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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.

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.

Background/Purpose: Even with the increasing recognition of primary aldosteronism (PA) as a cause of refractory hypertension and an issue of public health, the consensus of its optimal surgical or medical treatment in Taiwan has not been reached. Our objective was to develop a clinical practice guideline that is feasible for real-world management of PA patients in Taiwan. Methods: The Taiwan Society of Aldosteronism (TSA) Task Force recognized the above-mentioned issues and reached this Taiwan PA consensus at its inaugural meeting, in order to provide updated information of internationally acceptable standards, and also to incorporate our local disease characteristics and constraints into PA management. Results: In patients with lateralized PA, including aldosterone producing adenoma (APA), laparoscopic adrenalectomy is the ‘gold standard’ of treatment. Mini-laparoscopic and laparoendoscopic single-site approaches are feasible only in highly experienced surgeons. Patients with bilateral adrenal hyperplasia or those not suitable for surgery should be treated by mineralocorticoid receptor antagonists. The outcome data of PA patient management from the literature, especially from PA patients in Taiwan, are reviewed. Mental health screening is helpful in early detection and management of psychopathology among PA patients. Conclusion: We hope this consensus will provide a guideline to help medical professionals to manage PA patients in Taiwan to achieve a better quality of care. Keywords: Primary aldosteronism, Guideline, TAIPAI

As diagnostic techniques have advanced, primary aldosteronism (PA) has emerged as the most common cause of secondary hypertension. The excess of aldosterone caused by PA resulted in not only cardiovascular complications, including coronary artery disease, myocardial infarction, arrhythmia, and heart failure, but also cerebrovascular complications, such as stroke and transient ischemic attack. Moreover, PA is associated more closely with these conditions than is essential hypertension. In this review, we present up-to-date findings on the association between PA and cerebrovascular diseases.

Background: Long-term outcomes (especially mortality and/or major cardiovascular events [MACE]) of the clinical aldosterone producing adenoma (cAPA) patients who underwent medical targeted therapy or adrenalectomy, relative to those with essential hypertension (EH), have been scarcely reported. Methods: Using an inception observational cohort, we examined the longitudinal outcomes for all cAPA patients diagnosed throughout 2003-2017. We identified 858 cAPA cases among 1220 primary aldosteronism (PA) patients and another 1210 EH controls. cAPA patients underwent unilateral adrenalectomy or mineralocorticoid receptor antagonist (MRA) therapy as opposed to standard medical treatment for EH. Operated cAPA patients were grouped via their 1-year post-therapy statuses according to the Primary Aldosteronism Surgical Outcome (PASO) criteria. Long term all-cause mortality was the primary outcome. Secondary outcomes were incident MACE, atrial fibrillation (Af) or congestive heart failure (CHF) after the PA confirmatory diagnosis. Findings: 272 (49.9%) of the 545 surgically-treated cAPA patients achieved PASO clinical complete success (hypertension-remission without medications). After a follow-up of 6.3±4.0 years, both hypertension-remissive (HR, 0.54, p 27 ng/dL after adrenalectomy or plasma renin activity < 0.6 ng/mL/hr after MRA treatment could be associated with higher risks of mortality or MACE. Interpretation: Adrenalectomy, independent of post-surgical hypertension-remission, was associated with lower all-cause mortality of cAPA patients. However, post-adrenalectomy non-cured hypertension and/or MRA therapy in cAPA patients could still have higher MACE risk than that of the EH controls. We further documented a more beneficial effect of adrenalectomy over MRA treatment on long-term mortality, MACE, and CHF in cAPA patients. Trial Registration: NCT00917345 Funding Statement: This study was supported by Taiwan National Science Council (grants NSC 101- 2314-B-002-132-MY3, NSC100-2314-B-002-119, NSC 101-2314-B-002-085-MY3, MOST 104- 2314-B-002 -125 -MY3) and NTUH 100-N1776, 101-M1953, 102-S2097. Declaration of Interests: No competing interest was declared. No financial conflict of interest exists. Ethics Approval Statement: Ethical approval (approval number: 201801049RIND, NCT00917345) was obtained from the institutional review board of the National Taiwan University Hospital.

