The impact of health care on outcomes of suspected testicular torsion: results from the GRAND study.

BACKGROUND: Suspicion of testicular torsion represents a urological emergency, necessitating immediate surgery. Comprehensive data on the current trends and perioperative outcomes regarding surgical exploration are sparse. Therefore, we utilized nationwide data on the prevalence and results of this surgery, aiming to provide evidence on this matter. METHODS: We assessed the GeRmAn Nationwide inpatient Data (GRAND) from 2005 to 2021, provided by the Research Data Center of the Federal Bureau of Statistics. We performed multiple regression analyses to evaluate the perioperative outcomes (length of hospital stay, transfusion, and surgical wound infection) after surgical exploration due to suspected testicular torsion based on both the outcome of surgery (orchiectomy, detorsion with preservation of the testicle, and no testicular torsion) and on the department of operation (urological versus non-urological). RESULTS: A total of 81,899 males underwent surgical exploration due to suspected testicular torsion in Germany from 2005 to 2021. Of them, 11,725 (14%) underwent orchiectomy, 30,765 (38%) detorsion with preservation of the testicle and subsequent orchidopexy, and 39,409 (48%) presented no testicular torsion. Orchiectomy was significantly associated with longer length of hospital stay (day difference of 1.4 days, 95%CI: 1.3-1.4, p < 0.001), higher odds of transfusion (1.8, 95% CI: 1.2-2.6, p = 0.002) and surgical wound infections (1.8, 95%CI: 1.4-2.3, p < 0.001) compared to no testicular torsion. The proportion of patients undergoing orchiectomy was significantly lower in urological departments (14%) versus non-urological departments (16%) and the proportion of patients undergoing preservation of testicle after detorsion was significantly higher in urological departments (38%) versus non-urological departments (37%), p < 0.001. Patients undergoing treatment in a urological department were discharged earlier and presented lower odds of transfusion and surgical wound infection (p < 0.001) compared to patients undergoing treatment in a non-urological department. CONCLUSIONS: Nearly half of patients who underwent surgery for suspected testicular torsion did not have intraoperatively the condition confirmed. Patients treated in urological departments had significantly better perioperative outcomes compared to those treated in non-urological departments. Therefore, we advise to refer patients to urological treatment as early as possible.

The Prognostic Value of Perioperative Platelet and Leukocyte Values in Patients Undergoing Radical Cystectomy: A Prospective Long-Term Cohort Study.

INTRODUCTION: Studies assessing the impact of preoperative and first-day postoperative values of leukocytes, thrombocytes, and platelet/leukocyte ratio (PLR) after radical cystectomy (RC) are sparse. We aimed to assess the impact of these factors on long-term survival after RC. METHODS: An analysis of patients undergoing open RC from 2004 to 2023 at our center was performed. Leukocytosis was defined as ≥8,000 leukocytes/µL and thrombocytosis as ≥400,000 thrombocytes/µL. Similarly, the cutoff for PLR was set at 28. A multivariable Cox regression analysis was performed to assess the role of leukocytosis, thrombocytosis, and PLR on long-term survival after RC. For all analyses, hazard ratios (HRs) with the corresponding 95% confidence intervals (CIs) were estimated. RESULTS: A total of 1,817 patients with a median age of 70 years (interquartile range [IQR]: 62-77) were included. Overall, 804 (44%), 175 (10%), and 1,296 (71%) patients presented with leukocytosis, thrombocytosis, and PLR ≥28 preoperatively. Accordingly, 1,414 (78%), 37 (2%), and 249 (14%) patients presented with leukocytosis, thrombocytosis, and PLR ≥28 on the first day after RC. At a median follow-up of 26 months (IQR: 8-68) after RC, 896 (49%) patients died. In the multivariate Cox regression analysis after adjusting for major perioperative risk factors, only preoperative leukocytosis (HR: 1.3, 95% CI: 1.1-1.6, p = 0.01), as well as both preoperative and first-day thrombocytosis (HR: 2.1, 95% CI: 1.5-2.9, and HR: 2.8, 95% CI: 1.6-5.1, p < 0.001, accordingly) were associated with worse overall survival. CONCLUSION: PLR should not be used as a prognostic marker for survival after RC. On the contrary, preoperative leukocytosis, as well as preoperative and first-day thrombocytosis should raise awareness among clinicians performing RC since they were independently associated with worse survival after RC.

Trends and outcomes of hospitalized patients with priapism in Germany: results from the GRAND study.

