Optimising pre-operative imaging-surgery intervals for stones.

Introduction and objectives: The NICE guidelines for acute ureteric colic recommend diagnostic imaging, definitive management and definitive care within 24 and 48 h of symptoms and 4 weeks of temporisation, respectively. However, the NHS reality is fraught with long waiting times to definitive treatment, further compounded by a progressively increasing stone burden, paucity of on-site lithotripters and a decrease in non-cancer elective theatre sessions during the COVID-19 pandemic. By the time patients attended the elective surgeries, their reference images (RIs) were often significantly out of date. Scant direction exists on what interval between imaging and surgery invalidates the usefulness of the RIs in providing surgical guidance.This study aimed to evaluate the role of imaging-surgery intervals (ISIs) on upper tract stone negative surgery outcomes and derive a cut-off ISI warranting updated images, with a view to improving efficiency and patient safety. Materials and methods: Upper tract stone surgeries were retrospectively assessed. Each renal unit was considered independently in bilateral stones. Cases were grouped into renal/pelvic (referred to as 'RENAL') and URETERIC stones. Data retrieved included the ISI, intra-operative disparity (IOD) between stone-related features on RIs and the surgical findings. Receiver operating curves (ROCs) were used to determine ISI cut-offs more predictive of IODs. Results: Four hundred and twenty-seven surgeries on 174 (40.7%) RENAL and 253 (59.3%) URETERIC stones were appraised. No stones were found intraoperatively in 52 (12.1%) patients. Longer ISIs were associated with IODs, especially with URETERIC stones (p = 0.011, CI95 0.63; 4.84). The derived ROC ISI cut-offs beyond which IODs, including negative surgeries, were more likely were 9 weeks for URETERIC (AUC: 63%, CI95 0.56; 0.70) and 19 weeks (AUC: 58.6%, CI95 0.50; 0.68) for RENAL stones, respectively. Conclusion: There is a need to update reference imaging done more than 9 or 19 weeks before surgery for URETERIC and RENAL stones, respectively.

Application of Genomic Sequencing to Refine Patient Stratification for Adjuvant Therapy in Renal Cell Carcinoma.

PURPOSE: Patients with resected localized clear-cell renal cell carcinoma (ccRCC) remain at variable risk of recurrence. Incorporation of biomarkers may refine risk prediction and inform adjuvant treatment decisions. We explored the role of tumor genomics in this setting, leveraging the largest cohort to date of localized ccRCC tissues subjected to targeted gene sequencing. EXPERIMENTAL DESIGN: The somatic mutation status of 12 genes was determined in 943 ccRCC cases from a multinational cohort of patients, and associations to outcomes were examined in a Discovery (n = 469) and Validation (n = 474) framework. RESULTS: Tumors containing a von-Hippel Lindau (VHL) mutation alone were associated with significantly improved outcomes in comparison with tumors containing a VHL plus additional mutations. Within the Discovery cohort, those with VHL+0, VHL+1, VHL+2, and VHL+≥3 tumors had disease-free survival (DFS) rates of 90.8%, 80.1%, 68.2%, and 50.7% respectively, at 5 years. This trend was replicated in the Validation cohort. Notably, these genomically defined groups were independent of tumor mutational burden. Amongst patients eligible for adjuvant therapy, those with a VHL+0 tumor (29%) had a 5-year DFS rate of 79.3% and could, therefore, potentially be spared further treatment. Conversely, patients with VHL+2 and VHL+≥3 tumors (32%) had equivalent DFS rates of 45.6% and 35.3%, respectively, and should be prioritized for adjuvant therapy. CONCLUSIONS: Genomic characterization of ccRCC identified biologically distinct groups of patients with divergent relapse rates. These groups account for the ∼80% of cases with VHL mutations and could be used to personalize adjuvant treatment discussions with patients as well as inform future adjuvant trial design.

Adaptations in models of urological regulation and their application to sub-Saharan Africa.

