En bloc resection of bladder tumour: the rebirth of past through reminiscence.

PURPOSE: To learn about the history and development of en bloc resection of bladder tumour (ERBT), and to discuss its future directions in managing bladder cancer. METHODS: In this narrative review, we summarised the history and early development of ERBT, previous attempts in overcoming the tumour size limitation, consolidative effort in standardising the ERBT procedure, emerging evidence in ERBT, evolving concepts in treating large bladder tumours, and the future directions of ERBT. RESULTS: Since the first report on ERBT in 1980, there has been tremendous advancement in terms of its technique, energy modalities and tumour retrieval methods. In 2020, the international consensus statement on ERBT has been developed and it serves as a standard reference for urologists to practise ERBT. Recently, high-quality evidence on ERBT has been emerging. Of note, the EB-StaR study showed that ERBT led to a reduction in 1-year recurrence rate from 38.1 to 28.5%. An individual patient data meta-analysis is currently underway, and it will be instrumental in defining the true value of ERBT in treating non-muscle-invasive bladder cancer. For large bladder tumours, modified approaches of ERBT should be accepted, as the quality of resection is more important than a mere removal of tumour in one piece. The global ERBT registry has been launched to study the value of ERBT in a real-world setting. CONCLUSION: ERBT is a promising surgical technique in treating bladder cancer and it has gained increasing interest globally. It is about time for us to embrace this technique in our clinical practice.

The combined role of MRI prostate and prostate health index in improving detection of significant prostate cancer in a screening population of Chinese men / 亚洲男科学杂志(英文版)

Using prostate-specific antigen (PSA) for prostate cancer (PCa) screening led to overinvestigation and overdiagnosis of indolent PCa. We aimed to investigate the value of prostate health index (PHI) and magnetic resonance imaging (MRI) prostate in an Asian PCa screening program. Men aged 50-75 years were prospectively recruited from a community-based PSA screening program. Men with PSA 4.0-10.0 ng ml -1 had PHI result analyzed. MRI prostate was offered to men with PSA 4.0-50.0 ng ml -1 . A systematic prostate biopsy was offered to men with PSA 4.0-9.9 ng ml -1 and PHI ≥35, or PSA 10.0-50.0 ng ml -1 . Additional targeted prostate biopsy was offered if they had PI-RADS score ≥3. Clinically significant PCa (csPCa) was defined as the International Society of Urological Pathology (ISUP) grade group (GG) ≥2 or ISUP GG 1 with involvement of ≥30% of total systematic cores. In total, 12.8% (196/1536) men had PSA ≥4.0 ng ml -1 . Among 194 men with PSA 4.0-50.0 ng ml -1 , 187 (96.4%) received MRI prostate. Among them, 28.3% (53/187) had PI-RADS ≥3 lesions. Moreover, 7.0% (107/1536) men were indicated for biopsy and 94.4% (101/107) men received biopsy. Among the men received biopsy, PCa, ISUP GG ≥2 PCa, and csPCa was diagnosed in 42 (41.6%), 24 (23.8%), and 34 (33.7%) men, respectively. Compared with PSA/PHI pathway in men with PSA 4.0-50.0 ng ml -1 , additional MRI increased diagnoses of PCa, ISUP GG ≥2 PCa, and csPCa by 21.2% (from 33 to 40), 22.2% (from 18 to 22), and 18.5% (from 27 to 32), respectively. The benefit of additional MRI was only observed in PSA 4.0-10.0 ng ml -1 , and the number of MRI needed to diagnose one additional ISUP GG ≥2 PCa was 20 in PHI ≥35 and 94 in PHI <35. Among them, 45.4% (89/196) men with PSA ≥4.0 ng ml -1 avoided unnecessary biopsy with the use of PHI and MRI. A screening algorithm with PSA, PHI, and MRI could effectively diagnose csPCa while reducing unnecessary biopsies. The benefit of MRI prostate was mainly observed in PSA 4.0-9.9 ng ml -1 and PHI ≥35 group. PHI was an important risk stratification step for PCa screening.

Report of the third Asian Prostate Cancer study meeting.

