Mucomucosal anastomotic non-transecting augmentation (MANTA) urethroplasty: a ventral modification for obliterative strictures.

OBJECTIVES: To present a surgical modification for the repair of bulbar urethral strictures containing short, highly obliterative segments and report on long-term objective and patient-reported outcomes. PATIENTS AND METHODS: We considered patients undergoing bulbar buccal mucosal graft urethroplasty (BMGU) between July 2016 and December 2019. Eligibility criteria for mucomucosal anastomotic non-transecting augmentation (MANTA) urethroplasty were strictures of ≥2 cm with an obliterative segment of ≤1.5 cm. The stricture is approached ventrally to avoid extensive dissection and mobilisation. Dorsally, the scar is superficially excised and the spongiosum is left intact. Dorsal mucomucosal anastomosis is complemented by ventral onlay graft. Perioperative characteristics were prospectively collected including uroflowmetry data and validated patient-reported outcome measures on voiding, erectile, and continence function. We evaluated functional follow-up, incorporating patient-reported (lower urinary tract symptoms [LUTS] score) and functional success. Recurrence was defined as need of re-treatment. RESULTS: Of 641 men treated with anterior BMGU, 54 (8.4%) underwent MANTA urethroplasty. Overall, 26 (48%) and 45 (83%) had a history of dilatation and urethrotomy, respectively, and 14 (26%) were redo cases. Location was bulbar in 38 (70%) and penobulbar in 16 patients (30%), and the mean (SD) graft length was 4.5 (1.4) cm. At a median (interquartile range) follow-up of 41 (27-53) months, the functional success rate was 93%. Whereas the median LUTS score significantly improved from baseline to postoperatively (13 vs 3.5; P < 0.001), there was no change in erectile function (median International Index of Erectile Function - erectile function domain score 27 vs 24) or urinary continence (median International Consultation on Incontinence Questionnaire - Urinary Incontinence Short Form sum score 0 vs 0; all P ≥ 0.4). All patients were 'satisfied' (27%) or 'very satisfied' (73%) with the outcome of their operation. CONCLUSION: With excellent long-term objective and patient-reported outcomes, MANTA urethroplasty adds to the armamentarium for long bulbar strictures with a short obliterative segment.

European Association of Urology Guidelines on Testicular Cancer: 2023 Update.

CONTEXT: Each year the European Association of Urology (EAU) produce a document based on the most recent evidence on the diagnosis, therapy, and follow-up of testicular cancer (TC). OBJECTIVE: To represent a summarised version of the EAU guidelines on TC for 2023 with a focus on key changes in the 2023 update. EVIDENCE ACQUISITION: A multidisciplinary panel of TC experts, comprising urologists, medical and radiation oncologists, and pathologists, reviewed the results from a structured literature search to compile the guidelines document. Each recommendation in the guidelines was assigned a strength rating. EVIDENCE SYNTHESIS: For the 2023 EAU guidelines on TC, a review and restructure were undertaken. The key changes incorporated in the 2023 update include: new supporting text regarding venous thromboembolism prophylaxis in males with metastatic germ cell tumours receiving chemotherapy; quality of life after treatment; an update of the histological classifications and inclusion of the World Health Organization 2022 pathological classification; inclusion of the revalidation of the 1997 International Germ Cell Cancer Collaborative Group prognostic risk factors; and a new section covering oncology treatment protocols. CONCLUSIONS: The 2023 version of the EAU guidelines on TC include the highest available scientific evidence to standardise the management of TC. Better stratification and optimisation of treatment modalities will continue to improve the high survival rates for patients with TC. PATIENT SUMMARY: This article presents a summary of the European Association of Urology guidelines on testicular cancer published in 2023 and includes the latest recommendations for management of this disease. The guidelines are a valuable resource that may help patients in understanding treatment recommendations.

The Natural History of Renal-Cell Carcinoma with Sarcomatoid Differentiation, a Stage-by-Stage Analysis.

