Systematic Review of the Incidence of and Risk Factors for Urothelial Cancers and Renal Cell Carcinoma Among Patients with Haematuria.

CONTEXT: The current impact of haematuria investigations on health care organisations is significant. There is currently no consensus on how to investigate patients with haematuria. OBJECTIVE: To evaluate the incidence of bladder cancer, upper tract urothelial carcinoma (UTUC), and renal cell carcinoma (RCC) among patients undergoing investigation for haematuria and identify any risk factors for bladder cancer, UTUC, and RCC (BUR). EVIDENCE ACQUISITION: Medline, Embase, and Cochrane controlled trials databases and ClinicalTrials.gov were searched for all relevant publications from January 1, 2000 to June 2021 according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Prospective, retrospective, and cross-sectional studies with a minimum population of 50 patients with haematuria were considered for the review. EVIDENCE SYNTHESIS: A total of 44 studies were included. The total number of participants was 229701. The pooled incidence rate for urothelial bladder cancer was 17% (95% confidence interval [CI] 14-20%) for visible haematuria (VH) and 3.3% (95% CI 2.45-4.3%) for nonvisible haematuria (NVH). The pooled incidence rate for RCC was 2% (95% CI 1-2%) for VH and 0.58% (95% CI 0.42-0.77%) for NVH. The pooled incidence rate for UTUC was 0.75% (95% CI 0.4-1.2%) for VH and 0.17% (95% CI 0.081-0.299%) for NVH. On sensitivity analysis, the proportions of males (risk ratio [RR] 1.14, 95% CI 1.10-1.17 for VH; 1.54, 95% CI 1.34-1.78 for NVH; p < 0.00001; moderate certainty evidence) and individuals with a smoking history (RR 1.41, 95% CI 1.24-1.61 for VH; 1.53, 95% CI 1.36-1.72 for NVH; p < 0.00001; moderate certainty evidence) appeared to be higher in BUR than in non-BUR groups. CONCLUSIONS: Male gender and smoking history are risk factors for BUR cancer in haematuria, with bladder cancer being the commonest cancer. The incidence of RCC and UTUC in NVH is low. The review serves as a reference standard for future policy-making on investigation of haematuria by global organisations. PATIENT SUMMARY: Our review shows that male gender and smoking history are risk factors for cancers of the bladder, kidney, and ureter. The review also provides information on the proportion of patients who have cancer when they have blood in their urine (haematuria) and will allow policy-makers to decide on the most appropriate method for investigating haematuria in patients.

The 2021 Updated European Association of Urology Guidelines on Metastatic Urothelial Carcinoma.

CONTEXT: Treatment of metastatic urothelial carcinoma is currently undergoing a rapid evolution. OBJECTIVE: This overview presents the updated European Association of Urology (EAU) guidelines for metastatic urothelial carcinoma. EVIDENCE ACQUISITION: A comprehensive scoping exercise covering the topic of metastatic urothelial carcinoma is performed annually by the Guidelines Panel. Databases covered by the search included Medline, EMBASE, and the Cochrane Libraries, resulting in yearly guideline updates. EVIDENCE SYNTHESIS: Platinum-based chemotherapy is the recommended first-line standard therapy for all patients fit to receive either cisplatin or carboplatin. Patients positive for programmed death ligand 1 (PD-L1) and ineligible for cisplatin may receive immunotherapy (atezolizumab or pembrolizumab). In case of nonprogressive disease on platinum-based chemotherapy, subsequent maintenance immunotherapy (avelumab) is recommended. For patients without maintenance therapy, the recommended second-line regimen is immunotherapy (pembrolizumab). Later-line treatment has undergone recent advances: the antibody-drug conjugate enfortumab vedotin demonstrated improved overall survival and the fibroblast growth factor receptor (FGFR) inhibitor erdafitinib appears active in case of FGFR3 alterations. CONCLUSIONS: This 2021 update of the EAU guideline provides detailed and contemporary information on the treatment of metastatic urothelial carcinoma for incorporation into clinical practice. PATIENT SUMMARY: In recent years, several new treatment options have been introduced for patients with metastatic urothelial cancer (including bladder cancer and cancer of the upper urinary tract and urethra). These include immunotherapy and targeted treatments. This updated guideline informs clinicians and patients about optimal tailoring of treatment of affected patients.

European Association of Urology Guidelines on Primary Urethral Carcinoma-2020 Update.