We aimed to provide evidence on the trends and in-hospital outcomes of patients with low- and high-flow priapism through the largest study in the field. We used the GeRmAn Nationwide inpatient Data (GRAND), provided by the Research Data Center of the Federal Bureau of Statistics (2008-2021), and performed multiple patient-level analyses. We included 6,588 men with low-flow and 729 with high-flow priapism. Among patients with low-flow priapism, 156 (2.4%) suffered from sickle cell disease, and 1,477 (22.4%) patients required shunt surgery. Of them, only 37 (2.5%) received a concomitant penile prosthesis implantation (30 inflatable and 7 semi-rigid prosthesis). In Germany, the total number of patients with low-flow priapism requiring hospital stay has steadily increased, while the number of patients with high-flow priapism requiring hospital stay has decreased in the last years. Among patients with high-flow priapism, 136 (18.7%) required selective artery embolization. In men with low-flow priapism, sickle cell disease was associated with high rates of exchange transfusion (OR: 21, 95% CI: 14-31, p < 0.001). The length of hospital stay (p = 0.06) and the intensive care unit admissions (p = 0.9) did not differ between patients with low-flow priapism due to sickle cell disease versus other causes of low-flow priapism. Accordingly, in men with high-flow priapism, embolization was not associated with worse outcomes in terms of length of hospital stay (p > 0.9), transfusion (p = 0.8), and intensive care unit admission (p = 0.5). Low-flow priapism is an absolute emergency that requires shunt surgery in more than one-fifth of all patients requiring hospital stay. On the contrary, high-flow priapism is still managed, in most cases, conservatively.

[68Ga]Ga-FAPI-46 PET/CT for penile cancer - a feasibility study.

PURPOSE: Penile cancer is a rare entity and has a good prognosis in localized stage. Delayed surgical treatment of lymphatic disease is associated with poor overall survival but conventional imaging cannot detect occult lymph node metastasis sufficiently. Imaging cancer related fibroblasts has shown promising results as non-invasive staging tool in various tumor entities but has not yet been evaluated in penile cancer. METHODS: In this single-center pilot study, patients planned for surgical treatment for penile cancer underwent preoperatively [68Ga]Ga-FAPI-46 PET/CT. Post-operative histopathology was compared to [68Ga]Ga-FAPI-46 PET/CT results. RESULTS: From January 2022 to June 2022, a total number 11 patients with histopathologically proven penile cancer underwent surgery and received [68Ga]Ga-FAPI-46 PET/CT prior therapy. 8 primary tumor sites and 4 lymph node regions were analyzed. FAPI uptake was increased on primary tumor site (SUVmax 16.2 (9.1 - 25.8)). Histopathological proven lymph node regions showed highly increased FAPI uptakes (SUVmax 17.9 (16.4 - 23.5) on [68Ga]Ga-FAPI-46 PET/CT. CONCLUSION: In this first pilot cohort, there were no false-positive FAPI uptake which might allow the detection of occult lymph node metastasis by [68Ga]Ga-FAPI-46 PET/CT and might consequently lead to omitting lymph node regions during surgery that had no increased FAPI uptake pre-operatively.

The Vanishing Clinical Value of PD-L1 Status as a Predictive Biomarker in the First-Line Treatment of Urothelial Carcinoma of the Bladder.

BACKGROUND: Our study endeavors to elucidate the clinical implications of PD-L1 positivity in individuals afflicted with advanced urothelial carcinoma of the bladder (UCB). METHODS: Patients with advanced UCB were prospectively enrolled following a radical cystectomy (RC) performed within January 2017 to December 2022 at our tertiary referral center. The clinical outcome, defined as the progression-free survival (PFS) and overall survival (OS) on systemic treatment, was analyzed using an χ2-test, Mann-Whitney U-test, the Kaplan-Meier method, and a log-rank test. RESULTS: A total of 648 patients were included following an RC performed within January 2017 to December 2022. Their PD-L1 status was analyzed with the primary PD-L1-specific antibody (clone SP263, Ventana) and defined both by the CPS and IC-score in 282 patients (43.5%) with a high risk (pT3-pT4 and/or lymph node involvement) or metastatic UCB. While the median PFS was significantly prolonged 5-fold in PD-L1+ patients, we found no difference in OS, regardless of PD-L1 status, or treatment regimen. CONCLUSIONS: While PD-L1 positivity indicates prolonged PFS, the presence of PD-L1 does not influence OS rates, suggesting its limited usefulness as a prognostic biomarker in bladder cancer. However, the positive correlation between an PD-L1 status and a sustained response to ICI treatments indicates its potential role as a predictive biomarker. Further research is required to understand how the predictive value of PD-L1 positivity may extend to the use of ICIs in combination with antibody-drug conjugates.

