Publications by authors named "Yao-Chou Tsai"

81 Publications

A Novel Somatic Mutation of p.V1937M in Unilateral Primary Hyperaldosteronism.

Front Endocrinol (Lausanne) 2022 9;13:816476. Epub 2022 Jun 9.

Department of Urology, National Taiwan University College of Medicine and Hospital, Taipei, Taiwan.

Background: Somatic mutations for excess aldosterone production have been frequently identified as important roles in the pathogenesis of unilateral primary hyperaldosteronism (uPA). Although mutation represents a minor etiology in primary aldosteronism, it plays a significant role in causing uPAs in sporadic cases.

Objective: To identify novel somatic mutation in patients with uPA and investigate the pathophysiological, immunohistological, and clinical characteristics of the variant.

Methods: We applied a customized and targeted gene panel next-generation sequencing approach to detect mutations from the uPA cohort in Taiwan Primary Aldosteronism Investigation study group. Information from pre-diagnostic to postoperative data was collected, including past history, medications, blood pressure readings, biochemical data, and image studies. The functional role of the variant was confirmed by studies, demonstrating aldosterone production in variant-transfected human adrenal cell lines.

Results: We identified a novel somatic mutation c.5809G>A (p.Val1937Met) in a uPA case. The gene encodes the pore-forming alpha-1H subunit of the voltage-dependent T-type calcium channel Cav3.2. This somatic p.V1937M variant showed excellent clinical and biochemical outcomes after ipsilateral adrenalectomy. The functional effect of somatic p.V1937M variant results in increased CYP11B2 expression and aldosterone biosynthesis in HAC15 cells. A distinct heterogeneous foamy pattern of CYP11B2 and CYP17A1 expression was identified in immunohistological staining, supporting the pathological evidence of aldosterone synthesis.

Conclusions: The somatic mutation of p.V1937M might be a pathogenic driver in aldosterone overproduction. This study provides new insight into the molecular mechanism and disease outcomes of uPA.
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http://dx.doi.org/10.3389/fendo.2022.816476DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9218183PMC
June 2022

The Value of Preoperative Local Symptoms in Prognosis of Upper Tract Urothelial Carcinoma After Radical Nephroureterectomy: A Retrospective, Multicenter Cohort Study.

Front Oncol 2022 2;12:872849. Epub 2022 Jun 2.

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

Purpose: We aimed to evaluate the impact of preoperative local symptoms on prognosis after radical nephroureterectomy in patients with upper tract urothelial carcinoma (UTUC).

Methods: This retrospective study consisted of 2,662 UTUC patients treated at 15 institutions in Taiwan from 1988 to 2019. Clinicopathological data were retrospectively collected for analysis by the Taiwan UTUC Collaboration Group. The Kaplan-Meier method was used to calculate overall survival (OS), cancer-specific survival (CSS), disease-free survival (DFS), and bladder recurrence-free survival (BRFS). The prognostic value of preoperative local symptoms in OS, CSS, DFS, and BRFS was investigated using Cox proportional hazards models.

Results: The median follow-up was 36.6 months. Among 2,662 patients, 2,130 (80.0%) presented with hematuria and 398 (15.0%) had symptomatic hydronephrosis at diagnosis. Hematuria was associated with less symptomatic hydronephrosis (0.001), more dialysis status ( = 0.027), renal pelvic tumors (0.001), and early pathological tumor stage ( = 0.001). Symptomatic hydronephrosis was associated with female patients (0.001), less dialysis status ( = 0.001), less bladder cancer history (0.001), ureteral tumors (0.001), open surgery ( = 0.006), advanced pathological tumor stage (0.001), and postoperative chemotherapy ( = 0.029). Kaplan-Meier analysis showed that patients with hematuria or without symptomatic hydronephrosis had significantly higher rates of OS, CSS, and DFS (all 0.001). Multivariate analysis confirmed that presence of hematuria was independently associated with better OS (HR 0.789, 95% CI 0.661-0.942) and CSS (HR 0.772, 95% CI 0.607-0.980), while symptomatic hydronephrosis was a significant prognostic factor for poorer OS (HR 1.387, 95% CI 1.142-1.683), CSS (HR 1.587, 95% CI 1.229-2.050), and DFS (HR 1.378, 95% CI 1.122-1.693).

Conclusions: Preoperative local symptoms were significantly associated with oncological outcomes, whereas symptomatic hydronephrosis and hematuria had opposite prognostic effects. Preoperative symptoms may provide additional information on risk stratification and perioperative treatment selection for patients with UTUC.
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http://dx.doi.org/10.3389/fonc.2022.872849DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9201473PMC
June 2022

Is Lymph Node Dissection Necessary During Radical Nephroureterectomy for Clinically Node-Negative Upper Tract Urothelial Carcinoma? A Multi-Institutional Study.

Front Oncol 2022 29;12:791620. Epub 2022 Apr 29.

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

Purpose: This study aimed to compare the oncological outcomes of patients with upper tract urothelial carcinoma (UTUC) without clinical lymph node metastasis (cN0) undergoing lymph node dissection (LND) during radical nephroureterectomy (NU).

Methods: From the updated data of the Taiwan UTUC Collaboration Group, a total of 2726 UTUC patients were identified. We only include patients with ≥ pT2 stage and enrolled 658 patients. The Kaplan-Meier estimator and Cox proportional hazards model were used to analyze overall survival (OS), cancer-specific survival (CSS), disease-free survival (DFS), and bladder recurrence-free survival (BRFS) in LND (+) and LND (-) groups.

Results: A total of 658 patients were included and 463 patients without receiving LND and 195 patients receiving LND. From both univariate and multivariate survival analysis, there are no significant difference between LND (+) and LND (-) group in survival rate. In LND (+) group, 18.5% patients have pathological LN metastasis. After analyzing pN+ subgroup, it revealed worse CSS (p = 0.010) and DFS (p < 0.001) compared with pN0 patients.

Conclusions: We found no significant survival benefit related to LND in cN0 stage, ≥ pT2 stage UTUC, irrespective of the number of LNs removed, although pN+ affected cancer prognosis. However, from the result of pN (+) subgroup of LND (+) cohort analysis, it may be reasonable to not perform LND in patients with cT2N0 stage due to low positive predictive value of pN (+). In addition, performing LND may be considered for ureter cancer, which tends to cause lymphatic and hematogenous tumor spreading. Further large prospective studies are needed to validate our findings.
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http://dx.doi.org/10.3389/fonc.2022.791620DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9099435PMC
April 2022

Impact of Adjuvant Chemotherapy on Variant Histology of Upper Tract Urothelial Carcinoma: A Propensity Score-Matched Cohort Analysis.

Front Oncol 2022 22;12:843715. Epub 2022 Apr 22.

Division of Urology, Department of Surgery, Taipei Tzuchi Hospital, The Buddhist Tzu Chi Medical Foundation, New Taipei City, Taiwan.

Background: The advantage of adjuvant chemotherapy for upper urinary tract urothelial cancer (UTUC) has been reported, whereas its impact on upper tract cancer with variant histology remains unclear. We aimed to answer the abovementioned question with our real-world data.

