Current Clinical Practice Guidelines for the Treatment of Renal Cell Carcinoma: A Systematic Review and Critical Evaluation.

The landscape of local and systemic therapy of renal cell carcinoma (RCC) is rapidly changing. The increase in the incidental finding of small renal tumors has increased the application of nephron-sparing procedures, while ten novel agents targeting the vascular endothelial growth factor (VEGF) or the mammalian target of rapamycin pathways, or inhibiting the interaction of the programmed death 1 receptor with its ligand, have been approved since 2006 and have dramatically improved the prognosis of metastatic RCC (mRCC). These rapid developments have resulted in continuous changes in the respective Clinical Practice Guidelines/Expert Recommendations. We conducted a systematic review of the existing guidelines in MEDLINE according to the Preferred Reporting Items for Systematic Review and Meta-Analyses statement, aiming to identify areas of agreement and discrepancy among them and to evaluate the underlying reasons for such discrepancies. Data synthesis identified selection criteria for nonsurgical approaches in renal masses; the role of modern laparoscopic techniques in the context of partial nephrectomy; selection criteria for cytoreductive nephrectomy and metastasectomy in mRCC; systemic therapy of metastatic non-clear-cell renal cancers; and optimal sequence of available agents in mRCC relapsed after anti-VEGF therapy as the major areas of uncertainty. Agreement or uncertainty was not always correlated with the availability of data from phase III randomized controlled trials. Our review suggests that the combination of systematic review and critical evaluation can define practices of wide applicability and areas for future research by identifying areas of agreement and uncertainty among existing guidelines. IMPLICATIONS FOR PRACTICE: Currently, there is uncertainity on the role of surgery in MRCC and on the choice of available guidelines in relapsed RCC. The best practice is individualization of targeted therapies. Systematic review of guidelines can help to identify unmet medical needs and areas of future research.

Expression and prognostic significance of VEGF and mTOR pathway proteins in metastatic renal cell carcinoma patients: a prognostic immunohistochemical profile for kidney cancer patients.

PURPOSE: To identify prognostic molecular profiles in patients with mRCC treated with sunitinib, we performed immunohistochemical analysis for VEGF and PI3K/Akt/mTOR pathway components. METHODS: The immunohistochemical expression of VEGF, p85α, p110γ, PTEN, p-Akt, p-mTOR, p-4E-BP1 and p-p70S6K was studied in 79 patients with mRCC who received first-line treatment with sunitinib. Expression was correlated with clinicopathological features and survival. RESULTS: VEGF was highly expressed (median H-Score 150), while positivity for the markers of the PI3K/Akt/mTOR pathway was: p85α 43/66 (65 %), p110γ41/60 (68 %), PTEN 32/64 (50 %), p-Akt57/63 (90 %), p-mTOR48/64 (75 %), p-4E-BP1 58/64 (90 %) and p-p70S6K 60/65 (92 %). No single immunohistochemical marker was found to have prognostic significance. Instead, the combination of increased p-mTOR and low VEGF expression was adversely correlated with overall survival (OS) (3.2 vs. 16.9 months, P = 0.001). CONCLUSION: Immunohistochemistry for VEGF and p-mTOR proteins may discriminate patients refractory to first-line sunitinib with poor prognosis. Prospective validation of our findings is needed.

Clinical Importance of Cannabinoid Type 1 Receptor (CB1R) and Cannabinoid Type 2 Receptor (CB2R) Expression in Renal Cell Carcinoma.

