Rezvilutamide versus bicalutamide in combination with androgen-deprivation therapy in patients with high-volume, metastatic, hormone-sensitive prostate cancer (CHART): a randomised, open-label, phase 3 trial.

BACKGROUND: Rezvilutamide, a novel androgen-receptor inhibitor with low blood-brain barrier penetration, has shown potent antitumour activity against metastatic castration-resistant prostate cancer. In this study, we aimed to evaluate the efficacy and safety of rezvilutamide versus bicalutamide in combination with androgen-deprivation therapy (ADT) for high-volume, metastatic, hormone-sensitive prostate cancer. METHODS: CHART is a randomised, open-label, phase 3 study done at 72 hospitals in China, Poland, Czech Republic, and Bulgaria. Eligible patients were aged 18 years or older, had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, and had high-volume metastatic, hormone-sensitive prostate cancer. Previous chemotherapy or other localised treatment for prostate cancer were not allowed. Patients were randomly assigned (1:1) to receive ADT plus either rezvilutamide (240 mg) or bicalutamide (50 mg) orally once daily. Randomisation was done via an interactive response technology system (block size of four) and stratified according to ECOG performance status and presence of visceral metastasis (excluding lymph nodes). Herein, we present the results of the preplanned interim analyses for the two co-primary endpoints of radiographic progression-free survival assessed by a blinded independent review committee and overall survival in the intention-to-treat population. Safety was assessed in all patients who received at least one dose of study medication. This study is ongoing, but is closed to recruitment. This trial is registered with ClinicalTrials.gov, NCT03520478. FINDINGS: Between June 28, 2018, and Aug 6, 2020, 792 patients were screened and 654 patients were randomly assigned to receive rezvilutamide plus ADT (n=326) or bicalutamide plus ADT (n=328). At the preplanned interim analysis for radiographic progression-free survival (data cutoff May 16, 2021), the median follow-up duration was 21·2 months (IQR 16·6-25·8). Rezvilutamide significantly improved radiographic progression-free survival compared with bicalutamide (median radiographic progression-free survival not reached [95% CI not reached-not reached] vs 25·1 months [95% CI 15·7-not reached]; hazard ratio [HR] 0·44 [95% CI 0·33-0·58]; p<0·0001). At the preplanned interim analysis for overall survival (data cutoff Feb 28, 2022), the median follow-up duration was 29·3 months (IQR 21·0-33·3). Rezvilutamide significantly improved overall survival compared with bicalutamide (HR 0·58 [95% CI 0·44-0·77]; p=0·0001; median overall survival was not reached [95% CI not reached-not reached] vs not reached [36·2-not reached]). The most common grade 3 or worse adverse events of any cause in the safety population were hypertension (26 [8%] of 323 patients in the rezvilutamide group vs 24 [7%] of 324 patients in the bicalutamide group), hypertriglyceridaemia (24 [7%] vs seven [2%]), increased weight (20 [6%] vs 12 [4%]), anaemia (12 [4%] vs 16 [5%]), and hypokalaemia (11 [3%] vs four [1%]). Serious adverse events were reported in 90 (28%) of 323 patients in the rezvilutamide group and 69 (21%) of 324 patients in the bicalutamide group. No treatment-related deaths occurred in patients in the rezvilutamide group; one treatment-related death of unknown specific cause (<1%) occurred in the bicalutamide group. INTERPRETATION: In the two interim analyses, rezvilutamide plus ADT significantly improved radiographic progression-free survival and overall survival compared with bicalutamide plus ADT in patients with high-volume, metastatic, hormone-sensitive prostate cancer, with a tolerable safety profile. FUNDING: Jiangsu Hengrui Pharmaceuticals.

Development of a nomogram combining multiparametric magnetic resonance imaging and PSA-related parameters to enhance the detection of clinically significant cancer across different region.

