Effect of Robot-Assisted Radical Cystectomy With Intracorporeal Urinary Diversion vs Open Radical Cystectomy on 90-Day Morbidity and Mortality Among Patients With Bladder Cancer: A Randomized Clinical Trial.

Importance: Robot-assisted radical cystectomy is being performed with increasing frequency, but it is unclear whether total intracorporeal surgery improves recovery compared with open radical cystectomy for bladder cancer. Objectives: To compare recovery and morbidity after robot-assisted radical cystectomy with intracorporeal reconstruction vs open radical cystectomy. Design, Setting, and Participants: Randomized clinical trial of patients with nonmetastatic bladder cancer recruited at 9 sites in the UK, from March 2017-March 2020. Follow-up was conducted at 90 days, 6 months, and 12 months, with final follow-up on September 23, 2021. Interventions: Participants were randomized to receive robot-assisted radical cystectomy with intracorporeal reconstruction (n = 169) or open radical cystectomy (n = 169). Main Outcomes and Measures: The primary outcome was the number of days alive and out of the hospital within 90 days of surgery. There were 20 secondary outcomes, including complications, quality of life, disability, stamina, activity levels, and survival. Analyses were adjusted for the type of diversion and center. Results: Among 338 randomized participants, 317 underwent radical cystectomy (mean age, 69 years; 67 women [21%]; 107 [34%] received neoadjuvant chemotherapy; 282 [89%] underwent ileal conduit reconstruction); the primary outcome was analyzed in 305 (96%). The median number of days alive and out of the hospital within 90 days of surgery was 82 (IQR, 76-84) for patients undergoing robotic surgery vs 80 (IQR, 72-83) for open surgery (adjusted difference, 2.2 days [95% CI, 0.50-3.85]; P = .01). Thromboembolic complications (1.9% vs 8.3%; difference, -6.5% [95% CI, -11.4% to -1.4%]) and wound complications (5.6% vs 16.0%; difference, -11.7% [95% CI, -18.6% to -4.6%]) were less common with robotic surgery than open surgery. Participants undergoing open surgery reported worse quality of life vs robotic surgery at 5 weeks (difference in mean European Quality of Life 5-Dimension, 5-Level instrument scores, -0.07 [95% CI, -0.11 to -0.03]; P = .003) and greater disability at 5 weeks (difference in World Health Organization Disability Assessment Schedule 2.0 scores, 0.48 [95% CI, 0.15-0.73]; P = .003) and at 12 weeks (difference in WHODAS 2.0 scores, 0.38 [95% CI, 0.09-0.68]; P = .01); the differences were not significant after 12 weeks. There were no statistically significant differences in cancer recurrence (29/161 [18%] vs 25/156 [16%] after robotic and open surgery, respectively) and overall mortality (23/161 [14.3%] vs 23/156 [14.7%]), respectively) at median follow-up of 18.4 months (IQR, 12.8-21.1). Conclusions and Relevance: Among patients with nonmetastatic bladder cancer undergoing radical cystectomy, treatment with robot-assisted radical cystectomy with intracorporeal urinary diversion vs open radical cystectomy resulted in a statistically significant increase in days alive and out of the hospital over 90 days. However, the clinical importance of these findings remains uncertain. Trial Registration: ISRCTN Identifier: ISRCTN13680280; ClinicalTrials.gov Identifier: NCT03049410.

The Comparison of Imaging and Clinical Methods to Estimate Prostate Volume: A Single-Centre Retrospective Study.

