Comparison of systematic and combined biopsy for the detection of prostate cancer.

ABSTRACT: Systematic prostate biopsy has limitations, such as overdiagnosis of clinically insignificant prostate cancer and underdiagnosis of clinically significant prostate cancer. Magnetic resonance imaging (MRI)-guided biopsy, a promising alternative, might improve diagnostic accuracy. To compare the cancer detection rates of systematic biopsy and combined biopsy (systematic biopsy plus MRI-targeted biopsy) in Asian men, we conducted a retrospective cohort study of men who underwent either systematic biopsy or combined biopsy at two medical centers (Queen Mary Hospital and Tung Wah Hospital, Hong Kong, China) from July 2015 to December 2022. Descriptive statistics were calculated, and univariate and multivariate logistic regression analyses were performed. The primary and secondary outcomes were prostate cancer and clinically significant prostate cancer. A total of 1391 participants were enrolled. The overall prostate cancer detection rates did not significantly differ between the two groups (36.3% vs 36.6%, odds ratio [OR] = 1.01, 95% confidence interval [CI]: 0.81-1.26, P = 0.92). However, combined biopsy showed a significant advantage in detecting clinically significant prostate cancer (Gleason score ≥ 3+4) in patients with a total serum prostate-specific antigen (tPSA) concentration of 2-10 ng ml-1 (systematic vs combined: 11.9% vs 17.5%, OR = 1.58, 95% CI: 1.08-2.31, P = 0.02). Specifically, in the transperineal biopsy subgroup, combined biopsy significantly outperformed systematic biopsy in the detection of clinically significant prostate cancer (systematic vs combined: 12.6% vs 24.0%, OR = 2.19, 95% CI: 1.21-3.97, P = 0.01). These findings suggest that in patients with a tPSA concentration of 2-10 ng ml-1, MRI-targeted biopsy may be of greater predictive value than systematic biopsy in the detection of clinically significant prostate cancer.

Transurethral En Bloc Resection Versus Standard Resection of Bladder Tumour: A Randomised, Multicentre, Phase 3 Trial.

BACKGROUND AND OBJECTIVE: Conventionally, standard resection (SR) is performed by resecting the bladder tumour in a piecemeal manner. En bloc resection of the bladder tumour (ERBT) has been proposed as an alternative technique in treating non-muscle-invasive bladder cancer (NMIBC). The objective of this study is to investigate whether ERBT could improve the 1-yr recurrence rate of NMIBC, as compared with SR. METHODS: A multicentre, randomised, phase 3 trial was conducted in Hong Kong. Adults with bladder tumour(s) of ≤ 3cm were enrolled from April 2017 to December 2020, and followed up until 1 yr after surgery. Patients were randomly assigned to receive either ERBT or SR in a 1:1 ratio. The primary outcome was 1-yr recurrence rate. A modified intention-to-treat analysis on patients with histologically confirmed NMIBC was performed. The main secondary outcomes included detrusor muscle sampling rate, operative time, hospital stay, 30-d complications, any residual or upstaging of disease upon second-look transurethral resection, and 1-yr progression rate. KEY FINDINGS AND LIMITATIONS: A total of 350 patients underwent randomisation, and 276 patients were histologically confirmed to have NMIBC. At 1 yr, 31 patients in the ERBT group and 46 in the SR group developed recurrence; the Kaplan-Meier estimate of 1- yr recurrence rates were 29% (95% confidence interval, 18-37) in the ERBT group and 38% (95% confidence interval, 28-46) in the SR group (p = 0.007). Upon a subgroup analysis, patients with 1-3 cm tumour, single tumour, Ta disease, or intermediate-risk NMIBC had a significant benefit from ERBT. None of the patients in the ERBT group and three patients in the SR group developed progression to muscle-invasive bladder cancer; the Kaplan-Meier estimates of 1-yr progression rates were 0% in the ERBT group and 2.6% (95% confidence interval, 0-5.5) in the SR group (p = 0.065). The median operative time was 28 min (interquartile range, 20-45) in the ERBT group and 22 min (interquartile range, 15-30) in the SR group (p < 0.001). All other secondary outcomes were similar in the two groups. CONCLUSIONS AND CLINICAL IMPLICATIONS: In patients with NMIBC of ≤ 3cm, ERBT resulted in a significant reduction in the 1-yr recurrence rate when compared with SR. The study results support ERBT as the first-line surgical treatment for patients with bladder tumours of≤ 3cm.

The Impact of Prostate-Specific Antigen Screening on Prostate Cancer Incidence and Mortality in China: 13-Year Prospective Population-Based Cohort Study.