Design Setting And Participants: Patients who underwent radical nephroureterectomy (RNU) and were confirmed to have variant UTUC were retrospectively evaluated for eligibility of analysis. In the Taiwan UTUC Collaboration database, we identified 245 patients with variant UTUC among 3,109 patients with UTUC who underwent RNU after excluding patients with missing clinicopathological information.

Intervention: Those patients with variant UTUC were grouped based on their history of receiving adjuvant chemotherapy or not.

Outcome Measurements And Statistical Analysis: Propensity score matching was used to reduce the treatment assignment bias. Multivariable Cox regression model was used for the analysis of overall, cancer-specific, and disease-free survival.

Results And Limitations: For the patients with variant UTUC who underwent adjuvant chemotherapy compared with those without chemotherapy, survival benefit was identified in overall survival in univariate analysis (hazard ratio (HR), 0.527; 95% confidence interval (CI), 0.285-0.973; = 0.041). In addition, in multivariate analysis, patients with adjuvant chemotherapy demonstrated significant survival benefits in cancer-specific survival (OS; HR, 0.454; CI, 0.208-0.988; = 0.047), and disease-free survival (DFS; HR, 0.324; 95% CI, 0.155-0.677; ( = 0.003). The main limitations of the current study were its retrospective design and limited case number.

Conclusions: Adjuvant chemotherapy following RNU significantly improved cancer-related survivals in patients with UTUC with variant histology.
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http://dx.doi.org/10.3389/fonc.2022.843715DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9072967PMC
April 2022

Clinical Efficacy of Adjuvant Chemotherapy in Advanced Upper Tract Urothelial Carcinoma (pT3-T4): Real-World Data from the Taiwan Upper Tract Urothelial Carcinoma Collaboration Group.

J Pers Med 2022 Feb 6;12(2). Epub 2022 Feb 6.

Department of Urology, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan.

The clinical efficacy of adjuvant chemotherapy in upper tract urothelial carcinoma (UTUC) is unclear. We aimed to assess the therapeutic outcomes of adjuvant chemotherapy in patients with advanced UTUC (pT3-T4) after radical nephroureterectomy (RNU). We retrospectively reviewed the data of 2108 patients from the Taiwan UTUC Collaboration Group between 1988 and 2018. Comprehensive clinical features, pathological characteristics, and survival outcomes were recorded. Univariate and multivariate Cox proportional hazards models were used to evaluate overall survival (OS), cancer-specific survival (CSS), and disease-free survival (DFS). Of the 533 patients with advanced UTUC included, 161 (30.2%) received adjuvant chemotherapy. In the multivariate analysis, adjuvant chemotherapy was significantly associated with a reduced risk of overall death (hazard ratio (HR), 0.599; 95% confidence interval (CI), 0.419-0.857; = 0.005), cancer-specific mortality (HR, 0.598; 95% CI, 0.391-0.914; = 0.018), and cancer recurrence (HR, 0.456; 95% CI, 0.310-0.673; < 0.001). The Kaplan-Meier survival analysis revealed that patients receiving adjuvant chemotherapy had significantly better five-year OS (64% vs. 50%, = 0.002), CSS (70% vs. 62%, = 0.043), and DFS (60% vs. 48%, = 0.002) rates compared to those who did not receive adjuvant chemotherapy. In conclusion, adjuvant chemotherapy after RNU had significant therapeutic benefits on OS, CSS, and DFS in advanced UTUC.
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http://dx.doi.org/10.3390/jpm12020226DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8877034PMC
February 2022

Factors Predicting Oncological Outcomes of Radical Nephroureterectomy for Upper Tract Urothelial Carcinoma in Taiwan.

Front Oncol 2021 13;11:766576. Epub 2022 Jan 13.

Division of Urology, Department of Surgery, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan.

Background: Taiwan is one of the endemic regions where upper tract urothelial carcinoma (UTUC) accounts for approximately a third of all urothelial tumors. Owing to its high prevalence, extensive experience has been accumulated in minimally invasive radical nephroureterectomy (RNU). Although a variety of predictive factors have been explored in numerous studies, most of them were on a single-center or limited institutional basis and data from a domestic cohort are lacking.

Objective: This study aims to identify significant predicting factors of oncological outcomes, including overall survival (OS), cancer-specific survival (CSS), disease-free survival (DFS), and intravesical recurrence-free survival (IVRFS), following RNU for UTUC in Taiwan.

Methods: A multicenter registry database, Taiwan UTUC Collaboration Group, was utilized to analyze oncological outcomes of 3,333 patients undergoing RNU from 1988 to 2021 among various hospitals in Taiwan. Clinicopathological parameters were recorded according to the principles established by consensus meetings. The Kaplan-Meier estimator was utilized to estimate the survival rates, and the curves were compared using the stratified log-rank test. Univariate and multivariate analyses were performed with the Cox proportional hazard model to explore potential predicting factors.

Results: With a median follow-up of 41.8 months in 1,808 patients with complete information, the 5-year IVRFS, DFS, CSS, and OS probabilities were 66%, 72%, 81%, and 70%, respectively. In total, 482 patients experienced intravesical recurrence, 307 died of UTUC, and 583 died of any cause. Gender predominance was female (57%). A total of 1,531 patients (84.7%) had high-grade tumors; preoperative hydronephrosis presented in 1,094 patients (60.5%). Synchronous bladder UC was identified in 292 patients (16.2%). Minimally invasive procedures accounted for 78.8% of all surgeries, including 768 hand-assisted laparoscopic (42.5%) and 494 laparoscopic (27.3%) approaches. Synchronous bladder UC was the dominant adverse predicting factor for all survival outcomes. Other independent predicting factors for OS, CSS, and DFS included age ≧70, presence of preoperative hydronephrosis, positive surgical margin, LVI, pathological T and N staging, and laparoscopic RNU.

Conclusion: Synchronous UC of the urinary bladder is an independent adverse prognostic factor for survival in UTUC. The presence of preoperative hydronephrosis was also corroborated as a disadvantageous prognostic factor. Our multivariate analysis suggested that laparoscopic RNU might provide better oncological control.
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http://dx.doi.org/10.3389/fonc.2021.766576DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8793058PMC
January 2022

Impact of Pathology Review in Adverse Histological Characteristics and pT Stages of Upper Tract Urothelial Cancer in a Multicenter Study.

Front Oncol 2021 25;11:757359. Epub 2021 Nov 25.

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

Purpose: Pathology reviews for upper urinary tract cancer (UTUC) remained scarce in the literature. Here, we reported the interobserver variation among the review and local pathologies of featured histologic characteristics for UTUC.

Methods: Patients who underwent definitive surgical treatments for UTUC were retrospectively reviewed for eligibility of pathology review. In the Taiwan UTUC Collaboration cohort, 212 cases were reviewed, of which 154 cases were eligible for pathology review. Agreement between original pathology and review pathology was measured by the total percentage of agreement and by simple kappa statistics. The prognostic impact was analyzed by the Cox regression model with the estimation of hazard ratios (HR) and 95% confidence intervals.