Background and objective The purpose of our study was to assess the expression of cannabinoid type 1 receptor (CB1R) and cannabinoid type 2 receptor (CB2R), including positivity, intensity, percentage, site of distribution, and immunohistochemical score, in renal cell carcinomas (RCCs) and explore their correlation with various clinicopathological aspects. Methodology We retrospectively obtained data and specimens from 87 patients diagnosed with RCC after partial or radical nephrectomy, and the CB1R and CB2R expression was assessed immunohistochemically on paraffin-embedded tissues. The results were statistically analyzed uni- and multi-factorial along with clinicopathological parameters. Results CB1R was not expressed at all, and CB2R was highly expressed in 78 (89.7%) patients with RCC. In unifactorial analysis, no statistical significance was found in any of the analyzed parameters. However, in the multifactorial analysis, we found that patients with a papillary histologic type (P < 0.0005) were associated with a lower likelihood of expression of the CB2R in the membranous compared with those with clear-cell and were also associated with a higher likelihood of moderate or strong expression of CB2R immunohistochemical score compared with those with clear-cell (P = 0.03). Patients with stage T2 (P = 0.010) had more enhanced expression (grade 3 CB2R intensity) compared with those with stage T1. Males (beta coefficient ± standard error [SE] 13.70 ± 7.04; P = 0.056) and patients with chromophobe histologic type (beta coefficient ± SE 23.45 ± 9.86; P = 0.020) were associated with a higher percentage of CB2R expression. Conclusions Our data suggest that although the CB1R was not expressed in RCCs, CB2R was expressed in almost every patient and enhanced expression was noted in correlation with specific clinicopathological aspects of the patients. Thus, following well-designed studies, especially CB2R could be used as a prognostic marker or even as a potential therapeutic target in RCC.

Clinical Importance of Focal Adhesion Kinase (FAK)-Src and Paxillin Expression in Renal Cell Carcinoma.

BACKGROUND AND OBJECTIVE: The complex focal adhesion kinase (FAK)/Src and paxillin seem to play a key role in the pathogenesis and progression of cancer. The aim of this study is to evaluate the expression of these proteins in renal cell carcinomas (RCCs), considering the immunoreactive score (IRS), the positivity and the intensity, and to find any association with patients' clinical characteristics, histologic type and other pathological features that imply a possible pathophysiological or prognostic role of FAK/Src and paxillin in RCC. METHODS: Patients with RCC who had undergone partial or radical nephrectomy from January 2009 to September 2010 were eligible for this retrospective cross-sectional study. The immunohistochemical expression of FAK, Src and paxillin proteins in formalin-fixed paraffin-embedded tumour tissue was analysed in association with various clinicopathological features. RESULTS: Out of ninety patients, 58 had clear cell renal carcinoma, 15 had papillary, 11 had chromophobe and six had unclassified RCC. FAK, Src and paxillin were expressed in 55.6%, 32.2% and 18.9% of all cases, respectively. In univariate analysis, FAK positivity and IRS were more likely in patients with papillary and chromophobe histologic type versus clear cell RCC (p<0.005), Src positivity and IRS presented more frequently in stage T3 versus T1 (p<0.005) and paxillin positivity was more likely in patients with stage T3 versus T2 (p=0.021) and grades 3-4 versus grade 2 (p=0.013). Paxillin-IRS was not associated with any clinicopathological features. The same associations were also reproduced in the multifactorial analysis for the FAK and Src positivity and IRS, while it was found that paxillin positivity and IRS were associated with the female gender (p=0.052, p=0.024), and were higher in grades 3-4 versus grade 2 (p=0.022, p=0.020). CONCLUSIONS: Our study suggests that RCC shows immunohistochemical expression of FAK, Src and paxillin proteins, and this expression varies in relation to the histologic type, the stage and the stage/grade/gender, respectively. These findings imply a possible involvement of the FAK/Src signalling pathway in the pathogenesis and progression of cancer in RCC, providing future perspectives for targeted therapies with inhibitors.

Review on the Role of BRCA Mutations in Genomic Screening and Risk Stratification of Prostate Cancer.