OBJECTIVE: Prostate cancer (PCa) is the most prevalent cancer among males. This study attempted to develop a clinically significant prostate cancer (csPCa) risk nomogram including Prostate Imaging-Reporting and Data System (PI-RADS) score and other clinical indexes for initial prostate biopsy in light of the different prostate regions, and internal validation was further conducted. PATIENTS AND METHODS: A retrospective study was performed including 688 patients who underwent ultrasound-guided transperineal magnetic resonance imaging fusion prostate biopsy from December 2016 to July 2019. We constructed nomograms combining PI-RADS score and clinical variables (prostate-specific antigen [PSA], prostate volume (PV), age, free/total PSA, and PSA density) through univariate and multivariate logistic regression to identify patients eligible for biopsy. The performance of the predictive model was evaluated by bootstrap resampling. The area under the curve (AUC) of the receiver-operating characteristic (ROC) analysis was appointed to quantify the accuracy of the primary nomogram model for csPCa. Calibration curves were used to assess the agreement between the biopsy specimen and the predicted probability of the new nomogram. The χ2 test was also applied to evaluate the heterogeneity between fusion biopsy and systematic biopsy based on different PI-RADS scores and prostate regions. RESULTS: A total of 320 of 688 included patients were diagnosed with csPCa. csPCa was defined as Gleason score ≥7. The ROC and concordance-index both presented good performance. The nomogram reached an AUC of 0.867 for predicting csPCa at the peripheral zone; meanwhile, AUC for transitional and apex zones were 0.889 and 0.757, respectively. Statistical significance was detected between fusion biopsy and systematic biopsy for PI-RADS score >3 lesions and lesions at the peripheral and transitional zones. CONCLUSION: We produced a novel nomogram predicting csPCa in patients with suspected imaging according to different locations. Our results indicated that PI-RADS score combined with other clinical parameters showed a robust predictive capacity for csPCa before prostate biopsy. The new nomogram, which incorporates prebiopsy data including PSA, PV, age, and PI-RADS score, can be helpful for clinical decision-making to avoid unnecessary biopsy.

A 30-Year, Single-Center Experience of Unilateral Adrenalectomy for Primary Bilateral Macronodular Adrenal Hyperplasia.

OBJECTIVE: The aim was to assess the short- and long-term outcomes of unilateral adrenalectomy (UA) in patients with primary bilateral macronodular adrenal hyperplasia (PBMAH). METHODS: We conducted a retrospective study of 124 patients with PBMAH who underwent UA. RESULTS: One hundred sixteen patients were available for follow-up (median, 28.5 months). Cushingoid features remitted in 43 of 65 patients (70.8%) with overt Cushing syndrome (CS). Hypertension and diabetes mellitus improved in 79 of 96 (82.3%) and 29 of 42 patients (69.0%), respectively. Glucocorticoid insufficiency developed in 7 of 116 patients (6.0%) after the surgery, and it resolved in all the patients during follow-up. The mean 24-hour urinary free cortisol level decreased gradually from 456.02 ± 422.33 mg/24 h at baseline to 84.47 ± 70.06 mg/24 h within 3 months and then increased progressively in some patients. Sixty-four of the 116 patients (55.2%) had biochemical recurrence and 43 patients (67.2%) underwent contralateral adrenalectomy. The median time interval between the second operation and the first UA was 24 months. Patients with overt CS had a larger surgical-side or contralateral adrenal volume than patients without overt CS. Patients with a contralateral adrenal volume of >33.54 mL or with a preoperative urinary free cortisol level of >216.08 mg/24 h were more likely to have recurrence. CONCLUSION: The efficiency of UA is transient for the majority of patients, and the indications should be strictly limited to those with subclinical or milder CS. Patients who undergo successful UA still require close life-time follow-up for the recurrence of hypercortisolism.

Analysis of serum lipid parameters predicting lipid metabolic disorders in TSC-AML patients with treatment of mTOR inhibitors.