CONTEXT: Primary urethral carcinoma (PUC) is a rare cancer accounting for <1% of all genitourinary malignancies. OBJECTIVE: To provide updated practical recommendations for the diagnosis and management of PUC. EVIDENCE ACQUISITION: A systematic search interrogating Ovid (Medline), EMBASE, and the Cochrane Central Register of Controlled Trials and Cochrane Database of Systematic Reviews was performed. EVIDENCE SYNTHESIS: Urothelial carcinoma of the urethra is the predominant histological type of PUC (54-65%), followed by squamous cell carcinoma (16-22%) and adenocarcinoma (10-16%). Diagnosis of PUC depends on urethrocystoscopy with biopsy and urinary cytology. Pathological staging and grading are based on the tumour, node, metastasis (TNM) classification and the 2016 World Health Organization grading systems. Local tumour extent and regional lymph nodes are assessed by magnetic resonance imaging, and the presence of distant metastases is assessed by computed tomography of the thorax/abdomen and pelvis. For all patients with localised distal tumours (≤T2N0M0), partial urethrectomy or urethra-sparing surgery is a valid treatment option, provided that negative intraoperative surgical margins can be achieved. Prostatic Ta-Tis-T1 PUC can be treated with repeat transurethral resection of the prostate and bacillus Calmette-Guérin. In prostatic or proximal ≥ T2N0 disease, neoadjuvant cisplatin-based chemotherapy should be considered prior to radical surgery. All patients with locally advanced disease (≥T3N0-2M0) should be discussed within a multidisciplinary team. In men with locally advanced squamous cell carcinoma, curative radiotherapy combined with radiosensitising chemotherapy can be offered for definitive treatment and genital preservation. In patients with local urethral recurrence, salvage surgery or radiotherapy can be offered. For patients with distant metastatic disease, systemic therapy based on tumour characteristics can be evaluated. CONCLUSIONS: These updated European Association of Urology guidelines provide up-to-date guidance for the contemporary diagnosis and management of patients with suspected PUC. PATIENT SUMMARY: Primary urethral carcinoma (PUC) is a very rare, but aggressive disease. These updated European Association of Urology guidelines provide evidence-based guidance for clinicians treating patients with PUC.

The Importance of Hospital and Surgeon Volume as Major Determinants of Morbidity and Mortality After Radical Cystectomy for Bladder Cancer: A Systematic Review and Recommendations by the European Association of Urology Muscle-invasive and Metastatic Bladder Cancer Guideline Panel.

CONTEXT: In bladder cancer patients treated with radical cystectomy (RC), controversy exists regarding the impact of the annual hospital volume (HV) and/or surgeon volume (SV) on oncological outcomes and quality of care. OBJECTIVE: A systematic review was performed to evaluate the impact of HV and SV on clinical outcomes. Primary outcomes included in-hospital, 30-d, and 90-d mortality. Secondary outcomes included complications, long-term survival, positive surgical margin rate, lymphadenectomy performance, length of hospital stay, neobladder performance, and blood loss/transfusion rate. EVIDENCE ACQUISITION: Medline, Embase, and the Cochrane Central Register of Controlled Trials were searched. Comparative studies published after the year of 2000 including patients who underwent RC for bladder cancer were eligible for inclusion. Partial cystectomy was an exclusion criterion. Risk of bias (RoB) assessment was performed according to the ROBINS-1 tool. EVIDENCE SYNTHESIS: After screening of 1190 abstracts, 39 studies recruiting 549 542 patients were included. All studies were retrospective observation cohort studies (level of evidence 3). Twenty-two studies reported on HV only, six studies on SV only, and 12 on both. Higher HV, specifically an HV of >10, was associated with improved primary and secondary outcomes in most studies. In addition, there is some evidence that an HV of >20 improves outcomes. For SV, limited and conflicting data are reported. Most studies had moderate to high RoB. The results were synthesized narratively. CONCLUSIONS: Acknowledging the lower level of evidence, HV is likely associated with in-hospital, 30- and 90-d mortality, as well as the secondary outcomes assessed. Based on this study, the European Association of Urology Muscle-invasive and Metastatic Bladder Cancer Guideline Panel recommends hospitals to perform at least 10, and preferably >20, RCs annually or refer the patient to a center that reaches this number. For SV, limited and conflicting data are available. The available evidence suggests HV rather than SV to be the main driver of perioperative outcomes. PATIENT SUMMARY: Current literature suggests that the number of bladder removal operations per hospital per year is associated with postoperative survival as well as the quality of care provided.