The Asian Prostate Cancer (A-CaP) study is an Asia-wide initiative that was launched in December 2015 in Tokyo, Japan, with the objective of surveying information about patients who have received a histopathological diagnosis of prostate cancer (PCa) and are undergoing treatment and clarifying distribution of staging, the actual status of treatment choices, and treatment outcomes. The study aims to clarify the clinical situation for PCa in Asia and use the outcomes for the purposes of international comparison. Following the first meeting in Tokyo in December 2015, the second A-CaP meeting was held in Seoul, Korea, in September 2016. This, the third A-CaP meeting, was held on October 14, 2017, in Chiang Mai, Thailand, with the participation of members and collaborators from 12 countries and regions. In the meeting, participating countries and regions presented the current status of data collection, and the A-CaP office presented a preliminary analysis of the registered cases received from each country and region. Participants discussed ongoing challenges relating to data input and collection, institutional, and legislative issues that may present barriers to data sharing, and the outlook for further patient registrations through to the end of the registration period in December 2018. In addition to A-CaP-specific discussions, a series of special lectures were also delivered on the situation for health insurance in the United States, the correlation between insurance coverage and PCa outcomes, and the outlook for robotic surgery in the Asia-Pacific region. Members also confirmed the principles of authorship in collaborative studies, with a view to publishing original articles based on A-CaP data in the future.

Transurethral resection of prostate for acute urinary retention is linked to shorter survival in younger men / 亚洲男科学杂志(英文版)

It is largely unknown whether lower urinary tract symptoms (LUTS) or acute retention of urine (AROU) is linked to shorter life expectancy in men. We conducted a multicenter, retrospective database analysis of patients undergoing transurethral resection of prostate (TURP) to study their relationships. Multivariate Cox regression analysis and Kaplan-Meier analysis with stratification to age and indication of TURP were performed. We further performed an age- and sex-matched survival analysis with the general population using data from the Census and Statistics Department of the Hong Kong Special Administrative Region (Hong Kong, China). From January 2002 to December 2012, 3496 patients undergoing TURP were included in our study, with 1764 patients in the LUTS group and 1732 patients in the AROU group. Old age, ischemic heart disease, cerebrovascular accident, and AROU were risk factors of mortality. Patients aged <70 years (adjusted hazard ratio [HR]: 1.52, 95% confidence interval [CI]: 1.11-2.09, P = 0.010) and 70-80 years (adjusted HR: 1.39, 95% CI: 1.15-1.70, P = 0.001) in the AROU group had worse survival than those in the LUTS group, but such difference was not demonstrated in patients aged >80 years. Compared to the general population, younger patients in the LUTS group appeared to have better survival (<70 years, P = 0.091; 70-80 years, P = 0.011), but younger patients in the AROU group had worse survival (<70 years, P = 0.021; 70-80 years, P = 0.003). For patients aged >80 years, survival was similar with the general population in both the LUTS and AROU groups. In conclusion, AROU at young age was associated with mortality, while early detection and management of LUTS may improve survival.

Report of the Second Asian Prostate Cancer (A-CaP) Study Meeting.

The Asian Prostate Cancer (A-CaP) Study is an Asia-wide initiative that has been developed over the course of 2 years. The study was launched in December 2015 in Tokyo, Japan, and the participating countries and regions engaged in preparations for the study during the course of 2016, including patient registration and creation of databases for the purpose of the study. The Second A-CaP Meeting was held on September 8, 2016 in Seoul, Korea, with the participation of members and collaborators from 12 countries and regions. Under the study, each participating country or region will begin registration of newly diagnosed prostate cancer patients and conduct prognostic investigations. From the data gathered, common research themes will be identified, such as comparisons among Asian countries of background factors in newly diagnosed prostate cancer patients. This is the first Asia-wide study of prostate cancer and has developed from single country research efforts in this field, including in Japan and Korea. At the Second Meeting, participating countries and regions discussed the status of preparations and discussed various issues that are being faced. These issues include technical challenges in creating databases, promoting participation in each country or region, clarifying issues relating to data input, addressing institutional issues such as institutional review board requirements, and the need for dedicated data managers. The meeting was positioned as an opportunity to share information and address outstanding issues prior to the initiation of the study. In addition to A-CaP-specific discussions, a series of special lectures was also delivered as a means of providing international perspectives on the latest developments in prostate cancer and the use of databases and registration studies around the world.