BACKGROUND: Prostate volume (PV) is a useful tool in risk stratification, diagnosis, and follow-up of numerous prostatic diseases including prostate cancer and benign prostatic hypertrophy. There is currently no accepted ideal PV measurement method. OBJECTIVE: This study compares multiple means of PV estimation, including digital rectal examination (DRE), transrectal ultrasound (TRUS), and magnetic resonance imaging (MRI), and radical prostatectomy specimens to determine the best volume measurement style. METHODS: A retrospective, observational, single-site study with patients identified using an institutional database was performed. A total of 197 patients who underwent robot-assisted radical prostatectomy were considered. Data collected included age, serum PSA at the time of the prostate biopsy, clinical T stage, Gleason score, and PVs for each of the following methods: DRE, TRUS, MRI, and surgical specimen weight (SPW) and volume. RESULTS: A paired t test was performed, which reported a statistically significant difference between PV measures (DRE, TRUS, MRI ellipsoid, MRI bullet, SP ellipsoid, and SP bullet) and the actual prostate weight. Lowest differences were reported for SP ellipsoid volume (M = -2.37; standard deviation [SD] = 10.227; t[167] = -3.011; and p = 0.003), MRI ellipsoid volume (M = -4.318; SD = 9.53; t[167] = -5.87; and p = 0.000), and MRI bullet volume (M = 5.31; SD = 10.77; t[167] = 6.387; and p = 0.000). CONCLUSION: The PV obtained by MRI has proven to correlate with the PV obtained via auto-segmentation software as well as actual SPW, while also being more cost-effective and time-efficient. Therefore, demonstrating that MRI estimated the PV is an adequate method for use in clinical practice for therapeutic planning and patient follow-up.

Green synthesis, biological evaluation, molecular docking studies and 3D-QSAR analysis of novel phenylalanine linked quinazoline-4(3H)-one-sulphonamide hybrid entities distorting the malarial reductase activity in folate pathway.

A modified Grimmel's method for N-heterocyclization of phenylalanine linked sulphonamide side arm at position-2 was optimized leading to 2,3-disustituted-4-quinazolin-(3H)-ones. Further, [Bmim][BF4]-H2O (IL) was used as green solvent as well as catalyst for the synthesis of twenty two hybrid quinazolinone motifs (4a-4v) by N-heterocyclization reaction using microwave irradiation technique. The in vitro screening of the hybrid entities against the malarial species Plasmodium falciparum yielded five potent molecules 4l, 4n, 4r, 4t & 4u owing comparable antimalarial activity to the reference drugs. In continuation, anin silicostudy was carried out to obtain a pharmacophoric model and quantitative structure activity relationship. We also built a 3D-QSAR model to procure more information that could be applied to design new molecules with more potent Pf-DHFR inhibitory activity. The designed pharmacophore was recognized to be more potent for the selected molecules, exhibiting five pharmacophoric features. The active scaffolds were further evaluated for enzyme inhibition efficacy against alleged receptor Pf-DHFR computationally and in vitro, proving their candidature as lead dihydrofolate reductase inhibitors as well as the selectivity of the test candidates was ascertained by toxicity study against vero cells. The perception of good oral bioavailability was also proved by study of pharmacokinetic properties.

Design and synthesis of leucine-linked quinazoline-4(3H)-one-sulphonamide molecules distorting malarial reductase activity in the folate pathway.

Optimization of a modified Grimmel's method for N-heterocyclization of a leucine-linked sulfonamide side-arm at position 2 leading to 2,3-disustituted-4-quinazolin-(3H)-ones was accomplished. Further, 22 hybrid quinazolinone motifs (4a-v) were synthesized by N-heterocyclization reaction under microwave irradiation using the ionic liquid [Bmim][BF4 ]-H2 O as green solvent as well as the catalyst. The in vitro screening of the hybrid entities against the malarial species Plasmodium falciparum yielded five potent molecules 4l, 4n, 4o, 4t, and 4u owning antimalarial activity comparable to those of the reference drugs. In continuation, an in silico study was carried out to obtain a pharmacophoric model and quantitative structure-activity relationship. We also built a 3D-QSAR model to procure more information that could be applied to design new molecules with more potent Pf-DHFR inhibitory activity. The designed pharmacophore was recognized to be more potent for the selected molecules, exhibiting five pharmacophoric features. The active scaffolds were further evaluated for enzyme inhibition efficacy against alleged receptor Pf-DHFR computationally and in vitro, proving their candidature as lead dihydrofolate reductase inhibitors, and the selectivity of the test candidates was ascertained by toxicity study against Vero cells. Good oral bioavailability was also proved by studying pharmacokinetic properties.

