Publications by authors named "Chao-Yuan Huang"

225 Publications

Association between the polygenic liabilities for prostate cancer and breast cancer with biochemical recurrence after radical prostatectomy for localized prostate cancer.

Am J Cancer Res 2021 15;11(5):2331-2342. Epub 2021 May 15.

Department of Pharmacy, China Medical University Taichung 404, Taiwan.

Prostate and breast cancers are hormone-related malignancies and are characterized by a complex interplay of hundreds of susceptibility loci throughout the genome. Prostate cancer could be inhibited by eliminating androgens through castration or estrogen administration, thus facilitating long-term treatment of prostate cancer; however, the role of estrogen in prostate cancer remains unclear. This study aimed to determine whether polygenic risk scores (PRSs) comprising combinations of genome-wide susceptibility variants influence the clinical outcomes of prostate cancer patients. The study subjects were recruited from four medical centers in Taiwan, and genome-wide genotyping data were obtained from 643 prostate cancer patients. We derived the PRS for prostate cancer (PRS-PC) and for breast cancer (PRS-BC) for each patient. The association between the PRS-PC/PRS-BC at the age of prostate cancer onset and recurrence within seven years was evaluated using a regression model adjusted for population stratification components. A higher PRS-PC was associated with an earlier onset age for prostate cancer (beta in per SD increase in PRS = -0.89, = 0.0008). In contrast, a higher PRS-BC was associated with an older onset age for prostate cancer (beta = 0.59, = 0.02). PRS-PC was not associated with the risk of recurrence (hazard ratio = 1.03, = 0.67), whereas a higher PRS-BC was associated with a low recurrence risk (hazard ratio = 0.86, = 0.03). These results indicate that the genetic predisposition to breast cancer is associated with a low risk of prostate cancer recurrence. Further studies are warranted to explore the role of breast cancer susceptibility variants and estrogen signaling in prostate cancer progression.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8167673PMC
May 2021

Outcomes and Prediction Models for Exclusive Prostate Bed Salvage Radiotherapy among Patients with Biochemical Recurrence after Radical Prostatectomy.

Cancers (Basel) 2021 May 28;13(11). Epub 2021 May 28.

Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei 100233, Taiwan.

Background: The addition of androgen-deprivation therapy (ADT) or pelvic radiation to prostate bed salvage radiotherapy (SRT) has been debated for prostate cancer patients with biochemical recurrence (BCR) after radical prostatectomy. This study aimed to assess the outcomes and propose prediction models for exclusive prostate bed SRT.

Methods: This is a prospective observational cohort study with patients who underwent SRT with a pre-SRT PSA < 1.5 ng/mL after radical prostatectomy. Patients were treated with 70-Gy SRT to the prostate bed exclusively. Kaplan-Meier survival analyses and Cox regression analyses were applied for depicting and predicting BCR-free survival, ADT-free survival, and metastasis-free survival (MFS). Regression-based coefficients were used to develop nomograms.

Results: A total of 105 patients were included and 91 patients were eligible. The median follow-up period was 39 months. The 5-year BCR-free survival, ADT-free survival, and MFS were 37%, 50%, and 66%, respectively. Multivariable analysis showed that a pre-SRT PSA < 0.45 ng/mL was the only independent factor associated with longer BCR-free survival ( = 0.034), while a PSA-DT > 8 months had better ADT-free survival ( = 0.008). Patients with a PSA-DT > 8 months showed a 100% MFS and a 43% 5-year absolute benefit in MFS than a PSA-DT ≤ 8 months. All patients with a pre-SRT PSA < 0.45 ng/mL and PSA-DT > 8 months were free from subsequent ADT and any metastasis.

Conclusions: In patients with a PSA < 0.45 ng/mL and PSA-DT > 8 months for post-prostatectomy BCR, prostate bed SRT provided excellent outcomes without the need for concomitant ADT or pelvic radiotherapy.
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http://dx.doi.org/10.3390/cancers13112672DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8199341PMC
May 2021

Genetic Variant Influences the Efficacy of Androgen-Deprivation Therapy in Men with Prostate Cancer.

Biomedicines 2021 May 10;9(5). Epub 2021 May 10.

Department of Pharmacy, China Medical University, Taichung 404, Taiwan.

Neuregulins (NRGs) activate receptor tyrosine kinases of the ErbB family, and play essential roles in the proliferation, survival, and differentiation of normal and malignant tissue cells. We hypothesized that genetic variants of NRG signalling pathway genes may influence treatment outcomes in prostate cancer. To test this hypothesis, we performed a comprehensive analysis to evaluate the associations of 459 single-nucleotide polymorphisms in 19 NRG pathway genes with cancer-specific survival (CSS), overall survival (OS), and progression-free survival (PFS) in 630 patients with prostate cancer receiving androgen-deprivation therapy (ADT). After multivariate Cox regression and multiple testing correction, we found that rs144160282 C > T is significantly associated with worsening CSS, OS, and PFS during ADT. Further analysis showed that low expression of is closely related to prostate cancer, as indicated by a high Gleason score, an advanced stage, and a shorter PFS rate. Meta-analysis of 16 gene expression datasets of 1,081 prostate cancer samples and 294 adjacent normal samples indicate lower expression in the former compared with the latter ( < 0.001). These results suggest that rs144160282 might be a prognostic predictor of the efficacy of ADT. Further studies are required to confirm the significance of as a biomarker and therapeutic target for prostate cancer.
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http://dx.doi.org/10.3390/biomedicines9050528DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8151455PMC
May 2021

Genetic Variants Affect the Clinical Response to Androgen-deprivation Therapy in Patients With Prostate Cancer.

Cancer Genomics Proteomics 2021 May-Jun;18(3):325-334

Department of Pharmacy, China Medical University, Taichung, Taiwan, R.O.C.;

Background/aim: Heterogeneous nuclear ribonucleoproteins (hnRNPs) contribute to multiple cellular functions including RNA splicing, stabilization, transcriptional and translational regulation, and signal transduction. However, the prognostic importance of genetic variants of hnRNP genes in clinical outcomes of prostate cancer remains to be elucidated.

Patients And Methods: We studied the association of 78 germline single-nucleotide polymorphisms (SNPs) in 23 hnRNP genes with the overall survival (OS), cancer-specific survival (CSS), and progression-free survival (PFS) in 630 patients with prostate cancer receiving androgen-deprivation therapy (ADT).

Results: PTBP1 rs10420407 was the most significant SNP (false discovery rate q=0.003) and carriers of the A allele exhibited poor OS, CSS, and PFS. Multivariate Cox analysis confirmed PTBP1 rs10420407 A allele was an independent negative prognostic factor for OS and PFS. Expression quantitative trait loci analysis showed that the rs10420407 A allele had a trend towards increased PTBP1 mRNA expression, and higher expression was correlated with prostate cancer aggressiveness and poor patient prognosis. Meta-analysis of 16 independent studies further indicated a tumorigenic effect of PTBP1, with a higher expression in prostate cancers than in adjacent normal tissues (p<0.001).

