategy has been to look for cases in which multiple GWAS loci contain genes that act in the same biological pathway1-6. However, our knowledge of which genes act in which pathways is incomplete, particularly for cell-type-specific pathways or understudied genes. Here we introduce a method to connect GWAS variants to functions. This method links variants to genes using epigenomics data, links genes to pathways de novo using Perturb-seq and integrates these data to identify convergence of GWAS loci onto pathways. We apply this approach to study the role of endothelial cells in genetic risk for coronary artery disease (CAD), and discover 43 CAD GWAS signals that converge on the cerebral cavernous malformation (CCM) signalling pathway. Two regulators of this pathway, CCM2 and TLNRD1, are each linked to a CAD risk variant, regulate other CAD risk genes and affect atheroprotective processes in endothelial cells. These results suggest a model whereby CAD risk is driven in part by the convergence of causal genes onto a particular transcriptional pathway in endothelial cells. They highlight shared genes between common and rare vascular diseases (CAD and CCM), and identify TLNRD1 as a new, previously uncharacterized member of the CCM signalling pathway. This approach will be widely useful for linking variants to functions for other common polygenic diseases.

Female urethral condyloma acuminata mimicking urethral caruncle.

Condyloma acuminata are epidermal lesions caused by the human papillomavirus (HPV) most commonly affecting the anogenital region. Urethral involvement is uncommon, and may mimic other urethral lesions. In this case report, a 62-year-old patient presents with what was believed to be a urethral caruncle and underwent successful resection with the final pathologic diagnosis of urethral condyloma. The clinical features and diagnosis are reviewed. This condition should be considered in the differential diagnosis of females with known HPV or those who are deemed higher risk with unprotected sexual encounters.

Objective Assessment of Robotic Surgical Technical Skill: A Systematic Review.

PURPOSE: Robotic surgeries, especially in urology, have grown exponentially during the last decade. Various skills assessment tools have been developed. We reviewed the current status, the current challenges and the future needs of robotic evaluations with a focus on urological applications. MATERIALS AND METHODS: According to PRISMA (Preferred Reporting Items for Systematic Review and Meta-Analysis) criteria 2 paired investigators screened the PubMed®, Scopus® and Web of Science® databases for all full text, English language articles published between 2006 and 2018 using the query (evaluation OR assessment) AND (robot-assisted surgery OR robotic surgery) AND (surgical performance OR surgical skill) AND training. The research design, validity and reliability of each study were ascertained and analyzed. RESULTS: A total of 259 studies were identified, of which 109 were included in the final analysis. We grouped the studies into 2 categories, including manual and automated assessments. Manual evaluation included global skill, procedure specific and error based assessments. For automated assessment we summarized evaluations derived from robotic instrument kinematic tracking data, systems events and surgical video data, and we explored those associations with various domains by manual evaluation. We further reviewed the current progress in automated surgical segmentation and skill evaluation with machine learning and deep learning. Concerns remain regarding efficient and effective surgeon training and credentialing. CONCLUSIONS: No universally accepted robotic skills assessment currently exists. The purpose of assessment (training or credentialing) may dictate whether manual or automated surgeon assessment is more suitable. Moving forward, assessment tools must be objective and efficient to facilitate the training and credentialing of competent surgeons.

Use of Automated Performance Metrics to Measure Surgeon Performance during Robotic Vesicourethral Anastomosis and Methodical Development of a Training Tutorial.