BACKGROUND: The status of prostate-specific antigen (PSA) screening is unclear in China. Evidence regarding the optimal frequency and interval of serial screening for prostate cancer (PCa) is disputable. OBJECTIVE: This study aimed to depict the status of PSA screening and to explore the optimal screening frequency for PCa in China. METHODS: A 13-year prospective cohort study was conducted using the Chinese Electronic Health Records Research in Yinzhou study's data set. A total of 420,941 male participants aged ≥45 years were included between January 2009 and June 2022. Diagnosis of PCa, cancer-specific death, and all-cause death were obtained from the electronic health records and vital statistic system. Hazard ratios (HRs) with 95% CIs were estimated using Cox regression analysis. RESULTS: The cumulative rate of ever PSA testing was 17.9% with an average annual percent change (AAPC) of 8.7% (95% CI 3.6%-14.0%) in the past decade in China. People with an older age, a higher BMI, higher waist circumference, tobacco smoking and alcohol drinking behaviors, higher level of physical activity, medication use, and comorbidities were more likely to receive PSA screening, whereas those with a lower education level and a widowed status were less likely to receive the test. People receiving serial screening ≥3 times were at a 67% higher risk of PCa detection (HR 1.67; 95% CI 1.48-1.88) but a 64% lower risk of PCa-specific mortality (HR 0.36; 95% CI 0.18-0.70) and a 28% lower risk of overall mortality (HR 0.72; 95% CI 0.67-0.77). People following a serial screening strategy at least once every 4 years were at a 25% higher risk of PCa detection (HR 1.25; 95% CI 1.13-1.36) but 70% (HR 0.30; 95% CI 0.16-0.57) and 23% (HR 0.77; 95% CI 0.73-0.82) lower risks of PCa-specific and all-cause mortality, respectively. CONCLUSIONS: This study reveals a low coverage of PSA screening in China and provides the first evidence of its benefits in the general Chinese population. The findings of this study indicate that receiving serial screening at least once every 4 years is beneficial for overall and PCa-specific survival. Further studies based on a nationwide population and with long-term follow-up are warranted to identify the optimal screening interval in China.

Role of fatty liver index in risk-stratifying comorbid disease outcomes in non-alcoholic fatty liver disease.

Background & Aims: Population screening for non-alcoholic fatty liver disease (NAFLD) and associated comorbidities remains an unaddressed clinical need. We aimed to assess the utility of the fatty liver index (FLI) for risk stratification of NAFLD and related comorbidities using the UK Biobank. Methods: Electronic health records and liver MRI-proton density fat fraction (PDFF) were used to define NAFLD cases. FLI was calculated and individuals with high alcohol intake and other liver diseases were excluded. Using listwise deletion analysis, the area under receiver-operating characteristic curve (AUROC) of FLI for NAFLD risk was determined. Thereafter, time-dependent covariate-adjusted Cox regression models were used to estimate FLI's risk stratification potential for comorbidities of interest. Results: FLI was derived for 327,800 individuals with a median age of 58 (IQR 51.5-64.5), of whom 59.8% were females. Using Perspectum Diagnostics and AMRA protocols as references, FLI identified the risk of NAFLD with AUROCs (95% CI, n) of 0.858 (0.848-0.867, n = 7,566) and 0.851 (0.844-0.856, n = 10,777), respectively. Intermediate and high-risk FLI was associated with increased cardiometabolic and malignant disease. In the first 3 years, high-risk FLI conferred an increased risk (adjusted hazard ratio, 95% CI) of ischaemic heart disease (2.14, 1.94-2.36), hypertension (2.84, 2.70-2.98), type 2 diabetes mellitus (4.55, 4.04-5.12), dyslipidaemia (2.48, 2.32-2.64), ischaemic stroke (1.31, 1.20-1.42) and hepatic malignancy (1.69, 1.23-2.30). FLI was not associated with risk of extrahepatic malignancy but was associated with a higher risk of specific cancers (colon, upper gastrointestinal and breast). All-cause mortality was similarly stratified by FLI, independently of non-invasive fibrosis scores. Conclusions: FLI identifies NAFLD and holds potential for the risk stratification of cardiometabolic and malignant disease outcomes (including some extrahepatic malignancies), as well as all-cause mortality. Its use in population screening for primary and secondary prevention of NAFLD should be considered. Impact and implications: Our analysis using the UK Biobank study shows the potential of the fatty liver index as a risk stratification tool for identifying the risk of developing NAFLD, ischaemic heart disease, ischaemic stroke, type 2 diabetes mellitus, hypertension, hyperlipidaemia, hepatic malignancy, specific metabolism-related malignancies and all-cause mortality. These results suggest that the fatty liver index should be considered as a non-invasive steatosis score that may help guide primary prevention strategies for NAFLD and related outcomes.