BACKGROUND: Sarcomatoid differentiation in patients diagnosed with renal cell carcinoma (sRCC) imply aggressive behavior and often metastatic disease at the time of diagnosis. We aim to examine the overall survival (OS) in patients with sRCC using the National Cancer Database (NCDB). MATERIALS AND METHODS: We identified patients diagnosed with sRCC between 2010-2015. We employed Kaplan-Meier curves and multivariable Cox proportional hazards regression models to examine the impact of several potential risk factors on OS in patients diagnosed with sRCC. RESULTS: In total, 8582 patients with renal cancer were found to have sarcomatoid differentiation, with 4105 patients (47.8%) being diagnosed with AJCC stage IV disease. The median OS was 17.2 months (IQR 5.4, 68.7 months). Compared to patients who did not undergo surgery, OS was significantly longer in patients undergoing partial or total nephrectomy across all stages. This result remained consistent on multivariable Cox proportional hazards regression adjusting for patient and tumor characteristics (Surgery: Hazard ratio 0.54, 95%Confidence interval 0.43 - 0.68, P < .001). CONCLUSION: In our cohort sRCC was found to have an unfavorable median OS, which was mainly caused by the high number of cases diagnosed with late-stage disease. Additionally, surgery was associated with favorable OS across all stages. This study supports the notion that surgical therapy, even in the setting of cytoreductive surgery, provides a survival benefit in patients with sRCC.

Radiological features characterising indeterminate testes masses: a systematic review and meta-analysis.

CONTEXT: The use of scrotal ultrasonography (SUS) has increased the detection rate of indeterminate testicular masses. Defining radiological characteristics that identify malignancy may reduce the number of men undergoing unnecessary radical orchidectomy. OBJECTIVE: To define which SUS or scrotal magnetic resonance imaging (MRI) characteristics can predict benign or malignant disease in pre- or post-pubertal males with indeterminate testicular masses. EVIDENCE ACQUISITION: This systematic review was conducted in accordance with Cochrane Collaboration guidance. Medline, Embase, Cochrane controlled trials and systematic reviews databases were searched from (1970 to 26 March 2021). Benign and malignant masses were classified using the reported reference test: i.e., histopathology, or 12 months progression-free radiological surveillance. Risk of bias was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 tool (QUADAS-2). EVIDENCE SYNTHESIS: A total of 32 studies were identified, including 1692 masses of which 28 studies and 1550 masses reported SUS features, four studies and 142 masses reported MRI features. Meta-analysis of different SUS (B-mode) values in post-pubertal men demonstrated that a size of ≤0.5 cm had a significantly lower odds ratio (OR) of malignancy compared to masses of >0.5 cm (P < 0.001). Comparison of masses of 0.6-1.0 cm and masses of >1.5 cm also demonstrated a significantly lower OR of malignancy (P = 0.04). There was no significant difference between masses of 0.6-1.0 and 1.1-1.5 cm. SUS in post-pubertal men also had a statistically significantly lower OR of malignancy for heterogenous masses vs homogenous masses (P = 0.04), hyperechogenic vs hypoechogenic masses (P < 0.01), normal vs increased enhancement (P < 0.01), and peripheral vs central vascularity (P < 0.01), respectively. There were limited data on pre-pubertal SUS, pre-pubertal MRI and post-pubertal MRI. CONCLUSIONS: This meta-analysis identifies radiological characteristics that have a lower OR of malignancy and may be of value in the management of the indeterminate testis mass.

Placebo Response in Patients with Oral Therapy for Overactive Bladder: A Systematic Review and Meta-analysis.