Results: There were 80 women and 74 men enrolled in this study, and the median age at treatment was 71.7 years. The agreement is moderate agreement for surgical margin status (87.7%; κ = 0.61), tumor grade (82.5%; κ = 0.43), tumor invasiveness (76.6%; κ = 0.45), lymphovascular invasion (70.8%; κ = 0.42) and T stage (67.5%; κ = 0.52). The interobserver agreements for perineural invasion and variant histology identification were slight. Kaplan-Meier analysis for disease-free survival revealed comparable results in local and review pathology for localized (Tis, Ta, T1-2) or advanced T stage (T3-4).

Conclusions: Pathology review of UTUC had minimal impact on clinical practice based on current available disease treatment guidelines. However, significant interobserver variations were observed in featured adverse histopathological characters.
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http://dx.doi.org/10.3389/fonc.2021.757359DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8655678PMC
November 2021

Long-term mortality and cardiovascular events in patients with unilateral primary aldosteronism after targeted treatments.

Eur J Endocrinol 2021 Dec 20;186(2):195-205. Epub 2021 Dec 20.

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

Objective: Long-term outcomes (especially mortality and/or major cardiovascular events (MACE)) of the unilateral primary aldosteronism (uPA) patients who underwent medical or surgery-targeted treatment, relative to those with essential hypertension (EH), have been scarcely reported.

Design And Settings: Using the prospectively designed observational Taiwan Primary Aldosteronism Investigation cohort, we identified 858 uPA cases among 1220 primary aldosteronism patients and another 1210 EH controls.

Exposures: Operated uPA patients were grouped via their 1-year post-therapy statuses.

Results: Primary Aldosteronism Surgical Outcome clinical complete success (hypertension remission) was achieved in 272 (49.9%) of 545 surgically treated uPA patients. After follow-up for 6.3 ± 4.0 years, both hypertension-remissive (hazard ratio (HR): 0.54; P < 0.001) and not-cured (HR: 0.61; P < 0.001) uPA patients showed a lower risk of all-cause mortality than that of EH controls; whereas the not-cured group had a higher risk of incident MACE (sub-hazard ratio (sHR), 1.41; P = 0.037) but similar atrial fibrillation (Af) and congestive heart failure (CHF). Mineralocorticoid receptor antagonist (MRA)-treated uPA patients had higher risks of MACE (sHR: 1.38; P = 0.033), Af (sHR:1.62, P = 0.049), and CHF (sHR: 1.44; P = 0.048) than those of EH controls, with mortality as a competing risk. Using inverse probability of treatment-weighted matching and counting adrenalectomy as a time-varying factor, treatment with adrenalectomy was associated with lower risks of all-cause mortality (HR: 0.57; P = 0.035), MACE (HR: 0.67; P = 0.037), and CHF (HR: 0.49; P = 0.005) compared to those of MRA therapy.

Conclusions: Adrenalectomy, independent of post-surgical hypertension remission, was associated with lower all-cause mortality of uPA patients, compared to that of EH patients. We further documented a more beneficial effect of adrenalectomy over MRA treatment on long-term mortality, MACE, and CHF in uPA patients.
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http://dx.doi.org/10.1530/EJE-21-0836DOI Listing
December 2021

Comparison of oncological outcomes for hand-assisted and pure laparoscopic radical nephroureterectomy: results from the Taiwan Upper Tract Urothelial Cancer Collaboration Group.

Surg Endosc 2022 06 29;36(6):4342-4348. Epub 2021 Oct 29.

Division of Urology, Department of Surgery, Taipei Tzu Chi Hospital, The Buddhist Tzu Chi Medical Foundation, 289 Jianguo Road, Xindian, New Taipei City, Taiwan.

Purpose: Laparoscopic radical nephroureterectomy (LNU) has gradually become the new standard treatment for localized upper tract urothelial cancer (UTUC). With more blunt dissection and tactile sensation, hand-assisted LNU might shorten the operative time compared with the pure laparoscopic approach. However, whether the use of the hand-assisted or the pure laparoscopic approach has an effect on oncological outcomes remains unclear.

Methods: We retrospectively identified 629 patients with non-metastatic UTUC who underwent hand-assisted (n = 515) or pure LNU (n = 114) at 9 hospitals in Taiwan between 2004 and 2019. Overall survival, cancer-specific survival, recurrence-free survival, and bladder recurrence-free survival were compared between these two groups using inverse-probability of treatment weighting (IPTW) derived from the propensity scores for baseline covariate adjustment.

Results: The median follow-up period was 32.9 and 28.7 months in the hand-assisted and the pure groups, respectively. IPTW-adjusted Cox proportional hazards models showed that the laparoscopic approach (pure vs. hand-assisted) was not significantly associated with all-cause mortality (HR 0.79, 95% CI 0.49-1.24, p = 0.304), cancer-specific mortality (HR 0.88, 95% CI 0.51-1.51, p = 0.634), or extra-vesical recurrence (HR 0.65, 95% CI 0.41-1.04, p = 0.071). However, the pure laparoscopic approach was significantly associated with lower intra-vescial recurrence (HR 0.64, 95% CI 0.43-0.96, p = 0.029) for patients who underwent LNU. Kaplan-Meier curves also revealed that the pure laparoscopic approach was associated with better bladder recurrence-free survival compared with the hand-assisted laparoscopic approach in both the original cohort and the IPTW-adjusted cohort (log-rank p = 0.042 and 0.027, respectively).

Conclusions: The performance of hand-assisted or pure LNU does not significantly affect the all-cause mortality, cancer-specific mortality, or extra-vesical recurrence for patients with non-metastatic UTUC. However, the hand-assisted laparoscopic approach could increase the risk of intra-vesical recurrence for patients who undergo LNU.
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http://dx.doi.org/10.1007/s00464-021-08779-2DOI Listing
June 2022

Comparing Oncological Outcomes and Surgical Complications of Hand-Assisted, Laparoscopic and Robotic Nephroureterectomy for Upper Tract Urothelial Carcinoma.

Front Oncol 2021 4;11:731460. Epub 2021 Oct 4.

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

Purpose: This study aimed to compare the oncological outcomes and surgical complications of patients with upper tract urothelial carcinoma (UTUC) treated with different minimally invasive techniques for nephroureterectomy.

Methods: From the updated data of the Taiwan UTUC Collaboration Group, a total of 3,333 UTUC patients were identified. After excluding ineligible cases, we retrospectively included 1,340 patients from 15 institutions who received hand-assisted laparoscopic nephroureterectomy (HALNU), laparoscopic nephroureterectomy (LNU) or robotic nephroureterectomy (RNU) between 2001 and 2021. Kaplan-Meier estimator and Cox proportional hazards model were used to analyze the survival outcomes, and binary logistic regression model was selected to compare the risks of postoperative complications of different surgical approaches.

Results: Among the enrolled patients, 741, 458 and 141 patients received HALNU, LNU and RNU, respectively. Compared with RNU (41.1%) and LNU (32.5%), the rate of lymph node dissection in HALNU was the lowest (17.4%). In both Kaplan-Meier and univariate analysis, the type of surgery was significantly associated with overall and cancer-specific survival. The statistical significance of surgical methods on survival outcomes remained in multivariate analysis, where patients undergoing HALNU appeared to have the worst overall (p = 0.007) and cancer-specific (p = 0.047) survival rates among the three groups. In all analyses, the surgical approach was not related to bladder recurrence. In addition, HALNU was significantly associated with longer hospital stay (p = 0.002), and had the highest risk of major Clavien-Dindo complications (p = 0.011), paralytic ileus (p = 0.012), and postoperative end-stage renal disease (p <0.001).