Using dissolved organic matter fluorescence to identify the provenance of nutrients in a lowland catchment; the River Thames, England.

Catchment based solutions are being sought to mitigate water quality pressures and achieve multiple benefits but their success depends on a sound understanding of catchment functioning. Novel approaches to monitoring and data analysis are urgently needed. In this paper we explore the potential of river water fluorescence at the catchment scale in understanding nutrient concentrations, sources and pathways. Data were collected from across the River Thames basin from January 2012 to March 2015. Analysing emission excitation matrices (EEMs) using both PARAFAC and optimal area averaging produced consistent results for humic-like component 1 and tryptophan-like component 4 in the absence of a subset of samples that exhibited an unusual peak; illustrating the importance of inspecting the entire EEM before using peak averaging methods. Strong relationships between fluorescence components and dissolved organic carbon (DOC), soluble reactive phosphorus (SRP), and ammonium clearly demonstrated its potential, in this study basin, as a field based surrogate for nutrients. Analysing relationships between fluorescence, catchment characteristics and boron from across the basin enabled new insights into the provenance of nutrients. These include evidence for diffuse sources of DOC from near surface hydrological pathways (i.e. soil horizons); point source inputs of nutrients from sewage effluent discharges; and diffuse contributions of nutrients from agriculture and/or sewage (e.g. septic tanks). The information gained by broad scale catchment wide monitoring of fluorescence could support catchment managers in (a) prioritising subcatchments for nutrient mitigation; (b) providing information on relative nutrient source contributions; and (c) providing evidence of the effectiveness of investment in pollution mitigation measures. The collection of high resolution fluorescence data at the catchment scale and, in particular, over shorter event timescales would complement broad scale assessments by enhancing our hydro-biogeochemical process understanding.

Potential Benefit of Lymph Node Dissection During Radical Nephroureterectomy for Upper Tract Urothelial Carcinoma: A Systematic Review by the European Association of Urology Guidelines Panel on Non-muscle-invasive Bladder Cancer.

CONTEXT: The oncological efficacy of routine lymphadenectomy (lymph node dissection [LND]) at the time of radical nephroureterectomy (RNU) remains controversial. OBJECTIVE: To systematically review the available literature assessing the impact of LND in upper tract urothelial carcinoma (UTUC) patients. EVIDENCE ACQUISITION: Embase, Medline, and Cochrane databases were searched for all studies comparing outcomes of patients undergoing RNU without LND versus any form of LND. We identified nine retrospective studies eligible for inclusion in this systematic review. We took cancer-specific survival (CSS) as the primary end point, and performed a narrative review and risk of bias assessment. EVIDENCE SYNTHESIS: Six studies compared outcomes of no LND versus LND. Three studies compared complete LND versus incomplete LND versus no LND. The incidence of pN+ in patients with high-stage (≥pT2) tumours ranged from 14.3% to 40%. Pre- and postoperative characteristics differed among the study groups, potentially biasing the results, as demonstrated by the risk of bias assessment, potentially favouring the LND group. Oncological outcomes such as cancer-specific, overall, recurrence-free, and metastasis-free survival were reviewed, demonstrating a survival benefit with LND in high-stage disease of the renal pelvis. CONCLUSIONS: Template-based and complete LND improves CSS in patients with high-stage (≥pT2) UTUC and reduces the risk of local recurrence. The impact of LND in ureteral tumours remains uncertain. PATIENT SUMMARY: Studies comparing radical nephroureterectomy with or without the removal of nodes (lymph node dissection [LND]) were analysed. LND improves survival in patients with high-stage disease of the renal pelvis, if it is performed according to an anatomical template-based approach.

Implications of micropapillary urothelial carcinoma variant on prognosis following radical cystectomy: A multi-institutional investigation.