Conclusion: Our data suggest that PTBP1 rs10420407 may influence patient response to ADT, and PTBP1 may be involved in the pathogenesis of prostate cancer progression.
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http://dx.doi.org/10.21873/cgp.20263DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8126326PMC
February 2021

Real-World Evaluation of Modern Adjuvant Radiotherapy in Women with Stage IB Endometrial Cancer.

Cancers (Basel) 2021 Mar 18;13(6). Epub 2021 Mar 18.

Division of Radiation Oncology, Department of Oncology, National Taiwan University Hospital, Taipei 100, Taiwan.

The optimal adjuvant treatment for stage IB endometrial cancer remains undefined. We investigated the benefit of modern adjuvant radiotherapy for women with stage IB endometrial cancer. We retrospectively reviewed patients with surgically staged, pure stage IB endometrioid adenocarcinoma (2010 to 2018). Adjuvant modern radiotherapy consists of external-beam radiotherapy (EBRT) by intensity, volumetric-modulated arc radiotherapy, or image-guided vaginal brachytherapy (VBT). The study included 180 stage IB patients. Patients with grade 3 diseases had frequent aggressive histology patterns (lymphovascular space invasion (LVSI); low uterine segment involvement) and experienced significantly shorter recurrence-free survival (RFS) and overall survival (OS) than patients with grade 1/2 diseases. Adjuvant modern radiotherapy decreased the incidence of acute/chronic grade ≥2 gastrointestinal toxicity. In IB grade 1/2 patients, EBRT significantly lengthened survival (RFS/OS); patients with age >60 years, myometrial invasion beyond the outer third, or LVSI benefited the most from EBRT. EBRT also significantly improved survival (RFS/OS) in IB grade 3 patients, where patients with bulky tumors or LVSI benefited the most from EBRT. Therefore, EBRT may be beneficial for all stage IB patients.
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http://dx.doi.org/10.3390/cancers13061386DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8003240PMC
March 2021

Genetic variants in MAPK10 modify renal cell carcinoma susceptibility and clinical outcomes.

Life Sci 2021 Jun 24;275:119396. Epub 2021 Mar 24.

Department of Pharmacy, China Medical University, Taichung 406, Taiwan; Sex Hormone Research Center, China Medical University Hospital, Taichung 404, Taiwan; Department of Nursing, Asia University, Taichung 413, Taiwan. Electronic address:

Aims: The mitogen-activated protein kinase (MAPK) cascades integrate various upstream signals to regulate many cellular functions, including proliferation, differentiation, and survival. Dysregulation of these pathways has been implicated in the occurrence and progression of a variety of cancers.

Main Methods: This study aimed to assess the association of 192 single nucleotide polymorphisms in 22 MAPK cascade genes with renal cell carcinoma (RCC) risk and survival in 312 patients and 318 controls.

Key Findings: After multiple testing correction and multivariate analysis, the minor T allele of MAPK10 rs12648265 remained associated with a lower risk of RCC (adjusted odds ratio 0.64, 95% confidence interval 0.50-0.82, P = 0.000426) and metastasis (adjusted hazard ratio 0.50, 95% confidence interval 0.30-0.82, P = 0.006). Presence of the rs12648265 T allele demonstrated a trend towards being associated with increased MAPK10 expression, and meta-analysis of four RCC datasets indicated that high MAPK10 expression is associated with a favourable prognosis. Furthermore, activation of MAPK10 by the potent agonist anisomycin inhibited RCC cell growth in vitro, suggesting an involvement of MAPK10 in RCC progression.

Significance: In conclusion, MAPK10 may be a meaningful biomarker and a potential therapeutic target in RCC.
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http://dx.doi.org/10.1016/j.lfs.2021.119396DOI Listing
June 2021

Endoscopic management versus radical nephroureterectomy for localized upper tract urothelial carcinoma in a high endemic region.

Sci Rep 2021 Feb 17;11(1):4040. Epub 2021 Feb 17.

Department of Urology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.

Our aim was to analyze the clinical and survival differences among patients who underwent the two main treatment modalities, endoscopic ablation and radical nephroureterectomy. This study examined all patients who had undergone endoscopic management and RNU between Jul. 1988 and Mar. 2019 from the Taiwan UTUC registry. The inclusion criteria were low stage UTUC in RNU and all cases in endoscopic managed UTUC with a curative intent. The demographic and clinical characteristics were included for analysis. In total, 84 cases in the endoscopic group and 272 cases in the RNU group were enrolled for final analysis. The median follow-up period were 33.5 and 42.0 months in endoscopic and RNU group, respectively (p = 0.082). Comparison of Kaplan-Meier estimated survival curves between groups, the endoscopic group was associated with similar overall survival (OS), cancer specific survival (CSS), and intravesical recurrence free survival (IVRS) but demonstrated inferior disease free survival (DFS) (p = 0.188 for OS, p = 0.493 for CSS and p < 0.001 for DFS). Endoscopic management of UTUC was as safe as RNU in UTUC endemic region.
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http://dx.doi.org/10.1038/s41598-021-83495-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7889610PMC
February 2021

Outcomes of stratified transurethral resection of bladder tumor: A propensity score-matched analysis.

J Formos Med Assoc 2021 Feb 4. Epub 2021 Feb 4.

Department of Urology, National Taiwan University Hospital, National Taiwan University, College of Medicine, Taipei, Taiwan. Electronic address:

Background/purpose: Several strategies have been reported for improving the integrity of transurethral resection of bladder tumor (TURBT). However, no standard has been established. Stratified TURBT (SR) is one of protocols for TURBT, wherein exophytic tumors are first resected and retrieved, and tumor bases are then resected. In this study, we aimed to evaluate the outcomes of SR in patients with nonmuscle invasive bladder cancer (NMIBC).

Methods: From January 2012 to December 2017, patients newly diagnosed as having NMIBC with a follow-up period of more than 2 years were enrolled and categorized into SR and conventional TURBT (CR) groups. Propensity score matching at a 2:1 ratio was performed. Outcomes were the detrusor muscle sampling rate, recurrence-free survival (RFS), and progression-free survival (PFS).

Results: In total, 205 patients were included in our study. The detrusor muscle sampling rate was higher in the SR group (P = 0.043). After propensity score matching, 162 patients were selected for outcome analysis, with 108 and 54 patients undergoing SR and CR, respectively. Compared with the CR group, the SR group showed a lower recurrence rate (P = 0.015) and better RFS in univariate (P = 0.010) and multivariate (P = 0.006) Cox proportional hazards regression. Progression rate and PFS were not significantly different between the two groups.

Conclusion: SR results in a higher detrusor muscle sampling rate and better disease outcomes. Our findings suggest that SR is a promising strategy for TURBT in patients with NMIBC.
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http://dx.doi.org/10.1016/j.jfma.2021.01.012DOI Listing
February 2021

Genomic characterization of clear cell renal cell carcinoma using targeted gene sequencing.