WHAT IS KNOWN AND OBJECTIVE: Patients with tuberous sclerosis complex (TSC) demonstrate disrupted lipid homeostasis before and during treatment with mammalian target of rapamycin (mTOR) inhibitor. However, few previous reports focused on if the serum lipid status at baseline would influence lipid metabolic side-effects of mTOR inhibitors for TSC associated renal angiomyolipomas (TSC-AML). The present study was designed to evaluate the predictive function of serum lipid status at baseline for hyperlipidaemia by mTOR inhibitor treatment in TSC-AML patients. METHODS: The clinical data of TSC-AML patients who took mTOR inhibitors in Department of Urology of Peking Union Medical College Hospital (PUMCH) from 1 January 2014 to 1 January 2021, were retrospectively analysed. The record of lipid parameters at baseline and the highest levels of total cholesterol (TC) and triglyceride (TG) after treatment at least ≥3 months were collected. The correlation of serum lipid parameters at baseline with incidence of hyperlipidaemia during mTOR inhibitor treatment was analysed. Receiver operating characteristic (ROC) curve analysis was conducted to evaluate the ability of the serum lipid parameters in predicting hyperlipidaemia. RESULTS AND DISCUSSION: 19 patients experienced hyperlipidaemia and 13 patients still had normal TC and TG levels during mTOR inhibitor treatment. The levels of high-density lipoprotein cholesterol (HDL-C) (0.98 ± 0.30 mmol/L vs. 1.23 ± 0.31 mmol/L, p = 0.030), low-density lipoprotein cholesterol (LDL-C) (2.47 ± 0.69 mmol/L vs. 1.95 ± 0.53 mmol/L, p = 0.029) and apolipoprotein B (ApoB) (0.82 ± 0.21 g/L vs. 0.65 ± 0.16 g/L, p = 0.019) are higher in the patients who experienced hyperlipidaemia during mTOR inhibition therapy. TC, TG, LDL-C, ApoB and high-sensitivity C-reactive protein (hsCRP) at baseline had positive correlation with TC after treatment; ApoB at baseline had positive correlation, while HDL-C and free fat acid (FFA) at baseline had negative correlation with TG after treatment. Therefore, ApoB concentration at baseline has statistically significant correlation with both TC (p < 0.001) and TG (p = 0.012) levels after mTOR inhibitor treatment. ROC curve and AUC revealed that ApoB with a cut-off value of 0.640g/L may be the best parameter for predicting hyperlipidaemia during mTOR inhibitor treatment in TSC-AML patients. The incidence rates of hyperlipidaemia were 27.3% and 76.2% among the patients with ApoB level ≤0.640 g/L and >0.640 g/L respectively. WHAT IS NEW AND CONCLUSION: Some baseline serum lipid parameters could be used for predicting incidence of hyperlipidaemia during mTOR inhibition therapy in TSC-AML patients, and ApoB with 0.640 g/L as a cut-off value may be a potentially optimal indicator, which could help for diagnosis and treatment decision-making.

Analysis of renal lesions in Chinese tuberous sclerosis complex patients with different types of TSC gene mutations.

We sought to explore the relationship between renal lesion features and genetic mutations in tuberous sclerosis complex (TSC) patients. TSC patients with renal lesions were subjected to TSC1/2 gene next-generation sequencing (NGS). TSC1/2 mutation types and imaging examinations were screened for combined analysis of genetic and clinical features. Seventy-three probands among TSC patients with renal lesions were included. Twenty affected relatives were also included. In total, 93 patients were included. Eighty patients (86.0%) had bilateral renal angiomyolipomas (AMLs), and one had epithelioid AML. Two patients had polycystic kidney disease, one had renal cell carcinoma, and one had Wilms tumor. Among the 73 probands, four had TSC1 mutations, 53 had TSC2 mutations, and 16 had no mutations identified (NMI). There was no statistically significant difference between TSC1 mutation, TSC2 mutation and NMI group (P= 0.309), or between familial and sporadic groups (P= 0.775) when considering AML size. There was no statistically significant difference between pathogenic/likely pathogenic and benign/likely benign/NMI groups (P= 0.363) or among patients with different mutation types of TSC2 (P= 0.906). The relationship between the conditions of TSC gene mutations and the severity of renal lesions still needs more analysis. Patients with NMI, particularly those with familial disease, need more attention because the pathogenesis remains unknown.

Tislelizumab in Asian patients with previously treated locally advanced or metastatic urothelial carcinoma.

Tislelizumab, an anti-programmed death protein-1 (PD-1) monoclonal antibody, was engineered to minimize binding to the FcγR on macrophages to abrogate antibody-dependent phagocytosis, a mechanism of T-cell clearance and potential resistance to anti-PD-1 therapy. This single-arm phase 2 trial (NCT04004221/CTR20170071) assessed the safety, tolerability, and efficacy of tislelizumab in patients with PD-L1-positive urothelial carcinoma who progressed during/following platinum-containing therapy and had no prior PD-(L)1 inhibitor treatment. Patients were considered PD-L1 positive if ≥ 25% of tumor/immune cells expressed PD-L1 when using the VENTANA™ PD-L1 (SP263) assay. The primary endpoint was objective response rate by independent review committee. As of September 16, 2019, 113 patients had a median study follow-up time of 9.4 mo. Most patients (76%) had visceral metastases, including 24% with liver and 23% with bone metastases. Among 104 efficacy-evaluable patients, confirmed objective response rate was 24% (95% confidence interval, 16, 33), including 10 complete and 15 partial responses. Median duration of response was not reached. Among 25 responders, 17/25 (68%) had ongoing responses. Median progression-free survival and overall survival times were 2.1 and 9.8 mo, respectively. The most common treatment-related adverse events were anemia (27%) and pyrexia (19%). Anemia (7%) and hyponatremia (5%) were the only grade 3-4 treatment-related adverse events and occurred in ≥ 5% of patients. Three investigator-assessed deaths were considered to be possibly related to study treatment (hepatic failure, n = 2; respiratory arrest, n = 1). Tislelizumab demonstrated meaningful clinical benefits in patients with previously treated locally advanced or metastatic PD-L1-positive urothelial carcinoma and had a manageable safety profile.