The aim of this study was to update the information on internationally acceptable standards and clinical practice recommendations for the management of patients with primary aldosteronism (PA). The Taiwan Society of Aldosteronism (TSA) Task Force acknowledged the novel issues of PA and reached a group consensus on PA in Taiwan by collecting the best available evidence and conducting one group meeting, several conference calls, and multiple e-mail communications. Unilateral adrenalectomy is the preferred treatment for patients with aldosterone-producing adenoma (APA). For medical treatment with mineralocorticoid receptor antagonists (MRAs), spironolactone is the first-line treatment, and eplerenone is a reasonable alternative in PA patients intolerant or contraindicated to spironolactone. The dose of MRAs can be titrated according to plasma renin activity (PRA). For screening PA-related comorbidities, we suggest albuminuria to predict a post-treatment decline in renal function, echocardiography as cardiac evaluation, bone mineral density scan for osteoporosis, and obstructive sleep apnea. In tissue and genetic surveys, we suggest immunohistochemical staining and somatic mutation screening for post-operative adrenal specimens in APA patients. With this consensus, we hope to update the information on PA for clinical physicians to facilitate better identification, management and treatment of patients with PA.

Background Primary aldosteronism ( PA ) is associated with higher atrial fibrillation prevalence and other cardiovascular complications. However, the effect of target treatment to prevent new‐onset atrial fibrillation ( NOAF ) remains unclear. This study investigated incidence of NOAF under different treatment strategies in patients with PA. Methods and Results We analyzed longitudinal data for patients with PA without atrial fibrillation history from 1997 to 2009 within the National Health Insurance Research Database in Taiwan. Patients with essential hypertension matched by propensity score were enrolled as controls. The primary outcome measurement was NOAF , and secondary outcome measurements were mortality, major cardiac and cardiac/cerebrovascular events, and a combined end point of NOAF and mortality. We identified 2202 patients with PA (534 adrenalectomy, 1668 mineralocorticoid receptor antagonist [MRA] therapy) and 8808 essential hypertension controls with mean follow‐up of 4.4 years. In primary outcome measurement, patients with PA who underwent adrenalectomy had a lower incidence of NOAF (adjusted hazard ratio; 0.28, P =0.011) than controls. In contrast, the patients with PA who received MRA therapy had comparable risk of NOAF (adjusted hazard ratio, 1.20; P =0.224). In secondary outcome measurement, patients with PA who underwent adrenalectomy had a lower rate of mortality and combined end point of NOAF and mortality than controls. Patients with PA who received MRA therapy had a higher risk of mortality, major cardiac and cardiac/cerebrovascular events, and combined NOAF with mortality than the essential hypertension controls. Conclusions Compared with patients with essential hypertension, patients with PA who underwent adrenalectomy had a lower incidence of NOAF . However, this finding was not observed in patients with PA who received MRA therapy with a lower dose. Differences between the 2 strategies may reduce with a higher dose of MRA therapy.

