Achieving Benchmarks for National Quality Indicators Reduces Recurrence and Progression in Non-muscle-invasive Bladder Cancer.

BACKGROUND: Noncompliance with evidence-based interventions and guidelines contributes to significant and variable recurrence and progression in patients with non-muscle-invasive bladder cancer (NMIBC). The implementation of a quality performance indicator (QPI) programme in Scotland's National Health Service (NHS) aimed to improve cancer outcomes and reduce nationwide variance. OBJECTIVE: To evaluate the effect of hospitals achieving benchmarks for two specific QPIs on time to recurrence and progression in NMIBC. DESIGN, SETTING, AND PARTICIPANTS: QPIs for bladder cancer (BC) were enforced nationally in April 2014. NHS health boards collected prospective data on all new BC patients. Prospectively recorded surveillance data were pooled from 12 collaborating centres. INTERVENTION: QPIs of interest were (1) hospitals achieving detrusor muscle (DM) sampling target at initial transurethral resection of bladder tumour (TURBT) and (2) use of single instillation of mitomycin C after TURBT (SI-MMC). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary and secondary endpoints were time to recurrence and progression, respectively. Kaplan-Meier and Cox multivariable regression analyses were performed. KEY FINDINGS AND LIMITATIONS: Between April 1, 2014 and March 31, 2017, we diagnosed 3899 patients with new BC, of which 2688 were NMIBC . With a median follow up of 60.3 mo, hospitals achieving the DM sampling target had a 5.4% lower recurrence rate at 5 yr than hospitals not achieving this target (442/1136 [38.9%] vs 677/1528 [44.3%], 95% confidence interval [CI] = 1.6-9.2, p = 0.005). SI-MMC was associated with a 20.4% lower recurrence rate (634/1791 [35.4%] vs 469/840 [55.8%], 95% CI = 16.4-24.5, p < 0.001). On Cox multivariable regression, meeting the DM target and SI-MMC were associated with significant improvement in recurrence (hazard ratio [HR] 0.81, 95% CI = 0.73-0.91, p = 0.0002 and HR 0.66, 95% CI = 0.59-0.74, p < 0.004, respectively) as well as progression-free survival (HR 0.62, 95% CI = 0.45-0.84, p = 0.002 and HR 0.65, 95% CI = 0.49-0.87, p = 0.004, respectively). We did not have a national multicentre pre-QPI control. CONCLUSIONS: Within a national QPI programme, meeting targets for sampling DM and SI-MMC in the real world were independently associated with delays to recurrence and progression in NMIBC patients. PATIENT SUMMARY: Following the first 3 yr of implementing a novel quality performance indicator programme in Scotland, we evaluated compliance and outcomes in non-muscle-invasive bladder cancer. In 2688 patients followed up for 5 yr, we found that achieving targets for sampling detrusor muscle and the single instillation of mitomycin C during and after transurethral resection of bladder tumour, respectively, were associated with delays in cancer recurrence and progression.

Pubic hair and sexuality: a review.

INTRODUCTION: Hair is a distinguishing feature of mammals, though the persistence of visible head, axillary, and pubic hair remains anthropologically unclear. Humans throughout the ages have modified their head and body hair, but aesthetic removal of pubic hair has become the "the ultimate barometer of how fashionable you really are" in the 21st century. The aim of the article is to examine the trends in pubic hair removal and its impact on health and sexuality. METHODS: A literature search was performed, with a further search performed using an Internet-based search engine. For discussion, the results have been classified into the topics of "Development and anthropology","Cultural and artistic significance", "Medical implications", "Psychological and sexual significance and popular culture", "Impact of body hair loss on sexuality" and "Style and terminology." RESULTS: Pubic hair removal has been common since the ancient times. Pubic hair was rarely depicted in artistic representations of the nude until the late 19th century. It is postulated that the current trend of pubic hair removal may be related to the increased accessibility of Internet-based pornography. Anecdotally, pubic hair removal may carry benefits regarding increased sexual sensation and satisfaction though there is no quantative research in this field. There is a recognized morbidity to pubic hair removal, and also a lack of standardization of terms for styles adopted. We propose a definitive grading system for male and female body hair based on the widely used Tumor Node Metastasis staging system. CONCLUSIONS: Pubic hair removal appears to be an important aspect of expressing one's sexuality and participation in sexual activity. This practice has an interesting psychosexual basis which, to date, has not yet been fully explored in sexual medicine.