(1) Background: Somatic and germline alterations can be commonly found in prostate cancer (PCa) patients. The aim of our present study was to perform a comprehensive review of the current literature in order to examine the impact of BRCA mutations in the context of PCa as well as their significance as genetic biomarkers. (2) Methods: A narrative review of all the available literature was performed. Only "landmark" publications were included. (3) Results: Overall, the number of PCa patients who harbor a BRCA2 mutation range between 1.2% and 3.2%. However, BRCA2 and BRCA1 mutations are responsible for most cases of hereditary PCa, increasing the risk by 3-8.6 times and up to 4 times, respectively. These mutations are correlated with aggressive disease and poor prognosis. Gene testing should be offered to patients with metastatic PCa, those with 2-3 first-degree relatives with PCa, or those aged < 55 and with one close relative with breast (age ≤ 50 years) or invasive ovarian cancer. (4) Conclusions: The individualized assessment of BRCA mutations is an important tool for the risk stratification of PCa patients. It is also a population screening tool which can guide our risk assessment strategies and achieve better results for our patients and their families.

Radical cystectomy over the age of 75 is safe and increases survival.

BACKGROUND: Radical cystectomy (RC) is probably underused in elderly patients due to a potential increased postoperative complication risk, as reflected by their considerable comorbidities. Our objective was to estimate the overall complication rate and investigate a potential benefit to patients over the age of 75 subjected to RC in terms of disease-free survival. METHODS: A total of 81 patients, 61 men and 20 women, from two urological departments, with a mean age of 79.2 ± 3.7 years, participated in the study. The mean follow-up period was 2.6 ± 1.6 years. All patients underwent RC with pelvic lymphadenectomy. An ileal conduit, an orthotopic ileal neobladder and cutaneous ureterostomies were formed in 48.1%, 6.2% and 45.7% of the patients, respectively. The perioperative and 90-day postoperative complications were recorded and classified according to the modified Clavien classification system. Survival plots were created based on the oncological outcome and several study parameters. RESULTS: The perioperative morbidity rate was 43.2%; the 90-day morbidity rate was 37%, while the 30-day, 90-day and overall mortality rates were 3.7%, 3.7% and 21%, respectively. Overall mortality rates were recorded at the final year of data gathering (2009). Increased age, increased body mass index (BMI), longer hospitalization and age-adjusted Charlson comorbidity index (ACCI) more than six, were associated with greater hazard for 90-day morbidity. The cumulative mortality / metastasis-free rates for one, two, three and five years were 88.7%, 77.5%, 70.4%, and 62.3%, respectively. Tumour stage and positive nodes were prognostic predictors for oncological outcome. CONCLUSIONS: RC in patients over 75 is justified and feasible, due to acceptable complication rates and high 5-year cancer-specific survival, which support an aggressive approach. Prospective studies are needed for the verification of the above results.

Risk for Arterial Thromboembolic Events (ATEs) in Patients with Advanced Urinary Tract Cancer (aUTC) Treated with First-Line Chemotherapy: Single-Center, Observational Study.

Arterial thromboembolism has been associated with cancer or its treatment. Unlike venous thromboembolism, the incidence and risk factors have not been extensively studied. Here, we investigated the incidence of arterial thromboembolic events (ATEs) in an institutional series of advanced urinary tract cancer (aUTC) treated with cytotoxic chemotherapy. The ATE definition included peripheral arterial embolism/thrombosis, ischemic stroke and coronary events. A total of 354 aUTC patients were analyzed. Most patients (95.2%) received platinum-based chemotherapy. A total of 12 patients (3.4%) suffered an ATE within a median time of 3.6 months from the start of chemotherapy. The most frequent ATE was ischemic stroke (n = 7). Two ATEs were fatal. The 6-month and 24-month incidence were 2.1% (95% confidence interval [CI]: 0.9-4.1) and 3.6% (95% CI: 1.9-6.2), respectively. Perioperative chemotherapy increased the risk for ATE by 5.55-fold. Tumors other than UTC and pure non-transitional cell carcinoma histology were also independent risk factors. No association with the type of chemotherapy was found. Overall, ATEs occur in 4.6% of aUTC patients treated with chemotherapy and represent a clinically relevant manifestation. Perioperative chemotherapy significantly increases the risk for ATE. The role of prophylaxis in high-risk groups should be prospectively studied.