The impact of perioperative risk factors on long-term survival after radical cystectomy: a prospective, high-volume cohort study.

INTRODUCTION: Radical cystectomy (RC) is the gold standard for muscle-invasive bladder cancer. Nevertheless, RC is associated with substantial perioperative morbidity and mortality. We aimed to evaluate the role of important perioperative risk factors in predicting long-term survival after RC. METHODS: An analysis of the prospective cohort of patients undergoing open RC from 2004 to 2023 at our center was performed. Patients who died within one month after RC were excluded from the study. A univariate and multivariable Cox regression analysis was performed to assess the role of sex, age, urinary diversion, preoperative values of creatinine and hemoglobin, first-day postoperative values of CRP, leucocytes, and thrombocytes, perioperative Clavien-Dindo complications, perioperative chemotherapy, admission to the intensive or intermediate care unit, as well as type of histology, pathologic T-stage, positive lymph nodes, and positive surgical margins on predicting the long-term overall survival after RC. For all analyses hazard ratios (HRs) with the corresponding 95% confidence intervals (CIs) were estimated. RESULTS: A total of 1,750 patients with a median age of 70 years (IQR: 62-76) were included. Of them, 1,069 (61%) received ileal conduit and 650 (37%) neobladder. Overall, 1,016 (58%) perioperative complications occurred. At a median follow-up of 31 months (IQR: 12-71), 884 (51%) deaths were recorded. In the multivariable Cox regression analysis, increasing age (HR: 1.03, 95%CI: 1.02-1.04, p < 0.001), higher preoperative creatinine values (HR: 1.27, 95%CI: 1.12-1.44, p < 0.001), lower preoperative hemoglobin values (HR: 0.93, 95%CI: 0.89-0.97, p = 0.002), higher postoperative thrombocyte values (HR: 1.01, 95%CI: 1.01-1.02, p = 0.02), Clavien-Dindo 1-2 complications (HR: 1.26, 95%CI: 1.03-1.53, p = 0.02), Clavien-Dindo 3-4 complications (HR: 1.55, 95%CI: 1.22-1.96, p < 0.001), locally advanced bladder cancer (HR: 1.29, 95%CI: 1.06-1.55, p = 0.009), positive lymph nodes (HR: 1.74, 95%CI: 1.45-2.11, p < 0.001), and positive surgical margins (HR: 1.61, 95%CI: 1.29-2.01, p < 0.001) negatively affected long-term survival. CONCLUSION: Beside increased age and worse oncological status, impaired renal function, lower preoperative hemoglobin values, higher postoperative thrombocyte values, and perioperative complications are independent risk factors for mortality in the long term in patients undergoing open RC.

The effect of hospital caseload on perioperative mortality, morbidity and costs in bladder cancer patients undergoing radical cystectomy: results of the German nationwide inpatient data.

OBJECTIVES: To determine a data-based optimal annual radical cystectomy (RC) hospital volume threshold and evaluate its clinical significance regarding perioperative mortality, complications, length of hospital stay, and hospital revenues. MATERIAL AND METHODS: We used the German Nationwide inpatient Data, provided by the Research Data Center of the Federal Bureau of Statistics (2005-2020). 95,841 patients undergoing RC were included. Based on ROC analyses, the optimal RC threshold to reduce mortality, ileus, sepsis, transfusion, hospital stay, and costs is 54, 50, 44, 44, 71 and 76 cases/year, respectively. Therefore, we defined an optimal annual hospital threshold of 50 RCs/year, and we also used the threshold of 20 RCs/year proposed by the EAU guidelines to perform multiple patient-level analyses. RESULTS: 28,291 (29.5%) patients were operated in low- (< 20 RC/year), 49,616 (51.8%) in intermediate- (20-49 RC/year), and 17,934 (18.7%) in high-volume (≥ 50 RC/year) centers. After adjusting for major risk factors, high-volume centers were associated with lower inpatient mortality (OR 0.72, 95% CI 0.64-0.8, p < 0.001), shorter length of hospital stay (2.7 days, 95% CI 2.4-2.9, p < 0.001) and lower costs (457 Euros, 95% CI 207-707, p < 0.001) compared to low-volume centers. Patients operated in low-volume centers developed more perioperative complications such as transfusion, sepsis, and ileus. CONCLUSIONS: Centralization of RC not only improves inpatient morbidity and mortality but also reduces hospital stay and costs. We propose a threshold of 50 RCs/year for optimal outcomes.