Background: In primary aldosteronism (PA), kidney function impairment could be concealed by relative hyperfiltration and emerge after adrenalectomy. We hypothesized transtubular gradient potassium gradient (TTKG), a kidney aldosterone bioactivity indicator, could correlate to end organ damage and forecast kidney function impairment after adrenalectomy. Methods: In the present prospective study, we enrolled lateralized PA patients who underwent adrenalectomy and were followed up 12 months after operation in the Taiwan Primary Aldosteronism Investigation (TAIPAI) registry from 2010 to 2018. The clinical outcome was kidney function impairment, defined as estimated glomerular filtration rate (eGFR) 2 at 12 months after adrenalectomy. End organ damage is determined by microalbuminuria and left ventricular mass. Results: In total, 323 patients [mean, 50.8 ± 10.9 years old; female 178 (55.1%)] were enrolled. Comparing pre-operation and post-operation data, systolic blood pressure, serum aldosterone, urinary albumin to creatinine ratio and eGFR decreased. TTKG ⩾ 4.9 correlated with pre-operative urinary albumin to creatinine ratio >50 mg/g [odds ratio (OR) = 2.42; p = 0.034] and left ventricular mass (B = 20.10; p = 0.018). Multivariate logistic regression analysis demonstrated that TTKG ⩾ 4.9 could predict concealed chronic kidney disease (OR = 5.42; p = 0.011) and clinical success (OR = 2.90, p = 0.017) at 12 months after adrenalectomy. Conclusions: TTKG could predict concealed kidney function impairment and cure of hypertension in PA patients after adrenalectomy. TTKG more than 4.9 as an adverse surrogate of aldosterone and hypokalaemia correlated with pre-operative end organ damage in terms of high proteinuria and cardiac hypertrophy.

IntroductionPrimary 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 methodsWe 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.ResultsThe 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, p<0.001) 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 ConclusionsPatients 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.

Background Previous studies show that patients with primary aldosteronism are associated with higher risk of congestive heart failure ( CHF ). However, the effect of target treatment to the incidental CHF has not been elucidated. We aimed to investigate the risk of new‐onset CHF in patients with aldosterone‐producing adenomas ( APAs ) and explore the effect of adrenalectomy on new onset of CHF . Methods and Results From 1997 to 2009, 688 APA were identified and matched with essential hypertension controls. The risks of developing incidental CHF (hazard ratio, 0.49; 95% CI , 0.31–0.75; P =0.001) and mortality (hazard ratio, 0.29; 95% CI , 0.20–0.44; P APA group after targeted treatment. A total of 605 patients with APAs who underwent adrenalectomy lowered the risks of CHF (subdistribution hazard ratio, 0.55; 95% CI , 0.34–0.90; P =0.017) and mortality (adjusted hazard ratio, 0.27; 95% CI , 0.16–0.44; P Conclusions In conclusion, for patients with APAs, adrenalectomy can be associated with lower risk of incidental CHF and all‐cause mortality in a long‐term follow‐up.

Background Primary aldosteronism is the most common cause of secondary hypertension and is associated with left ventricular hypertrophy. However, whether aldosterone excess is responsible for left ventricular (LV) diastolic dysfunction is unknown. Methods and Results We prospectively enrolled 129 patients with aldosterone‐producing adenoma and 120 patients with essential hypertension, and analyzed their clinical, biochemical, and echocardiographic data, including tissue Doppler images. The patients with aldosterone‐producing adenoma were reevaluated 1 year after adrenalectomy. After propensity score matching, there were 105 patients in each group. The patients with aldosterone‐producing adenoma had worse diastolic function than the patients with essential hypertension, as reflected by lower e′ ( P P =0.003). Multivariate analysis showed that LV diastolic function was significantly correlated with age ( P P P =0.002), systolic blood pressure ( P =0.004), creatinine ( P =0.008), and log‐transformed aldosterone‐renin ratio ( P =0.003). After adrenalectomy, the patients with aldosterone‐producing adenoma had significant improvements in LV diastolic function as reflected by an increase in e′ ( P =0.003) and decrease in E/e′ ( P =0.002). The change in E/e′ was independently correlated with baseline E/e′ ( P P =0.006). Conclusions The patients with primary aldosteronism had worse LV diastolic function than the patients with essential hypertension after propensity score matching, and this could be reversed after adrenalectomy, suggesting that aldosterone excess may induce LV diastolic dysfunction.