Natural History of Complex Renal Cysts: Clinical Evidence Supporting Active Surveillance.

PURPOSE: We evaluated intervention rates, progression and cancer specific survival outcomes in patients with complex renal cysts in a single center experience. MATERIALS AND METHODS: We used the Montage™ radiology data mining system to retrospectively identify all reported cases of complex renal cyst at our institution from 2001 to 2013. The primary study end points were overall and cancer specific survival. The secondary end points included radiographic progression and upgrading, clinical progression and final histology on surgical pathology. RESULTS: We identified 336 patients with a complex renal cyst, of whom 185 (55.1%), 122 (36.3%) and 29 (8.6%) had Bosniak IIF, III and IV cysts, respectively. Median followup was 67.1 months (range 34.4 to 101.6). In the 332 patients with followup there was 1 cancer specific death (0.3%) and overall mortality was 6.2%. Ten (5.4%), 37 (30.3%) and 18 patients (62.1%) with Bosniak IIF, III and IV, respectively, underwent surgical or ablative intervention. The indication for intervention was predominantly age (intervention vs no intervention mean ± SD age 50.1 ± 15.9 vs 62.5 ± 13.9 years) and complexity. Surgery with radical and partial nephrectomy (23 patients or 35% and 37 or 57%, respectively) was most common and favorable final pathology was identified. Two treated patients experienced recurrence during followup. When excluding patients with von Hippel-Lindau syndrome, the cancer specific survival rate was 100%. CONCLUSIONS: Cancer survival and overall survival in patients with Bosniak IIF to IV renal cysts was high with only 1 cancer specific death. No cancer deaths were recorded in patients who did not undergo intervention. Reconsidering management guidelines for complex renal cysts is warranted, particularly consideration for initial surveillance of Bosniak III cysts.

Ionic liquid mediated stereoselective synthesis of alanine linked hybrid quinazoline-4(3H)-one derivatives perturbing the malarial reductase activity in folate pathway.

Grimmel's method was optimized as well as modified leading to the cyclization and incorporation of alanine linked sulphonamide in 4-quinazolin-(3H)-ones. Further, the generation of heterocyclic motif at position-3 of 4-quinazolinones was explored by synthesis of imines, which unfortunately led to an isomeric mixture of stereoisomers. The hurdle of diastereomers encountered on the path was eminently rectified by development of new rapid and reproducible methodology involving the use of imidazolium based ionic liquid as solvents as well as catalyst for cyclization as well as synthesis of imines in situ at position-3 leading to procurement of single E-isomer as the target hybrid heterocyclic molecules. The purity and presence of single isomer was also confirmed by HPLC and spectroscopic techniques. Further, the synthesized sulphonamide linked 4-quinazolin-(3H)-ones hybrids were screened for their antimalarial potency rendering potent entities (4b, 4c, 4 l, 4 t and 4u). The active hybrids were progressively screened for enzyme inhibitory efficacy against presumed receptor Pf-DHFR and h-DHFR computationally as well as in vitro, proving their potency as dihydrofolate reductase inhibitors. The ADME properties of these active molecules were also predicted to enhance the knowhow of the oral bioavailability, indicating good bioavailability of the active entities.

Diarylpyrazole Ligated Dihydropyrimidine Hybrids as Potent Non-Classical Antifolates and Their Efficacy Against Plasmodium falciparum.

A series of diarylpyrazole clubbed dihydropyrimidine derivatives (J1-J30) was synthesized under microwave-assisted heating conditions by employing Biginelli reaction methodology and utilizing triethylammonium acetate both as a catalyst and as reaction medium, leading towards a greener reaction pathway. The synthesized entities were screened for their antimalarial efficacy against a Plasmodium falciparum strain in vitro. The active entities (J9, J15, J21, J25, and J27) obtained out of the in vitro screening were further evaluated for their enzyme inhibitory potency against the Pf-DHFR enzyme in vitro as well as in silico using Glide. Furthermore, the active scaffolds were tested for their cytotoxicity against Vero cells, proving their nontoxic behavior and selectivity. The ADME parameters were also evaluated and predicted in silico, indicating good oral bioavailability of the compounds.