The longitudinal relationship between the systemic inflammatory response, circulating T-lymphocytes, interleukin-6 and -10 in patients undergoing immunotherapy for metastatic renal cancer.

OBJECTIVE: To examine the longitudinal relationship between the systemic inflammatory response, circulating T-lymphocyte subpopulations, interleukin-6 and -10 in patients undergoing immunotherapy for metastatic renal cancer, as the inflammation-based Glasgow Prognostic Score (GPS) provides additional prognostic information in patients with advanced renal cancer, but the basis of the relationship between the systemic inflammatory response and poorer survival is not clear, and nor is the effect of immunotherapy on related variables. PATIENTS AND METHODS: The study included 23 patients with metastatic renal cancer and starting immunotherapy. Samples of blood were drawn for routine laboratory analysis and to quantify cytokines using enzyme-linked immunosorbent assays before immunotherapy, and repeated after 2 weeks of treatment. RESULTS: Most patients had a good performance status, favourable or intermediate Memorial Sloane-Kettering Cancer Center (MSKCC) risk scores, and with elevated C-reactive protein (>10 mg/L), GPS (1 or 2), interleukin-6 (>4 pg/mL) and interleukin-10 (>10 pg/mL). Patients who completed one cycle of immunotherapy were more likely to have a normal MSKCC (P < 0.05) or GPS (P < 0.05) scores, whilst the percentage of lymphocytes was lower (P < 0.05). The MSKCC and the GPS scores did not alter significantly during one cycle of immunotherapy. Similarly, leukocyte counts, CD4+ and CD8+ T-lymphocytes, interleukin-6 and -10 concentrations did not change significantly. CONCLUSIONS: The pretreatment systemic inflammatory response and its related lymphopenia are important in determining the tolerance to immunotherapy in patients with metastatic renal cancer. Immunotherapy is not associated with changes in circulating T-lymphocytes, nor the systemic inflammatory response.

Prospective study of the relationship between the systemic inflammatory response, prognostic scoring systems and relapse-free and cancer-specific survival in patients undergoing potentially curative resection for renal cancer.

OBJECTIVE: To examine the prognostic value of markers of systemic inflammatory response, together with established scoring systems, in predicting relapse-free and cancer-specific survival in patients with primary operable renal cancer, as there is increasing evidence that such markers provide prognostic information, in addition to scoring systems, in patients with metastatic renal cancer. PATIENTS AND METHODS: In all, 83 patients undergoing potentially curative nephrectomy for localized renal cancer were recruited. The University of California Los Angeles Integrated Staging System (UISS), 'Stage Size Grade Necrosis' (SSIGN) and Kattan scores were constructed. The systemic inflammatory response was assessed by counting white cells, neutrophils, lymphocytes and platelets, and measuring albumin and C-reactive protein (CRP) concentrations. RESULTS: On multivariate analysis of the significant individual covariates, T stage (hazard ratio 2.38, 95% confidence interval 1.06- 5.36, P = 0.037), necrosis (3.73, 1.26-11.05, P = 0.018) and CRP (4.31, 1.20-15.49, P = 0.025) were significant independent predictors of relapse-free survival. On multivariate analysis of significant scoring systems and CRP, only UISS (3.50, 1.66-7.40, P = 0.001), SSIGN (2.83, 1.19-6.72, P = 0.018) and CRP (4.14, 1.16-14.73, P = 0.028) were significant independent predictors of relapse-free survival. CONCLUSION: Elevated circulating CRP levels appear to be better than other markers of the systemic inflammatory response, and independent of established scoring systems, in predicting relapse-free and cancer-specific survival in patients undergoing potentially curative nephrectomy for renal cancer.

The relationship between the local and systemic inflammatory responses and survival in patients undergoing resection for localized renal cancer.

OBJECTIVE: To examine the relationship between the systemic inflammatory response (C-reactive protein, CRP), tumour interleukin-6 receptor and cyclooxygenase (COX)-2 expression, tumour T-lymphocytic (CD4+, CD8+) infiltration and cancer survival in patients undergoing resection for renal cell carcinoma (RCC), as both the local and systemic inflammatory responses appear to predict the outcome in these patients. PATIENTS AND METHODS: The study included 60 patients undergoing nephrectomy for localized RCC. Pre-operative circulating CRP levels were measured and tumour interleukin-6 receptor and COX-2 expression, tumour CD4+ and CD8+ T lymphocytes were assessed using immunohistochemical analysis. RESULTS: The median follow-up was 78 months, with 14 patients relapsing from their disease and nine cancer-specific deaths. On univariate and multivariate survival analysis, tumour stage and grade and CRP levels were identified as significant factors associated with relapse-free and cancer-specific survival. There was a significant direct relationship between Fuhrman grade and CD4+ T-lymphocytic infiltrate (P < 0.05). An increase in tumour expression of interleukin-6 receptor was weakly associated with an increase in tumour CD8+ T-lymphocytic infiltration (P = 0.057). An increase in tumour CD4+ T-lymphocytic infiltration was associated with an increase in CD8+ T-lymphocytic infiltration (P < 0.01). CONCLUSIONS: The present results suggest that tumour-based factors such as interleukin-6 receptor and COX-2 expression or T-lymphocytic subset infiltration are subordinate to systemic factors such as CRP level in determining survival in patients with localized RCC.