Oncol Lett 2021 Feb 4;21(2):169. Epub 2021 Jan 4.

Division of Urology, Department of Surgery, Chang Gung Memorial Hospital at Linkou, Taoyuan 333, Taiwan, R.O.C.

Kidney cancer is one of the most lethal cancer types worldwide. The most common subtype of kidney cancer is clear cell renal cell carcinoma (ccRCC), and the somatic mutations of ccRCC have been identified through the development of large databases. The present study aimed to validate the status of the associated gene mutations in a Taiwanese cohort. Targeted sequencing was used to validate the mutation status of genes related to ccRCC in Taiwanese patients who had nephrectomy for kidney cancer. The top eight mutated genes in the Catalogue Of Somatic Mutations In Cancer (COSMIC) were selected. These genes were , protein polybromo-1 (), histone-lysine N-methyltransferase , BRCA1-associated protein-1 (), lysine-specific demethylase 5C (), and . The association between the gene mutation status of and was validated with clinicopathological parameters as well as overall survival time. Tumor cells from 96 patients with ccRCC were target sequenced. The order of mutation rate of the eight aforementioned genes was similar to that reported within COSMIC. The present Taiwanese cohort exhibited lower and mutation rates compared with average, with increased mutation rates for and . mutation was associated with the tumor and cancerous stage. None of these four genes were positively associated with the overall survival of patients. The and mutations were mutually exclusive to mutation. Overall, the present study provided data confirming gene alteration in Taiwanese patients with ccRCC and showed some differences when compared with Western countries. Further comprehensive genomic and epigenomic studies, as well as downstream validation, are necessary to evaluate the impact of these differences.
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http://dx.doi.org/10.3892/ol.2021.12430DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7802514PMC
February 2021

Additive Effects of Arsenic and Aristolochic Acid in Chemical Carcinogenesis of Upper Urinary Tract Urothelium.

Cancer Epidemiol Biomarkers Prev 2021 Feb 4;30(2):317-325. Epub 2020 Dec 4.

Department of Urology, National Taiwan University Hospital, Taipei, Taiwan.

Background: Aristolochic acids (AA) and arsenic are chemical carcinogens associated with urothelial carcinogenesis. Here we investigate the combined effects of AA and arsenic toward the risk of developing upper tract urothelial carcinoma (UTUC).

Methods: Hospital-based ( = 89) and population-based (2,921 cases and 11,684 controls) Taiwanese UTUC cohorts were used to investigate the association between exposure to AA and/or arsenic and the risk of developing UTUC. In the hospital cohort, AA exposure was evaluated by measuring aristolactam-DNA adducts in the renal cortex and by identifying A>T mutations in tumors. In the population cohort, AA exposure was determined from prescription health insurance records. Arsenic levels were graded from 0 to 3 based on concentrations in well water and the presence of arseniasis-related diseases.

Results: In the hospital cohort, 43, 26, and 20 patients resided in grade 0, 1+2, and 3 arseniasis-endemic areas, respectively. Aristolactam-DNA adducts were present in >90% of these patients, indicating widespread AA exposure. A>T mutations in were detected in 28%, 44%, and 22% of patients residing in grade 0, 1+2, and 3 arseniasis-endemic areas, respectively. Population studies revealed that individuals who consumed more AA-containing herbs had a higher risk of developing UTUC in both arseniasis-endemic and nonendemic areas. Logistic regression showed an additive effect of AA and arsenic exposure on the risk of developing UTUC.

Conclusions: Exposure to both AA and arsenic acts additively to increase the UTUC risk in Taiwan.

Impact: This is the first study to investigate the combined effect of AA and arsenic exposure on UTUC.
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http://dx.doi.org/10.1158/1055-9965.EPI-20-1090DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8083126PMC
February 2021

Prognostic Significance of Primary Tumor Location in Upper Tract Urothelial Carcinoma Treated with Nephroureterectomy: A Retrospective, Multi-Center Cohort Study in Taiwan.

J Clin Med 2020 Nov 27;9(12). Epub 2020 Nov 27.

Department of Urology, Kaohsiung Medical University Hospital, Kaohsiung 80756, Taiwan.

We sought to examine the effect of tumor location on the prognosis of patients with upper tract urothelial carcinoma (UTUC) treated with radical nephroureterectomy (RNU). This retrospective study came from the Taiwan UTUC Collaboration Group, which consisted of 2658 patients at 15 institutions in Taiwan from 1988 to 2019. Patients with kidney-sparing management, both renal pelvic and ureteral tumors, as well as patients lacking complete data were excluded; the remaining 1436 patients were divided into two groups: renal pelvic tumor (RPT) and ureteral tumor (UT), with 842 and 594 patients, respectively. RPT was associated with more aggressive pathological features, including higher pathological T stage ( < 0.001) and the presence of lymphovascular invasion ( = 0.002), whereas patients with UT often had synchronous bladder tumor ( < 0.001), and were more likely to bear multiple lesions ( = 0.001). Our multivariate analysis revealed that UT was a worse prognostic factor compared with RPT (overall survival: HR 1.408, 95% CI 1.121-1.767, = 0.003; cancer-specific survival: HR 1.562, 95% CI 1.169-2.085, = 0.003; disease-free survival: HR 1.363, 95% CI 1.095-1.697, = 0.006; bladder-recurrence-free survival: HR 1.411, 95% CI 1.141-1.747, = 0.002, respectively). Based on our findings, UT appeared to be more malignant and had a worse prognosis than RPT.
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http://dx.doi.org/10.3390/jcm9123866DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7761410PMC
November 2020

TD-92, a novel erlotinib derivative, depletes tumor-associated macrophages in non-small cell lung cancer via down-regulation of CSF-1R and enhances the anti-tumor effects of anti-PD-1.

Cancer Lett 2021 02 21;498:142-151. Epub 2020 Nov 21.

SupremeCure Pharma Inc., Taipei, Taiwan.

Recent advances in immune checkpoint inhibition, which augment T-cell immune responses, have highlighted the potential of exploiting one's immune system to combat cancer. However, only a relatively small number of non-small cell lung cancer (NSCLC) patients benefit from immune checkpoint blockade due to the immunosuppressive tumor microenvironment. Therefore, combination immunotherapies are now being developed to achieve maximal therapeutic benefits. In this study, we assessed whether a novel erlotinib derivative, TD-92, which possesses anti-tumor effects across several cancer cell lines, could enhance anti-PD-1 treatment. Our results demonstrated that the combined treatment of anti-PD-1 and TD-92 resulted in a potent anti-tumor response in a Lewis lung carcinoma cancer model, as evidenced by the reduced tumor growth and increased survival. Analysis of immune cell population counts revealed that TD-92 reduced the number of pro-tumorigenic CD11b F4/80 tumor-associated macrophages, without significantly affecting the total numbers of other major immunocytes. Further experiments showed that TD-92 induced a marked decline in colony stimulating factor 1 receptor (CSF-1R) expression in macrophage cell lines. The results also suggested that c-Cbl-mediated proteasome degradation was involved in TD-92-mediated CSF-1R downregulation. Our data paves the way for the development of additional combination immunotherapies for NSCLC patients.
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http://dx.doi.org/10.1016/j.canlet.2020.10.043DOI Listing
February 2021

Genetic Analysis Identifies the Role of in Renal Cell Carcinoma.