CONTEXT: The role of a placebo response in the management of overactive bladder (OAB) remains unclear. OBJECTIVE: The aim of this review is to methodically study the placebo response extracted from the control arms of randomized clinical trials assessing therapy in patients with OAB. EVIDENCE ACQUISITION: Medline (PubMed), The Cochrane Library, EMBASE, and Scopus were searched to identify randomized controlled trials (RCTs) published until September 2019. Randomized placebo-controlled trials investigating oral drug therapy for OAB were included. The articles were critically appraised by two reviewers. The primary outcomes were the placebo response in the main patient-reported urinary outcomes together with assessing the impact of patient demographic factors on the placebo response. EVIDENCE SYNTHESIS: The initial search resulted in 1982 records after reviewing the titles and abstracts, and reference lists of other systematic reviews; 57 studies with an overall estimated 12 901 patients were included in the meta-analysis. The included studies were of overall high/acceptable quality. The standardized mean difference was -0.45 (95% confidence interval [CI] -0.51 to -0.40; p<0.001) for daily micturition episodes, -0.33 (95% CI -0.42 to -0.24; p<0.001) for daily nocturia episodes, -0.46 (95% CI -0.55 to -0.37; p<0.001) for urgency urinary incontinence episodes, -0.50 (95% CI -0.61 to -0.39; p<0.001) for daily urgency episodes, -0.51 (95% CI -0.60 to -0.43; p<0.001) for daily incontinence episodes, and 0.25 (95% CI 0.211-0.290; p<0.001) for volume voided per micturition. The meta-regression of age-related impact of the placebo response on nocturia showed a slope of -0.02 (p<0.001). CONCLUSIONS: Placebo has a statistically significant effect on improving symptoms and signs associated with OAB; this effect is age dependent. However, there is no consensus on what change of OAB symptoms and signs is clinically meaningful for the affected patient. Taken together, the placebo response seems to be non-negligible in OAB, supporting the need for placebo control in RCTs. PATIENT SUMMARY: Placebo is an inert treatment method often used in clinical research for comparison with active treatment. However, studies show that placebo has an effect of its own. A placebo response means the total improvement resulting from receiving a placebo. In our study, placebo had a significant role in improving the symptoms of overactive bladder.

Treatment Options and Outcomes for Men with Penile Intraepithelial Neoplasia: A Systematic Review.

Penile intraepithelial neoplasia (PeIN) is a rare skin condition with potential to progress to invasive penile cancer. We performed a systematic review of treatment options and outcomes for PeIN. Topical agents showed response and recurrence rates of 40-100% and 20% for imiquimod, and 48-74% and 11% for 5-fluorouracil, respectively. Discontinuation of topical agents because of side effects was observed in 12% of cases. Response rates for laser therapies were 52-100%, with recurrence in 7-48% of cases and a change in penile sensitivity in 50%. Circumcision cleared preputial PeIN. Rates of recurrence after surgical treatment of glans PeIN were 25% for wide local excision, 4% for Mohs surgery, 5% for total glans resurfacing, and 10% for glansectomy. There are limited data on factors predictive of treatment response and on sequencing of treatment options. PATIENT SUMMARY: Several treatment options are available for men with precancerous lesions of the foreskin or glans. Close follow-up is necessary as lesions can recur or progress to invasive penile cancer.

Treatment and Outcome of Metastatic Renal Cell Carcinoma With Sarcomatoid Differentiation: A Single-Center, Real-World Analysis of Retrospective Data.

Background: Sarcomatoid differentiation/histology of renal cell carcinoma (sRCC) in patients with metastatic renal cell carcinoma (mRCC) is still underresearched in current therapy regimes. We aimed to evaluate the impact of sRCC on outcomes in patients with mRCC treated with tyrosine kinase inhibitors (TKIs). Methods: We collected complete data of 262 consecutive mRCC patients from our institutional database for this retrospective study. All patients were treated with TKIs within a single or multimodal treatment approach. All analyses were adjusted for the presence of sRCC. Descriptive statistics as well as uni- and multivariable outcome metrics, including progression-free (PFS) and overall survival (OS) as endpoints were performed. Results: Overall, 18 patients had sRCC (6.9%). Patients with sRCC had more often clear-cell histology (p = 0.047), a higher T-stage (p = 0.048), and underwent cytoreductive nephrectomy more frequently (p < 0.001). The most common first-line TKIs were Sunitinib (65.6%), Sorafenib (19.5%), and Pazopanib (10.3%), respectively. At a median follow-up of 32 months, patients with sRCC had significantly reduced PFS (p = 0.02) and OS (p = 0.01) compared to patients without sRCC. In multivariable analyses that adjusted for the effects of standard mRCC predictors, the sarcomatoid feature retained its independent association with inferior PFS (HR: 2.39; p = 0.007) and OS (HR: 2.37; p = 0.001). This association remained statistically significant in subgroup analyses of patients with Sunitinib as first-line therapy (PFS p < 0.001; OS: p < 0.001). Conclusion: Despite its rare occurrence, our findings confirm sRCC as a powerful predictor for inferior outcomes in mRCC treated with targeted therapies. This suggests a need for more tailored treatment strategies in patients harboring mRCC with sarcomatoid histology to improve oncological outcomes.