Background/purpose This study evaluated the long-term outcomes of nephrectomy and inferior vena cava (IVC) thrombectomy in patients with advanced renal cell carcinoma (RCC). Methods From January 1996 to December 2013, we retrospectively collected the clinical data of 31 patients with pathologically confirmed RCC and IVC tumor thrombus. All patients received nephrectomy and IVC thrombectomy. We examined the clinical outcomes, including cancer-specific survival, progression-free survival, and postoperative complications, during a 90-day period. The associated prognostic factors were also analyzed. This study is registered with the National Taiwan University Hospital Research Ethics Committee (number 201305059RINC). Results The median follow-up period was 24 months. Of 20 patients with nonmetastatic disease, 15 developed metastases during the study period. The overall 5-year cancer-specific survival rate was 30.8% in the nonmetastatic group versus 12.5% in the metastatic group. The level of IVC thrombus (levels I–II versus levels III–IV) was not significantly associated with the 5-year cancer-specific survival (p = 0.43). The Fuhrman grade and sarcomatoid type were statistically significant predictors of cancer-specific survival [Fuhrman grades III–IV versus grades I–II: hazard ratio (HR) = 0.11, p = 0.04; sarcomatoid type: HR = 0.136, p = 0.001]. Fuhrman grade, capsular invasion, and positive surgical margins were associated with 1-year progression-free survival (Fuhrman grades III–IV versus grades I–II: HR = 0.08, p = 0.04; capsular invasion: HR = 0.15, p = 0.04; positive surgical margins: HR = 0.16, p = 0.05). The most common perioperative complication was massive blood loss. The most common recurrence sites were bones, liver, and lungs. Conclusion The pathologic Fuhrman grade, sarcomatoid type, positive surgical margins, and capsular invasion were significant predictors of oncological outcomes in patients with advanced RCC and IVC thrombus.

Objective: Atypical small acinar proliferation (ASAP) and high-grade prostatic intraepithelial neoplasia (HGPIN) are two pathological findings occasionally noted in prostate biopsies. Previous Western studies reported that they were associated with prostate cancer. However, none Taiwanese series report the subsequent cancer detection in ASAP and HGPIN patients. This study aimed to examine the results of repeated biopsies in the patients with ASAP and HGPIN. Materials and Methods: A total of 220 consecutive patients with ASAP and/or HGPIN at our institute between January 1990 and December 2010 were enrolled. Patient demographics and clinical information were extracted from the electronic database of our institute. Prostate biopsies were performed through transrectal ultrasound guidance. The patients who had concurrent prostate cancer (n = 51) and no repeated prostate biopsies (n = 103) were excluded from the study. Patients with biopsy pathologies reporting low-grade prostatic intraepithelial neoplasia (n = 2) were also excluded. The remaining 64 patients were available for the final analysis. Results: Nearly, 38, 24, and 2 patients were initially diagnosed as ASAP, HGPIN, and ASAP along with HGPIN, respectively. After 10 years of follow-up, 36.8% patients in ASAP group developed prostate cancer, while 16.7% in HGPIN group and 100% in ASAP + HGPIN group. Median time to developing prostate cancer were 20 months in ASAP group, 31 months in HGPIN group, and 48 months in ASAP + HGPIN group. There was no significant difference of prostate cancer development between ASAP and HGPIN group (P = 0.291). Only older age, classified by 65 years, was significantly associated with a higher detection rate of prostate cancer. Conclusion: Patients with the initial diagnosis of ASAP or PIN has a high risk of developing prostate cancer. Therefore, those patients should be well announced and followed regularly.

Background/Purpose: Even though the increasing clinical recognition of primary aldosteronism (PA) as a public health issue, its heightened risk profiles and the availability of targeted surgical/medical treatment being more understood, consensus in its diagnosis and management based on medical evidence, while recognizing the constraints of our real-world clinical practice in Taiwan, has not been reached. Methods: The Taiwan Society of Aldosteronism (TSA) Task Force acknowledges the above-mentioned issues and reached this Taiwan PA consensus at its inaugural meeting, in order to provide updated information of internationally acceptable standards, and also to incorporate our local disease characteristics into the management of PA. Results: When there is suspicion of PA, a plasma aldosterone to renin ratio (ARR) should be obtained initially. Patients with abnormal ARR will undergo confirmatory laboratory and image tests. Subtype classification with adrenal venous sampling (AVS) or NP-59 nuclear imaging, if AVS not available, to lateralize PA is recommended when patients are considered for adrenalectomy. The strengths and weaknesses of the currently available identification methods are discussed, focusing especially on result interpretation. Conclusion: With this consensus we hope to raise more awareness of PA among medical professionals and hypertensive patients in Taiwan, and to facilitate reconciliation of better detection, identification and treatment of patients with PA. Index words: Primary aldosteronism, Guideline, TAIPAI, TSA