The management of female urinary retention.

Female acute urinary retention (AUR) is relatively uncommon and often poorly managed. There are several common precipitants though much of the literature refers to female AUR as a psychogenic condition. The underlying abnormality is often detrusor failure, not outlet obstruction. Investigations should focus on identifying serious or reversible causes and should include a detailed history and physical examination, urine dipstick, culture and pelvic ultrasound. Patients should be catheterised and reversible causes should be treated. Women who fail to void after catheter removal should be taught ISC. Alpha-blockers are no better than placebo in the treatment of female AUR. There is no role for urethral dilatation. Patients with apparently idiopathic retention should be referred to a urologist with an interest in bladder dysfunction for consideration of urodynamics.

Evidence-based drainage of infected hydronephrosis secondary to ureteric calculi.

INTRODUCTION: The obstructed, infected kidney is a urological emergency. It has been accepted that the management of infected hydronephrosis secondary to ureteric stones is through prompt decompression of the collecting system. However, the optimal method of decompression has yet to be established. MATERIALS AND METHODS: A PubMed and Medline search was performed of all English-language articles from 1960 using key words "sepsis," "urosepsis," "obstruction," "obstructive pyelonephritis," "pyonephrosis," "infection and hydronephrosis" "decompression," "stent," "nephrostomy," and "management." The Cochrane database and National Institute for Clinical Effectiveness guidelines were searched using the terms "sepsis," "urosepsis," "stent," "nephrostomy," or "obstruction." Scottish intercollegiate guidelines were reviewed and no relevant guidance was identified. RESULTS: Two randomised trials have compared retrograde stent insertion with percutaneous nephrostomy with one trial reporting specifically on patients with acute sepsis and obstruction. Neither trial showed one superior modality of decompression in effecting decompression and resolution of sepsis. A further literature search regarding the complications of percutaneous nephrostomy and stent insertion was carried out. An overall major complication rate from percutaneous nephrostomy insertion was found to be 4%, although the complication rates from stent insertion are less consistently reported. DISCUSSION: There appears little evidence to suggest that retrograde stent insertion leads to increased bacteraemia or is significantly more hazardous in the setting of acute obstruction. Further region-wide discussion between urologists and interventional radiologists is required to establish management protocols for these acutely unwell patients.

The role of the systemic inflammatory response as a biomarker in immunotherapy for renal cell cancer.

Treatment of metastatic renal cell cancer (RCC) has entered a new paradigm since the development of tyrosine kinase inhibitors such as sorafenib (Nexavar) and sunitinib (Sutent). Despite these advances, immunotherapy, the traditional mainstay of treatment, is not yet obsolete. Immunotherapy offers the possibility of a complete response for a small number of patients with favorable disease factors. However, immunotherapy is a toxic treatment, with a significant impact on quality of life in comparison with a relatively modest survival advantage for most. As such, the search for a biomarker to select patients for immunotherapy and to monitor their progress still remains a clinical and research goal for those involved in treating patients with metastatic renal cancer. At present, performance status and a number of prognostic scores incorporating performance status and laboratory variables are the most widely used indicators of suitability for immunotherapy. More recently, the histological expression of carbonic anhydrase IX has been reported as a biomarker of response to interleukin (IL)-2 immunotherapy. C-reactive protein (CRP) is an acute-phase protein synthesized as part of the systemic inflammatory response. It is readily measured by standardized assays and is reliable, without variability for age, sex, or bodyweight. The presence of an elevated CRP is a prognostic indicator in a number of solid tumors, both in localized and metastatic disease. In advanced renal cancer, the Glasgow Prognostic Score, which is based on elevated CRP and low albumin, has shown prognostic value. CRP is also superior to the widely used performance status in predicting survival for patients treated with either interferon (IFN)-alpha or IL-2. As such, CRP is an increasingly exciting biomarker for predicting outcomes in immunotherapy. Currently, no other biomarker has been applicable for use in both IFNalpha and IL-2 immunotherapy. More recently, changes in CRP kinetics have shown promise as a predictive tool, although more research is required. Use of CRP as a biomarker can improve stratification of patients with metastatic renal cancer, allowing the patients less likely to benefit from immunotherapy to avoid a potentially toxic treatment. The ongoing selection of patients based on biomarkers should enable continued research on the optimum dose and timing of immunotherapy while managing toxicity and optimizing outcomes.