Recommendations to Balance Benefits and Risks Of Thromboprophylaxis and to Avoid Central Venous-access Devices During First-line Chemotherapy in Men with Metastatic Germ Cell Tumors: The European Association Of Urology Testicular Cancer Panel Position in 2021.

Men with metastatic germ cell tumors undergoing chemotherapy are at high risk of venous thromboembolic events and low risk of bleeding. A central venous-access device should be avoided whenever possible. Thromboprophylaxis may be prescribed after balancing the risks and benefits for each individual patient.

Predictive value of De Ritis ratio in metastatic renal cell carcinoma treated with tyrosine-kinase inhibitors.

BACKGROUND: Predictive markers can help tailor treatment to the individual in metastatic renal cell carcinoma (mRCC). De Ritis ratio (DRR) is associated with oncologic outcomes in various solid tumors. OBJECTIVE: To assess the value of DRR in prognosticating survival in mRCC patients treated with tyrosine-kinase inhibitors (TKI). METHODS: Overall, 220 mRCC patients treated with TKI first-line therapy were analyzed. An optimal cut-off point for DRR was determined with Youden's J. We used multiple strata for DRR, performed descriptive, Kaplan-Meier and multivariable Cox-regression analyses to assess associations of DRR with progression-free (PFS) and overall survival (OS). RESULTS: Patients above the optimal cut-off point for DRR of ≥ 1.58 had fewer liver metastases (p = 0.01). There was no difference in PFS (p > 0.05) between DRR groups. DRR above the median of 1.08 (HR 1.42; p = 0.03), DRR ≥ 1.1(HR 1.44; p = 0.02), ≥ 1.8 (HR 1.56; p = 0.03), ≥ 1.9 (HR 1.59; p = 0.02) and ≥ 2.0 (HR 1.63; p = 0.047) were associated with worse OS. These associations did not remain after multivariable adjustment. In the intermediate MSKCC group, DRR was associated with inferior OS at cut-offs ≥ 1.0 (HR 1.78; p = 0.02), ≥ 1.1 (HR 1.81; p = 0.01) and above median (HR 1.88; p = 0.007) in multivariable analyses. In patients with clear-cell histology, DRR above median (HR 1.54; p = 0.029) and DRR ≥ 1.1 (HR 1.53; p = 0.029) were associated with OS in multivariable analyses. CONCLUSION: There was no independent association between DRR and survival of mRCC patients treated with TKI in the entire cohort. However, OS of patients with intermediate risk and clear-cell histology were affected by DRR. DRR could be used for tailored decision-making in these subgroups.

Learning benefits of live surgery and semi-live surgery in urology-informing the debate with results from the International Meeting of Reconstructive Urology (IMORU) VIII.

PURPOSE: To analyze the perceived learning opportunities of participants of the International Meeting on Reconstructive Urology (IMORU) VIII for both live surgery demonstrations (LSD) and semi-live surgery demonstrations (SLSD). Safety and educational efficacy of LSD and SLSD at live surgery events (LSE) have been debated extensively, however, objective data comparing learning benefits are missing. METHODS: We conducted a detailed survey, which employed the Kirkpatrick model, a well-established assessment method of training models, to investigate participants preferences as well as the learning benefit of LSE. Furthermore, we employed an audience response system and the Objective Structured Assessment of Technical Skills (OSATS), a well-established assessment method of surgery skills, to let our participants rate the perceived learning opportunity of LSD and SLSD. RESULTS: Of 229 participants at the IMORU VIII, 39.7% returned our questionnaires. 90% stated that they prefer LSD. On all levels of Kirkpatrick's training evaluation model, the IMORU received high ratings, suggesting a high learning benefit. For the assessment of OSATS, a total of 23 surgical cases were evaluable. For all six utilized items, LSD scored significantly better ratings than SLSD. CONCLUSION: Our study suggests that there is still a rationale for LSD, as participants attributed a statistically significant higher learning benefit to LSD over SLDS. Evaluation of the survey showed that for LSE such as the IMORU VIII, a high learning benefit can be expected. Considering that most of our participants are active surgeons with high caseloads, their opinion on the educational value of LSE is of high relevance.

