Proposal for an optimised definition of adverse pathology (unfavourable histology) that predicts metastatic risk in prostatic adenocarcinoma independent of grade group and pathological stage.

AIMS: Histological grading of prostate cancer is a powerful prognostic tool, but current criteria for grade assignment are not fully optimised. Our goal was to develop and test a simplified histological grading model, based heavily on large cribriform/intraductal carcinoma, with optimised sensitivity for predicting metastatic potential. METHODS AND RESULTS: Two separate non-overlapping cohorts were identified: a 419-patient post-radical prostatectomy cohort with long term clinical follow-up and a 209-patient post-radical prostatectomy cohort in which all patients had pathologically confirmed metastatic disease. All prostatectomies were re-reviewed for high-risk histological patterns of carcinoma termed 'unfavourable histology'. Unfavourable histology is defined by any classic Gleason pattern 5 component, any large cribriform morphology (> 0.25 mm) or intraductal carcinoma, complex intraluminal papillary architecture, grade 3 stromogenic carcinoma and complex anastomosing cord-like growth. For the outcome cohort, Kaplan-Meier analysis compared biochemical recurrence, metastasis and death between subjects with favourable and unfavourable histology, stratified by pathological stage and grade group. Multivariable Cox proportional hazards models evaluated adding unfavourable histology to the Memorial Sloan Kettering Cancer Center (MSKCC) post-prostatectomy nomogram and stratification by percentage of unfavourable histology. At 15 years unfavourable histology predicted biochemical recurrence, with sensitivity of 93% and specificity of 88%, metastatic disease at 100 and 48% and death at 100 and 46%. Grade group 2 prostate cancers with unfavourable histology were associated with metastasis independent of pathological stage, while those without had no risk. Histological models for prediction of metastasis based on only large cribriform/intraductal carcinoma or increasing diameter of cribriform size improved specificity, but with lower sensitivity. Multivariable Cox proportional hazards models demonstrated that unfavourable histology significantly improved discriminatory power of the MSKCC post-prostatectomy nomogram for biochemical failure (likelihood ratio test P < 0.001). In the retrospective review of a separate RP cohort in which all patients had confirmed metastatic disease, none had unequivocal favourable histology. CONCLUSIONS: Unfavourable histology at radical prostatectomy is associated with metastatic risk, predicted adverse outcomes better than current grading and staging systems and improved the MSKCC post-prostatectomy nomogram. Most importantly, unfavourable histology stratified grade group 2 prostate cancers into those with and without metastatic potential, independent of stage. While unfavourable histology is driven predominantly by large cribriform/intraductal carcinoma, the recognition and inclusion of other specific architectural patterns add to the sensitivity for predicting metastatic disease. Moreover, a simplified dichotomous model improves communication and could increase implementation.

Wound related complications and the anterior rectus sheath versus Gibson approach to kidney transplantation: A single center randomized controlled trial.

INTRODUCTION: Wound related complications (WRC) are a significant source of morbidity in kidney transplant recipients, and may be mitigated by surgical approach. We hypothesize that the anterior rectus sheath approach (ARS) may decrease WRC and inpatient opiate use compared to the Gibson Approach (GA). METHODS: This double-blinded randomized controlled trial allocated kidney transplant recipients aged 18 or older, exclusive of other procedures, 1:1 to ARS or GA at a single hospital. The ARS involves a muscle-splitting paramedian approach to the iliopsoas fossa, compared to the muscle-cutting GA. Patients and data analysts were blinded to randomization. RESULTS: Seventy five patients were randomized to each group between August 27, 2019 and September 18, 2020 with a minimum 12 month follow-up. There was no difference in WRC between groups (p = .23). Nine (12%) and three patients (4%) experienced any WRC in the ARS and GA groups, respectively. Three and one Clavien IIIb complications occurred in the ARS and GA groups, respectively. In a multiple linear regression model, ARS was associated with decreased inpatient opioid use (ß = -58, 95% CI: -105 to -12, p = .016). CONCLUSIONS: The ARS did not provide a WRC benefit in kidney transplant recipients, but may be associated with decreased inpatient opioid use.