PURPOSE: We sought to develop and validate automated performance metrics to measure surgeon performance of vesicourethral anastomosis during robotic assisted radical prostatectomy. Furthermore, we sought to methodically develop a standardized training tutorial for robotic vesicourethral anastomosis. MATERIALS AND METHODS: We captured automated performance metrics for motion tracking and system events data, and synchronized surgical video during robotic assisted radical prostatectomy. Nonautomated performance metrics were manually annotated by video review. Automated and nonautomated performance metrics were compared between experts with 100 or more console cases and novices with fewer than 100 cases. Needle driving gestures were classified and compared. We then applied task deconstruction, cognitive task analysis and Delphi methodology to develop a standardized robotic vesicourethral anastomosis tutorial. RESULTS: We analyzed 70 vesicourethral anastomoses with a total of 1,745 stitches. For automated performance metrics experts outperformed novices in completion time (p <0.01), EndoWrist® articulation (p <0.03), instrument movement efficiency (p <0.02) and camera manipulation (p <0.01). For nonautomated performance metrics experts had more optimal needle to needle driver positioning, fewer needle driving attempts, a more optimal needle entry angle and less tissue trauma (each p <0.01). We identified 14 common robotic needle driving gestures. Random gestures were associated with lower efficiency (p <0.01), more attempts (p <0.04) and more trauma (p <0.01). The finalized tutorial contained 66 statements and figures. Consensus among 8 expert surgeons was achieved after 2 rounds, including among 58 (88%) after round 1 and 8 (12%) after round 2. CONCLUSIONS: Automated performance metrics can distinguish surgeon expertise during vesicourethral anastomosis. The expert vesicourethral anastomosis technique was associated with more efficient movement and less tissue trauma. Standardizing robotic vesicourethral anastomosis and using a methodically developed tutorial may help improve robotic surgical training.

Preclinical analysis of the anti-tumor and anti-metastatic effects of Raf265 on colon cancer cells and CD26(+) cancer stem cells in colorectal carcinoma.

BACKGROUND: In colorectal carcinoma (CRC), activation of the Raf/MEK/ERK signaling pathway is commonly observed. In addition, the commonly used 5FU-based chemotherapy in patients with metastatic CRC was found to enrich a subpopulation of CD26(+) cancer stem cells (CSCs). As activation of the Raf/MEK/ERK signaling pathway was also found in the CD26(+) CSCs and therefore, we hypothesized that an ATP-competitive pan-Raf inhibitor, Raf265, is effective in eliminating the cancer cells and the CD26(+) CSCs in CRC patients. METHODS: HT29 and HCT116 cells were treated with various concentrations of Raf265 to study the anti-proliferative and apoptotic effects of Raf265. Anti-tumor effect was also demonstrated using a xenograft model. Cells were also treated with Raf265 in combination with 5FU to demonstrate the anti-migratory and invasive effects by targeting on the CD26(+) CSCs and the anti-metastatic effect of the combined treatment was shown in an orthotopic CRC model. RESULTS: Raf265 was found to be highly effective in inhibiting cell proliferation and tumor growth through the inhibition of the RAF/MEK/ERK signaling pathway. In addition, anti-migratory and invasive effect was found with Raf265 treatment in combination with 5FU by targeting on the CD26(+) cells. Finally, the anti-tumor and anti-metastatic effect of Raf265 in combination with 5FU was also demonstrated. CONCLUSIONS: This preclinical study demonstrates the anti-tumor and anti-metastatic activity of Raf265 in CRC, providing the basis for exploiting its potential use and combination therapy with 5FU in the clinical treatment of CRC.

Distinguishing characteristics of pediatric patients with primary hyperoxaluria type 1 in PEDSnet.