Prostate health index can stratify patients with Prostate Imaging Reporting and Data System score 3 lesions on magnetic resonance imaging to reduce prostate biopsies.

We aim to evaluate prostate health index as an additional risk-stratification tool in patients with Prostate Imaging Reporting and Data System score 3 lesions on multiparametric magnetic resonance imaging. Men with biochemical or clinical suspicion of having prostate cancer who underwent multiparametric magnetic resonance imaging in two tertiary centers (Queen Mary Hospital and Princess Margaret Hospital, Hong Kong, China) between January 2017 and June 2022 were included. Ultrasound-magnetic resonance imaging fusion biopsies were performed after prostate health index testing. Those who only had Prostate Imaging Reporting and Data System score 3 lesions were further stratified into four prostate health index risk groups and the cancer detection rates were analyzed. Out of the 747 patients, 47.3% had Prostate Imaging Reporting and Data System score 3 lesions only. The detection rate of clinically significant prostate cancer in this group was 15.0%. The cancer detection rates of clinically significant prostate cancer had statistically significant differences: 5.3% in prostate health index <25.0, 7.4% in prostate health index 25.0-34.9, 17.9% in prostate health index 35.0-54.9, and 52.6% in prostate health index ≥55.0 (P < 0.01). Among the patients, 26.9% could have avoided a biopsy with a prostate health index <25.0, at the expense of a 5.3% risk of missing clinically significant prostate cancer. Prostate health index could be used as an additional risk stratification tool for patients with Prostate Imaging Reporting and Data System score 3 lesions. Biopsies could be avoided in patients with low prostate health index, with a small risk of missing clinically significant prostate cancer.

Angioembolization for massive pelvic hematoma after prostatic urethral lift.

Introduction: Pelvic hematomas are a rare complication of prostatic urethral lift. We would like to report the first case of massive pelvic hematoma after prostatic urethral lift that was successfully managed by selective angioembolization. Case presentation: An 83-year-old gentleman with benign prostatic hyperplasia underwent prostatic urethral lift. Although the procedure was uneventful, he developed shock while in the recovery room. Urgent contrast computed tomography scan showed a large heterogenous hematoma at the right pelvis extending to the right retroperitoneum with contrast extravasation noted. Urgent angiogram confirmed extravasation from the right prostatic artery. Angioembolization with coils and 33% N-butyl cyanoacrylate glue was successfully performed. Conclusion: Prostatic urethral lift can be complicated by the rare massive pelvic hematoma, possibly more common in small prostates. With a prompt contrast computed tomography scan, pelvic hematomas can be managed with angioembolization first and hopefully prevent open exploratory surgery.

Causal Effects of Modifiable Behaviors on Prostate Cancer in Europeans and East Asians: A Comprehensive Mendelian Randomization Study.

OBJECTIVE: Early evidence is disputable for the effects of modifiable lifestyle behaviors on prostate cancer (PCa) risk. No research has yet appraised such causality in different ancestries using a Mendelian randomization (MR) approach. METHODS: A two-sample univariable and multivariable MR analysis was performed. Genetic instruments associated with lifestyle behaviors were selected based on genome-wide association studies. Summary-level data for PCa were obtained from PRACTICAL and GAME-ON/ELLIPSE consortia for Europeans (79,148 PCa cases and 61,106 controls), and ChinaPCa consortium for East Asians (3343 cases and 3315 controls). Replication was performed using FinnGen (6311 cases and 88,902 controls) and BioBank Japan data (5408 cases and 103,939 controls). RESULTS: Tobacco smoking was identified as increasing PCa risks in Europeans (odds ratio [OR]: 1.95, 95% confidence interval [CI]: 1.09-3.50, p = 0.027 per standard deviation increase in the lifetime smoking index). For East Asians, alcohol drinking (OR: 1.05, 95%CI: 1.01-1.09, p = 0.011) and delayed sexual initiation (OR: 1.04, 95%CI: 1.00-1.08, p = 0.029) were identified as risk factors, while cooked vegetable consumption (OR: 0.92, 95%CI: 0.88-0.96, p = 0.001) was a protective factor for PCa. CONCLUSIONS: Our findings broaden the evidence base for the spectrum of PCa risk factors in different ethnicities, and provide insights into behavioral interventions for prostate cancer.

Applying Lean Kaizen to Improve Timely Computed Tomography Scan Appointments for Oncology Patients in a Safety Net Hospital.