The characteristics and spatial distributions of prostate cancer in autopsy specimens.

BACKGROUND: The characteristics of prostate cancer on autopsy and early-stage prostate cancer are identical. Using autopsy specimens, we analysed prostate cancer characteristics and clarified the spatial distributions of lesions. METHOD: We obtained prostate specimens from Chinese donors without a prostate cancer diagnosis and analyzed prostate cancer pathological characteristics on autopsy by whole-mount sampling. We determined the distributions of lesions in horizontal and vertical dimensions. The horizontal dimension included four horizontal quadrants (left-anterior, left-posterior, right-anterior, and right-posterior quadrants), the peripheral zone, and the transition zone. RESULT: The overall positive rate of prostate cancer among 113 specimens was 35.4%. There were 73 lesions in 40 prostates with prostate cancer. The positive rates of lesions in the left-anterior, left-posterior, right-anterior, and right-posterior quadrants were 24.7% (18/73), 27.4% (20/73), 26.0% (19/73), and 21.9% (16/73), respectively. The positive rate of prostate cancer was 74% in the areas between the apex above 0.5-0.8 cm and the middle slice. There were 22 (30.1%) and 51 (69.9%) lesions in the superior and inferior half of the prostate. There were no significant differences in the median volume and Gleason grade group between the superior and inferior half (p = .876 and p = .228). CONCLUSION: In the horizontal dimension, the positive rate of prostate cancer was consistent in the four quadrants. Prostate cancer mainly originated from the areas between the apex above 0.5-0.8 cm and the middle slice. Compared with the superior half, the inferior half of the prostate had a higher positive rate but the same lesion characteristics.

Development and internal validation of a prediction model of prostate cancer on initial transperineal template-guided prostate biopsy.

BACKGROUND: Due to the invasiveness of prostate biopsy, a prediction model of the individual risk of a positive biopsy result could be helpful to guide clinical decision-making. Most existing models are based on transrectal ultrasonography (TRUS)-guided biopsy. On the other hand, transperineal template-guided prostate biopsy (TTPB) has been reported to be more accurate in evaluating prostate cancer. The objective of this study is to develop a prediction model of the detection of high-grade prostate cancer (HGPC) on initial TTPB. RESULT: A total of 1352 out of 3794 (35.6%) patients were diagnosed with prostate cancer, 848 of whom had tumour with Grade Group 2-5. Age, PSA, PV, DRE and f/t PSA are independent predictors of HGPC with p < 0.001. The model showed good discrimination ability (c-index 0.886) and calibration during internal validation and good clinical performance was observed through decision curve analysis. The external validation of CPCC-RC, an existing model, demonstrated that models based on TRUS-guided biopsy may underestimate the risk of HGPC in patients who underwent TTPB. CONCLUSION: We established a prediction model which showed good discrimination ability and calibration in predicting the detection of HGPC by initial TTPB. This model can be used to aid clinical decision making for Chinese patients and other Asian populations with similar genomic backgrounds, after external validations are conducted to further confirm its clinical applicability.

Sum of High-Risk Gene Mutation (SHGM): A Novel Attempt to Assist Differential Diagnosis for Adrenocortical Carcinoma with Benign Adenoma, Based on Detection of Mutations of Nine Target Genes.