PAN substitutions A37S, A37S/I61T and A37S/V63I attenuate the replication of H7N7 influenza A virus by impairing the polymerase and endonuclease activities.

Substitutions in the PA N-terminus (PAN) of influenza A viruses are associated with viral pathogenicity. During our previous study, which identified PAN-V63I and -A37S/I61T/V63I/V100A substitutions as virulence determinants, we observed a severe decrease in virus growth and transcription/replication capacity posed by PAN-A37S/V100A substitution. To further delineate the significance of substitutions at these positions, we generated mutant H7N7 viruses bearing the substitutions PAN-A37S, -A37S/I61T, -A37S/V63I, -V100A, -I61T/V100A and -V63I/V100A by reverse genetics. Our results showed that all mutant viruses except PAN-V100A showed a significantly reduced growth capability in infected cells. At the same time, the PAN-A37S, -A37S/I61T and -A37S/V63I mutant viruses displayed decreased viral transcription and replication by diminishing virus RNA synthesis activity. Biochemical assays indicated that the substitutions PAN-A37S, -A37S/I61T and -A37S/V63I suppressed the polymerase and endonuclease activities when compared with those of the wild-type. Together, our results demonstrated that the PAN-A37S, -A37S/I61T and -A37S/V63I substitutions contributed to a decreased pathogenicity of avian H7N7 influenza A virus.

The Risk of Upper Urinary Tract Involvement in Patients With Ketamine-Associated Uropathy / 대한배뇨장애요실금학회지

PURPOSE: The aims of this study were to investigate the prevalence of upper tract involvement in ketamine-associated uropathy, and to determine the predictors of hydronephrosis in patients with a history of ketamine abuse. METHODS: This was a cross-sectional study of a prospective cohort of patients with ketamine-associated uropathy. Data including demographics, pattern of ketamine abuse, pelvic pain and urgency or frequency (PUF) symptom score, uroflowmetry (UFM) parameters, serum renal function, and liver function tests were collected. Upon consultation, ultrasonography was performed to assess the function of the urinary system. RESULTS: From December 2011 to October 2015, we treated 572 patients with ketamine-associated uropathy. Of these patients, 207 (36.2%) had managed to achieve abstinence at the time of their first consultation. Ninety-six patients (16.8%) in the cohort were found to have hydronephrosis on ultrasonography. Univariate analysis identified age, duration of ketamine abuse, PUF symptom score, voided volume on UFM, serum creatinine levels >100 μmol/L, and an abnormal serum liver enzyme profile as factors associated with hydronephrosis. Logistic regression revealed the following parameters to be statistically related to hydronephrosis: age (adjusted odds ratio [OR], 1.090; 95% confidence interval [CI], 1.020–1.166; P=0.012), functional bladder capacity (adjusted OR, 0.997; 95% CI, 0.995–0.999; P=0.029), serum creatinine >100 μmol/L (adjusted OR, 3.107; 95% CI, 1.238–7.794; P=0.016, and an abnormal serum liver enzyme profile (adjusted OR, 1.967; 95% CI, 1.213–3.187; P=0.006). CONCLUSIONS: Ketamine-associated uropathy can involve the upper urinary tract. Patient demographics as well as investigations of UFM, renal function tests, and liver function tests may allow us to identify at-risk patients.

Asia prostate cancer study (A-CaP Study) launch symposium.