Regulation of medical care is something that has grown from humble roots in professional craft groups to huge establishment in well-resourced, high-income countries. Self-regulation was the preferred method of determining appropriate behaviour initially, but a lack of public trust in this, and the desire of patients to contribute to the establishment of the standard of care that they receive, has meant that most Anglophone countries have adopted some form of independent regulation. Regulators are responsible for the registration of doctor's qualifications, licensing them to practise, accrediting institutions to provide undergraduate and postgraduate education and certifying the attainment of accepted standards of achievement by some form of assessment process. Regulators also have powers to sanction individuals whose practice falls outside expected levels of competence. Both centralized and devolved models of regulation have evolved. Much of the accreditation for postgraduate education and training has been handed down to collegiate bodies, or non-governmental organizations, who can also certify completion of training. Evidence-based medicine and clinical practice guidelines have enforced an informal tier of regulation in high-income countries; guideline-derived practice is now widely regarded as an accepted standard of care. In low- and middle-income countries in sub-Saharan Africa the governmental and legislative structures and finance available to provide the regulation espoused in more privileged environments is rarely available. The workforce is structured in a completely different way and some care groups are totally unregulated. Medical councils in sub-Saharan Africa fulfil a registration and licensing function but surgical collegiate bodies provide the structure for postgraduate training. The East and West African Colleges of Surgeons have developed into robust organizations, who have verifiable, quality-assured, accreditation systems that have helped improve standards of care for the large populations for which their member surgeons are responsible. Formal regulation of continuing practice and sanctions are challenges that are, at present, largely unaddressed.

Challenges of early renal cancer detection: symptom patterns and incidental diagnosis rate in a multicentre prospective UK cohort of patients presenting with suspected renal cancer.

OBJECTIVES: To describe the frequency and nature of symptoms in patients presenting with suspected renal cell carcinoma (RCC) and examine their reliability in achieving early diagnosis. DESIGN: Multicentre prospective observational cohort study. SETTING AND PARTICIPANTS: Eleven UK centres recruiting patients presenting with suspected newly diagnosed RCC. Symptoms reported by patients were recorded and reviewed. Comprehensive clinico-pathological and outcome data were also collected. OUTCOMES: Type and frequency of reported symptoms, incidental diagnosis rate, metastasis-free survival and cancer-specific survival. RESULTS: Of 706 patients recruited between 2011 and 2014, 608 patients with a confirmed RCC formed the primary study population. The majority (60%) of patients were diagnosed incidentally. 87% of patients with stage Ia and 36% with stage III or IV disease presented incidentally. Visible haematuria was reported in 23% of patients and was commonly associated with advanced disease (49% had stage III or IV disease). Symptomatic presentation was associated with poorer outcomes, likely reflecting the presence of higher stage disease. Symptom patterns among the 54 patients subsequently found to have a benign renal mass were similar to those with a confirmed RCC. CONCLUSIONS: Raising public awareness of RCC-related symptoms as a strategy to improve early detection rates is limited by the fact that related symptoms are relatively uncommon and often associated with advanced disease. Greater attention must be paid to the feasibility of screening strategies and the identification of circulating diagnostic biomarkers.

UK Multicenter Prospective Evaluation of the Leibovich Score in Localized Renal Cell Carcinoma: Performance has Altered Over Time.