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 &lt, 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 &lt, 0.45 ng/mL was the only independent factor associated with longer BCR-free survival (p = 0.034), while a PSA-DT &gt, 8 months had better ADT-free survival (p = 0.008). Patients with a PSA-DT &gt, 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 &lt, 0.45 ng/mL and PSA-DT &gt, 8 months were free from subsequent ADT and any metastasis. Conclusions: In patients with a PSA &lt, 8 months for post-prostatectomy BCR, prostate bed SRT provided excellent outcomes without the need for concomitant ADT or pelvic radiotherapy.

Primary aldosteronism (PA) is characterized by excess production of aldosterone from the adrenal glands and is the most common and treatable cause of secondary hypertension. Aldosterone is a mineralocorticoid hormone that participates in the regulation of electrolyte balance, blood pressure, and tissue remodeling. The excess of aldosterone caused by PA results in an increase in cardiovascular and cerebrovascular complications, including coronary artery disease, myocardial infarction, stroke, transient ischemic attack, and even arrhythmia and heart failure. Endothelial dysfunction is a well-established fundamental cause of cardiovascular diseases and also a predictor of worse clinical outcomes. Accumulating evidence indicates that aldosterone plays an important role in the initiation and progression of endothelial dysfunction. Several mechanisms have been shown to contribute to aldosterone-induced endothelial dysfunction, including aldosterone-mediated vascular tone dysfunction, aldosterone- and endothelium-mediated vascular inflammation, aldosterone-related atherosclerosis, and vascular remodeling. These mechanisms are activated by aldosterone through genomic and nongenomic pathways in mineralocorticoid receptor-dependent and independent manners. In addition, other cells have also been shown to participate in these mechanisms. The complex interactions among endothelium, inflammatory cells, vascular smooth muscle cells and fibroblasts are crucial for aldosterone-mediated endothelial dysregulation. In this review, we discuss the association between aldosterone and endothelial function and the complex mechanisms from a molecular aspect. Furthermore, we also review current clinical research of endothelial dysfunction in patients with PA.