There has been no research on applying gene detection to differential diagnosis of adrenocortical carcinoma (ACC). We attempted to explore a novel auxiliary method for differential diagnosis between ACC with benign adrenocortical adenoma (ACA), based on mutations of target genes in tissues. Nine genes were chosen as target genes, including TP53, CTNNB1, ARMC5, PRKAR1A, ZNRF3, RB1, APC, MEN1, and RPL22. Exons sequencing of target genes were performed in 98 cases of tissue samples by FastTarget technology, including 41 ACC tissues, 32 ACA tissues, and 25 normal adrenal gland tissues. Significant mutations were detected and identified, and the clinical information was collected, for further comparative analysis and application to assist differential diagnosis of ACC. We identified 132 significant gene mutations and 227 significant mutation sites in 37 ACC tissues, much more than ACA and normal adrenal gland tissues. Mutation rates of 6 genes in ACC tissues were obviously higher than ACA tissues, including ZNRF3, ARMC5, TP53, APC, RB1, and PRKAR1A, regarded as high-risk genes. The sum of mutated high-risk genes detected in each sample was denominated sum of high-risk gene mutation (SHGM), and the rates of SHGM > 0 and SHGM > 1 in ACC tissues were 73.0% and 62.2%, respectively, both obviously higher than those in ACA tissues, with significant statistic differences. Especially for 8 cases of ACC with diameter < 5 cm, SHGM > 0 and SHGM > 1 were found in 6 samples (75%) and 4 samples (50%), respectively. However, no relevance was found between SHGM and clinical characteristics of ACC. We identified 6 high-risk genes in ACC tissues, with significantly higher mutation rates than ACA or normal adrenal gland tissues. The sum of mutated high-risk genes detected in ACC tissues was denominated SHGM, which was potential to assist the differential diagnosis of ACC with ACA, especially for the small-size ACC.

Tumor characteristics, treatments, and survival outcomes in prostate cancer patients with a PSA level < 4 ng/ml: a population-based study.

BACKGROUND: To examine the tumor characteristics, treatments and survival outcomes of prostate cancer (PCa) patients with a prostate-specific antigen (PSA) level < 4 ng/ml. METHODS: Of 205,913 men with primary prostate adenocarcinoma in the Surveillance, Epidemiology and End Results (SEER) database (2010 to 2015), 24,054 (11.68%) patients were diagnosed with a PSA level < 4 ng/ml. Comparisons of categorical variables among different groups were performed by using the Chi square test. Multivariate Cox regression analysis was adjusted for age, ethnicity, marital status, insurance status, TNM stage, Gleason grade, treatment and survival. Kaplan-Meier survival curves were constructed for overall mortality and tested by the log-rank test. RESULTS: PCa patients with a PSA level < 4 ng/ml generally had more favorable tumor characteristics: younger, lower T stage, lower Gleason grade and lower lymph node metastasis rate. However, there were more patients in stage M1 in the group of PSA level < 4 ng/ml than that in the groups of PSA level of 4-10 ng/ml, 10-20 ng/ml and > 20 ng/ml. The multivariate Cox regression model revealed that overall mortality was associated with age, marital status, race, Gleason grade, M stage and treatment approach. CONCLUSIONS: In conclusion, PCa patients with a PSA level < 4 ng/ml have more favorable tumor characteristics at diagnosis and receive more benefit from active treatment. However, those patients with advanced TNM stage and high Gleason grade should be paid more attention in clinical application.

Correction: miR-9-5p, miR-124-3p, and miR-132-3p regulate BCL2L11 in tuberous sclerosis complex angiomyolipoma.

Following the publication of this article, the authors noticed an error was in Figure 5C. In the miR-124-3p mimics, the same image was used accidentally for the miR-132-3p mimics. This does not affect the results and conclusions of the article.

Anlotinib Versus Sunitinib as First-Line Treatment for Metastatic Renal Cell Carcinoma: A Randomized Phase II Clinical Trial.

BACKGROUND: Anlotinib is a tyrosine kinase inhibitor inhibiting angiogenesis. This multicenter, randomized phase II trial aimed to investigate the efficacy and safety of anlotinib in comparison with sunitinib as first-line treatment for patients with metastatic renal cell carcinoma (mRCC). MATERIALS AND METHODS: Patients with mRCC from 13 clinical centers were randomly assigned in a 2:1 ratio to receive anlotinib (n = 90) or sunitinib (n = 43). Anlotinib was given orally at a dose of 12 mg once daily (2 weeks on/1 week off), and sunitinib was given orally at 50 mg once daily (4 weeks on/2 weeks off). The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS), objective response rate (ORR), disease control rate (DCR), and safety. RESULTS: The median PFS was similar with anlotinib and sunitinib (17.5 vs. 16.6 months, p > .05). The median OS (30.9 vs. 30.5 months, p > .05), ORR (30.3% vs. 27.9%), and 6-week DCR (97.8% vs. 93.0%) were similar in the two groups. Adverse events (AEs) of grade 3 or 4 were significantly less frequent with anlotinib than with sunitinib (28.9% vs. 55.8%, p < .01), especially in terms of thrombocytopenia and neutropenia. AEs occurring at a lower frequency with anlotinib were hand-foot syndrome, eyelid edema, hair depigmentation, skin yellowing, neutropenia, thrombocytopenia, and anemia. The incidence of serious AEs was lower with anlotinib than with sunitinib. CONCLUSION: The clinical efficacy of anlotinib was similar to that of sunitinib as the first-line treatment for mRCC, but with a more favorable safety profile. IMPLICATIONS FOR PRACTICE: This study evaluated the efficacy and safety of anlotinib for the first-line treatment of metastatic renal cell carcinoma. Anlotinib, which was developed independently in China, is a new tyrosine kinase inhibitor inhibiting multiple kinases involved in angiogenesis and tumor proliferation. Results indicated that the efficacy of anlotinib is comparable to and the safety is better than that of sunitinib.