Cancer Genomics Proteomics 2020 Nov-Dec;17(6):827-833

Department of Pharmacy, China Medical University, Taichung, Taiwan, R.O.C.

Background/aim: Circadian rhythm is an internal clock that regulates the cycles of many biological functions. Epidemiological studies have linked aberrant circadian rhythm to an increased susceptibility to cancer and poor patient prognosis. However, there remains a gap in our understanding of genetic variants related to the circadian pathway in renal cell carcinoma (RCC) progression.

Patients And Methods: We examined the associations of 150 single nucleotide polymorphisms (SNPs) in 12 core circadian pathway genes with RCC risk and survival in 630 patients with RCC and controls.

Results: After adjusting for multiple comparisons and performing multivariate analyses, we found that the HLF rs6504958 polymorphism was significantly associated with RCC risk (q<0.05), whereas, no SNP association was significant for survival. Furthermore, the rs6504958 G allele was associated with reduced expression of HLF; consequently, a lower HLF expression was correlated with more advanced RCC. Moreover, a meta-analysis of six kidney cancer gene expression datasets demonstrated that an elevated HLF expression was associated with a favorable prognosis in patients with RCC (hazard ratio=0.70, 95% confidence interval=0.65-0.76, p<0.001).

Conclusion: These findings implicate the potential protective role of HLF in the progression of RCC.
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http://dx.doi.org/10.21873/cgp.20236DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7675652PMC
June 2021

Acute Kidney Injury in Traumatic Brain Injury Patients: Results From the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury Study.

Crit Care Med 2021 01;49(1):112-126

Department of Medicine and Surgery, University of Milano - Bicocca, Monza, Italy.

Objectives: Acute kidney injury is frequent in polytrauma patients, and it is associated with increased mortality and extended hospital length of stay. However, the specific prevalence of acute kidney injury after traumatic brain injury is less recognized. The present study aims to describe the occurrence rate, risk factors, timing, and association with outcome of acute kidney injury in a large cohort of traumatic brain injury patients.

Design: The Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury is a multicenter, prospective observational, longitudinal, cohort study.

Setting: Sixty-five ICUs across Europe.

Patients: For the present study, we selected 4,509 traumatic brain injury patients with an ICU length of stay greater than 72 hours and with at least two serum creatinine values during the first 7 days of ICU stay.

Measurements And Main Results: We classified acute kidney injury in three stages according to the Kidney Disease Improving Global Outcome criteria: acute kidney injury stage 1 equals to serum creatinine × 1.5-1.9 times from baseline or an increase greater than or equal to 0.3 mg/dL in 48 hours; acute kidney injury stage 2 equals to serum creatinine × 2-2.9 times baseline; acute kidney injury stage 3 equals to serum creatinine × three times baseline or greater than or equal to 4 mg/dL or need for renal replacement therapy. Standard reporting techniques were used to report incidences. A multivariable Cox regression analysis was performed to model the cause-specific hazard of acute kidney injury and its association with the long-term outcome. We included a total of 1,262 patients. The occurrence rate of acute kidney injury during the first week was as follows: acute kidney injury stage 1 equals to 8% (n = 100), acute kidney injury stage 2 equals to 1% (n = 14), and acute kidney injury stage 3 equals to 3% (n = 36). Acute kidney injury occurred early after ICU admission, with a median of 2 days (interquartile range 1-4 d). Renal history (hazard ratio = 2.48; 95% CI, 1.39-4.43; p = 0.002), insulin-dependent diabetes (hazard ratio = 2.52; 95% CI, 1.22-5.197; p = 0.012), hypernatremia (hazard ratio = 1.88; 95% CI, 1.31-2.71; p = 0.001), and osmotic therapy administration (hazard ratio = 2.08; 95% CI, 1.45-2.99; p < 0.001) were significantly associated with the risk of developing acute kidney injury. Acute kidney injury was also associated with an increased ICU length of stay and with a higher probability of 6 months unfavorable Extended Glasgow Outcome Scale and mortality.

Conclusions: Acute kidney injury after traumatic brain injury is an early phenomenon, affecting about one in 10 patients. Its occurrence negatively impacts mortality and neurologic outcome at 6 months. Osmotic therapy use during ICU stay could be a modifiable risk factor.
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http://dx.doi.org/10.1097/CCM.0000000000004673DOI Listing
January 2021

Development and External Validation of an Online Clinical Prediction Model for Augmented Renal Clearance in Adult Mixed Critically Ill Patients: The Augmented Renal Clearance Predictor.

Crit Care Med 2020 12;48(12):e1260-e1268

Department of Pharmacy, Department of Pharmaceutical and Pharmacological Sciences, University Hospitals Leuven and Clinical Pharmacology and Pharmacotherapy, KU Leuven, Leuven, Belgium.

Objectives: Augmented renal clearance might lead to subtherapeutic plasma levels of drugs with predominant renal clearance. Early identification of augmented renal clearance remains challenging for the ICU physician. We developed and validated our augmented renal clearance predictor, a clinical prediction model for augmented renal clearance on the next day during ICU stay, and made it available via an online calculator. We compared its predictive performance with that of two existing models for augmented renal clearance.

Design: Multicenter retrospective registry-based cohort study.

Setting: Three Belgian tertiary care academic hospitals.

Patients: Adult medical, surgical, and cardiac surgery ICU patients.

Interventions: None.

Measurements And Main Results: Development of the prediction model was based on clinical information available during ICU stay. Out of 33,258 ICU days, we found augmented renal clearance on 19.6% of all ICU days in the development cohort. We retained six clinical variables in our augmented renal clearance predictor: day from ICU admission, age, sex, serum creatinine, trauma, and cardiac surgery. We assessed performance by measuring discrimination, calibration, and net benefit. We externally validated the final model in a single-center population (n = 10,259 ICU days). External validation confirmed good performance with an area under the curve of 0.88 (95% CI 0.87-0.88) and a sensitivity and specificity of 84.1 (95% CI 82.5-85.7) and 76.3 (95% CI 75.4-77.2) at the default threshold probability of 0.2, respectively.

Conclusions: Augmented renal clearance on the next day can be predicted with good performance during ICU stay, using routinely collected clinical information that is readily available at bedside. Our augmented renal clearance predictor is available at www.arcpredictor.com.
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http://dx.doi.org/10.1097/CCM.0000000000004667DOI Listing
December 2020

Effect of plasma selenium, red blood cell cadmium, total urinary arsenic levels, and eGFR on renal cell carcinoma.