Active Surveillance for Renal Neoplasms with Oncocytic Features is Safe.

PURPOSE: Oncocytomas are benign tumors often diagnosed incidentally on imaging. Small case series have suggested that the growth kinetics of oncocytomas are similar to those of malignant renal tumors. Biopsy material may be insufficient to exclude a diagnosis of chromophobe renal cell carcinoma. We evaluated and compared the growth rates of oncocytoma and chromophobe renal cell carcinoma to improve our understanding of their natural history. MATERIALS AND METHODS: This was a single center, retrospective study of patients diagnosed with lesions suggestive of oncocytoma or chromophobe renal cell carcinoma between 2003 and 2014. The growth rates were estimated using a mixed effect linear model. Patient and lesion characteristics were tested using a similar model for association with growth rate. RESULTS: Of the 95 lesions (oncocytoma 81, chromophobe renal cell carcinoma 14) included in the analysis 98% were diagnosed on biopsy. The annual growth rate was 0.14 cm and 0.38 cm for oncocytoma (median followup 34 months) and chromophobe renal cell carcinoma (median followup 25 months), respectively (p=0.5). Baseline lesion size was significantly associated with growth (p <0.001). The majority of oncocytomas (74%) and chromophobe renal cell carcinomas (67%) followed up to the 3-year mark had grown. Of these, 8 underwent surgery (6 in the chromophobe renal cell carcinoma group). The initial diagnosis was confirmed in all. Overall 5 patients died, all of nonrenal related causes. CONCLUSIONS: Although the majority of oncocytic renal neoplasms will grow with time, surveillance appears to remain safe. Patients opting for this strategy should be made aware that a diagnosis of oncocytoma following biopsy is associated with some degree of uncertainty due to the difficulty of differentiating them from other oncocytic renal neoplasms.

Multilocular Cystic Renal Cell Carcinoma: Pathological T Staging Makes No Difference to Favorable Outcomes and Should be Reclassified.

PURPOSE: We evaluated survival outcomes of cystic/multilocular cystic renal cell carcinomas in a long-term population based study based on size and pathological tumor stage. MATERIALS AND METHODS: We retrospectively reviewed a provincial cancer registry of all histologically proven cases of multilocular cystic renal cancers treated surgically between 1995 and 2008. All cases of cystic necrosis were excluded from study. Primary end points were overall and cancer specific survival estimated using Kaplan-Meier curves. Cox proportional hazards models of univariable and multivariable analyses were used to assess for factors associated with survival. RESULTS: Of 172 cases of cystic renal cancers 168 with complete data were analyzed, of which 98% were multilocular cystic. Median patient age at treatment was 55 years and 58% of the patients were male. More than 40% of cases were pT1b or greater, 15% were pT2 or greater and most cases were low Fuhrman grade (1-2). At a median followup of 9.75 years overall and cancer specific survival was 82.1% and 100%, respectively. No difference was noted in higher pathological T stage, size or grade. Limitations inherent in population based studies include under ascertainment of cause of death, lack of data on histologically benign cysts that are treated surgically and a lack of central pathology review. CONCLUSIONS: Multilocular cystic renal cell carcinoma has an excellent prognosis, which remains unchanged regardless of tumor size or pathological T stage. This suggests a strong case for nephron and adrenal sparing surgery when indicated, and nonsurgical management when feasible. Since postoperative followup protocols are dictated by staging, we propose that for this entity pathological T staging should be abandoned or reassigned as pT1c to guide clinicians.

Microwave Assisted Synthesis of Pyrimidines in Ionic Liquid and Their Potency as Non-Classical Malarial Antifolates.

Synthesis of pyrazole-linked triazolo-pyrimidine hybrids was achieved by employing Biginelli-type reaction methodology in an ionic liquid (triethylammonium acetate) under microwave irradiation. This method proved to be highly efficient and the ionic liquid employed was found recyclable for up to five consecutive cycles. The synthesized molecules were further screened for their antimalarial efficacy screening out the active scaffolds J15, J18, J21, J24, J27, and J30. The active molecules were evaluated in an enzyme inhibition study against the active Plasmodium falciparum dihydrofolate reductase (Pf-DHFR), computationally as well as in vitro, demonstrating their potency as DHFR inhibitors. The active entities were also investigated for their oral bioavailability by predicting ADME properties in silico, indicating good bioavailability.