[68 Ga]Ga-FAPI-46 PET/CT for locoregional lymph node staging in urothelial carcinoma of the bladder prior to cystectomy: initial experiences from a pilot analysis.

INTRODUCTION: [68 Ga]Ga-FAPI-46 PET/CT is a novel hybrid imaging method that previously showed additional diagnostic value in the assessment of distant urothelial carcinoma lesions. We hypothesized that patients with bladder cancer benefit from [68 Ga]Ga-FAPI-46 PET/CT prior to radical cystectomy for locoregional lymph node staging. MATERIALS AND METHODS: Eighteen patients underwent [68 Ga]Ga-FAPI-46 PET/CT for evaluation of lymph node (LN) status in predefined LN regions. Two hundred twenty-nine intraoperatively removed LN served as histopathological reference standard. RESULTS: Urothelial carcinoma (UC) spread was found in ten LN in seven different regions (14.3%). Hereby, [68 Ga]Ga-FAPI-46 PET/CT was positive in four out of seven regions (57.1%) and showed significantly increased FAPI uptake compared to non-pathological regions. In the remaining three out of seven (42.9%) regions, [68 Ga]Ga-FAPI-46 PET/CT was rated negative since no pathological increased FAPI uptake was detected or the proximity of the urinary tract prevented a differentiation from physiological uptake. CT was inconspicuous in these three regions. In total, two FAP-positive LN regions were found without histopathological counterpart. Overall, sensitivity, specificity, positive predictive value, and negative predictive value were 57.1%, 95.2%, 66.7%, and 93.0% for PET imaging. CONCLUSION: In summary, this innovative [68 Ga]Ga-FAPI-46 PET/CT method showed high specificity and negative predictive value in patients with bladder UC with a future potential to optimize therapy planning.

Upstaging after Transurethral Resection of the Bladder for Non-Muscle-Invasive Cancer of the Bladder: Who Is at Highest Risk?

INTRODUCTION: Transurethral resection of the bladder (TUR-BT) is the standard initial treatment and diagnosis of bladder cancer (BC). Of note, upstaging into muscle-invasive disease (MIBC) during re-resection occurs in a significant proportion of patients. This study aimed to define risk factors at initial TUR-BT for upstaging. METHODS: TUR-BT between 2009 and 2021 were retrospectively screened (n = 3,237). We included patients with visible tumors that received their primary and re-TUR-BT at our institution. Upstaging was defined as pathological tumor stage progression into MIBC at re-TUR-BT. Clinicopathological variables were analyzed for the impact on upstaging. RESULTS: Two hundred and sixty-six patients/532 TUR-BTs were included in the final analysis. Upstaging occurred in 7.9% (21/266) patients. Patients with upstaging presented with stroma-invasive and papillary non-muscle-invasive BC at primary resection in 85.7% (18/21) and 14.3% (3/21), respectively. Detrusor muscle at primary TUR-BT was significantly less present in patients with upstaging (4.1 vs. 95.9%; p < 0.001). After multivariate analysis, solid tumor configuration (HR: 4.17; 95% CI: 1.23-14.15; p = 0.022) and missing detrusor muscle at initial TUR-BT (HR: 3.58; 95% CI: 1.05-12.24; p = 0.043) were significant risk factors for upstaging into MIBC. CONCLUSIONS: The current study defined two major risk factors for upstaging: missing detrusor muscle and solid tumor configuration. We propose that a second resection should be performed earlier if these risk factors apply.

Perioperative Outcomes of Same-Session Bilateral vs Unilateral Ureteroscopy for Stone Removal: Results from the GRAND Study.