Sci Total Environ 2021 Jan 6;750:141547. Epub 2020 Aug 6.

Department of Public Health, College of Public Health, China Medical University, Taichung, Taiwan; Department of Medical Research, China Medical University and Hospital, Taichung, Taiwan. Electronic address:

High total urinary arsenic concentrations and low estimated glomerular filtration rate (eGFR) increase the risk of renal cell carcinoma (RCC). This study aimed to determine whether other metals or metalloids can affect RCC. A total of 401 patients with RCC and 774 age- and sex-matched controls were recruited between November 2006 and December 2012 in Taiwan. Surgical resection or image-guided biopsy of renal tumors was performed to pathologically verify RCC. High-performance liquid chromatography linked to a hydride generator and atomic absorption spectrometer were used to measure the urinary arsenic species concentrations. Inductively coupled plasma mass spectrometry was used to determine plasma selenium and red blood cell cadmium and lead concentration. Plasma selenium levels were inversely related to RCC, whereas red blood cell cadmium levels were directly related to RCC. The odds ratio (OR) and 95% confidence interval (CI) were 0.14 (95% CI, 0.10-0.20) and 1.33 (95% CI, 1.03-1.72), respectively. A low plasma selenium level tended to interact with high total urinary arsenic levels or with high red blood cell cadmium concentration to increase the OR of RCC. In particular, low eGFR multiplicatively interacted with high red blood cell cadmium concentration to increase the OR of RCC (P=0.003). This study was the first to find a significant multiplicative interaction between eGFR and the red blood cell cadmium levels on the increased OR of RCC.
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http://dx.doi.org/10.1016/j.scitotenv.2020.141547DOI Listing
January 2021

Effect of diabetes mellitus and glycemic control on the prognosis of non-muscle invasive bladder cancer: a retrospective study.

BMC Urol 2020 Aug 5;20(1):117. Epub 2020 Aug 5.

Department of Urology, National Taiwan University Hospital, National Taiwan University, College of Medicine, No.7, Chung-Shan South Road, Zhongzheng District, Taipei, 100, Taiwan.

Background: Hyperglycemia is associated with series of process leading to oncogenesis. Evidence has shown that diabetes mellitus (DM) seems to be associated with poor prognosis in patients with bladder cancer. However, evidence on the effect of glycemic control on the outcomes of bladder cancer is still limited. In the current study, we aimed to investigate the effect of DM and glycemic control on the prognosis of bladder cancer.

Methods: We conducted a retrospective chart review of a prospective database from January 2012 to December 2017. Patients with newly diagnosed non-muscle invasive bladder cancer (NMIBC) were included. They were classified into the DM and non-DM groups. Prognosis including recurrence rate, progression rate, recurrence-free survival (RFS), and progression-free survival was compared between the two groups. Subgroup analysis of the DM subgroup, in which patients were classified by HbA1C level, was conducted to investigate the effect of glycemic control.

Results: A total of 287 patients were included in our study, with 61 patients in the DM group and 226 patients in the non-DM group. No statistically significant difference was found in the prognosis between the DM and non-DM groups. Subgroup analysis revealed higher recurrence rate (P = 0.037) and worse RFS (log-rank P = 0.019) in patients with HbA1C ≥ 7.

Conclusions: DM is not a risk factor for recurrence and progression in patients with NMIBC. However, poor glycemic control is associated with poor prognosis in patients with both DM and NMIBC. Further prospective studies are needed to confirm current results.
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http://dx.doi.org/10.1186/s12894-020-00684-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7409398PMC
August 2020

Association between low prostate-specific antigen levels and greater disease progression in high-grade locally-advanced prostate cancer.

J Formos Med Assoc 2021 Jan 23;120(1 Pt 2):483-491. Epub 2020 Jun 23.

Institute of Biomedical Engineering, National Taiwan University, Taipei, Taiwan; Department of Urology, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan. Electronic address:

Purpose: In advanced or high-grade prostate cancer (PCa), prostate-specific antigen (PSA) is usually elevated, however, some patients may present with low initial PSA (iPSA) levels. The objective of this study was to evaluate whether different iPSA levels were associated with dissimilar clinical outcomes among men with high-grade PCa and advanced disease after robot-assisted laparoscopic radical prostatectomy (RaLRP).

Methods: This study enrolled 69 PCa patients with initial Gleason score ≥8 and pathologic T-stage ≥3a from April 2012 to December 2018. Patients were stratified into 3 groups based on iPSA levels at diagnosis: <5.0, 5.0-9.9, and ≥10.0. The patients' related parameters were compared among these groups.

Results: The median follow-up period was 33.1 months (IQR: 12.1-48.1). There was no difference in biochemical recurrence (BCR) between the 3 groups (Log-rank test, p = 0.484). We found a higher risk of biochemical recurrence in patients with positive surgical margins (HR: 5.04, 95% CI: 1.64-15.50, p = 0.005). In addition, patients with low iPSA levels (<5.0 ng/mL) had poor radiographic progression-free survival (Log-rank test, p = 0.001) and a higher risk of disease progression (HR: 12.2, 95% CI: 1.18-1260.99, p = 0.036) compared with patients with higher iPSA levels (≥10 ng/mL).

Conclusion: In patients with high-grade locally-advanced PCa, a low iPSA level was associated with a higher risk of disease progression, but not with biochemical recurrence. In this unique population, serum PSA may not be a reliable marker to detect disease progression. Monitoring of these patients may warrant other biomarkers or imaging.
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http://dx.doi.org/10.1016/j.jfma.2020.06.021DOI Listing
January 2021

Genetic Analysis Reveals a Significant Contribution of to Prostate Cancer Progression in Taiwanese Men.

Cancers (Basel) 2020 May 25;12(5). Epub 2020 May 25.

Department of Pharmacy, China Medical University, Taichung 404, Taiwan.

The genes that influence prostate cancer progression remain largely unknown. Since the carboxylesterase gene family plays a crucial role in xenobiotic metabolism and lipid/cholesterol homeostasis, we hypothesize that genetic variants in carboxylesterase genes may influence clinical outcomes for prostate cancer patients. A total of 478 (36 genotyped and 442 imputed) single nucleotide polymorphisms (SNPs) in five genes of the carboxylesterase family were assessed in terms of their associations with biochemical recurrence (BCR)-free survival in 643 Taiwanese patients with prostate cancer who underwent radical prostatectomy. The strongest association signal was shown in ( = 9.64×10 for genotyped SNP rs8192935 and = 8.96 × 10 for imputed SNP rs8192950). After multiple test correction and adjustment for clinical covariates, rs8192935 ( = 9.67 × 10) and rs8192950 ( = 9.34 × 10) remained significant. These SNPs were correlated with expression levels, which in turn were associated with prostate cancer aggressiveness. Furthermore, our meta-analysis, including eight studies, indicated that a high expression predicted better outcomes among prostate cancer patients (hazard ratio 0.82, 95% confidence interval 0.70-0.97, = 0.02). In conclusion, our findings suggest that rs8192935 and rs8192950 are associated with BCR and that plays a tumor suppressive role in prostate cancer.
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http://dx.doi.org/10.3390/cancers12051346DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7281132PMC
May 2020

Clinical prediction models for acute kidney injury.