The Intraoperative Complications Assessment and Reporting with Universal Standards (ICARUS) Global Surgical Collaboration Project: Development of Criteria for Reporting Adverse Events During Surgical Procedures and Evaluating Their Impact on the Postoperative Course.

BACKGROUND: Intraoperative adverse events (iAEs) are surgical and anesthesiologic complications. Despite the availability of grading criteria, iAEs are infrequently reported in the surgical literature and in cases for which iAEs are reported, these events are described with significant heterogeneity. OBJECTIVE: To develop Intraoperative Complications Assessment and Reporting with Universal Standards (ICARUS) Global Surgical Collaboration criteria to standardize the assessment, reporting, and grading of iAEs. The ultimate aim is to improve our understanding of the nature and frequency of iAEs and our ability to counsel patients regarding surgical procedures. DESIGN, SETTING, AND PARTICIPANTS: The present study involved the following steps: (1) collecting criteria for assessing, reporting, and grading of iAEs via a comprehensive umbrella review; (2) collecting additional criteria via a survey of a panel of experienced surgeons (first round of a modified Delphi survey); (3) creating a comprehensive list of reporting criteria; (4) combining criteria acquired in the first two steps; and (5) establishing a consensus on clinical and quality assessment utility as determined in the second round of the Delphi survey. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Panel inter-rater agreement and consistency were assessed as the overall percentage agreement and Cronbach's α. RESULTS AND LIMITATIONS: The umbrella review led to nine common criteria for assessing, grading, and reporting iAEs, and review of iAE grading systems led to two additional criteria. In the first Delphi round, 35 surgeons responded and two criteria were added. In the second Delphi round, 13 common criteria met the threshold for final guideline inclusion. All 13 criteria achieved the consensus minimum of 70%, with agreement on the usefulness of the criteria for clinical and quality improvement ranging from 74% to 100%. The mean inter-rater agreement was 89.0% for clinical improvement and 88.6% for quality improvement. CONCLUSIONS: The ICARUS Global Collaboration criteria might aid in identifying important criteria when reporting iAEs, which will support all those involved in patient care and scientific publishing. PATIENT SUMMARY: We consulted a panel of experienced surgeons to develop a set of guidelines for academic surgeons to follow when publishing surgical studies. The surgeon panel proposed a list of 13 criteria that may improve global understanding of complications during specific procedures and thus improve the ability to counsel patients on surgical risk.

A novel approach for the surgical management of Peyronie's disease using an acellular, human dermis tissue graft: preliminary results.

PURPOSE: To present for the first time, the use of an acellular, dermis tissue graft from serologically screened human donors (Εpiflex(®), Deutshes Institut für Zell- und Gewebeersatz) for covering cavernosal defects after plaque incision. METHODS: Five patients with a mean age of 57.4 ± 2.1 years and an International Index of Erectile Function (IIEF-5) score >20, diagnosed with Peyronie's disease (PD) with disease duration and a stable penile deformity of at least 12 and 6 months, respectively, underwent reconstructive surgery. The curvature was dorsal in two, dorsal and left in two and dorsal and right in one patient. The patients were scheduled for follow-up at 1, 3 and 6 months. RESULTS: Placement of the Epiflex(®) graft (size 20 × 40 mm) was performed after appropriate spatulation and fixation with 4-0 Monocryl sutures in all patients. Two of the patients also underwent a small plication of the convex side in order to achieve 100% straightening during artificial erection. All patients had an uneventful course and resumed successful sexual activity 1 month later. No penile deformity, infection, antigenicity or de novo erectile dysfunction was observed during the follow-up period. CONCLUSIONS: This is the first study on the use of an acellular, human dermis tissue graft for the surgical management of PD. Despite our small number of patients, we now routinely use this type of graft, due to its superior biomechanical properties, excellent results and maximum safety. Larger patient series with longer follow-up periods are needed to verify our results.