The significance of De Ritis ratio in patients with radiation-recurrent prostate cancer undergoing salvage radical prostatectomy.

OBJECTIVE: To evaluate the clinical prognostic value of preoperative serum De Ritis ratio (DRR; aspartate aminotransferase/alanine aminotransferase) on postoperative survival outcomes in patients with radiation-recurrent prostate cancer (PCa) who underwent salvage radical prostatectomy (SRP). PATIENTS AND METHODS: A retrospective review was conducted of patients with radiation-recurrent PCa who underwent SRP in five tertiary referral centres from 2007 to 2015. An increased preoperative serum DRR was defined as ≥1.35. The association between DRR and postoperative outcomes was tested. Multivariate Cox analyses were performed to identify the independent predictors of biochemical recurrence (BCR), metastases-free survival (MFS), overall survival (OS), and cancer-specific survival (CSS). RESULTS: Overall 214 patients underwent SRP, of them 98 (45.8%) with a high serum DRR were included in the study. In a multivariate analysis high DRR was an independent predictor of BCR [hazard ratio (HR) 1.79, 95% confidence interval (CI) 1.16-2.78; P = 0.009]. No significant association was found between preoperative DRR and MFS (HR 1.32, 95% CI 0.53-3.30; P = 0.55), OS (HR 2.35, 95% CI 0.84-6.57; P = 0.10), and CSS (HR 3.36, 95% CI 0.65-17.35; P = 0.15). CONCLUSION: Increased preoperative serum DRR is associated with the development of BCR in patients with radiation-recurrent PCa who underwent SRP. DRR might serve as an early indicator of BCR, which may facilitate recognition of potential relapse and could translate into more intense follow-up and even salvage therapy in selected patients. ABBREVIATIONS: ADT: androgen-deprivation therapy; BCR, biochemical recurrence; BCRFS: BCR-free survival; CSS: cancer-specific survival; DRR: De Ritis ratio; HR: hazard ratio; MFS: metastasis-free survival; PCa: Prostate Cancer; OS: overall survival; PLND: pelvic lymph node dissection; (EB)RT: (external beam) radiotherapy; SRP: salvage radical prostatectomy.

The impact of cytoreductive nephrectomy on survival outcomes in patients treated with tyrosine kinase inhibitors for metastatic renal cell carcinoma in a real-world cohort.

BACKGROUND: Tyrosine kinase inhibitor therapy (TKI) has changed the treatment paradigm of metastatic renal cell carcinoma (mRCC). The recent CARMENA and SURTIME trials challenged the role of the cytoreductive nephrectomy (CN). OBJECTIVE: To assess the impact of CN prior to TKI therapy in patients with mRCC in a real-world setting. METHODS: Overall, 262 consecutive patients with mRCC were treated with CN plus TKI or TKI only at our institution between 2000 and 2016. Patients with prior immunotherapy or metastasectomy were excluded. Multiple imputation and inverse probability of treatment weighting (IPTW) were performed to account for missing values and imbalances between the treatment groups, respectively. Unadjusted and adjusted Kaplan-Meier estimates were used to determine differences in progression-free (PFS), overall (OS), and cancer-specific survival (CSS). RESULTS: Overall, 104 (40%) patients received CN before TKI treatment. Most frequent first line therapy was Sunitinib (66%), followed by Sorafenib (20%) and Pazopanib (10%). After adjustment with IPTW, there was no difference in PFS, CSS, and OS (all P > 0.05) between the treatment groups. In subgroup analyses, CSS was improved when CN was performed in patients with sarcomatoid features and clear cell histology (P = 0.04 and P = 0.03) and PFS was improved in patients with clear cell histology when CN was performed [0.04]). CN did not improve OS in any subgroup analysis. CONCLUSION: The role of CN remains controversial. We found no difference in survival outcomes between patients treated with and without CN before TKI therapy. However, CN was associated with improved survival in specific patient subgroups. Tailored, individualized treatment is key to further improve oncological outcomes for mRCC.

The clinical pharmacology of the medical treatment for overactive bladder in adults.