BACKGROUND: Primary hyperoxaluria type 1 (PH1) is an autosomal recessive inborn error of metabolism that causes oxalate deposition, leading to recurrent calcium oxalate kidney stones, chronic kidney disease and systemic oxalosis, which produces a broad range of serious life-threatening complications. Patients with PH1 have delayed diagnosis due to the rarity of the disease and the overlap with early-onset kidney stone disease not due to primary hyperoxaluria. OBJECTIVE: The objective of this study was to determine the clinical features of individuals <21 years of age with PH1 that precede its diagnosis. We hypothesized that a parsimonious set of features could be identified that differentiate patients with PH1 from patients with non-primary hyperoxaluria-associated causes of early-onset kidney stone disease. STUDY DESIGN: We determined the association between clinical characteristics and PH1 diagnosis in a case-control study conducted between 2009 and 2021 in PEDSnet, a clinical research network of eight US pediatric health systems. Each patient with genetically confirmed PH1 was matched by sex and PEDSnet institution to up to 4 control patients with kidney stones without PH of any type. We obtained patient characteristics and diagnostic test results occurring before to less than 6 months after study entrance from a centralized database query and from manual chart review. Differences were examined using standardized differences and multivariable regression. RESULTS: The study sample included 37 patients with PH1 and 147 controls. Patients with PH1 were younger at diagnosis (median age of 3 vs 13.5 years); 75 % of children with PH1 were less than 8 years-old. Patients with PH1 were more likely to have combinations of nephrocalcinosis on ultrasound or CT (43 % vs 3 %), lower eGFR at diagnosis (median = 52 mL/min/1.73 m2 vs 114 mL/min/1.73 m2), and have normal mobility. Patients with PH1 had higher proportion of calcium oxalate monohydrate kidney stones than controls (median = 100 % vs 10 %). There were no differences in diagnosis of failure to thrive, stone size, or echocardiography results. CONCLUSIONS: Children with PH1 are characterized by presentation before adolescence, nephrocalcinosis, decreased eGFR at diagnosis, and calcium oxalate monohydrate stone composition. If externally validated, these characteristics could facilitate earlier diagnosis and treatment of children with PH1.

Reducing diagnostic delays in acute hepatic porphyria using health records data and machine learning.

BACKGROUND: Acute hepatic porphyria (AHP) is a group of rare but treatable conditions associated with diagnostic delays of 15 years on average. The advent of electronic health records (EHR) data and machine learning (ML) may improve the timely recognition of rare diseases like AHP. However, prediction models can be difficult to train given the limited case numbers, unstructured EHR data, and selection biases intrinsic to healthcare delivery. We sought to train and characterize models for identifying patients with AHP. METHODS: This diagnostic study used structured and notes-based EHR data from 2 centers at the University of California, UCSF (2012-2022) and UCLA (2019-2022). The data were split into 2 cohorts (referral and diagnosis) and used to develop models that predict (1) who will be referred for testing of acute porphyria, among those who presented with abdominal pain (a cardinal symptom of AHP), and (2) who will test positive, among those referred. The referral cohort consisted of 747 patients referred for testing and 99 849 contemporaneous patients who were not. The diagnosis cohort consisted of 72 confirmed AHP cases and 347 patients who tested negative. The case cohort was 81% female and 6-75 years old at the time of diagnosis. Candidate models used a range of architectures. Feature selection was semi-automated and incorporated publicly available data from knowledge graphs. Our primary outcome was the F-score on an outcome-stratified test set. RESULTS: The best center-specific referral models achieved an F-score of 86%-91%. The best diagnosis model achieved an F-score of 92%. To further test our model, we contacted 372 current patients who lack an AHP diagnosis but were predicted by our models as potentially having it (≥10% probability of referral, ≥50% of testing positive). However, we were only able to recruit 10 of these patients for biochemical testing, all of whom were negative. Nonetheless, post hoc evaluations suggested that these models could identify 71% of cases earlier than their diagnosis date, saving 1.2 years. CONCLUSIONS: ML can reduce diagnostic delays in AHP and other rare diseases. Robust recruitment strategies and multicenter coordination will be needed to validate these models before they can be deployed.

A Multi-Institutional Experience Utilizing Boari Flap in Robotic Urinary Reconstruction.