PURPOSE: Timely radiographic studies are essential to oncology care. At our institution, a safety net hospital in a large metropolitan area, baseline assessment determined that the overwhelming majority of outpatient computed tomographic (CT) scans for oncology patients were overdue and not scheduled within 2 weeks of their first requested date. METHODS: We conducted a series of structured, interdisciplinary meetings including staff from radiology, oncology, scheduling, and administration to critically review the scheduling process utilizing Lean Kaizen quality improvement methods. A new workflow was developed in which clinic staff scheduled CT scans before clinic discharge. Three months after our initial meeting, the new workflow was launched. We set a target of decreasing the percentage of overdue scans to below 20%. RESULTS: At baseline, 87% (65 of 75) of CT scans awaiting scheduling were overdue. Data were gathered at 5 and 10 weeks after implementation of our workflow. The percentage of CT scans overdue for scheduling was 17% (9 of 53) at 5 weeks and 0.97% (1 of 103) at 10 weeks after implementation. Clinic visit durations were not affected. CONCLUSION: The Lean Kaizen QI model was successful in decreasing the rate of oncology patients overdue for CT scan scheduling with minimal effects on clinic visit durations. This study demonstrated the importance of interdepartmental collaboration and continuous monitoring for improvement. Given the success of this project, this workflow will be expanded to other outpatient clinics within our institution.

Outcomes of radical prostatectomy in a 20-year localized prostate cancer single institution series in China.

The long-term survival outcomes of radical prostatectomy (RP) in Chinese prostate cancer (PCa) patients are poorly understood. We conducted a single-center, retrospective analysis of patients undergoing RP to study the prognostic value of pathological and surgical information. From April 1998 to February 2022, 782 patients undergoing RP at Queen Mary Hospital of The University of Hong Kong (Hong Kong, China) were included in our study. Multivariable Cox regression analysis and Kaplan-Meier analysis with stratification were performed. The 5-year, 10-year, and 15-year overall survival (OS) rates were 96.6%, 86.8%, and 70.6%, respectively, while the 5-year, 10-year, and 15-year PCa-specific survival (PSS) rates were 99.7%, 98.6%, and 97.8%, respectively. Surgical International Society of Urological Pathology PCa grades (ISUP Grade Group) ≥4 was significantly associated with poorer PSS (hazard ratio [HR] = 8.52, 95% confidence interval [CI]: 1.42-51.25, P = 0.02). Pathological T3 stage was not significantly associated with PSS or OS in our cohort. Lymph node invasion and extracapsular extension might be associated with worse PSS (HR = 20.30, 95% CI: 1.22-336.38, P = 0.04; and HR = 7.29, 95% CI: 1.22-43.64, P = 0.03, respectively). Different surgical approaches (open, laparoscopic, or robotic-assisted) had similar outcomes in terms of PSS and OS. In conclusion, we report the longest timespan follow-up of Chinese PCa patients after RP with different approaches.

Extended DNA-binding interfaces beyond the canonical SAP domain contribute to the function of replication stress regulator SDE2 at DNA replication forks.

Elevated DNA replication stress causes instability of the DNA replication fork and increased DNA mutations, which underlies tumorigenesis. The DNA replication stress regulator silencing-defective 2 (SDE2) is known to bind to TIMELESS (TIM), a protein of the fork protection complex, and enhances its stability, thereby supporting replisome activity at DNA replication forks. However, the DNA-binding activity of SDE2 is not well defined. Here, we structurally and functionally characterize a new conserved DNA-binding motif related to the SAP (SAF-A/B, Acinus, PIAS) domain in human SDE2 and establish its preference for ssDNA. Our NMR solution structure of the SDE2SAP domain reveals a helix-extended loop-helix core with the helices aligned parallel to each other, consistent with known canonical SAP folds. Notably, we have shown that the DNA interaction of this SAP domain extends beyond the core SAP domain and is augmented by two lysine residues in the C-terminal tail, which is uniquely positioned adjacent to the SAP motif and conserved in the pre-mRNA splicing factor SF3A3. Furthermore, we found that mutation in the SAP domain and extended C terminus not only disrupts ssDNA binding but also impairs TIM localization at replication forks, thus inhibiting efficient fork progression. Taken together, our results establish SDE2SAP as an essential element for SDE2 to exert its role in preserving replication fork integrity via fork protection complex regulation and highlight the structural diversity of the DNA-protein interactions achieved by a specialized DNA-binding motif.

Outcomes in Pediatric Thyroidectomy: Results From a Multinational, Multi-institutional Database.