INTRODUCTION: Overactive bladder is a prevalent symptom complex that affects the patient's quality of life. Any disruption between the neuronal micturition pathway can lead to bladder overactivity. Neurogenic causes, myogenic causes, aging, bladder outlet obstruction, sex, and psychological factors are some of the factors contributing to bladder overactivity. The complaint of any symptoms of OAB, which is highly prevalent and affects overall QOL, often needs therapeutic interventions. When conservative therapy methods fail, the addition of medications is recommended. The most commonly used agents for the treatment of OAB are antimuscarinic drugs. New classes of drugs, such as beta-3 agonists, have enriched our pharmacologic armamentarium. AREAS COVERED: In this review, with a special focus on oral pharmacological treatments, we discussed the definition, etiology, symptoms, diagnosis, and management of OAB. EXPERT OPINION: OAB is a multifactorial condition with every patient presenting with a different collection of symptoms and signs. Medical therapies should be given in conjunction with behavioral therapies. Using high or low doses, flexible doses, and stopping or changing the medications are interchangeable strategies based on the level of treatment efficacy and patient satisfaction.

Prognostic Value of Gleason Score at Positive Surgical Margin in Prostate Cancer: A Systematic Review and Meta-analysis.

The individual clinical significance of a positive surgical margin (PSM) after radical prostatectomy has remained controversial. Studies have suggested that the Gleason grade (GG) at the PSM could improve predictive accuracy and decision making. Our objective was to systematically review the reported data to determine the effect of the GG at the PSM on the prognosis after radical prostatectomy. A systematic review was conducted by searching MEDLINE/PubMed for studies reported by June 2019 in accordance with the Preferred Reporting Items for Systematic Review statement. The keywords used included prostate cancer, radical prostatectomy, positive surgical margin, Gleason score, and/or Gleason grade. After a systematic literature review, 10 studies were included, comprising 14,108 patients, of whom 2454 (17.4%) had a PSM and 428 (14%) eventually experienced biochemical recurrence (BCR) within a median follow-up of 18 to 156 months. Data on neoadjuvant or adjuvant therapy were not estimable. In a meta-analysis, GG4 at PSM was significantly associated with BCR compared with GG3 (pooled hazard ratio, 1.87; 95% confidence interval, 1.53-2.28; z = 6.16). The Cochrane Q test (χ2 = 5.88; P = .318) and I2 test (I2 = 15.0%) showed that no significant heterogeneity was present. GG4 at a PSM is a feature of biologically and clinically aggressive prostate cancer that is associated with a significant increase risk of BCR. GG at PSM should be recorded in each pathological report. Given this adverse prognostic value patients with GG4 at the PSM should be considered for multimodal therapy such as radiotherapy.

Prognostic role of preoperative De Ritis ratio in upper tract urothelial carcinoma treated with nephroureterectomy.

PURPOSE: To validate the predictive and prognostic role of the De Ritis ratio in patients with upper tract urothelial carcinoma (UTUC) treated with radical nephroureterectomy in a large multi-institutional cohort. MATERIALS AND METHODS: The preoperative De Ritis ratio was assessed in a multi-institutional cohort of 2,492 patients. An altered De Ritis ratio was defined as a ratio >1.35. Logistic regression analyses were performed to assess the association of the De Ritis ratio with advanced disease. The association of the De Ritis ratio with survival outcomes was evaluated using Cox proportional hazards regression models. RESULTS: An altered De Ritis ratio was observed in 985 (41.5%) patients; it was associated with a more advanced pathological features. In a preoperative model, the De Ritis ratio was an independent predictive factor for the presence of lymph node metastasis and muscle-invasive and nonorgan-confined disease (P < 0.05). Compared to patients with a normal De Ritis ratio, those with an altered De Ritis ratio had worse recurrence free (P <0.0001), cancer specific (P = 0.0003), and overall survival (P = 0.0014) in the Kaplan-Meier analyses. In the multivariable analyses that was adjusted for the effects of standard clinicopathologic features, the De Ritis ratio did not retain its independent prognostic value. CONCLUSIONS: In UTUC, the preoperative De Ritis ratio is associated with adverse clinicopathologic features and independently predicts features of biologically and clinically aggressive UTUC. Therefore, it might be useful to incorporate the De Ritis ratio into prognostic tools in selecting appropriate treatment strategies.