Early removal of nasogastric tube is beneficial for patients undergoing radical cystectomy with urinary diversion.

PURPOSE: Examine the beneficial effect of early nasogastric tube (NGT) removal in patients undergoing radical cystectomy with urinary diversion. PATIENTS AND METHODS: 43 consecutive patients underwent radical cystectomy with urinary diversion and were randomized into 2 groups. In the intervention group (n = 22), the NGT was removed 12 hours after the operation. Comparatively, in the control group (n = 21), the NGT remained in place until the appearance of the first flatus. The appearance of ileus, patient ambulation, time to regular diet, and hospital discharge of the two patient groups were assessed. Patient discomfort due to the NGT was also recorded. RESULTS: The 2 groups showed statistical homogeneity of their baseline characteristics. Two patients (9.09%) from the intervention and 3 patients (14.3%) from the control group developed postoperative ileus and were treated conservatively. No significant differences in intraoperative, postoperative, bowel outcomes or other complications were found between the two groups. All patients preferred the NGT to be removed first in comparison to their other co-existing drains. CONCLUSIONS: This is the first randomized, prospective study, to our knowledge, to assess early NGT removal after radical cystectomy. We advocate early removal, independently of the selected type of urinary diversion, since it is not correlated with ileus and is advantageous in terms of patient comfort and earlier ambulation.

Prediction of post radical nephrectomy complications based on patient comorbidity preoperatively.

OBJECTIVES: Comorbidity along with tumor and patient characteristics is taken into account when deciding for the surgical treatment of renal cell carcinoma (RCC). Comorbidity has also been used as an independent predictive factor for postoperative complications of several major urological procedures including radical nephrectomy for RCC. The aim of the present study was to objectively evaluate the association between comorbidity and postoperative complications after radical nephrectomy for RCC, using standardized systems to grade both comorbidity and severity of postoperative complications. MATERIALS AND METHODS: Clinicopathological data of 171 patients undergoing open radical nephrectomy for lesions suspected of RCC were prospectively recorded for a period of 3 years. Comorbidity was scored using the Charlson Comorbidity Index (CCI) while postoperative complications were graded according to the Clavien-Dindo system. RESULTS: Patients were predominantly males (59.1%); their age ranged from 35 to 88 years (mean ± SD: 63.6 ± 11.9 yrs) with 50.8% of them being ≤ 65 yrs. CCI ranged from 0 to 8 with the majority (85.3%) scoring ≤ 2. The procedure was uncomplicated in 57.3% cases; 10 patients suffered major (grade III/IV) complications and 4 patients died within the 40 days postoperative period. CCI correlated with the manifestation of any postoperative complication, Clavien ≥ 1, OR (95% CI): 1.47 (1.09-1.96), p = 0.011 and the occurrence of severe complications, Clavien > 2. OR (95% CI): 1.29 (1.01-1.63), p = 0.038. CONCLUSIONS: The present prospective study showed that considerable complications occur in patients with major comorbidities. CCI is easily calculated and should be incorporated in preoperative consultation especially in cases of elder patients with severe comorbidity and favorable tumor characteristics where less invasive interventions or even active surveillance could be applied.

Androgen deprivation monotherapy usage in non-metastatic prostate cancer: results from eight European countries.