Background: Same-session bilateral ureteroscopy may reduce the number of surgeries for stone removal but can lead to higher overall complication rates. We aimed to compare same-session bilateral ureteroscopy with unilateral ureteroscopy in terms of perioperative outcomes. Methods: We used the GeRmAn Nationwide inpatient Data (GRAND), provided by the Research Data Center of the Federal Bureau of Statistics (2005-2021). We assessed, through multiple patient-level analyses, severe perioperative complications, mortality, length of hospital stay, hospital revenues, intensive care unit admission, and the evolution of ureteroscopy during the last years in Germany. Results: We included 833,609 patients undergoing either same-session bilateral (n = 6914, 0.8%) or unilateral (n = 826,695, 99.2%) ureteroscopy for stone management. Patients undergoing bilateral ureteroscopy presented worse baseline characteristics. After adjusting for these characteristics, same-session bilateral ureteroscopy, compared to unilateral ureteroscopy, was significantly associated with higher odds of postoperative sepsis (odds ratio [OR]: 2.4, 95% confidence interval [CI]: 2-2.8, p < 0.001), myocardial infarction (OR: 2, 95% CI: 1.03-3.5, p = 0.024), acute kidney disease (OR: 2.8, 95% CI: 2.5-3.2, p < 0.001), transfusion (OR: 4.2, 95% CI: 3.6-4.8, p < 0.001), urinary tract infection (OR: 1.6, 95% CI: 1.5-1.7, p < 0.001), intensive care unit admission (OR: 1.9, 95% CI: 1.6-2.3, p < 0.001), and mortality (OR: 3.1, 95% CI: 2.1-4.5, p < 0.001). Similarly, the length of hospital stay was longer, and the in-hospital costs were higher (p < 0.001) after same-session bilateral ureteroscopy. Interestingly, the annual cases of ureteroscopy have undergone about a threefold increase in the last 17 years. Conclusions: The present real-world data demonstrate that same-session bilateral ureteroscopy leads to higher rates of perioperative myocardial infarction, acute kidney disease, transfusion, urinary tract infections, sepsis, and intensive care unit admission, as well as to increased length of hospital stay, costs, and inpatient mortality compared to unilateral ureteroscopy.

Oncological impact of perioperative blood transfusion in bladder cancer patients undergoing radical cystectomy: Do we need to consider storage time of blood units, donor age, or gender matching?

BACKGROUND: The oncological impact of perioperative blood transfusions (PBTs) of patients undergoing radical cystectomy (RC) because of bladder cancer (BCa) has been a controversial topic discussed in recent years. The main cause for the contradictory findings of existing studies might be the missing consideration of the storage time of red blood cell units (BUs), donor age, and gender matching. STUDY DESIGN AND METHODS: We retrospectively analyzed BCa patients who underwent RC in our department between 2004 and 2021. We excluded patients receiving BUs before RC, >10 BUs, or RC in a palliative setting. We assessed the effect of blood donor characteristics and storage time on overall survival (OS) and cancer-specific survival (CSS) through univariate and multivariable Cox regression analysis. We also performed a propensity score matching with patients who received BUs and patients who did not on a 1:1 ratio. RESULTS: We screened 1692 patients and included 676 patients for the propensity score matching. In the multivariable analysis, PBT was independently associated with worse OS and CSS (p < .001). Postoperative transfusions were associated with better OS (p = .004) and CSS (p = .008) compared to intraoperative or mixed transfusions. However, there was no influence of blood donor age, storage time, or gender matching on prognosis. DISCUSSION: In our study of BCa patients undergoing RC, we demonstrate that PBT, especially if administered intraoperatively, is an independent risk factor for a worse prognosis. However, storage time, donor age, or gender matching did not negatively affect oncological outcomes. Therefore, the specific selection of blood products does not promise any benefits.

Perioperative outcomes of penile prosthesis implantation in Germany: results from the GRAND study.

We aimed to assess the recommended annual hospital volume for inflatable penile prosthesis implantation (PPI) and to provide evidence on perioperative outcomes of semi-rigid and inflatable PPI in Germany. We used the GeRmAn Nationwide inpatient Data (GRAND) from 2005 to 2021 and report the largest study to date with 7,222 patients. 6,818 (94.4%) patients underwent inflatable and 404 (5.6%) semi-rigid PPI. Inflatable PPI was significantly associated with shorter length of hospital stay (difference of 2.2 days, 95%CI: 1.6-2.7, p < 0.001), lower odds of perioperative urinary tract infections (5.5% versus 9.2%; OR: 0.58, 95%CI: 0.41-0.84, p = 0.003) and surgical wound infections (1% versus 2.5%; OR: 0.42, 95%CI: 0.22-0.88, p = 0.012) compared to semi-rigid PPI. Overall, 4255 (62.4%) inflatable PPIs were undertaken in low- ( < 20 PPI/year) and 2563 (37.6%) in high-volume ( ≥ 20 PPI/year) centers. High-volume centers were significantly associated with shorter length of hospital stay (difference of 1.4 days, 95%CI: 1.2-1.7, p < 0.001) compared to low-volume centers. Our findings suggest that inflatable PPI leads to a shorter length of hospital stay and lower rates of perioperative urinary tract and surgical wound infections compared to semi-rigid PPI. Patients undergoing surgery in high-volume centers for inflatable PPI are discharged earlier from the hospital.

Penile fractures: the price of a merry Christmas.