// Chung-Hsin Chen 1 , Kathleen G. Dickman 2, 3 , Chao-Yuan Huang 1 , Chia-Tung Shun 4 , Huai-Ching Tai 1 , Kuo-How Huang 1 , Shuo-Meng Wang 1 , Yuan-Ju Lee 1 , Arthur P. Grollman 2, 3 , Yeong-Shiau Pu 1 1 Department of Urology, National Taiwan University Hospital, Taipei, Taiwan 2 Department of Pharmacological Sciences, Stony Brook University, Stony Brook, NY, USA 3 Department of Medicine, Stony Brook University, Stony Brook, NY, USA 4 Department of Forensic Medicine and Pathology, National Taiwan University Hospital, Taipei, Taiwan Correspondence to: Yeong-Shiau Pu, email: yspu@ntu.edu.tw Keywords: aristolochic acid, cigarette smoking, herbs, renal pelvis, ureter Received: March 26, 2016 Accepted: May 16, 2016 Published: June 07, 2016 ABSTRACT TP53 mutation patterns are associated with prognosis of various cancers. This study was designed to investigate the association between TP53 mutation patterns and recurrence patterns in upper urinary tract urothelial carcinoma (UTUC) patients. A total of 165 consecutive UTUC patients who underwent nephroureterectomies were enrolled for measuring mutation patterns of TP53 gene from exome 2 to 11. Bladder recurrence, contralateral UTUC recurrence, and metastases were compared among groups by using log-rank test and Cox proportional hazard model. Single base substitution as an A:T to T:A transversion was noted in 55 (33.3%) patients (AT group). Forty-two (25.5%) patients had TP53 mutations with only other than A:T to T:A transversion (NAT group), and 68 patients (41.2%) had wide-type TP53 (WT group). AT group was predominately female (64%, 52%, 29%, respectively), had a higher incidence of end-stage renal disease (24%, 14%, 10%, respectively), and had more high-grade tumors (82%, 74%, 62%, respectively) compared to NAT and WT groups. With adjustment of tumor grade/stages, bladder and contralateral UTUC recurrence-free survival duration was shortest in NAT ( p < 0.001) and AT group ( p < 0.001), respectively. NAT group had a shorter metastasis-free survival duration than the other two groups combined ( p = 0.018). As a result, A:T to T:A transversion increased contralateral UTUC recurrence risk, but other mutations in TP53 raised the hazard of bladder recurrence and metastases. Therefore, TP53 mutation pattern may be a useful biomarker to predict recurrence patterns of UTUC patients.

Purpose: The purpose of this study was to investigate the potential factors for sperm retrieval prediction. Materials and Methods: This is a retrospective and single-operator study at National Taiwan University Hospital. Between January 2009 and December 2017, 66 nonobstructive azoospermia (NOA) patients were collected. They received testicular biopsy and sperm retrieval including microsurgical epididymal sperm aspiration or microdissection testicular sperm extraction. Results: Eleven patients had normal spermatogenesis, with successful sperm retrieval (SSR) 90.9%; 21 patients hypospermatogenesis, with SSR 47.6%; 13 patients maturation arrest, with SSR 30.8%; and 21 patients Sertoli cell-only syndrome, with SSR 0%. SSR declined significantly when follicle-stimulating hormone (FSH) values rise: FSH 20 mIU/ml with SSR 6.7% (P = 0.003). Receiver operating characteristic curve to predict SSR by FSH achieved the area under the curve 0.792, with the best cutoff point of FSH being at 6.8 mIU/ml. Conclusion: We concluded that a higher sperm retrieval rate was statistically significantly related to lower FSH, lower luteinizing hormone, and better histology types among the NOA men. In the absence of testicular histopathology before surgery, preoperative FSH can be used for prediction and counseling. FSH ≤6.8 mIU/ml predicts SSR with a sensitivity of 63.2% and specificity of 88.2%.

Background Primary aldosteronism (PA) is one of the major etiologies for secondary hypertension featuring more prominent left ventricular hypertrophy. The purpose of the study was to investigate the predictive factors of left ventricular mass index (LVMI) regression in patients with PA after adrenalectomy. Methods We prospectively analyzed 30 patients with aldosterone-producing adenoma (APA) who received adrenalectomy from October 2006 to September 2008. Echocardiography was performed preoperation and 1 year after operation. Results Thirty patients with aldosterone-producing adenoma undergoing adrenalectomy were enrolled. In a 1-year follow-up, LVMI decreased significantly by an average of 18.6%. Net LVMI decrease (ΔLVMI) was associated with preoperative LVMI, preoperative serum potassium level, baseline systolic blood pressure (SBP), baseline diastolic blood pressure, net SBP decrease (ΔSBP), net diastolic blood pressure decrease, preoperative/postoperative change of log-transformed plasma aldosterone concentration, preoperative/postoperative change of log-transformed plasma renin activity, and preoperative/postoperative change of serum potassium level (Δserum potassium level). In a multiple regression analysis, preoperative LVMI (β = −0.287, P = 0.049), ΔSBP (β = 0.518, P = 0.01), and Δserum potassium level (β = −20.471, P = 0.014) were significantly correlated with ΔLVMI. Conclusions The LVMI in patients with PA regressed significantly after adrenalectomy. Preoperative LVMI, ΔSBP, and Δserum potassium levels are independent factors associated with the degree of LVMI regression.