Rev Bras Ter Intensiva 2020 Mar 8;32(1):123-132. Epub 2020 May 8.

Laboratory of Intensive Care Medicine, Academic Department of Cellular and Molecular Medicine, Katholieke Universiteit Leuven, Leuven, Belgium.

Objective: To report on the currently available prediction models for the development of acute kidney injury in heterogeneous adult intensive care units.

Methods: A systematic review of clinical prediction models for acute kidney injury in adult intensive care unit populations was carried out. PubMed® was searched for publications reporting on the development of a novel prediction model, validation of an established model, or impact of an existing prediction model for early acute kidney injury diagnosis in intensive care units.

Results: We screened 583 potentially relevant articles. Among the 32 remaining articles in the first selection, only 5 met the inclusion criteria. The nonstandardized adaptations that were made to define baseline serum creatinine when the preadmission value was missing led to heterogeneous definitions of the outcome. Commonly included predictors were sepsis, age, and serum creatinine level. The final models included between 5 and 19 risk factors. The areas under the Receiver Operating Characteristic curves to predict acute kidney injury development in the internal validation cohorts ranged from 0.78 to 0.88. Only two studies were externally validated.

Conclusion: Clinical prediction models for acute kidney injury can help in applying more timely preventive interventions to the right patients. However, in intensive care unit populations, few models have been externally validated. In addition, heterogeneous definitions for acute kidney injury and evaluation criteria and the lack of impact analysis hamper a thorough comparison of existing models. Future research is needed to validate the established models and to analyze their clinical impact before they can be applied in clinical practice.
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http://dx.doi.org/10.5935/0103-507x.20200018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7206939PMC
March 2020

Polymorphism of nucleotide binding domain-like receptor protein 3 (NLRP3) increases susceptibility of total urinary arsenic to renal cell carcinoma.

Sci Rep 2020 04 20;10(1):6640. Epub 2020 Apr 20.

Department of Family Medicine, Wan Fang Hospital, Taipei Medical University, Taipei City, Taiwan.

Our study showed that total urinary arsenic concentrations were positively correlated with renal cell carcinoma (RCC). Chronic inflammation is a key player in the development of RCC. This study explored the association between nucleotide-binding domain-like receptor protein 3 (NLRP3) genotypes and the development of RCC. We also investigated whether any of the NLRP3 genotypes modified the risk between arsenic and RCC. We recruited 350 RCC patients and 700 age-sex matched controls. RCC was confirmed by pathological assessment following surgical resection or image-guided biopsy of a renal tumor. Fifteen sites of NLRP3 gene polymorphisms were identified using the Agena Bioscience MassARRAY platform. The concentrations of the urinary arsenic species were determined by HPLC-HG-AAS. There was a significant dose-dependent association between arsenic and RCC. In addition, six of thirteen NLRP3 alleles, including rs12239046 C, rs10925025 G, rs1539019 C, rs10925026 A, rs10157379 T, and rs12143966 A, had increased odds ratios (ORs) for RCC than other NLRP3 alleles. Among these sites, we found the novel haplotype of five tag-SNPs (C-A-A-A-A) was significantly related to RCC, the OR and 95% confidence interval was 1.44 (1.08-1.92). Furthermore, participants with high total urinary arsenic levels and the NLRP3 rs1539019 C allele had significantly multiplicative and additive interactions for the risk of RCC (p  = 0.012). This study is the first to identify the modified effects of NLRP3 risk alleles involved in the association between arsenic and RCC risk in a population with low arsenic exposure.
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http://dx.doi.org/10.1038/s41598-020-63469-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7171170PMC
April 2020

Impact of adjuvant radiotherapy on the survival of women with optimally resected stage III endometrial cancer in the era of modern radiotherapy: a retrospective study.

Radiat Oncol 2020 Apr 6;15(1):72. Epub 2020 Apr 6.

Division of Radiation Oncology, Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan.

Background: The optimal adjuvant treatment for stage III endometrial cancer in the era of modern radiotherapy remains undefined. We investigated the benefit of adjuvant radiotherapy for women who underwent optimal resection for stage III endometrial cancer in the era of modern radiotherapy.

Methods: We retrospectively reviewed patients with endometrial cancer who were treated between 2010 and 2018. Adjuvant treatment included radiotherapy by modern radiotherapy techniques (intensity-modulated or volumetric modulated arc radiotherapy), chemotherapy, or both. Recurrence-free survival (RFS) and overall survival (OS) were calculated using the Kaplan-Meier method and analyzed via multivariate Cox proportional hazards models.

Results: One hundred sixty-one patients were initially included (52, 9, and 100 with stages IIIA, IIIB, and IIIC cancer, respectively); 154 patients (96%) received adjuvant therapy. Such adjuvant treatment was associated with improved RFS (p = 0.014) and OS (p = 0.044) over surgery alone. Adjuvant radiotherapy by modern radiotherapy techniques led to low incidence of acute (25%) and chronic (7%) grade ≥ 2 gastrointestinal toxicity. On univariate analysis, non-endometrioid histology and grade 3 status were associated with higher risks of tumor recurrence and death, whereas adjuvant radiotherapy alone or in combination chemotherapy reduced their risks. On multivariate analysis, non-endometrioid histology was associated with increased recurrence (hazard ratio [HR], 2.95; p = 0.009), whereas adjuvant radiotherapy alone or with chemotherapy was associated with lower recurrence (HR, 0.62; p = 0.042). Patients > 60 years of age (p = 0.038) as well as those with endometrioid histology (p = 0.045), lymphovascular space invasion (p = 0.031), and ≥ 2 positive lymph nodes (p = 0.044) benefited most from adjuvant radiotherapy.

Conclusions: Modern adjuvant radiotherapy (intensity-modulated or volumetric modulated arc radiotherapy) alone or with chemotherapy should be considered for women with optimally resected stage III endometrial cancer.

Trial Registration: ClinicalTrials.gov, NCT04251676. Registered 24 January 2020. Retrospectively registered.
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http://dx.doi.org/10.1186/s13014-020-01523-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7137232PMC
April 2020

Acrolein contributes to urothelial carcinomas in patients with chronic kidney disease.

Urol Oncol 2020 05 18;38(5):465-475. Epub 2020 Mar 18.