OBJECTIVES: To explore whether Christmas might be a risk factor for penile fractures due to the Christmas spirit related to the intimacy and euphoria of these holly jolly days. PATIENTS AND METHODS: We evaluated the incidence of penile fractures during Christmas and New Year's Eve through the GeRmAn Nationwide inpatient Data (GRAND) from the Research Data Center of the Federal Bureau of Statistics (Wiesbaden, Germany). Furthermore, we assessed the impact of COVID-19 on penile fractures and their seasonality. RESULTS: A total of 3,421 patients with a median, interquartile range (IQR) age of 42 (32-51) years had a penile fracture requiring a hospital stay from 2005 to 2021. In all, 40 (1.2%) penile fractures occurred in 51 days of Christmas (from 24/12 to 26/12 in each year). The daily incidence of penile fractures during Christmas was 0.78 with an incidence rate ratio (IRR) of 1.43 (95% confidence interval [CI] 1.05-1.95, P = 0.02). If every day was like Christmas, 43% more penile fractures would have occurred in Germany from 2005 on. Interestingly, only 28 (0.82%) penile fractures occurred during the New Year's Eve period (31/12 to 02/01 from 2005 to 2021). This resulted in an IRR of 0.98 (95% CI 0.69-1.5, P = 0.98) in the New Year's Eve period. Most patients with penile fractures were admitted to hospital at the weekend (n = 1,322; IRR 1.58, 95% CI 1.48-1.69; P < 0.001). Summer was also associated with more penile fractures (n = 929; IRR 1.11, 95% CI 1.03-1.19; P = 0.008). Both the COVID-19 pandemic (n = 385; IRR 1.06, 95% CI 0.95-1.18, P = 0.29) and its lockdown period (n = 93; IRR 1, 95% CI 0.82-1.23; P = 0.96) did not affect the incidence of penile fractures. CONCLUSION: The incidence of penile fractures displays a seasonality. Last Christmas penile fractures occurred more often. This year to save us from tears, we will NOT do something special (the new Christmas hit of the year).

Absence of detrusor muscle in TUR-BT specimen - can we predict who is at highest risk?

INTRODUCTION: As a high-quality TUR-BT is important to ensure adequate treatment for bladder cancer patients, the aim of the current study is to investigate the impact of patient-related, surgical and tumor-specific parameters on detrusor muscle (DM) absence (primary objective) and to assess the impact of DM on the prognosis after a TUR-BT (secondary objective). PATIENTS AND METHODS: Transurethral resection of bladder tumors (TUR-BTs) between 2009 and 2021 were retrospectively screened (n = 3237). We included 2058 cases (1472 patients) for the primary and 472 patients for secondary objective. Clinicopathological variables including tumor size, localization, multifocality, configuration, operation time and skill-level of the urologist were assessed. We analyzed predictors for missing DM and prognostic factors for recurrence-free survival (RFS) for the complete cohort and subgroups. RESULTS: DM was present in 67.6% (n = 1371/2058). Surgery duration (continuous, minutes) was an independent predictor for absence of DM in the complete cohort (OR:0.98, r:0.012, 95%CI:0.98-0.99, p = 0.001). Other significant risk factors for missing DM were papillary tumors (OR:1.99, r:0.251, 95%CI:1.22-3.27, p = 0.006) in the complete cohort and bladder-roof and posterior-bladder-wall localization for re-resections. Absence of DM in high-grade BC correlated with reduced RFS (HR:1.96, 95%CI:1.0-3.79, p = 0.045). CONCLUSION: Sufficient time for a TUR-BT is mandatory to assure DM in the TUR-BT specimen. Also, cases with more difficult locations of bladder tumors should be performed with utmost surgical diligence and endourological training should incorporate how to perform such operations. Of note, DM correlates with improved oncological prognosis in high-grade BC.

Complications After Radical Cystectomy: A Systematic Review and Meta-analysis of Randomized Controlled Trials with a Meta-regression Analysis.

CONTEXT: Radical cystectomy is considered a procedure of high complexity with a relative high complication rate. OBJECTIVE: To systematically summarize the literature regarding the complications of radical cystectomy and the factors that contribute to them. EVIDENCE ACQUISITION: We searched MEDLINE/PubMed, ClinicalTrials.gov, and Cochrane Library, according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines for randomized controlled trials (RCTs) on complications related to radical cystectomy. EVIDENCE SYNTHESIS: A total of 3766 studies were screened, and 44 studies were included in this systematic review and meta-analysis. Complications following radical cystectomy are quite common. The most common complications were gastrointestinal complications (20%), infectious complications (17%), and ileus (14%). The majority of complications occurring were Clavien I-II (45%). Specific measurable patient factors are related to certain complications and can be used to stratify risk and assist in preoperative counseling, while proper design of high-quality RCTs may better reflect real-life complication rates. CONCLUSIONS: In our study, RCTs with a low risk of bias had higher complication rates than studies with a high risk of bias, underlining the need for further improvement on complication reporting in order to refine surgical outcomes. PATIENT SUMMARY: Radical cystectomy is usually followed by high complication rates, which affect patients and are, in turn, strongly associated with patients' preoperative health status.