Conclusions: Minimally invasive surgery can be safe and feasible. We proved that compared with the HALNU group, the LNU and RNU groups have better survival rates and fewer surgical complications. It is crucial to uphold strict oncological principles with sophisticated technique to improve outcomes. Further prospective studies are needed to validate our findings.
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http://dx.doi.org/10.3389/fonc.2021.731460DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8522474PMC
October 2021

LTBP4 affects renal fibrosis by influencing angiogenesis and altering mitochondrial structure.

Cell Death Dis 2021 10 13;12(10):943. Epub 2021 Oct 13.

Renal Division, Department of Internal medicine, National Taiwan University Hospital Yunlin Branch, Douliu, Taiwan.

Transforming growth factor beta (TGFβ) signalling regulates extracellular matrix accumulation known to be essential for the pathogenesis of renal fibrosis; latent transforming growth factor beta binding protein 4 (LTBP4) is an important regulator of TGFβ activity. To date, the regulation of LTBP4 in renal fibrosis remains unknown. Herein, we report that LTBP4 is upregulated in patients with chronic kidney disease and fibrotic mice kidneys created by unilateral ureteral obstruction (UUO). Mice lacking the short LTBP4 isoform (Ltbp4S) exhibited aggravated tubular interstitial fibrosis (TIF) after UUO, indicating that LTBP4 potentially protects against TIF. Transcriptomic analysis of human proximal tubule cells overexpressing LTBP4 revealed that LTBP4 influences angiogenic pathways; moreover, these cells preserved better mitochondrial respiratory functions and expressed higher vascular endothelial growth factor A (VEGFA) compared to wild-type cells under hypoxia. Results of the tube formation assay revealed that additional LTBP4 in human umbilical vein endothelial cell supernatant stimulates angiogenesis with upregulated vascular endothelial growth factor receptors (VEGFRs). In vivo, aberrant angiogenesis, abnormal mitochondrial morphology and enhanced oxidative stress were observed in Ltbp4S mice after UUO. These results reveal novel molecular functions of LTBP4 stimulating angiogenesis and potentially impacting mitochondrial structure and function. Collectively, our findings indicate that LTBP4 protects against disease progression and may be of therapeutic use in renal fibrosis.
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http://dx.doi.org/10.1038/s41419-021-04214-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8514500PMC
October 2021

Tumor distribution affects bladder recurrence but not survival outcome of multifocal upper tract urothelial carcinoma treated with radical nephroureterectomy.

Sci Rep 2021 09 24;11(1):19059. Epub 2021 Sep 24.

Department of Urology, Kaohsiung Medical University Hospital, No. 100, Shih-Chuan 1st Road, Sanmin Dist., Kaohsiung, 80708, Taiwan.

Tumor multifocality and location are prognostic factors for upper tract urothelial carcinoma (UTUC). However, confounding effects can appear when these two factors are analyzed together. Therefore, we aimed to investigate the impact of tumor distribution on the outcomes of multifocal UTUC after radical nephroureterectomy. From the 2780 UTUC patients in the Taiwan UTUC Collaboration Group, 685 UTUC cases with multifocal tumors (defined as more than one tumor lesion in unilateral upper urinary tract) were retrospectively included and divided into three groups: multiple renal pelvic tumors, multiple ureteral tumors, and synchronous renal pelvic and ureteral tumors included 164, 152, and 369 patients, respectively. We found the prevalence of carcinoma in situ was the highest in the synchronous group. In multivariate survival analyses, tumor distribution showed no difference in cancer-specific and disease-free survival, but there was a significant difference in bladder recurrence-free survival. The synchronous group had the highest bladder recurrence rate. In summary, tumor distribution did not influence the cancer-specific outcomes of multifocal UTUC, but synchronous lesions led to a higher rate of bladder recurrence than multiple renal pelvic tumors. We believe that the distribution of tumors reflects the degree of malignant involvement within the urinary tract, but has little significance for survival or disease progression.
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http://dx.doi.org/10.1038/s41598-021-98696-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8463529PMC
September 2021

Influence of Vincristine, Clinically Used in Cancer Therapy and Immune Thrombocytopenia, on the Function of Human Platelets.

Molecules 2021 Sep 2;26(17). Epub 2021 Sep 2.

Department of Pharmacology, School of Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan.

Vincristine is a clinically used antimicrotubule drug for treating patients with lymphoma. Due to its property of increasing platelet counts, vincristine is also used to treat patients with immune thrombocytopenia. Moreover, antiplatelet agents were reported to be beneficial in thrombotic thrombocytopenic purpura (TTP). Therefore, we investigated the detailed mechanisms underlying the antiplatelet effect of vincristine. Our results revealed that vincristine inhibited platelet aggregation induced by collagen, but not by thrombin, arachidonic acid, and the thromboxane A analog U46619, suggesting that vincristine exerts higher inhibitory effects on collagen-mediated platelet aggregation. Vincristine also reduced collagen-mediated platelet granule release and calcium mobilization. In addition, vincristine inhibited glycoprotein VI (GPVI) signaling, including Syk, phospholipase Cγ2, protein kinase C, Akt, and mitogen-activated protein kinases. In addition, the in vitro PFA-100 assay revealed that vincristine did not prolong the closure time, and the in vivo study tail bleeding assay showed that vincristine did not prolong the tail bleeding time; both findings suggested that vincristine may not affect normal hemostasis. In conclusion, we demonstrated that vincristine exerts antiplatelet effects at least in part through the suppression of GPVI signaling. Moreover, this property of antiplatelet activity of vincristine may provide additional benefits in the treatment of TTP.
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http://dx.doi.org/10.3390/molecules26175340DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8434001PMC
September 2021

Effects of Proton Pump Inhibitors on Glycemic Control and Incident Diabetes: A Systematic Review and Meta-analysis.

J Clin Endocrinol Metab 2021 10;106(11):3354-3366

Division of Endocrinology, Diabetes and Nutrition, University of Maryland School of Medicine, Baltimore, MarylandUSA.

Context: Whether proton pump inhibitors (PPI) can improve glycemic control among individuals with diabetes or decrease the risk of incident diabetes in the general population is unclear.

Objective: To evaluate the impact of PPI therapy on glycemic control among individuals with diabetes and the risk of diabetes among those without diabetes.

Results: PubMed, Embase, Scopus, and ClinicalTrials.gov were searched from inception to November 21, 2020. We included studies comparing glycosylated hemoglobin (HbA1c) or fasting blood glucose (FBG) among individuals with diabetes treated with and without PPI therapy as an add-on to standard therapy. Studies evaluating the risk of incident diabetes among individuals taking PPI were assessed. We performed dual independent review, data extraction, and quality assessment. Weighted mean differences between groups or relative risks were imputed using random-effects models.