OBJECTIVE: Traditionally, data regarding thyroidectomy were extracted from billing databases, but information may be missed. In this study, a multi-institutional pediatric thyroidectomy database was used to evaluate recurrent laryngeal nerve (RLN) injury and hypoparathyroidism. STUDY DESIGN: Retrospective multi-institutional cohort study. SETTING: Tertiary care pediatric hospital systems throughout North America. METHODS: Data were individually collected for thyroidectomies, then entered into a centralized database and analyzed using univariate and multivariable regression models. RESULTS: In total, 1025 thyroidectomies from 10 institutions were included. Average age was 13.9 years, and 77.8% were female. Average hospital stay was 1.9 nights and 13.5% of patients spent at least 1 night in the pediatric intensive care unit. The most frequent pathology was papillary thyroid carcinoma (42%), followed by Graves' disease (20.1%) and follicular adenoma (18.2%). Overall, 1.1% of patients experienced RLN injury (0.8% permanent), and 7.2% experienced hypoparathyroidism (3.3% permanent). Lower institutional volume (odds ratio [OR], 3.57; 95% CI, 1.72-7.14) and concurrent hypoparathyroidism (OR, 3.51; 95% CI, 1.64-7.53) correlated with RLN injury on multivariable analysis. Graves' disease (OR, 2.27; 95% CI, 1.35-3.80), Hashimoto's thyroiditis (OR, 4.67; 95% CI, 2.39-9.09), central neck dissection (OR, 3.60; 95% CI, 2.36-5.49), and total vs partial thyroidectomy (OR, 7.14; 95% CI, 4.55-11.11) correlated with hypoparathyroidism. CONCLUSION: These data present thyroidectomy information and complications pertinent to surgeons, along with preoperative risk factor assessment. Multivariable analysis showed institutional volume and hypoparathyroidism associated with RLN injury, while hypoparathyroidism associated with surgical indication, central neck dissection, and extent of surgery. Low complication rates support the safety of thyroidectomy in pediatric tertiary care centers.

Second generation of temporary implantable nitinol device (iTind) in men with LUTS: 2 year results of the MT-02-study.

OBJECTIVES: Assessing medium-term functional results of a novel minimally-invasive treatment for lower urinary tract symptoms due to BPO with the second generation of the temporary implantable nitinol device (iTind; Medi-Tate Ltd®, Israel): 2-year follow-up of a single-arm, prospective, international multicenter study. Further, we aimed to identify preoperative baseline parameters predicting response to iTind treatment. METHODS: Following local ethical committee approval in every participating centre, 81 men with symptomatic BPO (IPSS ≥ 10, peak urinary flow < 12 ml/s, and prostate volume < 75 ml) were enrolled in this study. Patients with PVR > 250 ml, obstructive median lobe, previous prostatic surgery, confounding bladder or sphincter dysfunction based on medical history, active urinary infection and unable to interrupt antithrombotic or antiplatelet treatment were exclusion criteria. A wash-out period of 1 month for alpha-blockers and 6 months for 5-ARIs was mandatory to avoid confounders. The procedure was performed as previously described: implantation under light sedation and removal 5-7 days later with topical sedation. Patients were assessed for perioperative results including OR-time, pain (VAS) and complications (Clavien-Dindo-Grading System); and for functional results (PVR, Qmax, IPSS) and quality of life (QoL) including sexual and ejaculatory function using two yes/no questions. Follow-up assessments were done at 1, 3, and 6 months, and 1 and 2 years. RESULTS: Of the 81 patients initially enrolled in this study, follow-up included 67 men at 1 year and 51 men at 2 years. For the 51 men included in the present analysis, the median age was 65 years, median prostate volume 37 ml (range 16-65 ml). Baseline values for IPSS and QoL were 20.51 ± 4.58, 3.96 ± 0.87. Qmax and PVR were 7.62 ± 2.25 ml/s and 65.84 ± 38.46, respectively. No intraoperative complications were observed and the average pain level recorded on the visual analogue scale (VAS) was 3.2 ± 1.6. A significant reduction in symptoms and improvement in urinary flow was observed (p < 0.0001) at all assessment points: IPSS-score and QoL improved to 8.51 ± 5.51 and 1.76 ± 1.32, respectively; and Qmax increased to 16.00 ± 7.43 ml/s. None of the patients who were previously sexually active reported a deterioration in sexual or ejaculatory functions according to two yes/no questions over the follow-up period. Excluding the patients lost at follow-up, five patients underwent surgery between 12 and 24 months. Upon investigation, it was discovered that four of the five patients requiring surgery had median lobes and were protocol deviators. A failure analysis was carried out for all 81 patients in order to identify baseline parameters that could predict treatment failure. 58.33% of patients in the failure group (7 out of 12) had median lobes which was found to be statistically significant (p < 0.0001). None of the other preoperative variables (age, prostate volume, IPSS scores, Qmax, PVR, and PSA) were found to predict response to iTind treatment. CONCLUSION: iTind treatment for BPO-related LUTS showed marked and durable reduction in symptoms and improvement of functional parameters and quality of life at 24 months of follow-up. It was found that median lobe may predict failure of iTind treatment. According to the yes/no questions, ejaculatory and sexual functions do not seem to be effected following treatment, however, this finding must be supported with further studies using the accepted tools.