Objectives: There is presently scarce literature describing the outcomes of patients undergoing robotic ureteral reconstruction (RUR) using the Boari flap (BF) technique. Herein, we report our prospective, multi-institutional experience using BF in patients undergoing robotic urinary reconstruction. Patients and Methods: We reviewed our prospective, multicenter database for all patients undergoing RUR between September 2013 and September 2021 in which a BF was utilized. Preoperative, perioperative, and follow-up data were collected and analyzed. Major complications were defined as a Clavien-Dindo classification grade >2. Surgical failure was defined as recurrent symptoms, obstruction on imaging, or the need for additional surgical interventions. Results: We identified 50 patients who underwent RUR using a BF. Four (8%) underwent the Single Port approach. Twenty-four patients (48%) were active or former tobacco users. Thirty-four patients (68%) had previously undergone abdominal surgery, 17 (34%) had prior ureteral stricture interventions, and 9 (18%) had prior abdominopelvic radiation. The most common stricture etiology was malignancy (34.4%). The median follow-up was 15.0 months with a 90% (45/50) success rate. The five documented cases of failure occurred at a median of 1.8 months following the procedure. Conclusion: In the largest prospective, multi-institutional study of patients undergoing RUR with BF in the literature to date, we demonstrate a low rate of complications and a high rate of surgical success in three tertiary academic medical centers. All observed failures occurred within 2 months of surgical intervention.

Reducing diagnostic delays in Acute Hepatic Porphyria using electronic health records data and machine learning: a multicenter development and validation study.

Importance: Acute Hepatic Porphyria (AHP) is a group of rare but treatable conditions associated with diagnostic delays of fifteen years on average. The advent of electronic health records (EHR) data and machine learning (ML) may improve the timely recognition of rare diseases like AHP. However, prediction models can be difficult to train given the limited case numbers, unstructured EHR data, and selection biases intrinsic to healthcare delivery. Objective: To train and characterize models for identifying patients with AHP. Design Setting and Participants: This diagnostic study used structured and notes-based EHR data from two centers at the University of California, UCSF (2012-2022) and UCLA (2019-2022). The data were split into two cohorts (referral, diagnosis) and used to develop models that predict: 1) who will be referred for testing of acute porphyria, amongst those who presented with abdominal pain (a cardinal symptom of AHP), and 2) who will test positive, amongst those referred. The referral cohort consisted of 747 patients referred for testing and 99,849 contemporaneous patients who were not. The diagnosis cohort consisted of 72 confirmed AHP cases and 347 patients who tested negative. Cases were female predominant and 6-75 years old at the time of diagnosis. Candidate models used a range of architectures. Feature selection was semi-automated and incorporated publicly available data from knowledge graphs. Main Outcomes and Measures: F-score on an outcome-stratified test set. Results: The best center-specific referral models achieved an F-score of 86-91%. The best diagnosis model achieved an F-score of 92%. To further test our model, we contacted 372 current patients who lack an AHP diagnosis but were predicted by our models as potentially having it (≥ 10% probability of referral, ≥ 50% of testing positive). However, we were only able to recruit 10 of these patients for biochemical testing, all of whom were negative. Nonetheless, post hoc evaluations suggested that these models could identify 71% of cases earlier than their diagnosis date, saving 1.2 years. Conclusions and Relevance: ML can reduce diagnostic delays in AHP and other rare diseases. Robust recruitment strategies and multicenter coordination will be needed to validate these models before they can be deployed.

Leveraging polygenic enrichments of gene features to predict genes underlying complex traits and diseases.

Genome-wide association studies (GWASs) are a valuable tool for understanding the biology of complex human traits and diseases, but associated variants rarely point directly to causal genes. In the present study, we introduce a new method, polygenic priority score (PoPS), that learns trait-relevant gene features, such as cell-type-specific expression, to prioritize genes at GWAS loci. Using a large evaluation set of genes with fine-mapped coding variants, we show that PoPS and the closest gene individually outperform other gene prioritization methods, but observe the best overall performance by combining PoPS with orthogonal methods. Using this combined approach, we prioritize 10,642 unique gene-trait pairs across 113 complex traits and diseases with high precision, finding not only well-established gene-trait relationships but nominating new genes at unresolved loci, such as LGR4 for estimated glomerular filtration rate and CCR7 for deep vein thrombosis. Overall, we demonstrate that PoPS provides a powerful addition to the gene prioritization toolbox.