Department of Pharmacology, National Yang-Ming University, Taipei, Taiwan, ROC. Electronic address:

Background: Urothelial carcinomas (UCs) are highly prevalent in patients with end-stage renal disease. Chronic kidney disease (CKD) is the predecessor of end-stage renal disease, and it is also associated with UC. However, the interplay between CKD and UC lacks solid evidence. Acrolein is produced by polyamines and has been suggested to be the uremic "toxin." The level of acrolein correlates well with chronic renal failure. We recently found that acrolein-induced DNA damage and inhibited DNA repair in urothelial cells, which contribute to bladder cancer. Therefore, we hypothesize that acrolein is involved in the formation of UC in patients with CKD.

Materials And Methods: A total of 62 UC patients and 43 healthy control subjects were recruited. Acrolein-DNA (Acr-dG) adducts and p53 gene mutations in UC tissues, plasma acrolein-protein conjugates (Acr-PC) and S-(3-hydroxypropyl)-N-acetylcysteine levels, and urinary Acr metabolites were analyzed in these patients.

Results: Acr-dG levels were statistically correlated with CKD stages in UC patients (P < 0.01). Most p53 mutations were G to A and G to T mutations in these patients, and 50% of mutations at G:C pairs occurred in CpG sites, which is similar to the mutational spectra induced by Acr-dG adducts. Acr-PC levels in the plasma of UC patients with CKD were significantly higher than those of control subjects (P < 0.001). Altered urinary S-(3-hydroxypropyl)-N-acetylcysteine was also found in UC patients with CKD compared to control subjects (P < 0.005).

Conclusion: These results indicate that acrolein acts as an endogenous uremic toxin and contributes to UC formation in patients with CKD.
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http://dx.doi.org/10.1016/j.urolonc.2020.02.017DOI Listing
May 2020

Genetic Association Analysis of Cell Cycle Regulators Reveals Has Prognostic Significance in Prostate Cancer.

Cancer Genomics Proteomics 2020 Mar-Apr;17(2):209-216

Department of Pharmacy, China Medical University, Taichung, Taiwan, R.O.C.

Background/aim: This study aimed to identify the genes that cause biochemical recurrence (BCR) following radical prostatectomy (RP) in men with localized prostate cancer.

Patients And Methods: A two-stage genetic association study of 19 single-nucleotide polymorphisms in 11 key cell cycle regulation genes was carried out. BCR-free survival after RP was evaluated in a discovery cohort of 458 patients with prostate cancer, and replication was investigated in another cohort of 185 patients.

Results: A consistent association was found between BCR and rs2290291 (discovery: p=0.008; replication: p=0.029). rs2290291 is located in the tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein zeta (YWHAZ), and was predicted to possess a regulatory function that affected YWHAZ expression. Furthermore, YWHAZ expression was frequently up-regulated in advanced tumours, and associated with poorer survival in patients with prostate cancer.

Conclusion: YWHAZ rs2290291 was found to be associated with BCR. YWHAZ may function as a putative oncogene during prostate cancer progression.
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http://dx.doi.org/10.21873/cgp.20181DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7078838PMC
September 2020

Lower postoperative natural killer cell activity is associated with positive surgical margins after radical prostatectomy.

J Formos Med Assoc 2020 Nov 17;119(11):1673-1683. Epub 2020 Feb 17.

Graduate Institute of Anatomy and Cell Biology, College of Medicine, National Taiwan University, Taipei, Taiwan. Electronic address:

Background/purpose: The inflammatory milieu has been firmly established to affect cancer progression. However, the connection between natural killer (NK) cells and prostate cancer (PCa) has not been elucidated.

Methods: Prospective data on NK cell activity (NKA) and NK cell subset distribution patterns were evaluated from 51 patients treated with robot-assisted laparoscopic radical prostatectomy. Whole-blood samples were collected from patients preoperatively and 4-6 weeks postoperatively. The samples were subjected to NKA tests, NK cell number counts, determination of the NKG2D (activating receptor of NK cells), NKG2A (inhibiting receptor), and other surface markers. All the analyses were compared to the clinicopathological characteristics of patients. NKA was estimated by measuring interferon-γ (IFN-γ) levels after stimulation of the peripheral blood with PROMOCA™, which specifically stimulates the release of IFN-γ from NK cells.

Results: NKA was lower in patients with PCa than in healthy participants (484.66 vs. 1550 pg/mL). A paired comparison revealed significantly higher NKA postoperatively than preoperatively (1054 vs. 484.66 pg/mL; p = 0.011). Patients with negative surgical margins exhibited significantly higher postoperative NKA and NKA ratio (postoperative NKA/preoperative NKA) than those with positive margins (557 vs. 1921 pg/mL, p < 0.001; 3.6 vs. 1.59, p = 0.024). However, there was no difference in the postoperative NK cell number or the CD56/CD16/CD3 or CD56/CD16/CD3 cell numbers between the negative and positive margin groups. Postoperative NKA was significantly higher in lower-stage (1/2) than in higher-stage (3/4) PCa (1365 vs. 594 pg/mL, p = 0.014).

Conclusion: NKA was significantly higher postoperatively than preoperatively. Patients with positive surgical margins had lower postoperative NKA than those with negative margins. Lower postoperative NKA was also observed in higher-stage PCa. NKA could be used as a supplemental marker for detecting the remaining tumor cells after prostatectomy in combination of PSA.
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http://dx.doi.org/10.1016/j.jfma.2019.12.015DOI Listing
November 2020

Subsequent risk of acute urinary retention and androgen deprivation therapy in patients with prostate cancer: A population-based retrospective cohort study.

Medicine (Baltimore) 2020 Feb;99(7):e18842

Department of Public Health, College of Public Health, China Medical University.

Acute urinary retention (AUR) is associated with hormone imbalance in men. However, limited studies focused on exploring the complications of AUR in patients with prostate cancer (PC) who receive androgen deprivation therapy (ADT). Therefore, we aim to evaluate the subsequent risk of AUR in ADT-treated PC patients. We collected data from 24,464 male patients who were newly diagnosed with prostate malignancy from a longitudinal health insurance database of catastrophic illness in 2000 to 2008. All PC patients were categorized into 2 cohorts, namely, ADT cohort and non-ADT cohort, based on whether or not the patient receives ADT. The patients were followed up until the occurrence of AUR. Multivariate Cox proportional hazard regression and Kaplan-Meier analysis were performed. After a 12-year follow-up, the incidence rates of AUR were 12.49 and 9.86 per 1000 person-years in ADT and non-ADT cohorts, respectively. Compared with the non-ADT cohort, the ADT cohort had a 1.21-fold increase in AUR risk based on the adjusted model (95% CI = 1.03-1.43). In addition, PC patients receiving early ADT treatment within 6 months or receiving only luteinizing hormone-releasing hormone treatment also had significantly increased risk of AUR. ADT was positively associated with AUR risk. PC patients receiving ADT should be informed about the risks of bladder outlet obstruction and AUR, and they may benefit from screening for related risk factors. New guidelines and treatments should be proposed in the future to manage ADT-related lower urinary tract symptoms and reduce the risk of AUR.
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http://dx.doi.org/10.1097/MD.0000000000018842DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7035125PMC
February 2020

Genetic association analysis identifies a role for ANO5 in prostate cancer progression.