Results: Seven studies (n = 342) for glycemic control and 5 studies (n = 244 439) for risk of incident diabetes were included. Compared with standard therapy, add-on PPI was associated with a significant decrease in HbA1c (WMD, -0.36 %; 95% CI, -0.68 to -0.05; P = 0.025) and FBG (WMD, -10.0 mg/dL; 95% CI, -19.4 to -0.6; P = 0.037). PPI use did not reduce the risk of incident diabetes (pooled RR, 1.10; 95% CI, 0.89 to 1.34; P = 0.385).

Conclusion: Add-on PPI improved glycemic indices among individuals with diabetes but did not alter the risk of incident diabetes. The effects of PPI on glycemic control should be considered when prescribing antacids to patients with diabetes.
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http://dx.doi.org/10.1210/clinem/dgab353DOI Listing
October 2021

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

Sci Rep 2021 02 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

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

Presence of Subclinical Hypercortisolism in Clinical Aldosterone-Producing Adenomas Predicts Lower Clinical Success.

Hypertension 2020 11 14;76(5):1537-1544. Epub 2020 Sep 14.

From the Departments of Internal Medicine (K.-Y.P., S.-Y.Y., Y.-H.L., V.-C.W.), National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei.

The clinical characteristics and outcomes in patients with clinical aldosterone-producing adenomas harboring mutations with or without subclinical hypercortisolism remain unclear. This prospective study is aimed at determining factors associated with subclinical hypercortisolism in patients with clinical aldosterone-producing adenomas. Totally, 82 patients were recruited from November 2016 to March 2018 and underwent unilateral laparoscopic adrenalectomy with at least a 12-month follow-up postoperatively. Standard subclinical hypercortisolism (defined as cortisol >1.8 μg/dL after 1 mg dexamethasone suppression test [DST]) was detected in 22 (26.8%) of the 82 patients. Intriguingly, a generalized additive model identified the clinical aldosterone-producing adenoma patients with 1 mg DST>1.5 μg/dL had significantly larger tumors (=0.02) than those with 1 mg DST<1.5 μg/dL. Multivariable logistic regression showed that the presence of mutations (odds ratio, 0.22, =0.010) and body mass index (odds ratio, 0.87, =0.046) were negatively associated with 1 mg DST>1.5 μg/dL, whereas tumor size was positively associated with it (odds ratio, 2.85, =0.014). Immunohistochemistry revealed a higher degree of immunoreactivity for CYP11B1 in adenomas with wild-type (=0.018), whereas CYP11B2 was more commonly detected in adenomas with mutation (=0.007). Patients with wild-type and 1 mg DST>1.5 μg/dL exhibited the lowest complete clinical success rate (36.8%) after adrenalectomy. In conclusion, subclinical hypercortisolism is common in clinical aldosterone-producing adenoma patients without mutation or with a relatively larger adrenal tumor. The presence of serum cortisol levels >1.5 μg/dL after 1 mg DST may be linked to a lower clinical complete success rate.
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http://dx.doi.org/10.1161/HYPERTENSIONAHA.120.15328DOI Listing
November 2020

Association of visceral adiposity and clinical outcome among patients with aldosterone producing adenoma.

BMJ Open Diabetes Res Care 2020 07;8(1)

College of Medicine, National Taiwan University, Taipei, Taiwan

Introduction: Primary aldosteronism (PA) is a common form of secondary hypertension that has significant cardiovascular events and increased prevalence of metabolic syndrome and diabetics. Although plasma aldosterone concentration is positively correlated with visceral fat area (VFA) in non-PA individuals, the role of visceral adiposity associated with clinical success after surgery is not known.

Research Design And Methods: We analyzed patients who underwent adrenalectomy for aldosterone-producing adenoma (APA) at the Taiwan PA Investigator group. VFA was calculated from the abdominal CT scan at APA diagnosis, and all patients received adrenalectomy.

Results: The study involved 100 consecutive patients with APA (42 males; mean age 49.3 years) matched with 41 essential hypertension (EH) patients. Patients with APA had smaller VFA (p=0.010) than their EH counterparts. Multiple linear regression analysis revealed that the duration of hypertension (p=0.007), but not plasma aldosterone, was negatively correlated with VFA in patients with APA. Logistic regression analysis showed that log VFA (OR=0.065, p0.001) and duration of hypertension before PA diagnosis (OR=0.919, p=0.011) can predict complete clinical success after adrenalectomy. Multifactor-adjusted generalized additive model demonstrated that log VFA <9.2 was associated with complete cure of hypertension. Furthermore, VFA was increased at 6 months after adrenalectomy (p=0.045).

Conclusions: Patients with APA had smaller VFA than their EH counterparts, and VFA increased after adrenalectomy. Clinical complete cure of hypertension after surgery was associated with smaller VFA and shorter duration of hypertension at PA diagnosis, suggesting a potential interplay of visceral adiposity and aldosterone of the patients with APA.
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http://dx.doi.org/10.1136/bmjdrc-2019-001153DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7383952PMC
July 2020

Predictive factors of post-laparoscopic inguinal hernia acute and chronic pain: prospective follow-up of 807 patients from a single experienced surgeon.

Surg Endosc 2021 01 13;35(1):148-158. Epub 2020 Jan 13.

Department of Surgery, Taipei Tzu Chi Hospital, The Buddhist Tzu Chi Medical Foundation, New Taipei City, Taiwan.

Introduction: Convalescence after hernia repair is one of the main focuses for hernia surgeons. We analyzed our prospectively collected data to identify possible predictive factors for post-operative acute and chronic pain.

Materials And Methods: We prospectively collected the demographic data and peri-operative findings. Post-operative acute pain was evaluated with Visual Analog Pain Scale. The chronic pain (pain persists for > 6 months since operation) was also recorded.

Results: From June 2008 to August 2018, there were 807 patients with 1029 sites of inguinal hernia enrolled in our analysis. Pain before operation was associated with the severity of acute pain on OP (operation) day, POD 1 (post-operative day 1), and POD 7 (post-operative day 7). Younger patients had significantly higher post-operative acute pain on OP day, POD 1, and POD 7. The staple mesh fixation method resulted in a higher pain score at OP day and POD 1. The predictive factors for chronic pain were sex (female), young age (< 65 years), having no past history of hypertension, pain before operation, and mesh material.

Conclusion: A younger age and inguinal pain before operation were the main predictive factors for higher post-operative pain. Younger patients, females, having inguinal pain before surgery, and using heavy weight mesh have a higher risk of chronic pain.
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http://dx.doi.org/10.1007/s00464-020-07373-2DOI Listing
January 2021

Comparison of short- to mid-term efficacy of nonfixation and permanent tack fixation in laparoscopic total extraperitoneal hernia repair: A systematic review and meta-analysis.

Ci Ji Yi Xue Za Zhi 2019 Oct-Dec;31(4):244-253. Epub 2019 Sep 16.

Division of Urology, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei, Taiwan.

Objective: We systematically reviewed the literature and pooled data for a meta-analysis to compare the efficacy and safety of mesh fixation and nonfixation in laparoscopic total extraperitoneal (TEP) hernia repair.

Materials And Methods: We performed a systematic search of PubMed and a Cochrane review for all randomized controlled trials that compared the efficacy and complications of mesh fixation versus nonfixation in TEP hernia repair. The evaluated outcomes included perioperative (operative time and conversion rate) and postoperative parameters (pain scores, duration of hospital stay, surgical complications including seroma, delayed return of bladder function, chronic pain, and recurrence). Cochrane Collaboration Review Manager Software (RevMan, version 5.2.6) was used for statistical analysis.