Analysis of separate training and validation radical prostatectomy cohorts identifies 0.25 mm diameter as an optimal definition for "large" cribriform prostatic adenocarcinoma.

Cribriform growth pattern is well-established as an adverse pathologic feature in prostate cancer. The literature suggests "large" cribriform glands associate with aggressive behavior; however, published studies use varying definitions for "large". We aimed to identify an outcome-based quantitative cut-off for "large" vs "small" cribriform glands. We conducted an initial training phase using the tissue microarray based Canary retrospective radical prostatectomy cohort. Of 1287 patients analyzed, cribriform growth was observed in 307 (24%). Using Kaplan-Meier estimates of recurrence-free survival curves (RFS) that were stratified by cribriform gland size, we identified 0.25 mm as the optimal cutoff to identify more aggressive disease. In univariable and multivariable Cox proportional hazard analyses, size >0.25 mm was a significant predictor of worse RFS compared to patients with cribriform glands ≤0.25 mm, independent of pre-operative PSA, grade, stage and margin status (p < 0.001). In addition, two different subset analyses of low-intermediate risk cases (cases with Gleason score ≤ 3 + 4 = 7; and cases with Gleason score = 3 + 4 = 7/4 + 3 = 7) likewise demonstrated patients with largest cribriform diameter >0.25 mm had a significantly lower RFS relative to patients with cribriform glands ≤0.25 mm (each subset p = 0.004). Furthermore, there was no significant difference in outcomes between patients with cribriform glands ≤ 0.25 mm and patients without cribriform glands. The >0.25 mm cut-off was validated as statistically significant in a separate 419 patient, completely embedded whole-section radical prostatectomy cohort by biochemical recurrence, metastasis-free survival, and disease specific death, even when cases with admixed Gleason pattern 5 carcinoma were excluded. In summary, our findings support reporting cribriform gland size and identify 0.25 mm as an optimal outcome-based quantitative measure for defining "large" cribriform glands. Moreover, cribriform glands >0.25 mm are associated with potential for metastatic disease independent of Gleason pattern 5 adenocarcinoma.

A Critical Analysis of Reporting in Systematic Reviews and Meta-Analyses in the Peyronie's Disease Literature.

BACKGROUND: Despite an increasing number of publications on Peyronie's disease (PD), evidence-based clinical decision-making remains challenging due to the small number of well-designed clinical trials. AIM: To perform a critical analysis of reporting quality in PD systematic reviews (SR) and meta-analyses (MA). METHODS: Study protocol registration was performed on the Open Science Framework platform. In January 2021, a systematic electronic search of the Medline/PubMed, Embase, Ovid, Scopus, Joanne Briggs Institute, and Cochrane databases was performed. Search terms included "Peyronie's disease" and "systematic review OR meta-analysis OR meta-analysis." Eligibility criteria were English-language, relevance to PD and specification of "systematic review" or "meta-analysis" in the title or abstract. Oxford Center for Evidence-Based Medicine levels of evidence were used to classify original studies reviewed within each publication. Risk of bias was assessed using the ROBIS tool. Data were tabulated and reported as means with standard deviation, median with interquartile range and t-testing as appropriate. Strength of association between variables was calculated using Pearson correlation coefficient. Statistical analyses were performed on RStudio (version 1.4.1106). OUTCOMES: Outcomes included review type, level of evidence, authorship, journal, publication date, "A MeaSurement Tool to Assess systematic Reviews" (AMSTAR-2) score and "Preferred Reporting Items for Systematic Reviews and Meta-Analyses" (PRISMA) score. RESULTS: From 1974 to 2021, 340 articles were identified. After review, 17 full length articles were included. Thirteen were SR, 2 MA and 2 was combined. Significant heterogeneity was seen in evidence level of included studies. There was median 54% adherence to AMSTAR-2 criteria and 74% adherence to PRISMA criteria. Overall AMSTAR-2 confidence rating was Critically Low in 11 of 17 studies. Correlation analysis revealed very high positive association between AMSTAR 2 and PRISMA adherence (+0.95). ROBIS revealed "High" concern regarding methods used to collect data and appraise 12/17 studies (71%), and "High" concern regarding synthesis and findings in 8 of 17 studies (47%). CLINICAL IMPLICATIONS: Many SR include markedly heterogenous levels of evidence and fail to meet accepted methodological criteria for reporting. STRENGTHS AND LIMITATIONS: Main strengths include extensive literature review and analysis of standardized study reporting. One limitation is that aggregate scoring of AMSTAR-2 and PRISMA is not intended as primary method of quality assessment; however effect was minimized by reporting critical domains, overall quality assessments and specifics on globally poorly reported domains. CONCLUSION: More high quality randomized controlled PD trials are necessary; SR and MA should focus on these studies alone. Bole R, Gottlich HC, Ziegelmann MJ, et al. A Critical Analysis of Reporting in Systematic Reviews and Meta-Analyses in the Peyronie's Disease Literature. J Sex Med 2022;19:629-640.