Hyperactive LH Pulses and Elevated Kisspeptin and NKB Gene Expression in the Arcuate Nucleus of a PCOS Mouse Model.

Polycystic ovary syndrome (PCOS), a common reproductive disorder in women, is characterized by hyperandrogenemia, chronic anovulation, cystic ovarian follicles, and luteinizing hormone (LH) hyper-pulsatility, but the pathophysiology isn't completely understood. We recently reported a novel mouse model of PCOS using chronic letrozole (LET; aromatase inhibitor). Letrozole-treated females demonstrate multiple PCOS-like phenotypes, including polycystic ovaries, anovulation, and elevated circulating testosterone and LH, assayed in "one-off" measures. However, due to technical limitations, in vivo LH pulsatile secretion, which is elevated in PCOS women, was not previously studied, nor were the possible changes in reproductive neurons. Here, we used recent technical advances to examine in vivo LH pulse dynamics of freely moving LET female mice versus control and ovariectomized (OVX) mice. We also determined whether neural gene expression of important reproductive regulators such as kisspeptin, neurokinin B (NKB), and dynorphin, is altered in LET females. Compared to controls, LET females exhibited very rapid, elevated in vivo LH pulsatility, with increased pulse frequency, amplitude, and basal levels, similar to PCOS women. Letrozole-treated mice also had markedly elevated Kiss1, Tac2, and Pdyn expression and increased Kiss1 neuronal activation in the hypothalamic arcuate nucleus. Notably, the hyperactive LH pulses and increased kisspeptin neuron measures of LET mice were not as elevated as OVX females. Our findings indicate that LET mice, like PCOS women, have markedly elevated LH pulsatility, which likely drives increased androgen secretion. Increased hypothalamic kisspeptin and NKB levels may be fundamental contributors to the hyperactive LH pulse secretion in the LET PCOS-like condition and, perhaps, in PCOS women.

Risk factors in the prediction of long-term patency of Resonance metallic ureteric stent in malignant ureteric obstruction.

Objectives: Cancer is the second leading cause of death globally in 2018 with an estimated 9.6 million deaths. The costs of managing malignant ureteric obstruction (MUO) is a significant burden to any healthcare system. However, the management of MUO has long been a challenge for urologists. The standard options of percutaneous nephrostomy or polymer double J stents are fraught with problems. We report a large patient series with long-term follow-up in the use of Resonance metallic ureteric stents to relieve MUO, and identification of risk factors associated with stent failure. Patients and methods: All patients with MUO who were arranged to have Resonance metallic ureteric stent insertion at two university hospitals were included in this cohort study, starting from June 2011 to July 2016. Data were retrieved retrospectively. The primary outcome was the total duration of stent patency before stent failure due to malignant disease progression. Stent failure was defined as ureteric obstruction identified on imaging (functional radioisotope scan or antegrade pyelogram), acute renal failure resolved by subsequent percutaneous nephrostomy, or any other cause requiring stent removal prematurely. Secondary outcomes were identification of factors associated with stent failure, grade III or above complication, and development of a risk-adopted model to predict metallic ureteric stent patency rates in MUO patients. Median duration of functioning metallic ureteric stent was determined with Kaplan-Meier survival curve. Results: A total of 124 renal units in 95 patients with MUO were eligible for the study, with a median follow-up period of 22.9 months. About 106 (85.5%) renal units had successful metallic stent insertion, of whom 41 (33.1%) renal units ultimately progressed to ureteric obstruction despite the metallic stents, and required subsequent insertion of nephrostomies. Median duration of functioning metallic ureteric stents was 25 months. Female gender (HR 3.0, 95% CI: 1.3-7.2, P = .014) and suspicious bladder lesion (HR 2.9, 95% CI: 1.4-6.2, P = .005) were independent risk factors for stent failure, respectively. Stratifying patients into low (0 risk factor), intermediate (1 risk factor), and high (2 risk factors) risk groups, we found that this could predict the duration of stent patency in MUO with the metallic stents. (Low risk: 30.3 months vs intermediate group: 17.8 months vs high risk: 4.9 months, P < .001). Conclusion: Resonance metallic ureteral stents are able provide a median of 25 months of ureteric drainage in patients with MUO. Determining whether a patient has one or both risks factors (female gender and bladder lesion) will allow one to estimate the duration of metallic stent patency, which in turn may aid in determining cost-effectiveness in individual patients.