The Asian Prostate Cancer (A-CaP) Study is an Asia-wide initiative that has been developed over the course of 2 years. The A-CaP Study is scheduled to begin in 2016, when each participating country or region will begin registration of newly diagnosed prostate cancer patients and conduct prognosis investigations. From the data gathered, common research themes will be identified, such as comparisons among Asian countries of background factors in newly diagnosed prostate cancer patients. This is the first Asia-wide study of prostate cancer and has developed from single country research efforts in this field, including in Japan and Korea. The inaugural Board Meeting of A-CaP was held on December 11, 2015 at the Research Center for Advanced Science and Technology, The University of Tokyo, attended by representatives of all participating countries and regions, who signed a memorandum of understanding concerning registration for A-CaP. Following the Board Meeting an A-CaP Launch Symposium was held. The symposium was attended by representatives of countries and regions participating in A-CaP, who gave presentations. Presentations and a keynote address were also delivered by representatives of the University of California San Francisco, USA, and the Peter MacCallum Cancer Centre, Australia, who provided insight and experience on similar databases compiled in their respective countries.

A novel peptide with potent and broad-spectrum antiviral activities against multiple respiratory viruses.

A safe, potent and broad-spectrum antiviral is urgently needed to combat emerging respiratory viruses. In light of the broad antiviral activity of ß-defensins, we tested the antiviral activity of 11 peptides derived from mouse ß-defensin-4 and found that a short peptide, P9, exhibited potent and broad-spectrum antiviral effects against multiple respiratory viruses in vitro and in vivo, including influenza A virus H1N1, H3N2, H5N1, H7N7, H7N9, SARS-CoV and MERS-CoV. The antiviral activity of P9 was attributed to its high-affinity binding to viral glycoproteins, as well as the abundance of basic amino acids in its composition. After binding viral particles through viral surface glycoproteins, P9 entered into cells together with the viruses via endocytosis and prevented endosomal acidification, which blocked membrane fusion and subsequent viral RNA release. This study has paved the avenue for developing new prophylactic and therapeutic agents with broad-spectrum antiviral activities.

The aetiopathogenesis of fatigue: unpredictable, complex and persistent.

BACKGROUND: Chronic fatigue syndrome is a common condition characterized by severe fatigue with post-exertional malaise, impaired cognitive ability, poor sleep quality, muscle pain, multi-joint pain, tender lymph nodes, sore throat or headache. Its defining symptom, fatigue is common to several diseases. AREAS OF AGREEMENT: Research has established a broad picture of impairment across autonomic, endocrine and inflammatory systems though progress seems to have reached an impasse. AREAS OF CONTROVERSY: The absence of a clear consensus view of the pathophysiology of fatigue suggests the need to switch from a focus on abnormalities in one system to an experimental and clinical approach which integrates findings across multiple systems and their constituent parts and to consider multiple environmental factors. GROWING POINTS: We discuss this with reference to three key factors, non-determinism, non-reductionism and self-organization and suggest that an approach based on these principles may afford a coherent explanatory framework for much of the observed phenomena in fatigue and offers promising avenues for future research. AREAS TIMELY FOR DEVELOPING RESEARCH: By adopting this approach, the field can examine issues regarding aetiopathogenesis and treatment, with relevance for future research and clinical practice.

The effect of renal cortical thickness on the treatment outcomes of kidney stones treated with shockwave lithotripsy

PURPOSE: Because the shock wave passes through various body tissues before reaching the stone, stone composition may affect the treatment efficacy of shock wave lithotripsy (SWL). We investigated the effect of various tissue components along the shock wave path on the success of SWL. MATERIALS AND METHODS: From October 2008 to August 2010, a total of 206 patients with kidney stones sized 5 to 20 mm were prospectively recruited for a study of the factors that affect the outcome of treatment with a Sonolith Vision lithotripter. Successful SWL was defined as either stone-free status or residual fragments <4 mm at 12 weeks. Logistic regression analysis was performed to assess the factors that predicted treatment outcomes. Potential predictors included the patient's age, shock wave delivery rate, stone volume (SV), mean stone density (MSD), skin-to-stone distance (SSD), and the mean thickness of the three main components along the shock wave path: renal cortical thickness (KT), muscle thickness (MT), and soft-tissue thickness (ST). RESULTS: The mean age of the patients was 53.8 years (range, 25-82 years). The overall treatment success rate after one session of SWL was 43.2%. The mean KT, MT, and ST were 26.9, 16.6, and 40.8 mm, respectively. The logistic regression results showed that a slower shock wave delivery rate, smaller SV, a lower MSD, and a thicker KT were found to be significant predictors for successful SWL. SSD, MT, and ST were not predictors of successful treatment. CONCLUSIONS: Among the main tissue components along the shock wave path, a thicker KT was a favorable factor for successful SWL after adjustment for SV, MSD, and the shock wave delivery rate.