Autologous Adrenal Transplantation for the Treatment of Refractory Cushing's Disease.

OBJECTIVE: To report our management of bilateral adrenalectomy with autologous adrenal gland transplantation for persistent Cushing's disease, and to discuss the feasibility of autologous adrenal transplantation for the treatment of refractory Cushing's disease. MATERIAL AND METHODS: A retrospective analysis was performed in 4 patients (3 females, aged 14-36 years) who underwent autologous adrenal transplantation for persistent Cushing's disease after endonasal transsphenoidal resection of a pituitary tumor. The procedure was performed by implanting a vascularized adrenal graft into the left iliac fossa with direct and indirect anastomoses. Postoperative follow-up was performed in 1, 1.5, 8, and 10 years, and an over 8-year long-term follow-up was reached in 2 out of the 4 cases. Hormone replacement dosage was guided by clinical symptoms and endocrine results including serum cortisol (F), 24 h urine-free cortisol, and adrenocorticotrophic hormone levels. RESULTS: All 4 patients with symptomatic Cushing's disease experienced resolution of symptoms after autotransplantation without Nelson Syndrome. Functional autografts were confirmed through clinical evaluation and endocrine results. One year after transplantation, adrenal function and hormone replacement dosage remained stable without adrenal hyperplasia. After long-term follow-up, dosages of hormone replacement were reduced in all patients. CONCLUSIONS: In this series of 4 patients, we demonstrate the long-term efficacy of bilateral adrenalectomy with autologous adrenal transplantation and propose this procedure as a viable treatment option for refractory Cushing's disease.

Efficacy and safety of tadalafil 5 mg once-daily in Asian men with both lower urinary tract symptoms associated with benign prostatic hyperplasia and erectile dysfunction: A phase 3, randomized, double-blind, parallel, placebo- and tamsulosin-controlled study.

OBJECTIVE: To evaluate the efficacy and safety of tadalafil in Asian men with both lower urinary tract symptoms associated with benign prostatic hyperplasia and erectile dysfunction. METHODS: The present phase 3, randomized, double-blind, parallel, placebo- and tamsulosin-controlled study was carried out at 40 study centers in the Asia-Pacific region (mainland China, Taiwan and Korea; NCT01937871). Participants were randomized to receive a placebo (n = 361), tadalafil 5 mg (n = 362) or tamsulosin 0.2 mg (n = 185) in a 2:2:1 ratio for 12 weeks. RESULTS: A total of 909 Asian men were randomized into three groups. After 12 weeks of treatment, a statistically significant improvement in least squares mean change from baseline in total International Prostate Symptom Score was observed in the tadalafil versus the placebo group (-5.49 vs -4.08, respectively; P < 0.001). A statistically significant improvement in the change from baseline for the International Index of Erectile Function-Erectile Function domain score, was observed in tadalafil compared with the placebo at 12 weeks (5.24 vs 1.88, respectively; P < 0.001). A significant improvement was observed in the change from baseline in the percentage of "Yes" responses to Sexual Encounter Profile questions 2 and 3 in the tadalafil versus placebo group at 12 weeks (23.87% vs 10.90%; P < 0.001 and 36.62% vs 15.96%; P < 0.001, respectively). Safety results were consistent with the known tadalafil safety profile. CONCLUSIONS: Tadalafil is efficacious and well tolerated in the treatment of Asian men with both lower urinary tract symptoms associated with benign prostatic hyperplasia and erectile dysfunction.