Ureteral inguinoscrotal hernia recurrence following robotic hernia repair: an uncommon hernia recurrence.

Ureteral inguinoscrotal hernias are a rare occurrence and commonly occur without evidence of obstructive uropathy. We present a patient found on a preoperative CT scan to have a recurrent left inguinal hernia with the left ureter passing through the hernia defect adjacent to the hernia sac into the scrotum. At surgery the redundant dilated ureter required a ureteroureterostomy because it could not be safely straightened or reduced. Preoperative imaging allowed for identification of the ureter in the hernia sac and allowed for extensive preoperative planning with the urology team, and efficient definitive treatment of his condition at the time of surgery.

Single Port vs Multiport Robotic Pyeloplasty: Propensity-Score Matched Analysis of Perioperative and Follow-Up Outcomes.

OBJECTIVES: To compare the perioperative and postoperative outcomes of single port (SP) robotic pyeloplasty and multiport (MP) robotic pyeloplasty using a propensity-score matched analysis. MATERIALS AND METHODS: We performed a chart review of all patients who underwent SP robotic pyeloplasty from January 2019 to October 2020 and MP robotic pyeloplasty from January 2016 to October 2020. Patient demographics, intraoperative data, and postoperative outcomes were collected and analyzed. Propensity-score matching was performed on sex, body mass index, and history of previous pyeloplasty to adjust for potential baseline confounders. A post hoc sensitivity analysis for operative time was performed to examine the robustness of the results. RESULTS: In total, 24 and 41 patients underwent sSP and MP robotic pyeloplasty, respectively. Following propensity-score matching, 21 MP cases were matched 1:1 to SP cases. The SP group was shown to have longer median operative times (128.0 vs 88.0 minutes, P = .0411) and shorter follow up time (9.3 vs 18.7 months, P = .0066). In a sensitivity analysis, SP robotic pyeloplasty was marginally associated with increased operative time (95% CI -0.25, 29.72, P = .0540). CONCLUSIONS: SP robotic pyeloplasty is a safe and acceptable alternative to MP robotic pyeloplasty, achieving comparable perioperative and postoperative outcomes.

Leveraging supervised learning for functionally informed fine-mapping of cis-eQTLs identifies an additional 20,913 putative causal eQTLs.

The large majority of variants identified by GWAS are non-coding, motivating detailed characterization of the function of non-coding variants. Experimental methods to assess variants' effect on gene expressions in native chromatin context via direct perturbation are low-throughput. Existing high-throughput computational predictors thus have lacked large gold standard sets of regulatory variants for training and validation. Here, we leverage a set of 14,807 putative causal eQTLs in humans obtained through statistical fine-mapping, and we use 6121 features to directly train a predictor of whether a variant modifies nearby gene expression. We call the resulting prediction the expression modifier score (EMS). We validate EMS by comparing its ability to prioritize functional variants with other major scores. We then use EMS as a prior for statistical fine-mapping of eQTLs to identify an additional 20,913 putatively causal eQTLs, and we incorporate EMS into co-localization analysis to identify 310 additional candidate genes across UK Biobank phenotypes.

Ureteral Rest is Associated With Improved Outcomes in Patients Undergoing Robotic Ureteral Reconstruction of Proximal and Middle Ureteral Strictures.