Can Perioperative Antibiotic Choice Impact Rates of Infectious Complications After Percutaneous Nephrolithotomy? A Single-Blind, Prospective Randomized Trial.

Objective: National guidelines recommend periprocedural antibiotics before percutaneous nephrolithotomy (PCNL), yet it is not clear which is superior. We conducted a randomized trial to compare two guideline-recommended antibiotics: ciprofloxacin (cipro) vs cefazolin, on PCNL outcomes, focusing on the development of systemic inflammatory response syndrome (SIRS) criteria. Methods: Adult patients who were not considered high risk for surgical or infectious complications and undergoing PCNL were randomized to receive either cipro or cefazolin perioperatively. All had negative preoperative urine cultures. Demographic and perioperative data were collected, including SIRS criteria, intraoperative urine culture, duration of hospitalization, and need for intensive care. SIRS is defined by ≥2 of the following: body temperature <96.8°F or >100.4°F, heart rate >90 bpm, respiratory rate >20 per minute, and white blood cell count <4000 or >12,000 cells/mm3. Results: One hundred forty-seven patients were enrolled and randomized (79 cefazolin and 68 cipro). All preoperative characteristics were similar (p > 0.05), except for mean age, which was higher in the cipro group (64 vs 57 years, p = 0.03). Intra- and postoperative findings were similar, with no difference between groups (p > 0.05), except a longer mean hospital stay in the cefazolin group (2 hours longer, p = 0.02). There was no difference between SIRS episodes in both univariate and multivariate analyses. Conclusions: Despite the relatively broader coverage for urinary tract pathogens with ciprofloxacin, this prospective randomized trial did not show superiority over cefazolin. Our findings therefore support two appropriate options for perioperative antibiotic prophylaxis in patients undergoing PCNL who are nonhigh risk for infectious complications.

AI-generated R.E.N.A.L.+ Score Surpasses Human-generated Score in Predicting Renal Oncologic Outcomes.

OBJECTIVE: To determine whether we can surpass the traditional R.E.N.A.L. nephrometry score (H-score) prediction ability of pathologic outcomes by creating artificial intelligence (AI)-generated R.E.N.A.L.+ score (AI+ score) with continuous rather than ordinal components. We also assessed the AI+ score components' relative importance with respect to outcome odds. METHODS: This is a retrospective study of 300 consecutive patients with preoperative computed tomography scans showing suspected renal cancer at a single institution from 2010 to 2018. H-score was tabulated by three trained medical personnel. Deep neural network approach automatically generated kidney segmentation masks of parenchyma and tumor. Geometric algorithms were used to automatically estimate score components as ordinal and continuous variables. Multivariate logistic regression of continuous R.E.N.A.L. components was used to generate AI+ score. Predictive utility was compared between AI+, AI, and H-scores for variables of interest, and AI+ score components' relative importance was assessed. RESULTS: Median age was 60years (interquartile range 51-68), and 40% were female. Median tumor size was 4.2 cm (2.6-6.12), and 92% were malignant, including 27%, 37%, and 23% with high-stage, high-grade, and necrosis, respectively. AI+ score demonstrated superior predictive ability over AI and H-scores for predicting malignancy (area under the curve [AUC] 0.69 vs 0.67 vs 0.64, respectively), high stage (AUC 0.82 vs 0.65 vs 0.71, respectively), high grade (AUC 0.78 vs 0.65 vs 0.65, respectively), pathologic tumor necrosis (AUC 0.81 vs 0.72 vs 0.74, respectively), and partial nephrectomy approach (AUC 0.88 vs 0.74 vs 0.79, respectively). Of AI+ score components, the maximal tumor diameter ("R") was the most important outcomes predictor. CONCLUSION: AI+ score was superior to AI-score and H-score in predicting oncologic outcomes. Time-efficient AI+ score can be used at the point of care, surpassing validated clinical scoring systems.