When to Introduce Three-Dimensional Visualization Technology into Surgical Residency: A Randomized Controlled Trial.

Three-dimensional (3D) reconstructed images have been increasingly applied for medical education. Although many studies have described the benefits of such applications, the best time to introduce 3D technology into surgical training has not been determined. Therefore, we conducted a randomized study to determine a suitable period for the introduction of this technology. Seventy-one surgical residents were randomized into 2 groups (two-dimensional computed tomography (CT) group and 3D image group), and they completed a test on anatomy and imaging as well as a questionnaire. Post-graduate year 1 (PGY1) residents in the 3D group performed significantly better than those in the CT group, although the third-year residents did not present significant differences in either the score or the time spent answering the questions. Although residents in different years of training held different attitudes toward the difficulty of anatomy and imaging learning, they all showed a high level of acceptance of the 3D training. This study revealed that 3D images improved the junior residents' performance in imaging reasoning. Thus, systematically introducing 3D images early in a surgical resident training program may help produce a better anatomy-imaging-surgery system.

miR-9-5p, miR-124-3p, and miR-132-3p regulate BCL2L11 in tuberous sclerosis complex angiomyolipoma.

Tuberous sclerosis complex (TSC) is a genetic disorder characterized by tumor formation in multiple organs, with over 80% of TSC patients developing angiomyolipomas (TSC-AMLs). However, the molecular events that contribute to TSC-AMLs are not well understood. Recent reports have demonstrated that microRNAs (miRNAs) are critical in TSC cortical tubers. However, little is known about the role of miRNAs in TSC-AMLs. In the current study, we analyzed changes in the miRNA and mRNA profiles in TSC-AMLs and matched normal adjacent tissues. A total of 15 differentially expressed miRNAs and 2664 mRNAs were identified. Using quantitative real-time PCR, we confirmed the results of the miRNA and mRNA profile experiments. Through bioinformatic analysis and luciferase reporter assays, we found that BCL2L11, an apoptotic activator, was the direct target of miR-9-5p, miR-124-3p, and miR-132-3p. Engineered expression of miR-9-5p, miR-124-3p, or miR-132-3p significantly regulated proliferation and apoptosis in Tsc2-/- cells. Manipulated expression of BCL2L11 also led to proliferation and apoptosis alterations in Tsc2-/- cells, in agreement with the effects of the above three miRNAs. In addition, BCL2L11 rescued the proliferation and apoptotic inhibition induced by miR-9-5p, miR-124-3p, and miR-132-3p in Tsc2-/- cells. This study provides supportive evidence that miR-9-5p, miR-124-3p, and miR-132-3p play a role in TSC-AMLs through the regulation of BCL2L11.

The transverse and vertical distribution of prostate cancer in biopsy and radical prostatectomy specimens.

BACKGROUND: Prostate biopsy is the most common method for the diagnosis of prostate cancer and the basis for further treatment. Confirmation using radical prostatectomy specimens is the most reliable method for verifying the accuracy of template-guided transperineal prostate biopsy. The study aimed to reveal the spatial distribution of prostate cancer in template-guided transperineal saturation biopsy and radical prostatectomy specimens. METHODS: Between December 2012 to December 2016, 171 patients were diagnosed with prostate cancer via template-guided transperineal prostate biopsy and subsequently underwent laparoscopic radical prostatectomy. The spatial distributions of prostate cancer were analyzed and the consistency of the tumor distribution between biopsy and radical prostatectomy specimens were compared. RESULTS: The positive rate of biopsy in the apex region was significantly higher than that of the other biopsy regions (43% vs 28%, P < 0.01). In radical prostatectomy specimens, the positive rate was highest at the region 0.9-1.3 cm above the apex, and it had a tendency to decrease towards the base. There was a significant difference in the positive rate between the cephalic and caudal half of the prostate (68% vs 99%, P < 0.01). There were no significant differences between the anterior and posterior zones for either biopsy or radical prostatectomy specimens. CONCLUSION: The tumor spatial distribution generated by template-guided transperineal prostate biopsy was consistent with that of radical prostatectomy specimens in general. The positive rate was consistent between anterior and posterior zones. The caudal half of the prostate, especially the vicinity of the apex, was the frequently occurred site of the tumor.

Comparison of lesions detected and undetected by template-guided transperineal saturation prostate biopsy.