Is prostate specific antigen (PSA) density necessary in selecting prostate cancer patients for active surveillance and what should be the cutoff in the Asian population?

BACKGROUND: To investigate the role of Prostate Specific Antigen density (PSAD) in selecting prostate cancer patients for active surveillance (AS) and to determine a cutoff PSAD in identifying adverse pathological outcomes. METHODS: Data from 287 patients who underwent radical prostatectomy for prostate cancer were retrospectively reviewed. Six different AS protocols, the University of Toronto; Royal Marsden; John Hopkins; University of California San Francisco (UCSF); Memorial Sloan Kettering Cancer Center (MSKCC) and Prostate Cancer Research International: Active Surveillance (PRIAS), were applied to the cohort. Pre-operative demographics and pathological outcomes were analysed. Statistical analyses on the predictive factors of adverse pathological outcomes and significance of PSAD were performed. A cutoff PSAD with best balance between sensitivity and specificity in identifying adverse pathological outcome was determined. RESULTS: PSAD predicted adverse pathological outcomes better than Prostate Specific Antigen (PSA) level alone. The PSAD was significantly lower (0.12-0.13 ng/dl/ml) in protocols including PSAD (the John Hopkins and PRIAS) compared with the other four protocols not including PSAD as a selection criteria (0.21-0.25 ng/dl/dl, P = 0.00). PSAD predicted adverse pathological outcomes in all protocols not incorporating PSAD as an inclusion criteria (P = 0.00-0.02). By the receiver operator characteristics curve analysis, it was found that a PSAD level of 0.19 ng/ml/ml had the best balance between sensitivity and specificity in predicting pathological adverse disease (Area under curve = 0.63, P = 0.004). CONCLUSION: PSAD is necessary in selecting prostate cancer patients for active surveillance. It predicts adverse pathological outcomes in patients eligible for active surveillance better than PSA level alone. A PSAD cutoff at 0.19 ng/ml/ml has the best balance between sensitivity and specificity in predicting pathological adverse disease. We recommend using AS protocol incorporating PSAD as a selection criteria (in particular the PRIAS protocol with a cutoff PSAD at 0.2 ng/ml/ml) when recruiting prostate cancer patients for AS.

Multi-material three dimensional printed models for simulation of bronchoscopy.

BACKGROUND: Bronchoscopy involves exploration of a three-dimensional (3D) bronchial tree environment using just two-dimensional (2D) images, visual cues and haptic feedback. Sound knowledge and understanding of tracheobronchial anatomy as well as ample training experience is mandatory for technical mastery. Although simulated modalities facilitate safe training for inexperienced operators, current commercial training models are expensive or deficient in anatomical accuracy, clinical fidelity and patient representation. The advent of Three-dimensional (3D) printing technology may resolve the current limitations with commercial simulators. The purpose of this report is to develop and test the novel multi-material three-dimensional (3D) printed airway models for bronchoscopy simulation. METHODS: Using material jetting 3D printing and polymer amalgamation, human airway models were created from anonymized human thoracic computed tomography images from three patients: one normal, a second with a tumour obstructing the right main bronchus and third with a goitre causing external tracheal compression. We validated their efficacy as airway trainers by expert bronchoscopists. Recruited study participants performed bronchoscopy on the 3D printed airway models and then completed a standardized evaluation questionnaire. RESULTS: The models are flexible, life size, anatomically accurate and patient specific. Five expert respiratory physicians participated in validation of the airway models. All the participants agreed that the models were suitable for training bronchoscopic anatomy and access. Participants suggested further refinement of colour and texture of the internal surface of the airways. Most respondents felt that the models are suitable simulators for tracheal pathology, have a learning value and recommend it to others for use in training. CONCLUSION: Using material jetting 3D printing to create patient-specific anatomical models is a promising modality of simulation training. Our results support further evaluation of the printed airway model as a bronchoscopic trainer, and suggest that pathological airways may be simulated using this technique.

Second-generation of temporary implantable nitinol device for the relief of lower urinary tract symptoms due to benign prostatic hyperplasia: results of a prospective, multicentre study at 1 year of follow-up.