Long-term comparative outcomes of partial nephrectomy and cryoablation in patients with solitary kidneys: a single-center analysis.

BACKGROUND: Patients with solitary kidneys are amenable to postoperative acute kidney injury (AKI) after PN. We compared the functional and oncological outcomes of cryoablation (CA) and PN in patients with a solitary kidney and a cT1a renal mass. METHODS: From a single-institution series, we analyzed 74 patients (31 PN, 43 CA) with a solitary kidney who underwent treatment for a cT1a renal mass. The functional outcomes were AKI and estimated glomerular filtration rate (eGFR) preservation. Oncological outcomes were recurrence and death. Linear mixed-effects and logistic regression models were used for functional outcomes analysis, whereas oncological outcomes were analyzed using the Kaplan-Meier method. RESULTS: Median follow-up was 63.9 months. PN group had lower median age (59 years vs. 68, P<0.001) and larger median tumor size (2.80 cm vs. 2.0, p =0.003). AKI was more common in the PN group on postoperative day 1 (58% vs. 2.8%, P<0.001). However, only one patient in the PN group required temporary dialysis in the perioperative period. eGFR preservation was similar at postoperative 3 months (89% vs. 90%, P=0.083), or 12 months (85% vs. 94%, P=0.2) follow-up. CA group had higher recurrence rate (29% vs. 3.2%, P=0.005), and worse recurrence-free survival (P=0.027). Overall survival (OS) was comparable (P=0.31). CONCLUSIONS: In a solitary kidney setting, CA is associated with a lower risk of AKI at postoperative day 1 compared to PN. Functional outcome is comparable upon longer follow-up. The local recurrence rates are significantly higher in the CA group with no significant difference in OS.

Survival outcomes following radical cystectomy in patients with prior pelvic radiation for prostate cancer: A matched cohort analysis.

OBJECTIVES: To determine the impact of prior pelvic radiation therapy (XRT) on outcomes following radical cystectomy (RC) for bladder cancer. MATERIALS AND METHODS: We performed a retrospective review comparing patients with bladder cancer requiring RC and prior history of XRT for prostate cancer to those undergoing RC without XRT history at our institution from 2011-2018. Propensity score matching was performed with the following variables: age, chronic kidney disease, nutritional deficiency, neoadjuvant chemotherapy use, Charlson comorbidity index, surgical approach, urinary diversion type, and pathologic T-stage. Perioperative, pathologic and oncologic outcomes were analyzed. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Categorical variables were assessed utilizing the Pearson Chi Square Test, and continuous variables with the Wilcoxon rank-sum test. The Kaplan-Meier method with stratified-log rank was used to compare survival outcomes. Multivariable Cox proportional hazards models were utilized to identify predictors of overall and recurrence free survival. RESULTS: 227 patients were included, of which 47 had radiotherapy for prostate cancer. 47% of patients in the radiation cohort received external beam radiation therapy, 47% received brachytherapy and 7% received both. There were no differences in recurrence-free survival (P = 0.82) or overall survival (P = 0.25). Statistically significant differences in perioperative or postoperative outcomes such as 90-day complication, readmission, mortality rates, or ureteroenteric anastomotic stricture rates were not found. Rates of node-positive disease, median lymph node yield, positive surgical margin rates, lymphovascular invasion, or variant histology were not significantly different between cohorts. CONCLUSIONS: After matching for T-stage and other clinical variables, history of pelvic XRT for prostate cancer in patients who later required RC for bladder cancer, was not associated with an increased rate of perioperative complications or an independent predictor of RFS or OS.