INTRODUCTION: The aim of this study was to investigate the attitudes towards use of androgen deprivation therapy (ADT) as monotherapy for localized or locally advanced prostate cancer (PC). MATERIAL AND METHODS: A survey using a 28-item, structured, quantitative questionnaire about the management of patients with PC was conducted in eight European countries between February and May 2018. Survey recipients were selected from a private database of healthcare providers. RESULTS: Overall, 375 physicians completed the survey (response rate, 58%). Participants were urologists (71.2%) or medical oncologists (28.8%), with a mean practice duration of 19.9 years and with university hospital or cancer center (41.6%), non-teaching hospital (38.4%) or private-sector clinic (20.0%) affiliations. Median proportions of physicians considering ADT as monotherapy to treat patients with PC in different risk groups varied between countries, but overall were: high/very high-risk, 60%; intermediate-risk, 30%; low-risk, 7.5%. The use of ADT monotherapy in the different risk groups also varied by medical specialty and type of affiliation. Proportions of participants applying different target thresholds for testosterone (T) levels also varied by country, but overall were: <50 ng/dL, 29.9%; <32 ng/dL, 4.8%; <20 ng/dL, 54.3%; castration but no specific target, 11%. More than half of participants (58.7%) determined target T levels only when prostate-specific antigen level was increased. CONCLUSIONS: Our multinational survey provides evidence that PC management varies across European countries and with clinical context, and frequently diverges from European Association of Urology (EAU) - European Society for Radiotherapy and Oncology (ESTRO) - European Society of Urogenital Radiology (ESUR) - International Society of Geriatric Oncology (SIOG) guidelines. Strategies for effective implementation of evidence-based recommendations in clinical practice may be needed to optimize patient outcomes.

Impact of the Implementation of the EAU Guidelines Recommendation on Reporting and Grading of Complications in Patients Undergoing Robot-assisted Radical Cystectomy: A Systematic Review.

In 2012, the European Association of Urology (EAU) Ad Hoc Panel proposed a standardised methodology on reporting and grading complications after urological surgical procedures. The aim of the current study was to assess the impact of this implementation on complications reporting for patients undergoing robot-assisted radical cystectomy (RARC). A systematic review of all English-language original articles published on RARC until March 2020 was performed using PubMed, Scopus, and Web of Science databases. The study selection process followed the Preferred Reporting Items for Systematic Review and Meta-analyses (PRISMA) criteria. The quality of reporting and grading complication was evaluated according to the EAU recommendations. Our analysis failed to observe a statistically significant improvement in reporting outcomes after the EAU guidelines recommendations except for three of the 14 criteria proposed (ie, follow-up duration, utilisation of a severity grade system, and risk factors included in the analyses). A lower statistically significant adherence to outcome reporting in terms of inclusion of readmissions and causes (p = 0.02), was observed. PATIENT SUMMARY: In this study, we evaluated the impact of the proposed European Association of Urology (EAU) standardised reporting tool for urological complications, in patients treated with robot-assisted radical cystectomy. A low adherence to EAU guidelines recommendations for complications reporting was observed.

ERCC1 19007 Polymorphism in Greek Patients with Advanced Urothelial Cancer Treated with Platinum-Based Chemotherapy: Effect of the Changing Treatment Paradigm: A Cohort Study by the Hellenic GU Cancer Group.

We previously showed that ERCC1 19007 C>T polymorphism was associated with cancer-specific survival (CSS) after platinum-based chemotherapy in patients with advanced urothelial cancer (aUC). We aimed to confirm this association in a different cohort of patients. Genotyping of the 19007C>T polymorphism was carried out by polymerase chain reaction (PCR) amplification and restriction fragment length polymorphism (RFLP) in 98 aUC patients, treated with platinum-based chemotherapy. Median age of the patients was 68.8, 13.3% of them were female, 90.8% had ECOG PS of 0 or 1, and 48% received cisplatin-based chemotherapy. In addition to chemotherapy, 32.7% of the patients received immunotherapy, and 19.4% vinflunine. Eighty-one patients (82.7%) were carriers of the 19007T polymorphic allele: 46 (46.9%) were heterozygotes, and 35 (35.7%) were homozygotes. The ERCC1 polymorphism was not associated with CSS, progression-free (PFS), or overall (OS) survival in the total population. Nevertheless, there was a significant interaction between the prognostic significance of ERCC1 polymorphism and the use of modern immunotherapy: the T allele was associated with worse outcome in patients who received chemotherapy only, while this association was lost in patients who received both chemotherapy and immune checkpoint inhibitors. Our study suggests that novel therapies may influence the significance of ERCC1 polymorphism in patients with aUC. Its determination may be useful in the changing treatment landscape of the disease.