The prognostic value of the urokinase-plasminogen activator system (uPA) in bladder cancer patients treated with radical cystectomy (RC).

PURPOSE: Urokinase-plasminogen activator (uPA), its receptor (uPAR), and the plasmin-activator inhibitor type 1 (PAI-1) have been associated with oncologic outcomes in various malignancies and could help identify bladder cancer (BC) patients treated with radical cystectomy (RC) who are likely to benefit from intensification of therapy to prevent disease progression. Our aim was to assess the value of uPA, uPAR, and PAI-1 for prognosticating survival outcomes of patients treated with RC for BC. MATERIALS AND METHODS: Tumor specimens from 272 consecutive patients treated with RC for advanced BC were assessed with immunohistochemical staining for uPA, uPAR, and PAI-1. Overexpression was assessed by pathological image analysis. Kaplan-Meier estimates and multivariable Cox-regression were used to analyze survival. Harrell's C-index was used to assess for clinical impact of the uPA system. RESULTS: uPA, uPAR, and PAI-1 were overexpressed in 48.2%, 51.1%, and 52.2% of patients, respectively. uPA overexpression was associated with lymphovascular invasion (P = 0.034) and nodal status (P = 0.013); PAI-1 overexpression was associated with primary muscle-invasive BC (P = 0.015) and lymphovascular invasion (P = 0.024). uPA, uPAR, and the number of overexpressed markers were all 3 significantly associated with shorter overall recurrence-free-, distant recurrence-free-, and cancer-specific survival. In multivariable analyses, uPA overexpression remained associated with shorter recurrence-free survival (hazard ratio [HR] = 1.79; P = 0.036) in the entire cohort, in patients without lymph node metastasis (HR = 1.98; P = 0.018) and those with nonorgan-confined disease (HR = 1.98; P = 0.022). uPAR overexpression was associated with shorter recurrence-free survival in patients without lymph node metastasis (HR = 2.01; P = 0.021) and those with organ-confined disease (HR = 4.11; P = 0.037). CONCLUSION: Members of the uPA system are associated with features of biologically aggressive BC and oncologic outcomes. However, their value beyond currently available information remains limited.

Prognostic value of preoperative blood-based biomarkers in upper tract urothelial carcinoma treated with nephroureterectomy: A systematic review and meta-analysis.

PURPOSE: This systematic review and meta-analysis assessed the prognostic value of preoperative blood-based biomarkers in patients with upper tract urothelial carcinoma (UTUC) treated with nephroureterectomy. METHODS: PUBMED, Web of Science, Cochrane Library, and Scopus databases were searched in June 2019 according to the Preferred Reporting Items for Systematic Review and Meta-analysis statement. Studies were deemed eligible if they compared cancer-specific survival in UTUC patients with and without pretreatment laboratory abnormalities. Formal meta-analyses were performed for this outcome. RESULTS: The review identified 54 studies with 23,118 patients, of these, 52 studies with 22,513 patients were eligible for the meta-analysis. Several preoperative blood-based biomarkers were significantly associated with cancer-specific survival as follows: neutrophil-lymphocyte ratio (pooled hazard ratio [HR]: 1.66, 95% confidence interval [CI]: 1.34-2.06), C-reactive protein (pooled HR: 1.17, 95% CI: 1.07-1.29), platelet-lymphocyte ratio (pooled HR: 1.68, 95% CI: 1.30-2.17), white blood cell (pooled HR: 1.58, 95% CI: 1.02-2.46), De Ritis ratio (pooled HR: 2.40, 95% CI: 1.92-2.99), fibrinogen (pooled HR: 2.23, 95% CI: 1.86-2.68), albumin-globulin ratio (pooled HR: 3.00, 95% CI: 1.87-4.84), hemoglobin (pooled HR: 1.51, 95% CI: 1.22-1.87), and estimate glomerular filtration rate (pooled HR: 1.52, 95% CI: 1.19-1.94). The Cochrane's Q test and I2 test revealed significant heterogeneity for neutrophil-lymphocyte ratio, C-reactive protein, white blood cell, hemoglobin, and estimated glomerular filtration rate (P = 0.022; I2 = 50.7%, P = 0.000; I2 = 80.4%, P = 0.000; I2 = 88.3%, P = 0.010; I2 = 62.0%, P = 0.000; I2 = 83.9%, respectively). CONCLUSIONS: Several pretreatment laboratory abnormalities in patients with UTUC were associated with increased risks of cancer-specific mortality. Therefore, blood-based biomarkers may have the potential to serve as prognostic factors to assist patients and physicians in selecting appropriate treatment strategies for UTUC. However, considering the study limitations including heterogeneity and retrospective nature of the primary data, the conclusions should be interpreted with caution.