PURPOSE: To determine the association of micropapillary urothelial carcinoma (MUC) variant histology with bladder cancer outcomes after radical cystectomy. MATERIALS AND METHODS: Information on MUC patients treated with radical cystectomy was obtained from five academic centers. Data on 1,497 patients were assembled in a relational database. Tumor histology was categorized as urothelial carcinoma without any histological variants (UC; n = 1,346) or MUC (n = 151). Univariable and multivariable models were used to analyze associations with recurrence-free (RFS) and overall (OS) survival. RESULTS: Median follow-up was 10.0 and 7.8 years for the UC and MUC groups, respectively. No significant differences were noted between UC and MUC groups with regard to age, gender, clinical disease stage, and administration of neoadjuvant and adjuvant chemotherapy (all, P ≥ 0.10). When compared with UC, presence of MUC was associated with higher pathologic stage (organ-confined, 60% vs. 27%; extravesical, 18% vs. 23%; node-positive, 22% vs. 50%; P < 0.01) and lymphovascular invasion (29% vs. 58%; P < 0.01) at cystectomy. In comparison with UC, MUC patients had poorer 5-year RFS (70% vs. 44%; P < 0.01) and OS (61% vs. 38%; P < 0.01). However, on multivariable analysis, tumor histology was not independently associated with the risks of recurrence (P = 0.27) or mortality (P = 0.12). CONCLUSIONS: This multi-institutional analysis demonstrated that the presence of MUC was associated with locally advanced disease at radical cystectomy. However, clinical outcomes were comparable to those with pure UC after controlling for standard clinicopathologic predictors.

Randomized clinical trial of short or long interval between neoadjuvant chemoradiotherapy and surgery for rectal cancer.

BACKGROUND: The optimal timing of surgery following preoperative chemoradiotherapy (CRT) is controversial. This trial aimed to compare pathological complete response (pCR) rates obtained after an interval of 8 weeks or less versus more than 8 weeks. METHODS: Patients with locally advanced rectal adenocarcinoma situated within 12 cm of the anal verge (T3-4 or N+ disease) were randomized to undergo total mesorectal excision (TME) within 8 weeks (classical interval, CI group) or after 8 weeks (long interval, LI group) following CRT. RESULTS: Among the 327 included patients (CI 160, LI 167), the pCR rate was significantly higher in the LI group than in the CI group (10·0 versus 18·6 per cent; P = 0·027). The highest pCR rate (29 per cent) was observed between 10 and 11 weeks. There was statistically significant disease regression in the LI group, with better stage (P = 0·004) and T category (P = 0·001) than in the CI group. There was no significant difference in surgical quality (rates of tumour-positive margins, TME quality, anastomotic leakage and intraoperative perforation) between the groups. The overall morbidity rate was 22·5 per cent in the CI group and 19·8 per cent in the LI group (P = 0·307). Regression analysis including sex, age, clinical stage, tumour location, tumour differentiation, TME quality, concomitant chemotherapy and interval to surgery revealed no statistically significant predictors of pCR. CONCLUSION: Disease regression and pCR rate are increased with an interval between CRT and surgery exceeding 8 weeks. Registration number: NCT03287843 (http://www.clinicaltrials.gov).

Conflict of Evidence: Resolving Discrepancies When Findings from Randomized Controlled Trials and Meta-analyses Disagree.

CONTEXT: Clinicians and treatment guideline developers are faced with a dilemma when the results of a new, large, well-conducted randomized controlled trial (RCT) are in direct conflict with the results of a previous systematic review (SR) and meta-analysis (MA). OBJECTIVE: To explore and discuss possible reasons for disagreement in results from SRs/MAs and RCTs and to provide guidance to clinicians and guideline developers for making well-informed treatment decisions and recommendations in the face of conflicting data. EVIDENCE ACQUISITION: The advantages and limitations of RCTs and SRs/MAs are reviewed. Two practical examples that have a direct bearing on European Association of Urology guidelines on treatment recommendations are discussed in detail to illustrate the points to be considered when conflicts exist between the results of large RCTs and SRs/MAs. EVIDENCE SYNTHESIS: RCTs are the gold standard for providing evidence of the effectiveness of interventions. However, concerns regarding the internal and external validity of an RCT may limit its applicability to clinical practice. SRs/MAs synthesize all evidence related to a given research question, but two urologic examples show that the validity of the results depends on the quality of the individual studies, the clinical and methodological heterogeneity of the studies, and publication bias. CONCLUSIONS: Although SRs/MAs can provide a higher level of evidence than RCTs, the quality of the evidence from both RCTs and SRs/MAs should be investigated when their results conflict to determine which source provides the better evidence. Guideline developers should have a well-defined and robust process to assess the evidence from MAs and RCTs when such conflicts exist. PATIENT SUMMARY: We discuss the advantages and limitations of using data from randomized controlled trials and systematic reviews/meta-analyses in informing clinical practice when there are conflicting results. We provide guidance on how such conflicts should be dealt with by guideline organizations.

Acrokeratosis verruciformis of Hopf exhibiting Darier disease-like cytological features.