Intraoperative Adverse Incident Classification (EAUiaiC) by the European Association of Urology ad hoc Complications Guidelines Panel.

BACKGROUND: A surgical adverse incident (AI) is defined as any deviation from the normal operative course. Current complication-grading systems mostly focus on postoperative events. OBJECTIVE: To propose an intraoperative AI classification (EAUiaiC) to facilitate reporting. DESIGN, SETTING, AND PARTICIPANTS: The classification was developed using a modified Delphi process in which experts answered two rounds of survey questionnaires organised by the European Association of Urology ad hoc Complications Guidelines Panel. Experts evaluated AI terminology using a 5-point Likert scale for clarity, exhaustiveness, hierarchical order, mutual exclusivity, clinical utility, and quality improvement. OUTCOME MEASURES AND STATISTICAL ANALYSIS: We considered ≥70% agreement for inclusion or exclusion. The resultant EAUiaiC was evaluated using ten sample clinical scenarios. Numerical and graphical statistical techniques were used to report the results. RESULTS AND LIMITATIONS: In total, 343 respondents participated. The proposed EAUiaiC system comprises eight AI grades ranging from grade 0 (no deviation and no consequence to the patient) to grade 5B (wrong surgery site or intraoperative death). In the validation stage, EAUiaiC was rated highly favourably in terms of relevance and reliability (consistency) by 126 experts. Ratings for self-reported ease of use were at acceptable levels. CONCLUSIONS: We propose a novel intraoperative AI classification (EAUiaiC) for use for urological procedures. Both the initial assessment of feasibility and the subsequent assessment of reliability suggest that it is a simple and effective tool for classifying intraoperative complications. PATIENT SUMMARY: Complications in surgery are common. It is helpful to classify complications in a uniform and objective manner so that surgeons can easily compare outcomes and learn from complications. Here we propose a new classification system for complications that occur during urological surgical procedures. An abstract of this work was presented at the 2018 congress of the European Association of Urology.

Postoperative Delirium after Urological Surgery: A Literature Review.

PURPOSE: We aimed to thoroughly search and identify studies referring to risk factors associated with postoperative delirium (POD) in patients undergoing open as well as en-doscopic urological surgery. METHODS: The review after a systematic literature search included 5 studies. RESULTS: The incidence of POD was reported to be between 7.8 and 30% depending on the type of the urologic surgery, while in the majority of the studies the onset happened on the first postoperative day and the symptoms lasted 3 ± 0.8 days. Seventeen different risk factors for POD were identified and presented in detail. CONCLUSION: The Mini-Mental State Examination score and older age were significantly associated with the development of POD. However, the Confusion Assessment Method is very well validated against the diagnosis of delirium from the specialists.

Management of advanced prostate cancer: A systematic review of existing guidelines and recommendations.

The therapeutic landscape of advanced prostate cancer is continuously changing under the light of new available treatment options and the improved understanding of the molecular characteristics of the disease. The lack of high quality evidence regarding the sequencing of these treatments along with the earlier implementation of these therapeutic approaches during the course of the disease have created issues of dispute regarding the optimal treatment of patients with advanced prostate cancer. Therefore, we conducted a systematic review of the existing guidelines and recent randomized trials not included in these guidelines, and present a comprehensive analysis of the available treatment options in each of the stages of advanced prostate cancer, as well as the supportive treatments available for these patients.