Modulation of lamellipodial structure and dynamics by NO-dependent phosphorylation of VASP Ser239.

The initial step in directed cell movement is lamellipodial protrusion, an action driven by actin polymerization. Enabled/vasodilator-stimulated phosphoprotein (Ena/VASP) family proteins are key regulators of this actin polymerization and can control lamellipodial protrusion rate. Ena/VASP proteins are substrates for modification by cyclic-nucleotide-dependent protein kinases at a number of sites. Phosphorylation of Ser239 of VASP in vitro inhibits its anti-capping and filament-bundling activity but the effects of this modification on lamellipodial structure and function are unknown. To examine the functional effects of this modification in living cells, we studied VASP phosphorylation at Ser239 by nitric oxide (NO) stimulation of cGMP-dependent protein kinase. Using live cell imaging of primary cells transfected with GFP-VASP constructs, we found that NO produced rapid retraction of lamellipodia together with cell rounding that was dependent on guanylate cyclase and type II cGMP-dependent protein kinase. In cells expressing a mutant VASP (Ser239Ala) lacking the site preferentially phosphorylated by this kinase, NO had no effect. Phosphorylation of Ser239 of VASP results in loss of lamellipodial protrusions and cell rounding, and is a powerful means of controlling directed actin polymerization within lamellipodia.

Evaluation of an inflammation-based prognostic score in patients with metastatic renal cancer.

BACKGROUND: Recently, it was shown that an inflammation-based prognostic score, the Glasgow Prognostic Score (GPS), provides additional prognostic information in patients with advanced cancer. The objective of the current study was to examine the value of the GPS compared with established scoring systems in predicting cancer-specific survival in patients with metastatic renal cancer. METHODS: One hundred nineteen patients who underwent immunotherapy for metastatic renal cancer were recruited. The Memorial Sloan-Kettering Cancer Center (MSKCC) score and the Metastatic Renal Carcinoma Comprehensive Prognostic System (MRCCPS) score were calculated as described previously. Patients who had both an elevated C-reactive protein level (>10 mg/L) and hypoalbuminemia (<35 g/L) were allocated a GPS of 2. Patients who had only 1 of those 2 biochemical abnormalities were allocated a GPS of 1. Patients who had neither abnormality were allocated a GPS of 0. RESULTS: On multivariate analysis of significant individual factors, only calcium (hazard ratio [HR], 3.21; 95% confidence interval [95% CI], 1.51-6.83; P = .002), white cell count (HR, 1.66; 95% CI, 1.17-2.35; P = .004), albumin (HR, 2.63; 95% CI, 1.38-5.03; P = .003), and C-reactive protein (HR, 2.85; 95% CI; 1.49-5.45; P = .002) were associated independently with cancer-specific survival. On multivariate analysis of the different scoring systems, the MSKCC (HR, 1.88; 95% CI, 1.22-2.88; P = .004), the MRCCPS (HR, 1.42; 95% CI, 0.97-2.09; P = .071), and the GPS (HR, 2.35; 95% CI, 1.51-3.67; P < .001) were associated independently with cancer-specific survival. CONCLUSIONS: An inflammation-based prognostic score (GPS) predicted survival independent of established scoring systems in patients with metastatic renal cancer.

Treatment for renal cancer: are we beyond the cytokine era?

Cytokines have been the mainstay of treatment for metastatic renal cancer for the past 20 years. Response rates of patients treated with these agents are low, and toxicity is high, but there is evidence from large multicenter randomized trials that indicate that there are survival benefits with interferon-based immunotherapy. A large number of new small molecule inhibitors are emerging that have caused considerable interest in the oncology community. The evidence for benefit from these compounds is based on small studies, using progression-free survival as an end-point. New compounds may provide an improvement in survival for patients with metastatic renal cancer; however, any trial of these agents should be tested against established, standard cytokine therapy.