The relationship between acrokeratosis verruciformis (AVH; also known as Hopf disease) and Darier disease (DD) has been debated for several decades. There is still substantial controversy over the characterization and association of AVH with DD. Certain histopathological features overlapping with those of DD have been demonstrated in patients with AVH. Although cytological findings have been described in DD, no study has identified the cytological changes in AVH. We report a case of AVH exhibiting a DD-like cytological manifestation. The samples from the most prominent lesions were examined by split-skin smear test. Cytological examination showed acantholytic keratinocytes, dyskeratotic acantholytic cells, corps ronds and grains. Histopathological examination showed compact hyperkeratosis, hypergranulosis, slight acanthosis, circumscribed epidermal elevations resembling church spires, and a cleft in the granular layer with several acantholytic cells. Our case indicates that the cytological findings of AVH are similar to those of DD.

Oncologic Outcomes of Kidney-sparing Surgery Versus Radical Nephroureterectomy for Upper Tract Urothelial Carcinoma: A Systematic Review by the EAU Non-muscle Invasive Bladder Cancer Guidelines Panel.

CONTEXT: There is uncertainty regarding the oncologic effectiveness of kidney-sparing surgery (KSS) compared with radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC). OBJECTIVE: To systematically review the current literature comparing oncologic outcomes of KSS versus RNU for UTUC. EVIDENCE ACQUISITION: A computerised bibliographic search of the Medline, Embase, and Cochrane databases was performed for all studies reporting comparative oncologic outcomes of KSS versus RNU. Approaches considered for KSS were segmental ureterectomy (SU) and ureteroscopic (URS) or percutaneous (PC) management. Using the methodology recommended by the Preferred Reporting Items for Systematic Reviews and Meta-analysis guidelines, we identified 22 nonrandomised comparative retrospective studies published between 1999 and 2015 that were eligible for inclusion in this systematic review. A narrative review and risk-of-bias (RoB) assessment were performed using cancer-specific survival (CSS) as the primary end point. EVIDENCE SYNTHESIS: Seven studies compared KSS overall (n=547) versus RNU (n=1376). Information on the comparison of SU (n=586) versus RNU (n=3692), URS (n=162) versus RNU (n=367), and PC (n=66) versus RNU (n=114) was available in 10, 5, and 2 studies, respectively. No significant difference was found between SU and RNU in terms of CSS or any other oncologic outcomes. Only patients with low-grade and noninvasive tumours experienced similar CSS after URS or PC when compared with RNU, despite an increased risk of local recurrence following endoscopic management of UTUC. The RoB assessment revealed, however, that the analyses were subject to a selection bias favouring KSS. CONCLUSIONS: Our systematic review suggests similar survival after KSS versus RNU only for low-grade and noninvasive UTUC when using URS or PC. However, selected patients with high-grade and invasive UTUC could safely benefit from SU when feasible. These results should be interpreted with caution due to the risk of selection bias. PATIENT SUMMARY: We reviewed the studies that compared kidney-sparing surgery versus radical nephroureterectomy for upper tract urothelial carcinoma. We found similar oncologic outcomes for favourable tumours when using ureteroscopic or percutaneous management, whereas indications for segmental ureterectomy could be extended to selected cases of aggressive tumours.

Understanding the controls on deposited fine sediment in the streams of agricultural catchments.

Excessive sediment pressure on aquatic habitats is of global concern. A unique dataset, comprising instantaneous measurements of deposited fine sediment in 230 agricultural streams across England and Wales, was analysed in relation to 20 potential explanatory catchment and channel variables. The most effective explanatory variable for the amount of deposited sediment was found to be stream power, calculated for bankfull flow and used to index the capacity of the stream to transport sediment. Both stream power and velocity category were highly significant (p ≪ 0.001), explaining some 57% variation in total fine sediment mass. Modelled sediment pressure, predominantly from agriculture, was marginally significant (p<0.05) and explained a further 1% variation. The relationship was slightly stronger for erosional zones, providing 62% explanation overall. In the case of the deposited surface drape, stream power was again found to be the most effective explanatory variable (p<0.001) but velocity category, baseflow index and modelled sediment pressure were all significant (p<0.01); each provided an additional 2% explanation to an overall 50%. It is suggested that, in general, the study sites were transport-limited and the majority of stream beds were saturated by fine sediment. For sites below saturation, the upper envelope of measured fine sediment mass increased with modelled sediment pressure. The practical implications of these findings are that (i) targets for fine sediment loads need to take into account the ability of streams to transport/retain fine sediment, and (ii) where agricultural mitigation measures are implemented to reduce delivery of sediment, river management to mobilise/remove fines may also be needed in order to effect an improvement in ecological status in cases where streams are already saturated with fines and unlikely to self-cleanse.