OBJECTIVES: To evaluate the effect of ureteral rest on outcomes of robotic ureteral reconstruction. METHODS: We retrospectively reviewed all patients who underwent robotic ureteral reconstruction of proximal and/or middle ureteral strictures in our multi-institutional database between 2/2012-03/2019 with ≥12 months follow-up. All patients were recommended to undergo ureteral rest, which we defined as the absence of hardware (ie. double-J stent or percutaneous nephroureteral tube) across a ureteral stricture ≥4 weeks prior to reconstruction. However, patients who refused percutaneous nephrostomy tube placement did not undergo ureteral rest. Perioperative outcomes were compared after grouping patients according to whether or not they underwent ureteral rest. Continuous and categorical variables were compared using Mann-Whitney U and 2-tailed chi-squared tests, respectively; P <.05 was considered significant. RESULTS: Of 234 total patients, 194 (82.9%) underwent ureteral rest and 40 (17.1%) did not undergo ureteral rest prior to ureteral reconstruction. Patients undergoing ureteral rest were associated with a higher success rate compared to those not undergoing ureteral rest (90.7% versus 77.5%, respectively; P = .027). Also, patients undergoing ureteral rest were associated with lower estimated blood loss (50 versus 75 milliliters, respectively; p<0.001) and less likely to undergo buccal mucosa graft ureteroplasty (20.1% versus 37.5%, respectively; p=0.023). CONCLUSIONS: Implementing ureteral rest prior to ureteral reconstruction may allow for stricture maturation and is associated higher surgical success rates, lower estimated blood loss, and decreased utilization of buccal mucosa graft ureteroplasty.

A Multi-Institutional Experience With Robotic Ureteroplasty With Buccal Mucosa Graft: An Updated Analysis of Intermediate-Term Outcomes.

OBJECTIVE: To update our prior multi-institutional experience with robotic ureteroplasty with buccal mucosa graft and analyze our intermediate-term outcomes. Although our previous multi-institutional report provided significant insight into the safety and efficacy associated with robotic ureteroplasty with buccal mucosa graft, it was limited by small patient numbers. METHODS: We retrospectively reviewed our multi-institutional database to identify all patients who underwent robotic ureteroplasty with buccal mucosa graft between October 2013 and March 2019 with ≥12 months follow up. Indication for surgery was a complex proximal and/or middle ureteral stricture not amenable to primary excision and anastomosis secondary to stricture length or peri-ureteral fibrosis. Surgical success was defined as the absence of obstructive flank pain and ureteral obstruction on functional imaging. RESULTS: Of 54 patients, 43 (79.6 %) patients underwent an onlay, and 11 (20.4%) patients underwent an augmented anastomotic robotic ureteroplasty with buccal mucosa graft. Eighteen of 54 (33.3%) patients previously failed a ureteral reconstruction. The median stricture length was 3.0 (IQR 2.0-4.0, range 1-8) centimeters. There were 3 of 54 (5.6%) major postoperative complications. The median length of stay was 1.0 (IQR 1.0-3.0) day. At a median follow-up of 27.5 (IQR 21.3-38.0) months, 47 of 54 (87.0%) cases were surgically successful. Stricture recurrences were diagnosed ≤2 months postoperatively in 3 of 7 (42.9%) patients, and ≥10 months postoperatively in 4 of 7 (57.1%) patients. CONCLUSION: Robotic ureteroplasty with buccal mucosa graft is associated with low peri-operative morbidity and excellent intermediate-term outcomes.

Robotic Ureteral Reconstruction in Patients with Radiation-Induced Ureteral Strictures: Experience from the Collaborative of Reconstructive Robotic Ureteral Surgery.