OBJECTIVE: To examine changes in outcome by the Leibovich score using contemporary and historic cohorts of patients presenting with renal cell carcinoma (RCC) PATIENTS AND METHODS: Prospective observational multicenter cohort study, recruiting patients with suspected newly diagnosed RCC. A historical cohort of patients was examined for comparison. Metastasis-free survival (MFS) formed the primary outcome measure. Model discrimination and calibration were evaluated using Cox proportional hazard regression and the Kaplan-Meier method. Overall performance of the Leibovich model was assessed by estimating explained variation. RESULTS: Seven hundred and six patients were recruited between 2011 and 2014 and RCC confirmed in 608 (86%) patients. Application of the Leibovich score to patients with localized clear cell RCC in this contemporary cohort demonstrated good model discrimination (c-index = 0.77) but suboptimal calibration, with improved MFS for intermediate- and high-risk patients (5-year MFS 85% and 50%, respectively) compared to the original Leibovich cohort (74% and 31%) and a historic (1998-2006) UK cohort (76% and 37%). The proportion of variation in outcome explained by the model is low and has declined over time (28% historic vs 22% contemporary UK cohort). CONCLUSION: Prognostic models are widely employed in patients with localized RCC to guide surveillance intensity and clinical trial selection. However, the majority of the variation in outcome remains unexplained by the Leibovich model and, over time, MFS rates among intermediate- and high-risk classified patients have altered. These findings are likely to have implications for all such models used in this setting.

Diethylstilboestrol for the treatment of prostate cancer: past, present and future.

The aim of this review was to discuss the most recent data from current trials of diethylstilboestrol (DES) to identify its present role in advanced prostate cancer treatment as new hormonal therapies emerge. The most relevant clinical studies using DES in castration-refractory prostate cancer (CRPC) were identified from the literature. The safety, efficacy, outcomes and mechanisms of action are summarized. In the age of chemotherapy this review highlights the efficacy of oestrogen therapy in CRPC. The optimal point in the therapeutic pathway at which DES should be prescribed remains to be established.

National practice and outcomes of laparoscopic pyeloplasty in the United Kingdom.

BACKGROUND AND PURPOSE: Laparoscopic pyeloplasty is now widely practiced in the United Kingdom and considered the gold standard in the treatment of patients with ureteropelvic junction obstruction. The aim of this audit was to determine the national practice and outcomes for this procedure. PATIENTS AND METHODS: The British Association of Urological Surgeons sent out standardized audit proformas in May 2008 to units across the United Kingdom inviting surgeons who were performing laparoscopic pyeloplasties to submit their results over the last 4 years. Data on the presentation, preoperative investigations, intra-perative details, and postoperative follow-up were collected centrally and inserted into a national database for analysis. RESULTS: There were 323 returns from a total of 30 surgeons. At a median follow-up of 4 months (1-24), the overall symptomatic and renographic failure rates were 10.3% and 8.7%, respectively. Mean operative time was 181 minutes (3--425 min); there were 18 (6%) conversions, 33 (10.5%) complications, and one (0.3%) mortality. Surgeons who submitted 10 or more returns had a lower conversion rate than surgeons submitting fewer than 10 (2.9% vs 14.7%). The median hospital stay was 3 days (1-34 d). There was no difference in failure and complication rate for the retroperitoneal and transperitoneal approaches, although the conversion rate was higher with the retroperitoneal approach. CONCLUSIONS: The results show that laparoscopic pyeloplasty, although achieving acceptable outcomes at a national level in the United Kingdom, had areas of practice that could be improved. It highlights the importance of a high-volume practice in achieving optimum results and the potential problems associated with the retroperitoneal approach.

A prospective diary study of stuttering priapism in adolescents and young men with sickle cell anemia: report of an international randomized control trial--the priapism in sickle cell study.