Validation of a model-based measurement of the minimum insert thickness of knee prostheses: a retrieval study.

INTRODUCTION: Wear of polyethylene inserts plays an important role in failure of total knee replacement and can be monitored in vivo by measuring the minimum joint space width in anteroposterior radiographs. The objective of this retrospective cross-sectional study was to compare the accuracy and precision of a new model-based method with the conventional method by analysing the difference between the minimum joint space width measurements and the actual thickness of retrieved polyethylene tibial inserts. METHOD: Before revision, the minimum joint space width values and their locations on the insert were measured in 15 fully weight-bearing radiographs. These measurements were compared with the actual minimum thickness values and locations of the retrieved tibial inserts after revision. RESULTS: The mean error in the model-based minimum joint space width measurement was significantly smaller than the conventional method for medial condyles (0.50 vs 0.94 mm, p < 0.01) and for lateral condyles (0.06 vs 0.34 mm, p = 0.02). The precision (standard deviation of the error) of the methods was similar (0.84 vs 0.79 mm medially and both 0.46 mm laterally). The distance between the true minimum joint space width locations and the locations from the model-based measurements was less than 10 mm in the medial direction in 12 cases and less in the lateral direction in 13 cases. CONCLUSION: The model-based minimum joint space width measurement method is more accurate than the conventional measurement with the same precision. Cite this article: Bone Joint Res 2014;3:289-96.

The impact of the extent of lymphadenectomy on oncologic outcomes in patients undergoing radical cystectomy for bladder cancer: a systematic review.

CONTEXT: Controversy exists regarding the therapeutic value of lymphadenectomy (LND) in patients undergoing radical cystectomy (RC) for muscle-invasive bladder cancer (MIBC). OBJECTIVE: To systematically review the relevant literature assessing the impact of LND on oncologic and perioperative outcomes in patients undergoing RC for MIBC. EVIDENCE ACQUISITION: Medline, Medline In-Process, Embase, the Cochrane Central Register of Controlled Trials, and the Latin American and Caribbean Center on Health Sciences Information (LILACS) were searched up to December 2013. Comparative studies reporting on no LND, limited LND (L-LND), standard LND (S-LND), extended LND (E-LND), superextended LND (SE-LND), and oncologic and perioperative outcomes were included. Risk-of-bias and confounding assessments were performed. EVIDENCE SYNTHESIS: Twenty-three studies reporting on 19,793 patients were included. All but one study were retrospective. Planned meta-analyses were not possible because of study heterogeneity; therefore, data were synthesized narratively. There were high risks of bias and confounding across most studies as well as extreme heterogeneity in the definition of the anatomic boundaries of LND templates. All seven studies comparing LND with no LND favored LND in terms of better oncologic outcomes. Seven of 14 studies comparing (super)extended LND with L-LND or S-LND reported a beneficial outcome for (super)extended LND in at least a subset of patients. No difference in outcome was reported in two studies comparing E-LND and S-LND. The comparative harms of different extents of LND remain unclear. CONCLUSIONS: Although the quality of the data was poor, the available evidence indicates that any kind of LND is advantageous over no LND. Similarly, E-LND appears to be superior to lesser degrees of dissection, while SE-LND offered no additional benefits. It is hoped that data from ongoing randomized clinical trials will clarify remaining uncertainties. PATIENT SUMMARY: The current literature suggests that removal of lymph nodes in bladder cancer surgery is beneficial and might result in better outcomes in terms of prolonging survival; however, the quality of the available studies is poor, and high-quality studies are needed.

Radical cystectomy in a Dutch University hospital: long-term outcomes and prognostic factors in a homogeneous surgery-only series.