Objectives: Management of radiation-induced ureteral stricture (RIUS) is complex, requiring chronic drainage or morbid definitive open reconstruction. Herein, we report our multi-institutional comprehensive experience with robotic ureteral reconstruction (RUR) in patients with RIUSs. Patients and Methods: In a retrospective review of our multi-institutional RUR database between January 2013 and January 2020, we identified patients with RIUSs. Five major reconstruction techniques were utilized: end-to-end (anastomosing the bladder to the transected ureter) and side-to-side (anastomosing the bladder to an anterior ureterotomy proximal to the stricture without ureteral transection) ureteral reimplantation, buccal or appendiceal mucosa graft ureteroplasty, appendiceal bypass graft, and ileal ureter interposition. When necessary, adjunctive procedures were performed for mobility (i.e., psoas hitch) and improved vascularity (i.e., omental wrap). Outcomes of surgery were determined by the absence of flank pain (clinical success) and absence of obstruction on imaging (radiological success). Results: A total of 32 patients with 35 ureteral units underwent RUR with a median stricture length of 2.5 cm (interquartile range [IQR] 2-5.5). End-to-end and side-to-side reimplantation techniques were performed in 21 (60.0%) and 8 (22.9%) RUR cases, respectively, while 4 (11.4%) underwent an appendiceal procedure. One patient (2.9%) required buccal mucosa graft ureteroplasty, while another needed an ileal ureter interposition. The median operative time was 215 minutes (IQR 177-281), estimated blood loss was 100 mL (IQR 50-150), and length of stay was 2 days (IQR 1-3). One patient required repair of a small bowel leak. Another patient died from a major cardiac event and was excluded from follow-up calculations. At a median follow-up of 13 months (IQR 9-22), 30 ureteral units (88.2%) were clinically and radiologically effective. Conclusion: RUR can be performed in patients with RIUSs with excellent outcomes. Surgeons must be prepared to perform adjunctive procedures for mobility and improved vascularity due to poor tissue quality. Repeat procedures for RIUSs heighten the risk of necrosis and failure.

Bioregenerative Umbilical Cord Amniotic Membrane Allograft Ureteral Wrap During Robot-Assisted Ureterolysis.

Omental wrap is commonly performed after ureterolysis to prevent ureteral obstruction from recurrence of periureteral adhesions and fibrosis. We present the case of a 37-year-old Caucasian woman with a history of two cesarean sections and laparotomy for the treatment of endometriosis. She subsequently developed right flank pain caused by a right distal ureteral stricture requiring a chronic indwelling ureteral stent. Diagnostic laparoscopy revealed extrinsic compression of the ureter for which robot-assisted ureterolysis was performed. Because of inadequate omentum, we report the initial use of a cryopreserved bioregenerative umbilical cord amniotic membrane allograft to perform a ureteral wrap to promote ureteral tissue healing and serve as an adhesion barrier to prevent recurrence of the fibrosis.

Multi-institutional Experience Comparing Outcomes of Adult Patients Undergoing Secondary Versus Primary Robotic Pyeloplasty.

OBJECTIVE: To describe surgical techniques and peri-operative outcomes with secondary robotic pyeloplasty (RP), and compare them to those of primary RP. METHODS: We retrospectively reviewed our multi-institutional, collaborative of reconstructive robotic ureteral surgery (CORRUS) database for all consecutive patients who underwent RP between April 2012 and September 2019. Patients were grouped according to whether they underwent a primary or secondary pyeloplasty (performed for a recurrent stricture after previously failed pyeloplasty). Perioperative outcomes and surgical techniques were compared using nonparametric independent sample median tests and chi-square tests; P < .05 was considered significant. RESULTS: Of 158 patients, 28 (17.7%) and 130 (82.3%) underwent secondary and primary RP, respectively. Secondary RP, compared to primary RP, was associated with a higher median estimated blood loss (100.0 vs 50.0 milliliters, respectively; P < .01) and longer operative time (188.0 vs 136.0 minutes, respectively; P = .02). There was no difference in major (Clavien >2) complications (P = .29). At a median follow-up of 21.1 (IQR: 11.8-34.7) months, there was no difference in success between secondary and primary RP groups (85.7% vs 92.3%, respectively; P = .44). Buccal mucosa graft onlay ureteroplasty was performed more commonly (35.7% vs 0.0%, respectively, P < .01) and near-infrared fluorescence imaging with indocyanine green was utilized more frequently (67.9% vs 40.8%, respectively; P < .01) for secondary vs primary repair. CONCLUSION: Although performing secondary RP is technically challenging, it is a safe and effective method for recurrent ureteropelvic junction obstruction after a previously failed pyeloplasty. Buccal mucosa graft onlay ureteroplasty and utilization of near-infrared fluorescence with indocyanine green may be particularly useful in the re-operative setting.