Priapism is defined as a prolonged, persistent, and purposeless penile erection. It is a common (35%) but frequently understated complication in young men and adults with sickle cell disease. We had previously demonstrated an association between stuttering attacks (<4 hours) and an acute catastrophic event with its consequent problems of erectile dysfunction and impotence. We describe a randomized, placebo-controlled, clinical study looking at medical prophylaxis with 2 oral α-adrenergic agonists, etilefrine and ephedrine, in preventing stuttering attacks of priapism. One hundred thirty-one patients were registered into a 2-phase (observational and intervention phase) study, and 86 patients (66%) completed Phase A diary charts. Forty-six patients (59%) completed a 6-month treatment phase (Phase B), and the remaining patients were lost to follow-up despite persistent efforts to contact them. Various reasons are postulated for the high attrition rates. The drugs were well tolerated, and no serious adverse events were reported. There was no significant difference among the 4 treatment groups in the weekly total number of attacks in Phase B (analysis of covariance P = .99) nor among the average pain score per attack after adjusting for attack rates and pain scores in Phase A (analysis of covariance P = .33). None of the patients who completed the study required penile aspiration at study sites while on medical prophylaxis. Young men with sickle cell disease are not comfortable engaging with health care providers about issues relating to their sexual health. The full impact of an improved awareness campaign and early presentation to hospital merits further standardized study. Priapism still contributes seriously to the comorbidity experienced by this previously inaccessible group of patients and medical prophylaxis with oral α-adrenergic agonists is feasible. Future international collaborative efforts using some of the lessons learnt in this study should be undertaken.

The '2-week wait' rule for referrals for suspected urological cancers--urgent need for refinement of criteria.

INTRODUCTION: All NHS-suspected cancers should be seen within 2 weeks of referral and are referred under government guidelines (Health Service Circular 205; HSC 205). This policy will be subject to review in 2009. Review is vital to allow the appropriate detection of malignancy without overburdening the premium clinic slots with the healthy. PATIENTS AND METHODS: A total of 170 consecutive patients were referred from January-June 2005. Referral details, patient information, events and time to diagnosis were recorded. RESULTS: Of these 170 patients, 143 were suitable for analysis. Forty-three patients (30%) were referred with frank haematuria, of whom 30% had bladder cancer. Nine percent of patients (n = 13) had microscopic haematuria none of whom had cancer. A quarter of the patients (n = 35) were referred with suspected testis cancer but none had cancer. Forty-one patients were referred with serum prostate-specific antigen (PSA) elevation; 18 cancers were detected in this group. Ten men had PSA values greater than 50 ng/ml. Only two cancers were suitable for radical prostatectomy. No cancer was found in patients less than 50 years of age. CONCLUSIONS: A high cancer incidence was found (27.9%), the majority of which was bladder cancer or advanced prostate cancer. Out of the 143 patients, no malignancy was diagnosed in any patient less than 50 years of age, no malignancy was diagnosed in any of the microscopic haematuria group and there was no cancer diagnosed in the group of patients referred with scrotal swellings. We suggest that some guidelines are leading to referral of patients with low cancer risk. When the HSC 205 is revised in 2009, we hope studies such as ours are taken into consideration in order to improve resource utilisation.

Do anatomic factors pose a significant risk in the formation of lower pole stones?

OBJECTIVES: To determine whether various anatomic factors predispose to a lower pole stone on one side compared with the other. METHODS: We analyzed the intravenous urography pictures of 40 consecutive patients presenting with a single lower pole stone. Measurements were taken of the infundibulopelvic angle (IPA), ureteroinfundibular angle, infundibular width, pelvicaliceal height, infundibular length, and pelvicaliceal angle of the affected and normal kidney. The IPA was measured according to the methods of Sampaio, Bagley, and Elbahnasy. A comparison was made to determine whether any of these measurements predisposed one side to form stones. RESULTS: The mean age was 47 years (range 20 to 80). The mean stone size was 9.2 mm (range 5 to 20). The mean IPA was 94.82 degrees (Sampaio), 56.17 degrees (Bagley), 60.40 degrees (Elbahnasy), and 49.15 degrees (Sampaio) on the affected kidney and 95.97 degrees (P = 0.66), 57.47 degrees (P = 0.57), 65.9 degrees (P = 0.04), and 54 degrees (P = 0.07) on the normal side. A statistically significant difference was found only when we measured the IPA as described by Elbahnasy. The mean infundibular width was 4.4 mm on both sides (P = 0.99). The caliceopelvic height was 21.6 mm on the affected side and 22.6 mm on the normal side (P = 0.30). The infundibular length was 28.6 mm and 27.4 mm (P = 0.16) and the caliceopelvic angle was 48 degrees and 47.6 degrees (P = 0.8) on the affected and normal kidneys, respectively CONCLUSIONS: Lower pole anatomy as a risk factor for stones depends on the type of measurement used. A consensus should be reached to define how exactly the IPA should be measured. Other anatomic factors were not significantly different between the affected and normal side in our study.