Enucleation of the prostate as retreatment for recurrent or residual benign prostatic obstruction: a systematic review and a meta-analysis.

BACKGROUND: Anatomical endoscopic enucleation of the prostate (AEEP) is recommended for first line surgical treatment of benign prostatic obstruction (BPO) caused by moderate and large prostatic adenoma. However, its role in the retreatment setting after failed previous surgical treatment for BPO remains uncaptured. In this scope, we performed a systematic review and meta-analysis aiming to assess the safety and efficacy of AEEP in the retreatment setting. METHODS: We searched PubMed, Cochrane Library and Embase databases from inception to March 2022 for prospective or retrospective studies involving patients undergoing prostatic enucleation for recurrent or residual BPO after previous standard or minimally invasive surgical treatments for BPO. Based on data availability, we performed a meta-analysis comparing AEEP in patients with recurrent or residual BPO versus AEEP for primary BPO. PROSPERO: CRD42022308941). RESULTS: We included 15 studies in the systematic review and 10 in the meta-analysis (6553 patients, 841 with recurrent or residual BPO and 5712 with primary BPO). All included studies involved patients undergoing HoLEP or ThuLEP. In terms of Qmax, post-void residual, International Prostate Symptom Score, removed adenoma, operative time, duration of catheterization and hospital stay, as well as complications, HoLEP for recurrent or residual BPO was equally effective compared to HoLEP for primary BPO up to 1 year postoperatively. Importantly, the beneficial effect of HoLEP on the retreatment setting was observed after previous standard or minimally invasive surgical treatments for BPO. The overall strength of evidence for all outcomes was deemed very low. CONCLUSIONS: HoLEP may be safely and effectively used in experienced hands for the surgical treatment of recurrent or residual BPO in patients with large or moderate prostates following previous open, endoscopic or minimally invasive surgical treatment for BPO.

Intratumoral Heterogeneity of Molecular Subtypes in Muscle-invasive Bladder Cancer-An Extensive Multiregional Immunohistochemical Analysis.

BACKGROUND: Molecular bladder cancer (BC) subtypes define distinct biological entities and were shown to predict treatment response in neoadjuvant and adjuvant settings. The extent of intratumoral heterogeneity (ITH) might affect subtyping of individual patients. OBJECTIVE: To comprehensively assess the ITH of molecular subtypes in a cohort of muscle-invasive BC. DESIGN, SETTING, AND PARTICIPANTS: A total of 251 patients undergoing radical cystectomy were screened. Three cores of the tumor center (TC) and three cores of the invasive tumor front (TF) of each patient were assembled in a tissue microarray. Molecular subtypes were determined employing 12 pre-evaluated immunohistochemical markers (FGFR3, CCND1, RB1, CDKN2A, KRT5, KRT14, FOXA1, GATA3, TUBB2B, EPCAM, CDH1, and vimentin). A total of 18 072 spots were evaluated, of which 15 002 spots were assessed based on intensity, distribution, or combination. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Allocation to one of five different molecular subtypes-urothelial like, genomically unstable, small-cell/neuroendocrine like, basal/squamous cell carcinoma like, and mesenchymal like-was conducted for each patient for the complete tumor, individual cores, TF, and TC separately. The primary objective was to assess the ITH between the TF and TC (n = 208 patients). The secondary objective was the evaluation of multiregion ITH (n = 191 patients). An analysis of the composition of ITH cases, association with clinicopathological parameters, and prognosis was conducted. RESULTS AND LIMITATIONS: ITH between the TF and TC was seen in 12.5% (n = 26/208), and ITH defined by at least two different subtypes of any location was seen in 24.6% (n = 47/191). ITH was more frequent in locally confined (pT2) versus advanced (pT ≥3) BC stages (38.7% vs 21.9%, p = 0.046), and pT4 BC presented with significantly more basal subtypes than pT2 BC (26.2% vs 11.5%, p = 0.049). In our cohort, there was no association of subtype ITH with prognosis or accumulation of specific molecular subtypes in ITH cases. The key limitations were missing transcriptomic and mutational genetic validation as well as investigation of ITH beyond subtypes. CONCLUSIONS: Several molecular subtypes can be found in nearly every fourth case of muscle-invasive BC, when using immunohistochemistry. ITH must be given due consideration for subtype-guided strategies in BC. Genomic validation of these results is needed. PATIENT SUMMARY: Different molecular subtypes can be found in many cases of muscle-invasive bladder cancer. This might have implications for individualized, subtype-based therapeutic approaches.