Cancer Med 2020 04 6;9(7):2372-2378. Epub 2020 Feb 6.

Department of Pharmacy, China Medical University, Taichung, Taiwan.

Anoctamins were originally identified as a family of calcium-activated chloride channels, but recently their roles in the development of different types of malignancies were suggested. Here, we evaluated the associations between 211 common single-nucleotide polymorphisms in 10 anoctamin genes with biochemical recurrence (BCR) after radical prostatectomy (RP) for localized prostate cancer. Four SNPs (ANO4 rs585335, ANO5 rs4622263, ANO7 rs62187431, and ANO10 rs118005571) remained significantly associated with BCR after multiple test correction (P < .05 and q = 0.232) and adjustment for known prognostic factors. Expression quantitative trait loci analysis found that ANO5 rs4622263 C and ANO10 rs118005571 C alleles were associated with decreased mRNA expression levels. Moreover, lower expression of ANO5 was correlated with more advanced tumors and poorer outcomes in two independent prostate cancer cohorts. Taken together, ANO5 rs4622263 was associated with BCR, and ANO5 gene expression was correlated with patient prognosis, suggesting a pivotal role for ANO5 in prostate cancer progression.
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http://dx.doi.org/10.1002/cam4.2909DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7131841PMC
April 2020

Preoperative %p2PSA and Prostate Health Index Predict Pathological Outcomes in Patients with Prostate Cancer Undergoing Radical Prostatectomy.

Sci Rep 2020 01 21;10(1):776. Epub 2020 Jan 21.

Department of Urology, National Taiwan University Hospital, Taipei, Taiwan.

To evaluate the predictive accuracy of the %p2PSA and prostate health index (PHI) in predicting aggressive pathological outcomes in patients with prostate cancer (PCa) undergoing radical prostatectomy (RP), we enrolled 91 patients with organ-confined PCa who were treated with robot-assisted RP. p2PSA levels and the PHI were investigated for their ability to predict pathological results. The %p2PSA and PHI were both significantly higher in patients with ≥pT3 disease, high-risk disease, positive surgical margin, or seminal vesical invasion (SVI). In univariable analysis, p2PSA derivatives were significant predictors of the presence of ≥pT3 disease, high-risk disease, positive surgical margin, and SVI. To predict adverse pathological outcomes at a sensitivity of 90%, p2PSA derivatives had higher specificity than standard PSA derivatives. In multivariable analysis, additional increases in the area under the receiver operating characteristic curve (AUC) were observed with the %p2PSA and PHI for ≥pT3 disease, high-risk disease, and positive surgical margin (8.2% and 2.7%, 6.2% and 4.1%, and 8.6% and 5.4%, respectively). A PHI ≥61.26 enhanced the predictive accuracy of the model for SVI by increasing the AUC from 0.624 to 0.819 (p = 0.009). The preoperative %p2PSA and PHI accurately predict adverse pathological results and are useful for decision-making.
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http://dx.doi.org/10.1038/s41598-020-57618-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6972898PMC
January 2020

Different androgen deprivation therapies might have a differential impact on cognition - An analysis from a population-based study using time-dependent exposure model.

Cancer Epidemiol 2020 02 7;64:101657. Epub 2020 Jan 7.

Department of Public Health, College of Public Health, China Medical University, Taichung, Taiwan; Department of Medical Research, China Medical University Hospital, Taichung, Taiwan. Electronic address:

Background: Androgen deprivation therapy (ADT) remains the mainstay treatment for locally advanced or metastatic prostate cancer (PC). However, potential effects of ADT treatment on neurocognitive dysfunction remain unclear. The present study was conducted to assess the relation between ADT treatment and risk of cognitive decline in Asian men with PC.

Methods: A population-based cohort of 24,464 men with PC, each newly diagnosed between 2000 and 2008, was selected from the Taiwan National Health Insurance Database. Subjects were further grouped by treatment as non-ADT (n = 4685) or ADT (n = 12,740), members of the latter subjected to bilateral orchiectomy or medical treatment (ie, luteinizing hormone-releasing hormone agonists, antiandrogens, or combination therapy). A multivariable Cox proportional hazard model with ADT as time-dependent covariate was used to generate adjusted hazard ratios (HRs) of subsequent cognitive decline, including dementia, Alzheimer's disease (AD), and Parkinson's disease (PD).

Results: ADT showed a significant association with overall risk of cognitive decline (HR = 1.51, 95 % CI: 1.31-1.74), especially for PD, dementia, and non-Alzheimer dementia (non-AZD). When stratified by various ADT regimens, antiandrogen-only recipients displayed significantly heightened risks of subsequent AD, non-AZD, and PD. However, combined androgen blockade also imposed an increased risk of PD. There was no apparent correlation between duration of ADT exposure and cognitive dysfunction.

Conclusions: Various ADT therapies may have disparate impacts on cognitive function. Prospective studies exploring pertinent clinical characteristics more fully are needed to confirm these findings.
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http://dx.doi.org/10.1016/j.canep.2019.101657DOI Listing
February 2020

Extended-field bone marrow sparing radiotherapy for primary chemoradiotherapy in cervical cancer patients with para-aortic lymphadenopathy: Volumetric-modulated arc therapy versus helical tomotherapy.

J Xray Sci Technol 2020 ;28(1):111-124

Division of Radiation Oncology, Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan.

Background: Extended-field (EF) bone marrow-sparing (BMS) radiotherapy is attracting interest for cervical cancer patients with para-aortic lymphadenopathy.

Objective: To compare dosimetric quality of volumetric-modulated arc therapy (VMAT) vs. helical tomotherapy (HT) during EF BMS radiotherapy.

Methods: HT dose-volume histogram parameters including (1) coverage, homogeneity, and conformity of target volumes, (2) sparing of organs-at-risk, (3) monitor units, and (4) estimated treatment time were compared with those of VMAT in 20 cervical cancer patients who underwent EF BMS radiotherapy. The pelvic and para-aortic regions received 45-Gy dose (25 fractions), with simultaneous integrated boost of 55 Gy (25 fractions) for pelvic and para-aortic lymphadenopathy, followed by a parametrial boost of 9 Gy (5 fractions).

Results: The HT-based and VMAT techniques achieved adequate and similar target volume coverage with good dose homogeneity and conformity, while sparing all organs-at-risk, including the rectum, bladder, bowel, bone marrow, femoral head, kidney, and spinal cord. The HT treatment plan had significantly higher monitor units (p < 0.001) and longer estimated treatment times (p < 0.001).

Conclusions: VMAT and HT plans are suitable for EF BMS radiotherapy, which can achieve adequate target volume coverage while sufficiently sparing normal tissue. In addition, VMAT, compared to HT planning, yielded shorter estimated treatment times.
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http://dx.doi.org/10.3233/XST-190593DOI Listing
May 2021
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