Validation of the Clavien-Dindo Grading System in Urology by the European Association of Urology Guidelines Ad Hoc Panel.

CONTEXT: Since 2012 uniformed reporting of complications after urological procedures has been advocated by the European Association of Urology (EAU) guidelines. The Clavien-Dindo grading system was recommended to report the outcomes of urologic procedures. OBJECTIVE: To validate the Clavien-Dindo grading system in urology. DESIGN, SETTING, AND PARTICIPANTS: Members of the EAU working group compiled a list of case scenarios including those with minor and major complications. A survey was administered online via Survey Monkey to the members of EAU committees for the appropriate grading according to the Clavien-Dindo classification of surgical complications. Scenarios with intraoperative complications were intentionally included to assess respondents' awareness of the Clavien-Dindo applicability. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Survey data collected were used to calculate agreement rates and to estimate the overall inter-rater agreement on all cases using Fleiss' kappa (κ). Differences in agreement rates for each scenario among groups with different criteria about the system were estimated using the chi-square test. RESULTS AND LIMITATIONS: Evaluable responses were received from 81 out of 174 invited raters (46.5%). Of them 56.9% believed that the Clavien-Dindo system was adequate for grading postoperative complications. The agreement rate was over a score of ≥80% in nine cases, 60-79% in 10 cases, 40-59% in 14 cases, and <40% in two cases. Interestingly, the agreement rate on the nonapplicability of the Clavien-Dindo system was quite low, ranging from 27.5% to 67.2% (κ=0.147). Being a resident rather than a specialist affected only the distribution of agreement rates in case 1 (ie, score IIIb: 83.3% vs 94.1%). Being an academic or having affiliation did not have any impact on the distribution of agreement rates in all cases but one. CONCLUSIONS: The Clavien-Dindo classification is a standardised approach to grade and report postoperative complications in urology and should be used systematically. However, it does not apply for intraoperative complications, and there is a need for an additional tool. PATIENT SUMMARY: A rigorous methodology is mandatory when surgeons report about complications after surgery. In this study, the European Association of Urology Guidelines Panel has validated the use of the Clavien-Dindo grading system in urology.

Outcome of patients with nonmetastatic muscle-invasive bladder cancer not undergoing cystectomy after treatment with noncisplatin-based chemotherapy and/or radiotherapy: a retrospective analysis.

Transurethral resection of bladder tumor (TURBT), radiotherapy, chemotherapy, or combinations can be used in patients with muscle-invasive bladder cancer (MIBC) not undergoing cystectomy. Nevertheless, unfitness for cystectomy is frequently associated with unfitness for other therapeutic modalities. We report the outcome of patients with MIBC who did not undergo cystectomy and did not receive cisplatin-based chemotherapy. Selection criteria for the study were nonmetastatic MIBC, no cystectomy, no cisplatin-based chemotherapy. Chemotherapy and/or radiotherapy should have been used aside from TURBT. Forty-nine patients (median age 79), managed between April 2001 and January 2012, were included in this analysis. Median Charlson Comorbidity Index was 5, while 76% were unfit for cisplatin. Treatment included radiotherapy (n = 7), carboplatin-based chemotherapy (n = 25), carboplatin-based chemotherapy followed by radiotherapy (n = 10), and radiochemotherapy (n = 7). Five-year event-free rate was 26% (standard error [SE] = 7) for overall survival, 23% (SE = 7) for progression-free survival, and 30 (SE = 8) for cancer-specific survival (CSS). Patients who were treated with combination of radiotherapy and chemotherapy had significantly longer CSS compared to those treated with radiotherapy or chemotherapy only (5-year CSS rate: 16% [SE 8] vs. 63% [SE 15], P = 0.053). Unfit-for-cystectomy patients frequently receive suboptimal nonsurgical treatment. Their outcome was poor. Combining chemotherapy with radiotherapy produced better outcomes and should be prospectively evaluated.