Assessment of single-probe dual-energy lithotripters in percutaneous nephrolithotomy: a systematic review and meta-analysis of preclinical and clinical studies.

PURPOSE: To evaluate the safety and efficacy of single-probe dual-energy (SPDE) lithotripters in patients undergoing percutaneous nephrolithotripsy (PCNL) through a systematic review and meta-analysis. METHODS: We searched PubMed, Cochrane Library, Scopus and Embase databases until July 2022 for any preclinical or clinical studies, exploring the safety and efficacy of different SPDE lithotripters in patients undergoing PCNL. We performed a meta-analysis to compare stone-free rate, bleeding, or other complications and mean operative time between SPDE lithotripters and other lithotripters (PROSPERO: CRD42021285631). RESULTS: We included 16 studies (six preclinical, seven observational and three randomized with 625 participants) in the systematic review and four in the meta-analysis. Preclinical studies suggest that SPDE lithotripters are safe and effective for the management of renal stones. Among clinical studies, four studies assessed Trilogy with no comparative arm, two compared Trilogy or ShockPulse with a dual-probe dual-energy lithotripter, two compared Trilogy with a laser, one compared ShockPulse with a pneumatic lithotripter, and one directly compared Trilogy with ShockPulse. Comparing SPDE lithotripters to other lithotripters, no significant differences were demonstrated in stone free rate (OR 1.13, 95% CI 0.53-2.38, I2 = 0%), postoperative blood transfusion (OR 1.33, 95% CI 0.34-5.19, I2 = 0%), embolization (OR 0.45, 95% CI 0.02-12.06), operative time (WMD: 2.82 min, 95% CI -7.31-12.95, I2 = 78%) and postoperative complications based on the Clavien-Dindo classification. CONCLUSIONS: SPDE lithotripters represent a promising treatment modality for patients requiring PCNL. Despite the initial encouraging findings of preclinical and isolated clinical studies, it seems that Trilogy or ShockPulse provide similar efficiency compared to older generation devices.

Radiomics Signature Using Manual Versus Automated Segmentation for Lymph Node Staging of Bladder Cancer.

BACKGROUND: Bladder cancer (BC) treatment algorithms depend on accurate tumor staging. To date, computed tomography (CT) is recommended for assessment of lymph node (LN) metastatic spread in muscle-invasive and high-risk BC. However, the diagnostic efficacy of radiologist-evaluated CT imaging studies is limited. OBJECTIVE: To evaluate the performance of quantitative radiomics signatures for detection of LN metastases in BC. DESIGN, SETTING, AND PARTICIPANTS: Of 1354 patients with BC who underwent radical cystectomy (RC) with lymphadenectomy who were screened, 391 with pathological nodal staging (pN0: n = 297; pN+: n = 94) were included and randomized into training (n = 274) and test (n = 117) cohorts. Pelvic LNs were segmented manually and automatically. A total of 1004 radiomics features were extracted from each LN and a machine learning model was trained to assess pN status using histopathology labels as the ground truth. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Radiologist assessment was compared to radiomics-based analysis using manual and automated LN segmentations for detection of LN metastases in BC. Statistical analysis was performed using the receiver operating characteristics curve method and evaluated in terms of sensitivity, specificity, and area under the curve (AUC). RESULTS AND LIMITATIONS: In total, 1845 LNs were manually segmented. Automated segmentation correctly located 361/557 LNs in the test cohort. Manual and automatic masks achieved an AUC of 0.80 (95% confidence interval [CI] 0.69-0.91; p = 0.64) and 0.70 (95% CI: 0.58-0.82; p = 0.17), respectively, in the test cohort compared to radiologist assessment, with an AUC of 0.78 (95% CI 0.67-0.89). A combined model of a manually segmented radiomics signature and radiologist assessment reached an AUC of 0.81 (95% CI 0.71-0.92; p = 0.63). CONCLUSIONS: A radiomics signature allowed discrimination of nodal status with high diagnostic accuracy. The model based on manual LN segmentation outperformed the fully automated approach. PATIENT SUMMARY: For patients with bladder cancer, evaluation of computed tomography (CT) scans before surgery using a computer-based method for image analysis, called radiomics, may help in standardizing and improving the accuracy of assessment of lymph nodes. This could be a valuable tool for optimizing treatment options.