Results: Ten trials met the inclusion criteria and were included in a pooled analysis. In total, 1099 patients (1467 hernias) had received TEP hernia repair (748 and 719 hernia defects in the nonfixation and fixation groups, respectively). The nonfixation group required shorter operative time (weighted mean difference [WMD] = -2.36 min, = 0.0006) and had less pain on postoperative day 1 (WMD = -0.44, = 0.04) than the fixation group. No significant differences were observed between groups with regard to conversion rate, hospital stay, recurrence rate, or complication rate. However, the incidence of postoperative urine retention was higher in the fixation group (odds ratio = 0.26, = 0.03).

Conclusion: For patients with a nonrecurrent uncomplicated hernia defect with the size <3 cm, nonfixation yielded comparable efficacy with mesh fixation, but less short-term postoperative pain, and a lower risk of urine retention. In addition, the nonfixation method involved a shorter operative time and lower costs. However, no difference in the incidence of chronic pain was observed.
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http://dx.doi.org/10.4103/tcmj.tcmj_47_18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6905242PMC
September 2019

Risk of new-onset autoimmune diseases in primary aldosteronism: a nation-wide population-based study.

J Hypertens 2020 04;38(4):745-754

Department of Internal Medicine, National Taiwan University Hospital.

Objective: The association between hyperaldosteronism and autoimmune disorders has been postulated. However, long-term incidence of a variety of new-onset autoimmune diseases (NOAD) among patients with primary aldosteronism has not been well investigated.

Methods: From Taiwan's National Health Insurance Research Database with a 23-million population insurance registry, the identification of primary aldosteronism, essential hypertension and NOAD as well as all-cause mortality were ascertained by a validated algorithm.

Results: From 1997 to 2009, 2319 primary aldosteronism patients without previously autoimmune disease were identified and propensity score-matched with 9276 patients with essential hypertension. Among those primary aldosteronism patients, 806 patients with aldosterone-producing adenomas (APA) were identified and matched with 3224 essential hypertension controls. NOAD incidence is augmented in primary aldosteronism patients compared with its matched essential hypertension (hazard ratio 3.82, P < 0.001, versus essential hypertension). Furthermore, NOAD incidence is also higher in APA patients compared with its matched essential hypertension (hazard ratio = 2.96, P < 0.001, versus essential hypertension). However, after a mean 8.9 years of follow-up, primary aldosteronism patients who underwent adrenalectomy (hazard ratio = 3.10, P < 0.001, versus essential hypertension) and took mineralocorticoid receptor antagonist (MRA) still had increased NOAD incidence (hazard ratio = 4.04, P < 0.001, versus essential hypertension).

Conclusion: Primary aldosteronism patients had an augmented risk for a variety of incident NOAD and all-cause of mortality, compared with matched essential hypertension controls. Notably, the risk of incident NOAD remained increased in patients treated by adrenalectomy or MRA compared with matched essential hypertension controls. This observation supports the theory of primary aldosteronism being associated with a higher risk of multiple autoimmune diseases.
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http://dx.doi.org/10.1097/HJH.0000000000002300DOI Listing
April 2020

A comprehensive study comparing tack and glue mesh fixation in laparoscopic total extraperitoneal repair for adult groin hernias.

Surg Endosc 2020 10 18;34(10):4486-4493. Epub 2019 Nov 18.

Department of Surgery, Taipei Tzuchi Hospital, The Buddhist Tzu Chi Medical Foundation, New Taipei City, Taiwan.

Background: Glue mesh fixation is thought to cause less pain compared to tack mesh fixation during laparoscopic total extraperitoneal inguinal hernia repair (TEP). However, the clinical benefits of glue mesh fixation are still controversial. This study aimed to evaluate the acute pain, chronic pain, and recurrence rate between these two fixation methods.

Methods: After reviewing all patients in our prospective hernia repair database from February 2008 to December 2017, we identified 583 patients who underwent TEP with tack mesh fixation and 70 patients with glue fixation by a single surgeon. Acute post-operative pain and activity level were evaluated using a Visual Analog Score (VAS) and the modified Medical Outcome Study (MOS) score. The primary endpoint was chronic pain 6 months after TEP. The secondary endpoints were acute pain, activity level, complications, and recurrence.

Results: After adjustment for potential confounding factors, the glue mesh fixation had significant lower VAS at 2 h post operation during rest and coughing and on the first day after surgery during coughing (p = 0.005, p < 0.001, and p = 0.011). The modified MOS on the first day was higher in the glue group (p < 0.001). There were no reduced risk of chronic pain or increased risk of recurrence for the glue group compared to the tack group [Odds ratio (OR) = 0.237, p = 0.169; OR = 2.498, p = 0.299]. In the sub-group analysis for recurrent hernia repair, glue fixation is associated with better modified MOS (p = 0.031) on first day and lower VAS on the operative day and first day at rest (p = 0.003 and p = 0.024) after surgery.

Conclusions: Glue fixation method was superior to tack fixation method in acute post-operative pain and early post-operative activity level after laparoscopic TEP repair. However, both fixation methods had similar incidence of chronic pain-, recurrence-, and procedure-related complications after laparoscopic TEP repair.
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http://dx.doi.org/10.1007/s00464-019-07234-7DOI Listing
October 2020

Novel robot-assisted laparoscopic total extra-peritoneal repair with primary fascial closure plus pre-peritonea mesh for large groin defects.

Int J Med Robot 2020 Feb 3;16(1):e2052. Epub 2019 Dec 3.

Department of Surgery, Taipei Tzu Chi Hospital, The Buddhist Medical Foundation, New Taipei City, Taiwan.

Background: Since the introduction of robot-assisted laparoscopic surgery, a variety of conventional laparoscopic procedures have been explored via this approach. In the robotic era, most of the reported robot-assisted laparoscopic hernia repairs were performed with the trans-abdominal pre-peritoneal approach. According to the evidence extrapolated from laparoscopic ventral hernia repair, simultaneous fascial defect closure and mesh repair can significantly decrease the risk of seroma formation and recurrence over those without fascial closure. Therefore, we describe our novel technique of robot-assisted total extra-peritoneal (TEP) repair with primary fascial closure and pre-peritoneal mesh and its preliminary clinical outcomes.

Methods: We retrospectively reviewed our prospectively collected hernia database from October 2017 to July 2019, which included 26 consecutive patients with primary or recurrent groin hernias. Patients' baseline characteristics and perioperative outcomes were compared and analyzed. Perioperative factors included operative time, visual analog scale (VAS) score (0-100), hospital stay, perioperative complications, time to return to normal activity, and the modified Medical Outcome Study (MOS; item 3-12/36 items) score.

Results: All procedures were completed successfully without conversion to open or conventional laparoscopic surgery. The patients' age ranged from 28 to 74 years (median 57.5). The mean operative time was 115 minutes (range 95-172 min). There were no major procedure-related complications. Only four cases experienced asymptomatic seromas, which were detected by ultrasonography; and all resolved spontaneously within 6 weeks after the operation. The VAS and modified MOSs revealed quick recovery after robot-assisted endoscopic TEP repair.