The Perineural Invasion Paradox: Is Perineural Invasion an Independent Prognostic Indicator of Biochemical Recurrence Risk in Patients With pT2N0R0 Prostate Cancer? A Multi-Institutional Study.

PURPOSE: Perineural invasion (PNI) is a histologic feature that is present in as many as 84% of patients with prostate cancer. The prognostic significance of PNI is controversial, with recent studies yielding contradictory results. This study aims to assess whether PNI, on the surgical pathology of patients with pT2N0M0 disease and with negative surgical margins, is an independent prognostic indicator of the risk of biochemical recurrence. METHODS AND MATERIALS: We identified 1549 patients who received a diagnosis of margin-negative pT2N0M0 prostate cancer at 3 separate institutions between January 1, 2008 and December 31, 2014. We reviewed the electronic medical records of these patients and collected clinical and histologic data. A multivariable analysis was performed to assess the association between PNI and biochemical recurrence. RESULTS: Of the 1549 patients identified, 936 (60.4%) had PNI and 96 (6.2%) had biochemical recurrence. The median time until recurrence was 16 months. The median follow-up in patients without recurrence was 26.5 months. PNI was associated with pT2c disease. The proportion of patients with pT2c was 89% in patients with PNI compared with 79% in patients without PNI (P < .001). PNI was also associated with a higher surgical Gleason score (of those with vs without PNI, 21% vs 50% had Gleason score 3 + 3; 62% vs 41% had a Gleason score 3 + 4, 12% vs 5% had a Gleason score 4 + 3; and 5% vs 3% had a Gleason score 8-10; P < .001). On univariate analysis, patients with PNI appeared to be more likely to have disease recurrence (hazard ratio: 1.7; 95% confidence interval, 1.1-2.6; P = .015). However, after adjusting for other variables, there was not a significant association between PNI and recurrence (hazard ratio: 1.1; 95% confidence interval, 0.70-1.8: P = .65). CONCLUSIONS: We found that PNI was not an independent indicator of the risk of biochemical recurrence. Instead, PNI may be an indicator of unfavorable histology such as a high Gleason score or diffuse disease within the prostate in pT2N0 patients.

Esophageal adenocarcinoma stage III: Survival based on pathological response to neoadjuvant treatment.

BACKGROUND: Neoadjuvant chemoradiotherapy is the standard treatment for locally advanced esophageal adenocarcinomas (EAC). Pathological response is thought to be a major prognostic factor. Aims of this study were to determine the frequency of complete response and to compare the survival of complete and incomplete responders in stage III EAC. METHODS: A retrospective review was performed of all stage III patients that underwent neoadjuvant therapy followed by esophagectomy between 1999 and 2015. Patients were classified into complete (pCR) versus incomplete responders (pIR). RESULTS: 110 patients were included. Neoadjuvant chemotherapy was applied in 25 (23%) and chemoradiotherapy in 85 (77%) patients. Pathologic response was complete in 25% (n = 27) and was more common after chemoradiotherapy. Mean F/U interval was 36 months (0.3-173). There was a significant difference in the overall survival between complete and incomplete responders (p = 0.036). Median survival in the pIR group was 24.4 months and the median survival was not reached during the observation time in pCR. The 3-year-survival-rate was 70% in pCR and 40% in pIR (p = 0.01). Positive lymph nodes (ypN+) were present in 56 patients (51%). The 3-year-survival-rate was 59% in pIR with ypN0 and 29% in pIR with ypN+ (p = 0.005). CONCLUSIONS: Complete response to neoadjuvant therapy has a significantly better overall and 3-year-survival after esophagectomy than incomplete response. In incomplete responders, residual lymph node disease was associated with a significantly worse survival. These findings suggest that the degree of pathologic response and lymph node status are major prognostic factors for survival in EAC patients with stage III disease.