BACKGROUND: The aim of this study was to present survival outcomes and identify prognostic factors in patients undergoing radical cystectomy (RC) for urothelial bladder cancer (UBC) in a homogeneous surgery-only series. PATIENTS AND METHODS: Patients who underwent RC for UBC with intent-to-cure between January 1998 and December 2010 without neoadjuvant or adjuvant treatment were included in this retrospective study. Clinical and histopathologic data were collected and institutional review board approval was obtained. Outcomes of interest were 30-day mortality (30dM), RFS, and OS. Univariable and multivariable analysis were performed. Median follow-up was 9.1 years. RESULTS: Two hundred forty-five patients were included with a median age of 65 years (range, 34-92 years). 30dM rate was in 5 out of 245 patients (2.0%) and 5-year RFS and OS rates were 67% and 58%, respectively. A total of 223 patients (91%) underwent lymph node (LN) dissection. Median number of removed and positive LNs were 9 and 1.5, respectively. Variables independently associated with decreased OS and RFS were tumor stage and LN status. In addition, positive soft tissue surgical margin (STSM) status was independently associated with decreased OS. In LN-positive patients, presence of extranodal extension (ENE) was associated with decreased RFS (39.7% vs. 7.3%; P = .005). CONCLUSION: Radical cystectomy for UBC was associated with low perioperative mortality rate and provided 5-year disease control in approximately two-thirds of patients. Independent prognostic factors included tumor stage, LN status (RFS and OS), and STSM status (OS). Presence of ENE in LN-positive patients was univariably associated with decreased RFS and OS.

Incidence and location of lymph node metastases in patients undergoing radical cystectomy for clinical non-muscle invasive bladder cancer: results from a prospective lymph node mapping study.

OBJECTIVES: The objective of this study is to investigate the incidence and location of lymph node metastases (LNMs) in patients undergoing radical cystectomy (RC) and lymph node dissection (LND) for clinical non-muscle invasive bladder cancer (NMIBC). METHODS AND MATERIALS: Prospectively collected data of 637 patients who underwent RC and 'superextended' LND with intent-to-cure for urothelial carcinoma of the bladder between 2002 and 2008 were examined. Inclusion criteria were (a) clinical stage Ta, Tis-only, or T1, (b) muscle presence at diagnostic transurethral resection in clinical T1 patients, (c) no prior diagnosis of ≥ T2 disease, (d) no neoadjuvant therapy, and (e) lymphatic tissue sample submitted from all 13 predesignated locations. Lymph node mapping was performed in all patients to determine the location of metastatic lymph nodes. Median follow-up time was 4.7 years. Recurrence-free survival and overall survival were reported. RESULTS: A total of 114 patients were included of whom 9 patients (7.9%) had LNM. Stratified by clinical stage, LNM was present in 6/67 (9.0%) patients with cT1, 3/25 (12.0%) patients with cTis-only, and none of the 22 patients with cTa. Of the 9 node-positive patients (33.3%), 3 had LNM proximal to the aortic bifurcation. No skip metastases were found. After RC, 27 patients (23.7%) were upstaged to muscle invasive disease; of whom 16.7% had cT1, 2.6% had cTa, and 4.4% had cTis-only. Of the remaining 87 patients with pathologic NMIBC, 1 patient (1.1%) had LNM, limited to the true pelvis. Five-year RFS was 82.3%, 81.5%, and 62.0% in patients with pathologic NMIBC, clinical NMIBC, and pathologic muscle invasive bladder cancer, respectively. CONCLUSIONS: Routine LND is important in patients with cT1 and cTis-only bladder cancer, but may have limited value in patients with cTa. LNM beyond the boundaries of a standard LND occurred in up to one-third of node-positive patients. In the absence of skip metastases, however, performing a standard LND would correctly identify all node-positive patients. Whether removal of LNM proximal to the common iliac vessels provides a survival benefit remains to be evaluated in future prospective studies.

Long-term outcomes of salvage radical cystectomy for recurrent urothelial carcinoma of the bladder following partial cystectomy.

UNLABELLED: Study Type - Therapy (outcomes) Level of Evidence 2b What's known on the subject? and What does the study add? Data on the oncological outcomes in patients undergoing salvage cystectomy for recurrent disease following bladder-sparing treatment is limited and mostly based on case reports. We present the clinical outcomes and prognostic factors in patients undergoing radical cystectomy for recurrent disease following partial cystectomy with long-term follow-up. OBJECTIVE: To report the clinical outcomes and prognostic factors in patients undergoing salvage radical cystectomy (sRC) for recurrent urothelial carcinoma (UC) of the bladder following partial cystectomy (PC). PATIENTS AND METHODS: Between 1971 and 2011, a total of 2290 patients underwent radical cystectomy for UC of the bladder, including 72 patients (3.1%) who underwent sRC following PC. Clinical and pathological data at the time of both PC and sRC were collected. Median follow-up time after sRC was 10.9 years. Overall survival and recurrence-free survival were the primary outcomes of interest. Univariate and multivariate analyses were performed to identify prognostic factors after sRC. RESULTS: The median time from PC to sRC was 1.6 years. Median age at sRC was 64 years. Peri-operative mortality was 2.8%. After sRC, 44 patients (61.2%) had pathologically organ-confined disease, 14 patients (19.4%) extravesical disease and 14 patients (19.4%) lymph node positive disease. Five-year recurrence-free survival and overall survival following sRC were 56% and 41%, respectively. On multivariate analysis, the presence of pathological tumor stage ≥pT3a (hazard ratio 6.86, P < 0.001) and the presence of lymph node metastases (hazard ratio 8.78, P < 0.001) were associated with increased risk of recurrence after sRC. CONCLUSIONS: sRC can provide prolonged survival following failure of PC. Prognosis, however, is highly dependent on pathological tumour stage and nodal status at sRC. Only 15% of patients with locally advanced recurrent disease were salvaged by sRC.