Conclusions: Robot-assisted endoscopic TEP repair combined with primary fascial closure and pre-peritoneal mesh is a safe and feasible technique for groin hernia repair.
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http://dx.doi.org/10.1002/rcs.2052DOI Listing
February 2020

Plasma Aldosterone After Seated Saline Infusion Test Outperforms Captopril Test at Predicting Clinical Outcomes After Adrenalectomy for Primary Aldosteronism.

Am J Hypertens 2019 10;32(11):1066-1074

Fu Jen Catholic University, New Taipei City, Taiwan.

Objective: The saline infusion test (SIT) and the captopril test (CT) are widely used as confirmatory tests for primary aldosteronism (PA). We hypothesized that post-SIT and post-CT plasma aldosterone concentrations (PAC) indicate the severity of aldosterone-producing adenoma (APA) and might predict clinical outcome.

Methods: We recruited 216 patients with APA in the Taiwan Primary Aldosteronism Investigation (TAIPAI) registry who received both seated SIT and CT as confirmatory tests. The data of 143 patients who underwent adrenalectomy with complete follow-up after diagnosis were included in the final analysis. We determined the proportion of patients achieving clinical success in accordance with the Primary Aldosteronism Surgical Outcome consensus. Logistic regression analysis was conducted to identify preoperative factors associated with cure of hypertension.

Results: Complete clinical success was achieved in 48 (33.6%) patients and partial clinical success in 59 (41.2%) patients; absent clinical success was seen in 36 (25.2%) of 143 patients. Post-SIT PAC but not post-CT PAC was independently associated with clinical outcome. Higher levels of post-SIT PAC had a higher likelihood of clinical benefit (complete plus partial clinical success; odds ratio = 1.04 per ng/dl increase, 95% confidence interval = 1.01, 1.06; P = 0.004). Patients with post-SIT PAC > 25 ng/dl were more likely to have a favorable clinical outcome after adrenalectomy. This cutoff value translated into a positive predictive value of 86.0%.

Conclusions: We suggest that post-SIT PAC is a better predictor than post-CT PAC for clinical success in PA post adrenalectomy.
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http://dx.doi.org/10.1093/ajh/hpz098DOI Listing
October 2019

Risk of severe erectile dysfunction in primary hyperaldosteronism: A population-based propensity score matching cohort study.

Surgery 2019 03 23;165(3):622-628. Epub 2018 Nov 23.

Taiwan Primary Aldosteronism Investigation (TAIPAI) Study Group, Taipei; Division of Urology, Department of Surgery, Taipei Tzu Chi Hospital, The Buddhist Medical Foundation, New Taipei City, Taiwan. Electronic address:

Background: An elevated plasma aldosterone level has been reported as an independent risk factor for severe erectile dysfunction in men. The aim of this study was to explore whether primary hyperaldosteronism patients experience erectile dysfunction after targeted treatment.

Methods: We conducted a population-based cohort study of men with newly identified primary hyperaldosteronism/aldosterone-producing adenoma from January 1, 1997, to December 31, 2009. Men with essential hypertension and normotension were matched to the primary hyperaldosteronism group according to propensity score matching.

Results: We identified 1,067 men with primary hyperaldosteronism (mean age, 46.7 ± 12.8 years) and matched them with the same number of men with essential hypertension or normotension. During the mean follow-up interval of 5.4 years, the incident rates of total erectile dysfunction were 5.7, 3.9, and 3.1 per 1,000 person-years for the primary hyperaldosteronism, essential hypertension, and normotension groups, respectively. Men with primary hyperaldosteronism exhibited a higher risk of erectile dysfunction compared with men with normotension (competing risks hazard ratio, 1.83), and no difference was seen in comparison with men who have essential hypertension. After adrenalectomy, men who have primary hyperaldosteronism had a higher risk of exhibiting severe erectile dysfunction compared with men who have essential hypertension (competing risks hazard ratio, 2.44) or normotension (competing risks hazard ratio, 2.90).

Conclusion: Men with primary hyperaldosteronism reported a higher incidence of severe erectile dysfunction than normotension controls despite targeted treatment. The risk of severe erectile dysfunction increased after men who have primary hyperaldosteronism underwent adrenalectomy. This result raises the possibility of severe erectile dysfunction after adrenalectomy and calls for a prospective large-scale study of men who have aldosterone-producing adenoma regarding their erectile function both before and after adrenalectomy.
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http://dx.doi.org/10.1016/j.surg.2018.08.020DOI Listing
March 2019

Higher Screening Aldosterone to Renin Ratio in Primary Aldosteronism Patients with Diabetes Mellitus.

J Clin Med 2018 Oct 16;7(10). Epub 2018 Oct 16.

Division of Nephrology, Department of Internal Medicine, National Taiwan University Hospital, Taipei 10002, Taiwan.

Accumulated evidence has shown that low renin hypertension is common in patients with diabetic nephropathy. However, the performance of aldosterone to renin ratio (ARR) in primary aldosteronism (PA) patients with diabetes has not been well validated. Here, we report the performance of screening ARR in PA patients with diabetes. The study enrolled consecutive patients and they underwent ARR testing at screening. Then the diagnosis of PA was confirmed from the Taiwan Primary Aldosteronism Investigation registration dataset. Generalized additive model smoothing plot was used to validate the performance of screening ARR in PA patients with or without diabetes. During this study period, 844 PA patients were confirmed and 136 (16.0%) among them had diabetes. Other 816 patients were diagnosed with essential hypertension and used as the control group and 89 (10.9%) among them had diabetes. PA patients with diabetes were older and had a longer duration of hypertensive latency, higher systolic blood pressure and lower glomerular filtration rate than those PA patients without diabetes. The cut-off value of ARR in the generalized additive model predicting PA was 65 ng/dL per ng/mL/h in diabetic patients, while 45 ng/dL per ng/mL/h in non-diabetic patients. There was a considerable prevalence of diabetes among PA patients, which might be capable of interfering with the conventional screening test. The best cut-off value of ARR, more than 65 ng/dL per ng/mL/h in PA patients with diabetes, was higher than those without diabetes.
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http://dx.doi.org/10.3390/jcm7100360DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6209946PMC
October 2018

Laparoscopic total extraperitoneal inguinal hernia repair is safe and feasible in patients with continuation of antithrombotics.

J Minim Access Surg 2019 Oct-Dec;15(4):299-304

Department of Surgery, Taipei Tzuchi Hospital, The Buddhist Tzu Chi Medical Foundation, Taipei; Department of Urology, Medical College, Tzu Chi University, Hualien, Taiwan.

Aims: We aimed to evaluate the safety and feasibility of laparoscopic total extraperitoneal (TEP) inguinal hernia repair in patients with the continuation of their antithrombotic agents.

Settings And Design: This was prospective cohort study.

Materials And Methods: A total of 115 patients who underwent TEP inguinal hernia repair between January 2015 and September 2016 were included in the analysis. Seventeen patients continued their antithrombotics (antithrombotic group); the other 98 had not been on antithrombotics (control group).