Ability of the surgical Apgar score to predict acute kidney injury following radical cystectomy.

PURPOSE: Acute kidney injury (AKI) is a common complication after radical cystectomy (RC). Previous literature has shown that intraoperative hemodynamic instability measured via the surgical Apgar score is an independent predictor of major complications following RC. We sought to determine whether the surgical Apgar score is predictive of postoperative AKI. METHODS: We performed a retrospective review of RC patients at our institution from 2010 to 2017. Intraoperative hemodynamic instability was captured via the Apgar score based on the lowest intraoperative mean arterial blood pressure, lowest heart rate, and estimated blood loss. Patients were divided into 3 groups: high-risk (HR; Apgar ≤4), intermediate-risk (IR; Apgar score 5-6), and low-risk (LR; Apgar score ≥7). AKIs were graded according to the Kidney Disease Improving Global Outcomes (KDIGO) criteria. High grade AKIs were defined as KDIGO grade 2 or 3. Categorical variables were assessed using the Pearson Chi-Square test, quantitative with the Kruskal-Wallis test, and multivariable logistic regression to identify predictors of AKI and high grade AKIs within 30 days of RC. RESULTS: Eight hundred and seventy-three patients were included with a median follow-up of 35 months. AKI within 30 days was observed in 28% of patients. Predictors of AKI within 30 days on adjusted analysis included IR (OR: 1.83, P = 0.002) and HR (OR: 3.53, P < 0.001) Apgar scores. IR (OR: 2.23, P = 0.007) and HR (OR: 4.87, P < 0.001) Apgar scores were also predictors of high-grade AKIs. CONCLUSION: Intraoperative hemodynamic instability measured via the Apgar score can be predictive of AKI, which can guide individualized fluid management in the postoperative period.

The role of enhanced recovery after surgery protocols in the development of acute kidney injury following radical cystectomy.

PURPOSE: Recent reports have suggested that fluid restriction as part of Enhanced Recovery after Surgery (ERAS) pathways may increase the risk of AKI in radical cystectomy (RC) patients. We sought to evaluate the impact of ERAS initiation on AKI incidence at a high-volume tertiary care center. MATERIALS AND METHODS: We performed a retrospective review of our IRB approved database to identify patients receiving RC from 2010 to 2019. ERAS was initiated at our institution in October 2016. Acute kidney injuries were graded according to the Kidney Disease Improving Global Outcomes (KDIGO) criteria and must have occurred within 7 days of indexed RC. Estimated glomerular filtration rate (eGFR) was captured at baseline, 1, 3, 6, and 12 months respectively. Categorical variables were compared with the Pearson-Chi square test. Quantitative variables were analyzed with the Wilcoxon-Rank sum test. Multivariable binary logistic regression and interaction analysis was used to identify predictors of AKI. RESULTS: Twelve hundred patients were included. Twenty-two percent of patients experienced an AKI within 7 days. Patients in the ERAS cohort experienced less AKIs after RC (18% vs. 25%, P = 0.003). When adjusting for year of surgery, ERAS was not a significant predictor for AKI on multivariable analysis (OR: 0.87, P = 0.73). On interaction analysis, during the ERAS era, intracorporeal robot-assisted radical cystectomy (iRARC) was associated with decreased odds of AKI (OR: 0.39, P = 0.034). There were no significant differences in eGFR at 12 months postoperatively (P = 0.16). CONCLUSION: Unlike previous reports, ERAS initiation was not associated with increased risk of AKI at a tertiary care high-volume center.