Phase II, randomised, double-blind, placebo-controlled trial of methylphenidate for reduction of fatigue levels in patients with prostate cancer receiving LHRH-agonist therapy.

OBJECTIVES: To investigate whether methylphenidate can alleviate fatigue, as measured by the Functional Assessment of Cancer Therapy: Fatigue subscale, in men with prostate cancer (PCa) treated with a luteinizing hormone-releasing hormone (LHRH) for a minimum of 6 months, and to assess changes in global fatigue and quality of life (QoL) as measured by the Bruera Global Fatigue Severity Scale (BFS) and the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36), respectively. PARTICIPANTS AND METHODS: We performed a single-centre, randomised, double-blind, placebo-controlled trial with the aim of recruiting 128 participants. Men treated with a LHRH agonist for PCa were screened between February 2008 and June 2012 for fatigue at our outpatient clinics using the BFS. Participants were randomised to receive either 10 mg daily of methylphenidate or placebo. Change in fatigue levels and in SF-36 scores between both groups were compared using linear regression, adjusted for baseline scores. RESULTS: The study was closed prematurely because of poor accrual. Of the 790 subjects screened, 24 men were randomised to methylphenidate or placebo (12 per group). After 10 weeks, the improvement in mean [sd] fatigue score was greater in the methylphenidate than in the placebo arm (+7.7 [7.7] vs +1.4 [7.6]; P = 0.022). The within-group analysis showed a significant improvement in fatigue scores in the methylphenidate arm (P = 0.008) but not in the placebo arm (P = 0.82). The use of methylphenidate also resulted in a significantly greater improvement in QoL as measured by the physical and mental component summary scores than did the use of placebo (P = 0.04 for both component scores). CONCLUSIONS: Our findings support the beneficial effect of methylphenidate on fatigue and QoL among men with LHRH-induced fatigue. Clinicians should be aware of these benefits and should consider discussing these findings with patients who have high levels of fatigue.

Pyrazole clubbed triazolo[1,5-a]pyrimidine hybrids as an anti-tubercular agents: Synthesis, in vitro screening and molecular docking study.

A series of novel pyrazole linked triazolo-pyrimidine hybrids were synthesized and evaluated for their anti-tuberculosis activity against M.tb H37Rv strain. Some of the screened entities rendered promising anti-tb activity (MIC: 0.39µg/mL) and were found non toxic against Vero cells (IC50: ⩾20µg/mL). Further, the docking study against wild type InhA enzyme of Mycobacterium tuberculosis using Glide reproduced the most active inhibitors (J21 and J27) with lowest binding energies and highest Glide XP scores demonstrating efficient binding to the active pocket. Additionally, the enzyme inhibition assay and ADME prediction of the active proved to be an attest to the possibility of developing compound J27 as a potent anti-tubercular lead.

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.

Clinical and prostate multiparametric magnetic resonance imaging findings as predictors of general and clinically significant prostate cancer risk: A retrospective single-center study.

Background: To evaluate the predictive values of Prostate Imaging Reporting and Data System version 2 (PI-RADS v2), prostate-specific antigen (PSA) level, PSA density (PSAD), digital rectal examination findings, and prostate volume, individually and in combination, for the detection of prostate cancer (PCa) in biopsy-naive patients. Methods: We retrospectively analyzed 630 patients who underwent transrectal systematic prostate biopsy following prostate multiparametric magnetic resonance imaging. A standard 12-core biopsy procedure was performed. Univariate and multivariate analyses were performed to determine the significant predictors of clinically significant cancer but not PCa. Results: The median age, PSA level, and PSAD were 70 years, 8.6 ng/mL, and 0.18 ng/mL/mL, respectively. A total of 374 (59.4%) of 630 patients were biopsy-positive for PCa, and 241 (64.4%) of 374 were diagnosed with clinically significant PCa (csPCa). The PI-RADS v2 score and PSAD were independent predictors of PCa and csPCa. The PI-RADS v2 score of 5 regardless of the PSAD value, or PI-RADS v2 score of 4 plus a PSAD of <0.3 ng/mL/mL, was associated with the highest csPCa detection rate (36.1%-82.1%). Instead, the PI-RADS v2 score of <3 and PSAD of <0.3 ng/mL/mL yielded the lowest risk of csPCa. Conclusion: The combination of the PI-RADS v2 score and PSAD could prove to be a helpful and reliable diagnostic tool before performing prostate biopsies. Patients with a PI-RADS v2 score of <3 and PSAD of <0.3 ng/mL/mL could potentially avoid a prostate biopsy.