Statistical Analysis Used: The analysis was performed by using Mann-Whitney U-test, Chi-square or Fisher's exact test.

Results: The antithrombotic group had a greater mean age (65.9 ± 8.0 vs. 57.7 ± 13.6,P= 0.002) and higher prevalence of hypertension (64.7% vs. 33.7%,P= 0.015), cardiovascular diseases (64.7% vs. 7.1%,P < 0.001), atrial fibrillation (23.5% vs. 0,P < 0.001), ischaemic heart disease (35.3% vs. 0,P < 0.001) and the American Society of Anaesthesiologists ≥2 (94.1% vs. 81.6%,P= 0.005). The operation time for the antithrombotic group was longer than that of the control group (92.06 ± 32.81 min vs. 72.33 ± 20.99 min,P= 0.015). None experienced conversion to open surgery in either group. There was no difference in the post-operative complications (29.4% vs. 28.6%) and sero-haematoma formation (23.5% vs. 11.1%). The analgesic requirement, hospital stays (23.72 ± 7.74 vs. 22.35 ± 10.33 h) and the time for return to normal daily activity (3.56 ± 1.74 vs. 3.63 ± 1.90) were not statistically different between the two groups. None in either group experienced major cardiovascular events within 30 days.

Conclusions: Laparoscopic TEP inguinal hernia repair can be safely performed in patients with the continuation of their antithrombotic agents in experienced hands.
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http://dx.doi.org/10.4103/jmas.JMAS_128_18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6839354PMC
August 2018

Surgical outcomes of patients with primary aldosteronism lateralized with I-131-6 β-iodomethyl-norcholesterol single photon emission/computed tomography without discontinuation or modification of antihypertensive medications.

Ci Ji Yi Xue Za Zhi 2018 Jul-Sep;30(3):169-175

Division of Endocrinology and Metabolism, Department of Internal Medicine, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei, Taiwan.

Objectives: Adrenocortical scintigraphy for patients with primary aldosteronism (PA) without discontinuation or modification of antihypertensive medications is of concern because of drug interference with the renin-angiotensin-aldosterone system. We report the surgical outcomes of patients with PA lateralized with adrenocortical scintigraphy without drug discontinuation or modification.

Materials And Methods: We retrospectively reviewed 34 patients with PA with computed tomography (CT)-documented adrenal tumors who had undergoing subsequent I-131-6 β-iodomethyl-norcholesterol (NP-59) single photon emission CT (SPECT)/CT followed by unilateral adrenalectomy according to the results of NP-59 uptake between May 2005 and December 2014. All enrolled patients underwent standard confirmatory tests and lateralization with NP-59 SPECT/CT without discontinuation of existing antihypertensive medications, including spironolactone. The pathological findings, hypertension outcomes, and biochemical changes were reported. The accuracy of NP-59 SPECT/CT without drug discontinuation or modification was also evaluated.

Results: None of the 34 enrolled patients (M:F = 16:18) had complications such as a hypertensive crisis, life-threatening hypokalemic event, or cardiac arrhythmia. Pathology disclosed 31 (91%) adenomas and three cases of hyperplasia. Hypertension cure and improvement were observed in 12 (35%) and 18 (53%) patients, respectively. All of the 30 patients (100%) without postoperative use of beta-blockers and with an available postoperative aldosterone/renin ratio achieved a biochemical cure. The positive predictive values of NP-59 SPECT/CT were 91%, 88%, and 100% for the pathological findings, hypertension outcomes, and biochemical changes, respectively.

Conclusion: Noninvasive NP-59 SPECT/CT without discontinuation or modification of antihypertensive medications not only provided accurate lateralization and safety but also resulted in a high improvement rate for PA-associated hypertension.
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http://dx.doi.org/10.4103/tcmj.tcmj_106_17DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6047325PMC
August 2018

Possible predictor of early recovery on urinary continence after laparoscopic radical prostatectomy - Bladder neck level and urodynamic parameters.

J Formos Med Assoc 2019 Jan 24;118(1 Pt 2):237-243. Epub 2018 May 24.

Department of Urology, Buddhist Tzu-Chi General Hospital, Hualien, Taiwan. Electronic address:

Background/purpose: To investigate the relationship between post-operative bladder neck levels and urodynamic parameters and their effect on urinary incontinence after laparoscopic radical prostatectomy (LRP).

Methods: Forty-eight consecutive patients undergoing LRP were retrospectively reviewed. All patients were assessed using retrograde cystography after LRP and were grouped according to their bladder neck position: Level 0: at or above the superior margin of the symphysis pubis (SMSP); Level -1: at <2 cm below SMSP; and Level -2: at >2 cm below SMSP. Urodynamic studies were conducted at baseline as well as at 1 and 3 months post-operatively. Early recovery of urinary continence was defined as no urine leakage or only one pad/day used within 3 months after surgery. Demographic characteristics, changes in urodynamic parameters, and continence outcomes were analyzed.

Results: Overall rate of early recovery of urinary continence was 33.3%. Patients with higher bladder neck levels experienced a significantly earlier recovery of urinary continence in univariate analysis (77.8%, 29.2%, and 13.3% for bladder neck levels 0, -1, and -2, respectively, p = 0.004). Patients with early recovery of urinary continence had significantly longer functional profile lengths (FPLs) 1 month post-surgery (21.0 mm vs 14.8 mm, p = 0.019). Higher bladder neck levels were significantly associated with longer FPLs at 1 month (p = 0.032).

Conclusion: Bladder neck level is associated with FPLs at 1 month post-surgery, which is the possible predictor of early recovery of urinary continence after LRP. Patients with longer FPL at 1 month after LRP have a higher rate of early recovery of urine continence.
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http://dx.doi.org/10.1016/j.jfma.2018.04.009DOI Listing
January 2019

Removal of emerging contaminants using spent mushroom compost.

Sci Total Environ 2018 Sep 11;634:922-933. Epub 2018 Apr 11.

Department of Microbiology, Soochow University, Taipei, Taiwan, ROC. Electronic address:

Acetaminophen and sulfonamides are emerging contaminants. Conventional wastewater treatment systems fail to degrade these compounds properly. Mycoremediation, is a form of novel bioremediation that uses extracellular enzymes of white-rot fungi to degrade pollutants in the environment. In this study, spent mushroom compost (SMC), which contains fungal extracellular enzymes, was tested for acetaminophen and sulfonamides removal. Among the SMCs of nine mushrooms tested in batch experiments, the SMC of Pleurotus eryngii exhibited the highest removal rate for acetaminophen and sulfonamides. Several fungal extracellular enzymes that might be involved in removal of acetaminophen and sulfonamides were identified by metaproteomic analysis. The bacterial classes, Betaproteobacteria and Alphaproteobacteria, were revealed by metagenomic analysis and may be assisting with acetaminophen and sulfonamide removal, respectively, in the SMC of Pleurotus eryngii. Bioreactor experiments were used to simulate the capability of Pleurotus eryngii SMC for the removal of acetaminophen and sulfonamides from wastewater. The results of this study provide a feasible solution for acetaminophen and sulfonamide removal from wastewater using the SMC of Pleurotus eryngii.
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http://dx.doi.org/10.1016/j.scitotenv.2018.03.366DOI Listing
September 2018
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