OBJECTIVES: To report the clinical experience with a second-generation of temporary implantable nitinol device (iTIND; Medi-Tate Ltd, Or-Akiva, Israel) for the treatment of lower urinary tract symptoms (LUTS) due to benign prostatic hyperplasia (BPH) after 1 year of follow-up. PATIENTS AND METHODS: In all, 81 patients with LUTS, International Prostate Symptom Score (IPSS) ≥10, maximum urinary flow rate (Qmax ) ≤12 mL/s, and prostate volume <75 mL, were enrolled in this prospective Research Ethics Committee-approved multicentre study. The main exclusion criteria were: haemostatic disorders, post-void residual urine volume (PVR) >250 mL, obstructive median lobe, and previous prostate surgery. The iTIND was implanted within the bladder neck and the prostatic urethra under light sedation, using a rigid cystoscope. The device was removed 5-7 days later in an outpatient setting. Demographics, perioperative results, complications (according to the Clavien-Dindo system), functional results and quality of life (QoL) were evaluated. Follow-up assessments were conducted at 1, 3, 6 and 12 months postoperatively. RESULTS: The mean (sd) patient age was 65 (8.9) years, prostate volume was 40.5 (12.25) mL, Qmax was 7.3 (2.6) mL/s, IPSS was 22.5 (5.6), and the median (interquartile range) IPSS QoL score was 4 (2-5). All the implantations were successful, with no intraoperative complications recorded; all patients were discharged on the same day of surgery. The devices were retrieved at a mean (SD) of 5.9 (1.1) days after implantation, typically under topical anaesthesia. No Clavien-Dindo Grade >II complications were recorded. The mean (SD) Qmax at the 1 month follow-up visit was 11.2 (5.7) mL/s and continued to improve thereafter, reaching 14.7 (8.1) mL/s at the 12-month follow-up visit (+100%). The mean (SD) IPSS urinary symptom scores were 11.7 (8.0) after 1 month and further improved to 8.8 (6.4) at the 12-month follow-up (-60%). In parallel, the mean (SD) IPSS QoL score drop reached 1.6 (1.3) by the end of the study. During the 12-month period, two patients (2.4%) required medical therapy for BPH, two patients (2.4%) required transurethral resection of the prostate, whilst 10 patients were lost to follow-up (12.3%). As compared to baseline, none of the 61 sexually active patients who completed the 12-month follow-up period reported sexual or ejaculatory dysfunction. CONCLUSION: iTIND implantation is feasible, safe and effective in providing relief of BPH-related symptoms, at least until 12 months postoperatively. Sexual and ejaculatory functions are fully preserved. Further studies with a longer follow-up period are needed to assess the durability of these results and to clearly define the indications for iTIND implantation.

GEL THE NEC: a prospective registry evaluating the safety, ease of use, and efficacy of the HydroSoft coil as a finishing device.

BACKGROUND AND PURPOSE: The HydroSoft coil was developed as a finishing coil, ideally to be placed along the aneurysm neck to enhance intracranial aneurysm healing. The GEL THE NEC (Gaining Efficacy Long Term: Hydrosoft, an Emerging, New, Embolic Coil) multicenter registry was developed to assess the safety and efficacy of HydroSoft coils in treating intracranial aneurysms. We report angiographic and clinical results of this prospective registry. MATERIALS AND METHODS: GEL THE NEC was performed at 27 centers in five countries. Patients aged 21-90 years with a ruptured or unruptured aneurysm 3-15 mm in size were eligible for enrollment. The following variables were obtained: demographics/comorbidities, aneurysm geometry, adjunctive devices used, proportion of patients in whom HydroSoft coils were successfully placed, and long-term angiographic outcomes (graded by an independent core laboratory using the Modified Raymond Scale), and procedure-related adverse events. Predictors of good angiographic outcome were studied using χ2 and t-tests. RESULTS: A total of 599 patients with 599 aneurysms were included in this study. HydroSoft coils were successfully deployed in 577 (96.4%) patients. Procedure-related major morbidity and mortality were 0.5% (3/599) and 1.3% (8/599), respectively. The most common perioperative complications were iatrogenic vasospasm (30/599, 5.0%), thromboemboli (27/599, 4.5%), and aneurysm perforation (16/599, 2.7%). At last angiographic follow-up (mean 9.0±6.3 months), the complete occlusion rate was 63.2% (280/442) and near complete occlusion rate was 25.2% (107/442). The core laboratory read recanalization rate was 10.8% (46/425) and the retreatment rate was 3.4% (20/599). CONCLUSIONS: Endovascular treatment of intracranial aneurysms with HydroSoft coils resulted in complete/near complete occlusion rates of 88% and a major complication rate of 1.8%. TRIAL REGISTRATION NUMBER: NCT01000675.