The Royal College of Physicians and Surgeons of Glasgow: a Global Commitment to Surgical Education.

The Royal College of Physicians and Surgeons of Glasgow is a community of health professionals working together to develop and improve patient care. The College is dedicated to supporting its members through education, training and continuing professional development. Furthermore, the College is committed to good global citizenship and has supported Fellows, Members and staff in their volunteering efforts.

Natural History of Renal Angiomyolipoma Favors Surveillance as an Initial Approach.

BACKGROUND: Traditionally, intervention was recommended for angiomyolipomas (AMLs) >4 cm due to the risk of catastrophic hemorrhage. OBJECTIVE: To delineate the natural history of AMLs, including growth rates and need for intervention. DESIGN, SETTING, AND PARTICIPANTS: A retrospective review was performed of an AML series from 2002 to 2013, which have been followed prospectively until 2018. We defined lesion size by maximum axial diameter and categorized lesion size at baseline. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: A total of 458 patients with 593 AMLs, with a median follow-up of 65.2 mo, were identified. At diagnosis, 534 (90.1%) lesions were ≤4 cm. Forty-three interventions were required for 34 (5.7%) AMLs: 30 were treated with embolization, seven surgery, two with radiofrequency ablation (RFA), three with mammalian target of rapamycin (mTOR) inhibitors, and one with nivolumab when epithelioid AML was confirmed. The median size at intervention was 4.9 cm (range 1.1-29 cm). RESULTS AND LIMITATIONS: Most (94%) of the lesions grew slowly (growth rate of <0.25 cm/yr) during the period of observation. The number of AMLs <4 cm needed to treat (NNT) prophylactically to prevent one emergent bleed would have been 136 or that to prevent one blood transfusion would have been 205. The NNT (<4 cm) prophylactically to prevent one elective intervention would have been 82. On multivariate analysis, there were significant differences in intervention rates based on tuberous sclerosis complex, size at presentation, and clinical presentation. CONCLUSIONS: This large single-institution updated series of renal AMLs demonstrates that early intervention is not required, regardless of the traditional 4 cm cut-off. The vast majority of AMLs are indolent lesions that are predominantly asymptomatic and slow growing. Follow-up should be no more frequent than annually. PATIENT SUMMARY: The majority of angiomyolipomas (AMLs) are indolent, slow-growing lesions that do not require intervention, regardless of size at presentation. We suggest that surveillance is a safe initial approach for patients presenting with AMLs.

Enhanced Quality and Effectiveness of Transurethral Resection of Bladder Tumour in Non-muscle-invasive Bladder Cancer: A Multicentre Real-world Experience from Scotland's Quality Performance Indicators Programme.