OBJECTIVES: To compare the characteristics of lesions detected or undetected by template-guided transperineal saturation prostate biopsy and to evaluate the potential impact of undetected lesions. MATERIALS AND METHODS: We evaluated the characteristics of lesions in radical prostatectomy (RP) specimens, compared the differences between lesions detected and undetected by systematic transperineal ultrasonography-guided 11-region biopsy with regard to tumour volume, Gleason score, surgical margin, spatial location and clinical significance, and assessed the potential impact of undetected clinically significant lesions. RESULTS: The median number of biopsy cores was 24. Sixty-four percent of the clinically significant lesions (170/264) were detected. There were significant differences between the detected and undetected lesions in tumour volume, Gleason score and clinical significance. Inconsistencies found in lesion position between biopsy and RP specimens in the anterior and posterior zones and the left and right sides was 3.4% (7/203) and 5.4% (11/203), respectively. Of the 129 patients, 13 (10.1%) were found to have undetected clinically significant lesions in the biopsy lying on the same side but in a different zone from the detected clinically significant lesions, whereas 23 patients (17.8%) had undetected clinically significant lesions in the biopsy lying on the opposite side from the detected clinically significant lesions. CONCLUSIONS: Template-guided transperineal saturation prostate biopsy detected approximately two-thirds of clinically significant lesions. Most of the undetected lesions were those with small tumour volume. Approximately 20-30% of patients had clinically significant undetected lesions in a different lobe or different quadrant from the detected lesions in the biopsy.

INTERLEUKIN-6-PRODUCING PHEOCHROMOCYTOMA AS A NEW REASON FOR FEVER OF UNKNOWN ORIGIN: A RETROSPECTIVE STUDY.

OBJECTIVE: To explore the fever of unknown origin (FUO) in patients with interleukin-6 (IL-6)-producing pheochromocytoma. METHODS: Patients with pheochromocytoma were enrolled from June 2014 to April 2017. Clinical characteristics were recorded including sex, age, 24-h urinary catecholamines (norepinephrine, epinephrine, dopamine), tumor size, axillary temperature (AT), white blood cells (WBC), and serum IL-6 and high-sensitivity C-reactive protein (hsCRP) levels. IL-6 secretion by pheochromocytoma was analyzed by immunohistochemistry (IHC). RESULTS: We identified 29 cases of pheochromocytoma (7 with high AT and 22 with normal AT). Serum IL-6 and hsCRP levels were increased in the high AT group compared with the normal AT group (both P = .001). After pheochromocytoma resection, AT and IL-6 and hsCRP levels decreased significantly ( P<.001, P = .002 and P = .003, respectively). IHC revealed significantly higher IL-6 expression in the high AT group ( P = .002). CONCLUSION: IL-6-producing pheochromocytoma should be included in the differential diagnosis of FUO. ABBREVIATIONS: AT = axillary temperature; CT = computed tomography; FUO = fever of unknown origin; IHC = immunohistochemistry; IL-6 = interleukin-6; hsCRP = high-sensitivity C-reactive protein; WBC = white blood cells.

Preliminary Application of WCX Magnetic Bead-Based Matrix-Assisted Laser Desorption Ionization Time-of-Flight Mass Spectrometry in Analyzing the Urine of Renal Clear Cell Carcinoma.

Objective To evaluate the application of weak cation exchange (WCX) magnetic bead-based Matrix-Assisted Laser Desorption Ionization Time-of-Flight Mass Spectrometry (MALDI-TOF MS) in detecting differentially expressed proteins in the urine of renal clear cell carcinoma (RCCC) and its value in the early diagnosis of RCCC.Methods Eleven newly diagnosed patients (10 males and 1 female, aged 46-78, mean 63 years) of renal clear cell carcinoma by biopsy and 10 healthy volunteers (all males, aged 25-32, mean 29.7 years) were enrolled in this study. Urine samples of the RCCC patients and healthy controls were collected in the morning. Weak cation exchange (WCX) bead-based MALDI-TOF MS technique was applied in detecting differential protein peaks in the urine of RCCC. ClinProTools2.2 software was utilized to determine the characteristic proteins in the urine of RCCC patients for the predictive model of RCCC. Results The technique identified 160 protein peaks in the urine that were different between RCCC patients and health controls; and among them, there was one peak (molecular weight of 2221.71 Da) with statistical significance (P=0.0304). With genetic algorithms and the support vector machine, we screened out 13 characteristic protein peaks for the predictive model. Conclusions The application of WCX magnetic bead-based MALDI-TOF MS in detecting differentially expressed proteins in urine may have potential value for the early diagnosis of RCCC.