Effect of weight reduction on the severity of lower urinary tract symptoms in obese male patients with benign prostatic hyperplasia: A randomized controlled trial

PURPOSE: We assessed whether weight reduction is an effective intervention for the management of lower urinary tract symptoms (LUTS) and investigated the relationship between obesity and LUTS. MATERIALS AND METHODS: This was a prospective randomized controlled trial that enrolled obese men older than 50 years with LUTS. The study period was 52 weeks. All patients received standardized alpha-adrenergic blocker therapy for the treatment of benign prostatic hyperplasia (BPH) during the run-in period. Patients were randomized to receive either a standardized prerecorded video program on the general principle of weight reduction or a comprehensive weight reduction program. Patients were assessed at different time points with symptom assessment, uroflowmetry, transrectal ultrasound, and metabolic assessment. RESULTS: Sixty-five patients were allocated to each study arm. After the study period, no significant difference in weight reduction was found between the two arms. When the pre- and postintervention parameters were compared, none were statistically different between the 2 arms, namely nocturia, International Prostate Symptom Score, quality of life assessment, and uroflowmetry parameters. When the whole study population was taken as a single cohort, these parameters were also not significantly different between the group with a body mass index of 25 to <30 kg/m2 and the group with a BMI of 30 to 35 kg/m2. CONCLUSIONS: We found no association between obesity and LUTS. This could have been due to the less marked weight difference in our cohort. Whereas weight reduction may be an effective measure to improve LUTS, the implementation of a successful program remains a challenge.

The TRACTISS protocol: a randomised double blind placebo controlled clinical trial of anti-B-cell therapy in patients with primary Sjögren's Syndrome.

BACKGROUND: Primary Sjögren's Syndrome (PSS) mainly affects women (9:1 female:male ratio) and is one of the commonest autoimmune diseases with a prevalence of 0.1 - 0.6% of adult women. For patients with PSS there is currently no effective therapy that can alter the progression of the disease. The aim of the TRACTISS study is to establish whether in patients with PSS, treatment with rituximab improves clinical outcomes. METHODS/DESIGN: TRACTISS is a UK multi-centre, double-blind, randomised, controlled, parallel group trial of 110 patients with PSS. Patients will be randomised on a 1:1 basis to receive two courses of either rituximab or placebo infusion in addition to standard therapy, and will be followed up for up to 48 weeks. The primary objective is to assess the extent to which rituximab improves symptoms of fatigue and oral dryness. Secondary outcomes include ocular dryness, salivary flow rates, lacrimal flow, patient quality of life, measures of disease damage and disease activity, serological and peripheral blood biomarkers, and glandular histology and composition. DISCUSSION: The TRACTISS trial will provide direct evidence as to whether rituximab in patients with PSS leads to an improvement in patient symptoms and a reduction in disease damage and activity. TRIAL REGISTRATION: UKCRN Portfolio ID: 9809 ISRCTN65360827.

Prostate cancer in Asia: A collaborative report.

The incidence of prostate cancer (PCa) within Asian population used to be much lower than in the Western population; however, in recent years the incidence and mortality rate of PCa in some Asian countries have grown rapidly. This collaborative report summarized the latest epidemiology information, risk factors, and racial differences in PCa diagnosis, current status and new trends in surgery management and novel agents for castration-resistant prostate cancer. We believe such information would be helpful in clinical decision making for urologists and oncologists, health-care ministries and medical researchers.

Calcitriol restores renovascular function in estrogen-deficient rats through downregulation of cyclooxygenase-2 and the thromboxane-prostanoid receptor.