Prognostic Value of Hemoglobin in Metastatic Hormone-sensitive Prostate Cancer: A Systematic Review and Meta-analysis.

The purpose of this study was to assess the prognostic value of hemoglobin (Hb) in patients with metastatic hormone-sensitive prostate cancer (HSPC). The PUBMED, Web of Science, Cochrane Library, and Scopus databases were searched in December 2019 according to the Preferred Reporting Items for Systematic Review and Meta-analysis statement. Studies were deemed eligible if they compared patients with HSPC with normal and low Hb levels to determine their ability to predict overall survival, cancer-specific survival, progression-free survival, and castration-resistant prostate cancer-free survival. Formal meta-analyses were performed for these outcomes. The systematic review identified 25 studies including 6614 patients; 21 studies comprising 5782 patients were eligible for meta-analysis. Low Hb levels were associated with worse overall survival (pooled hazard ratio [HR], 1.21; 95% confidence interval [CI], 1.15-1.29), cancer-specific survival (pooled HR, 1.46; 95% CI, 1.24-1.72), progression-free survival (pooled HR, 1.21; 95% CI, 1.14-1.28), and castration-resistant prostate cancer-free survival (pooled HR, 1.37; 95% CI: 1.18-1.57). Subgroup analyses revealed that low Hb levels were also associated with poor overall survival in patients with both "high-volume" (pooled HR, 1.49; 95% CI, 1.29-1.72) and "low-volume" HSPC (pooled HR, 1.40; 95% CI, 1.13-1.73). This meta-analysis revealed that low Hb serum levels in patients with metastatic HSPC were associated with increased risks of overall mortality, cancer-specific mortality, disease progression, and biochemical recurrence. Furthermore, Hb levels were independently associated with overall survival in the "high-volume" and "low-volume" HSPC subgroups. Therefore, it might be useful to incorporate Hb testing into prognostic tools for metastatic HSPC.

Comparison Between Endoscopic Vacuum Therapy and Conventional Treatment for Leakage After Rectal Resection.

BACKGROUND: Anastomotic leakage after rectal resection represents a severe complication for the patient and requires an early and appropriate management. Endoscopic vacuum therapy (EVT) has become the treatment of choice for anastomotic leakage after rectal resection in several institutions in Germany, and commercially available systems are currently distributed in approximately 30 countries worldwide. However, there is no evidence that EVT is superior to any other treatment for anastomotic leakage after rectal resection. METHODS: Twenty-one patients treated with EVT for anastomotic leakage after rectal resection were retrospectively compared to a historical cohort of 41 patients that received conventional treatment. Primary endpoints were death, treatment success and long-term preservation of intestinal continuity. Secondary endpoints were length of hospital stay and duration of treatment. RESULTS: There was no difference in mortality (p = 0.624). The intention-to-treat analysis showed a significantly higher success rate of EVT compared to conventional treatment (95.2% vs. 65.9%, p = 0.011). EVT was associated with preservation of intestinal continuity in a significant higher percentage of patients than patients undergoing conventional treatment (86.7% vs. 37.5%, p = 0.001). Conventional treatment tended to a shorter length of hospital stay (31.1 vs. 42.2 days, p = 0.066) but with no difference in overall duration of treatment. Time until closing of a diverting stoma did not differ between groups (10.2 months in the EVT group vs. 9.4 months in the conventional treatment group, p = 0.721). CONCLUSION: According to this retrospective study, conventional therapy and EVT are both options for the treatment of anastomotic leakage after rectal resection. EVT might be more effective in terms of definite healing and preservation of intestinal continuity.