Principal component analysis based pre-cystectomy model to predict pathological stage in patients with clinical organ-confined bladder cancer.

OBJECTIVE: To develop a model that integrates the clinical and pathological information prior to radical cystectomy to increase the accuracy of current clinical stage in prediction of pathological stage in patients with bladder cancer (BC) using a modelling approach called principal component analysis (PCA). PATIENTS AND METHODS: In a single-centre retrospective study, demographic and clinicopathological information of 1186 patients with clinically organ-confined (OC) BC was reviewed. Putative predictors of post-cystectomy pathological stage were identified using a stepwise logistic regression model. Patients were randomly divided into training data set (two-thirds of the study population, 790 patients) and test data set (one-third of the study population, 396 patients). The PCA method was used to develop the model in the training data set and the cut-off point (PCA score) to differentiate pathological OC disease from extravesical disease was determined. The model was then applied to the test data set without recalculation. RESULTS: In all, 685 patients (57.7%) had pathological OC disease. Age, clinical stage, number of intravesical treatments, lymphovascular invasion, multiplicity of tumours, hydronephrosis and palpable mass were incorporated into the PCA model as predictors of pathological stage. The sensitivity and specificity of the PCA model in the test data set were 62.8% (95% CI 55.6%-68.1%) and 68.9% (95% CI 60.8%-76.0%), respectively. The positive and negative predictive values were 75.8% (95% CI 69.0%-81.6%) and 51.5% (95% CI 44.4%-58.5%), respectively. CONCLUSIONS: The pre-cystectomy PCA model improved the ability to differentiate OC disease from extravesical BC and especially decreased the under-staging rate. The pre-cystectomy PCA model represented a user-friendly staging aid without the need for sophisticated statistical interpretation.

Bi-unicondylar knee prosthesis functional assessment utilizing force-control wear testing.

Recent in vivo studies have identified variations in knee prosthesis function depending on prosthesis geometry, kinematic conditions, and the absence/presence of soft-tissue constraints after knee replacement surgery. In particular, unicondylar knee replacements (UKR) are highly sensitive to such variations. However, rigorous descriptions of UKR function through experimental simulation studies, performed under physiological force-controlled conditions, are lacking. The current study evaluated the long-term functional performance of a widely used fixed-bearing unicompartmental knee replacement, mounted in a bi-unicondylar configuration (Bi-UKR), utilizing a force-controlled knee simulator during a simulated (ISO 14243) walking cycle. The wear behaviour, the femoral-tibial kinematics, and the incurred damage scars were analysed. The wear rates for the medial and the lateral compartments were 10.27 +/- 1.83 mg/million cycles and 4.49 +/- 0.53 mg/million cycles, respectively. Although constant-input force-controlled loading conditions were maintained throughout the simulation, femoral-tibial contact point kinematics decreased by 65 to 68 per cent for average anterior/posterior travel and by 58 to 74 per cent for average medial/lateral travel with increasing cycling time up to 2 million cycles. There were no significant differences in damage area or damage extent between the medial and the lateral compartments. Focal damage scars representing the working region of the femoral component on the articular surface extended over a range of 16-21 mm in the anterior-posterior direction. Kinematics on the shear plane showed slight variations with increasing cycling time, and the platform exhibited medial pivoting over the entire test. These measures provide valuable experimental insight into the effect of the prosthesis design on wear, kinematics, and working area. These functional assessments of Bi-UKR under force-controlled knee joint wear simulation show that accumulated changes in the UKR articular conformity manifested as altered kinematics both for anterior/posterior translations and internal/external rotations.