Cardiovascular risks increase in postmenopausal women. While vitamin D is supplemented for osteoporosis, it is not known whether it protects renal arterial function during estrogen deficiency. Here we measured changes in renovascular reactivity induced by ovariectomy in rats and examined whether calcitriol, the most active form of vitamin D, was able to correct such changes. The impairment of endothelium-dependent relaxation in renal arteries from ovariectomized rats was effectively reversed by long-term calcitriol treatment. It was also corrected by acute exposure to cyclooxygenase-2 (COX-2) inhibitors and a thromboxane-prostanoid receptor antagonist, respectively. Calcitriol normalized the overexpression of COX-2 and thromboxane-prostanoid receptors in intralobal renal artery segments and aortic endothelial cells isolated from ovariectomized rats. In vitro exposure of the arterial segments to calcitriol for 12 h improved relaxation and downregulated thromboxane-prostanoid receptors. The attenuated nitric oxide production in ovariectomized rat aortic endothelial cells was restored following a 12-h treatment with calcitriol, COX-2 inhibition, or thromboxane-prostanoid receptor antagonism. Thus, impaired endothelium-dependent renal artery relaxation in ovariectomized rats is mediated largely through increased activity and expression of COX-2 and the thromboxane-prostanoid receptor. Calcitriol restores endothelial function through downregulating both signaling proteins during estrogen deficiency.

Randomized controlled trial of antibiotic prophylaxis regimens for transrectal ultrasound-guided prostate biopsy / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>A prior study showed significant antibiotic resistance to quinolone in our population. In this study we aimed to evaluate and compare the efficacy of a single versus a combined prophylactic antibiotic regimen before transrectal ultrasound-guided prostate biopsy (TRUGPB).</p><p><b>METHODS</b>A prospective randomized study was conducted at a university hospital. Patients undergoing TRUGPB were randomized into an amoxicillin-clavulanate alone (1 mg; one dose before and two doses after biopsy) or an amoxicillin-clavulanate + ciprofloxacin group (250 mg; one dose before and two doses after biopsy). Patients were surveyed for infection symptoms by phone on days 3 and 30 after TRUGPB. We defined an infective complication as the occurrence of symptoms including fever, chills or rigor within 30 days after prostate biopsy, requiring medical treatment or hospitalization, aided by a territory-wide electronic medical record system.</p><p><b>RESULTS</b>Between November 2007 and July 2009, 367 patients were randomized to either amoxicillin-clavulanate alone or amoxicillin-clavulanate + ciprofloxacin group. The infection rates after TRUGPB were 3.91% in the former group (7 out of 179 patients) versus 0.53% (1 out of 188 patients) in the latter. Sixty-three percent (5/8) of patients with infective complications needed hospitalization. There was no intensive care unit admission or mortality during the study period.</p><p><b>CONCLUSIONS</b>Combining prophylactic antibiotics with amoxicillin-clavulanate + ciprofloxacin significantly reduced the incidence of infective complications after TRUGPB. We recommended a combination regimen, especially in centre with high incidence of post-TRUGPB infection.</p>

Sick building syndrome and perceived indoor environmental quality: A survey of apartment buildings in Hong Kong.

The outbreak of a highly communicable disease, SARS, in Asia in 2003 has revealed the health risk of living in a high-density environment. To show the important connection between human health and environmental quality, this study surveys the prevalence of sick building syndrome (SBS) among apartment residents and their evaluation of indoor environmental quality (IEQ). Based on a sample of 748 households living in Hong Kong, two interesting findings are revealed: (1) nasal discomfort was the commonest home-related SBS symptom despite the absence of any central ventilation system in apartment buildings; (2) noise, rather than ventilation, was the major IEQ problem perceived by residents. Our statistical analysis further showed that residents with SBS symptoms were less satisfied with their IEQ than those without. That is, despite a positive evaluation of specific IEQ criteria with respect to the building residents lived in, if they reported feeling SBS related symptoms, the overall IEQ evaluation of their building could still be negative. This perception bias gives rise to a sample selection problem in measuring perceived IEQ, which has implications on housing management practices and the formulation of a healthy housing policy.