Diclofenac for treatment of nocturia caused by nocturnal polyuria: a prospective, randomised, double-blind, placebo-controlled crossover study.

OBJECTIVES: To investigate the efficacy of diclofenac 50 mg enteric-coated tablet (Non-Steroidal Anti-Inflammatory Drug) in the treatment of nocturnal polyuria. MATERIALS AND METHODS: 26 patients (20 male and 6 female) with a mean age of 72 years (range 52-90) diagnosed with nocturnal polyuria were recruited. The study period comprised 2 weeks of either placebo or active medication taken at 2100 h. Following one-week rest period, patients were crossed over to the other medication for a further 2 weeks. Frequency volume charts were completed during the second week of each of the two study periods along with feedback forms to assess any subjective improvement in symptoms during each of the study periods. RESULTS: A significant improvement in the symptoms was noted for diclofenac when compared with the placebo. The mean nocturnal frequency decreased from 2.7 to 2.3 (p<0.004) and the mean ratio of night-time to 24 h urine volume decreased from 44% to 39% (p<0.001). No significant side effects were reported. CONCLUSIONS: NSAIDs are effective in the treatment of nocturnal polyuria causing a decrease in nocturnal frequency with subjective symptom improvement. Our study suggests a novel treatment option for this common condition.

Troponin T and N-terminal pro-brain natriuretic peptide changes in patients undergoing transurethral resection of the prostate.

PURPOSE: We investigated whether transurethral resection of the prostate (TURP) caused subclinical myocardial damage or cardiac dysfunction by measuring troponin T (Trop T) and N-terminal pro-brain natriuretic peptide (pro-BNP). MATERIALS AND METHODS: A total of 52 consenting patients took part in this study. All had a detailed medical history including cardiac history taken. On the day of the operation all patients had troponin T, pro-BNP, full blood count and urea, electrolytes and creatinine measured preoperatively. A preoperative and postoperative electrocardiogram was performed. Patients in renal failure were excluded from analysis. During the operations factors such as blood loss, operative time, tissue resected and fluid absorption were monitored. On postoperative day 1 all the previously mentioned tests were repeated. RESULTS: Mean patient age was 71 years (range 52 to 85). Eight patients had a history of associated cardiac problems. Mean preoperative and postoperative hemoglobin were 14.1 gm/dl (range 10.5 to 17) and 13.3 gm/dl (range 9.9 to 16.2), respectively. None of the patients had significant (greater than 1,000 ml) fluid absorption during TURP, which was calculated using ethanol tagged glycine. Mean blood loss measured with a photometer was 129.7 ml (range 0 to 1,800). Mean operative time was 28.4 minutes (range 5 to 50) and mean weight of prostatic tissue resected was 15.2 gm (range 1 to 47). Preoperative Trop T was less than 0.01 mcg/ml in all patients and mean pro-BNP was 39.2 pg/ml (range 0.5 to 866). Postoperative Trop T was less than 0.01 mcg/ml in all but 1 patient who experienced chest pain after TURP and had an increased Trop T (0.28 mcg/ml). Mean postoperative pro-BNP was 54.57 pg/ml (range 1 to 679). A total of 37 patients had an increase in pro-BNP which was still within the reference range for the age group. There were no significant electrocardiogram changes postoperatively. The Trop T changes were not statistically significant (Wilcoxon sign ranked test p = 0.31) although they may be clinically significant. CONCLUSIONS: Our study indicates that in patients with no prior cardiac history TURP does not cause myocardial damage indicated by nonincrease of Trop T. There are slight increases in pro-BNP after TURP in some patients although the exact clinical significance is uncertain.