BACKGROUND: Clinical outcomes from non-muscle-invasive bladder cancer (NMIBC) are partly determined by the quality of initial interventions. To improve and standardise treatment for cancer, Scotland implemented a national Quality Performance Indicator (QPI) programme for bladder cancer (BC). OBJECTIVE: To evaluate compliance with specific quality indicators (QIs) related to transurethral resection of bladder tumour (TURBT) and to understand clinical outcomes from NMIBC following the introduction of the QPI programme. DESIGN, SETTING, AND PARTICIPANTS: Within a robust governance framework, 12 mandatory evidence-based QPIs were implemented nationally in April 2014. We report prospectively collected data for all new BC patients (between April 2014 and March 2017). We include follow-up data for 2689 patients. INTERVENTION: The TURBT-related QPIs were (1) using a bladder diagram, (2) single post-TURBT instillation of mitomycin C (SPI-MMC), (3) detrusor muscle (DM) in the specimen, and (4) early re-TURBT in high-risk NMIBC. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We measured compliance with these QPIs and (1) recurrence rate at first follow-up cystoscopy (RRFFC), (2) rates of residual cancer, and (3) pT2 cancer at re-TURBT. Associations between QPI compliance, tumour features, and outcomes were assessed with multivariable logistic regression models. RESULTS AND LIMITATIONS: Among 4246 new BC patients, SPI-MMC was used in 67% (2029/3023) NMIBC patients. In 1860 NMIBC patients undergoing TURBT, RRFFC, rate of residual cancer, and rate of pT2 at re-TURBT were 13% (116/888), 33% (212/653), and 2.9% (19/653), respectively. SPI-MMC was associated with lower RRFFC, independent of all variables including hospital volume and surgeon. Presence of DM in the specimen halved the likelihood of residual disease in pT1 cancers. The main limitation is the lack of a pre-QPI introduction cohort for comparison. CONCLUSIONS: The implementation of a QI programme in Scotland appears to facilitate high-quality TURBT, which in a real-world setting is associated with low early recurrence/residual cancer and accurate pathological staging. PATIENT SUMMARY: Following the first 3 yr of implementing a novel Quality Performance Indicator (QPI) programme in Scotland, we assessed compliance and outcomes in non-muscle-invasive bladder cancer. Evaluating over 4000 new bladder cancer patients, we found that the QPI programme was associated with low recurrence and accurate staging following the initial transurethral resection of bladder tumour.

The kidney cancer research priority-setting partnership: Identifying the top 10 research priorities as defined by patients, caregivers, and expert clinicians.

It is critically important to define disease-specific research priorities to better allocate limited resources. There is growing recognition of the value of involving patients and caregivers, as well as expert clinicians in this process. To our knowledge, this has not been done this way for kidney cancer. Using the transparent and inclusive process established by the James Lind Alliance, the Kidney Cancer Research Network of Canada (KCRNC) sponsored a collaborative consensus-based priority-setting partnership (PSP) to identify research priorities in the management of kidney cancer. The final result was identification of 10 research priorities for kidney cancer, which are discussed in the context of current initiatives and gaps in knowledge. This process provided a systematic and effective way to collaboratively establish research priorities with patients, caregivers, and clinicians, and provides a valuable resource for researchers and funding agencies.

Setting Research Priorities for Kidney Cancer.

Defining disease-specific research priorities in cancer can facilitate better allocation of limited resources. Involving patients and caregivers as well as expert clinicians in this process is of value. We undertook this approach for kidney cancer as an example. The Kidney Cancer Research Network of Canada sponsored a collaborative consensus-based priority-setting partnership that identified ten research priorities in the management of kidney cancer. These are discussed in the context of current initiatives and gaps in knowledge.

Overtreatment in cancer - is it a problem?

The word "cancer" invokes fear even today in those diagnosed with it, largely due to the deep-rooted stigma associated with this emotive word, one associated with an incurable and fatal disease. This was true in years gone by, when cancer patients presented late with symptoms from advanced disease. Today, however, in the era of screening and an awareness of the value of early detection, it is no longer the case. The last half century has heralded an unparalleled rise in every aspect of cancer research, diagnostics and therapeutics, with a better understanding of basic science, pathological classifications, risk factors, prognosis and treatments. Screening programs have been adopted or suggested for many cancers. The pendulum is shifting. A new concept has emerged - that of cancer overdiagnosis, and together with this, cancer overtreatment. Medicine still remains a science of uncertainty and an art of assessing probability. Until personalized medicine evolves to a level that a person's lifetime risk of clinically significant cancer formation and expected outcome can be computed with a great degree of precision and confidence, clinicians and patients have to be cognizant of the problem of cancer overdiagnosis and overtreatment. In this editorial, we explore the current evidence and magnitude of this problem.