Objective Extra-adrenal pheochromocytomas are known as paragangliomas. The majority of extra-adrenal tumors occur intra-abdominally along the sympathetic chain. However, they may also occur in the urinary tract, including the urinary bladder. Materials and methods In this study, we report a clinical series of six patients diagnosed with bladder paragangliomas in our hospital over the past two decades, and review the literature regarding this unusual disease. Results Among the six cases, two were male and four were female. The most common presentation was painless gross hematuria, with five of the six patients (83.3%) having this chief complaint. Two patients presented with hypertension and one with palpitations. Two had malignant bladder paragangliomas, and one died within one year after the diagnosis. Four patients received transurethral resection of the bladder tumors, and one patient developed tumor recurrence within one year of follow-up. Conclusion Bladder paraganglioma is an extremely rare tumor with a high recurrence rate, and the most common presenting symptom in our series was painless gross hematuria. Large, polypoid, and multiple tumors indicate malignancy.

Scientific Reports 6: Article number: 32103; published online: 02 September 2016; updated: 24 March 2017 The original version of this Article contained an error in the Abstract. “While need for receptor antagonist (MRA) MRA after diagnosis suggests that a defined daily dose (DDD) of MRA between 12.5and 50 mg may alleviate risk of death in a U-shape pattern”.

Constitutive activation of the Wnt pathway/β-catenin signaling may be important in aldosterone-producing adenoma (APA). However, significant gaps remain in our understanding of the prevalence and clinical outcomes after adrenalectomy in APA patients harboring CTNNB1 mutations. The molecular expression of CYP11B2 and gonadal receptors in adenomas were also explored. Adenomas from 219 APA patients (95 men; 44.2%; aged 50.5 ± 11.9 years) showed a high rate of somatic mutations (n = 128, 58.4%). The majority of them harbored KCNJ5 mutations (n = 116, 52.9%); 8 patients (3.7%, 6 women) had CTNNB1 mutations. Patients with APAs harboring CTNNB1 mutations were older and had shorter duration of hypertension. After adrenalectomy, CTNNB1 mutation carriers had a higher possibility (87.5%) of residual hypertension than other APA patients. APAs harboring CTNNB1 mutations have heterogeneous staining of β-catenin and variable expression of gonadal receptors and both CYP11B1 and CYP11B2. This suggests that CTNNB1 mutations may be more related to tumorigenesis rather than excessive aldosterone production.

To develop algorithms of locating patients with primary aldosteronism (PA) using insurance reimbursement data and to validate the algorithms using medical charts.We extracted National Health Insurance (NHI) reimbursement data and medical charts in seven enrolled hospitals and analyzed diagnosis-related information for 1999-2010. The NHI codes PA as 255.1x, using the International Classification of Diseases, Ninth Revision, Clinical Modification. Confirmation of PA was based on suppression tests.We reviewed medical charts for 1,094 cases with at least one PA diagnosis. PA was confirmed for 563 cases. Compared with patients with essential hypertension, PA patients had higher systolic blood pressure, higher aldosterone, lower renin activity, and lower potassium level (all P-values0.05). An algorithm based on PA diagnosis reported in at least one hospital stay or three outpatient visits had modest performance (sensitivity = 0.94 and specificity = 0.20). The best additional condition for the algorithm was use of mineralocorticoid receptor antagonist (MRA; sensitivity = 0.89 and specificity = 0.88).Using information on PA diagnosis and MRA prescription reported in insurance claims data can precisely locate PA patients in high-risk groups. This algorithm can construct a reliable PA sample for conducting research in various fields, including epidemiology and clinical practice.

Objective: The diagnosis of primary aldosteronism (PA) among the older-aged population has posed a crucial challenge. Among patients over 50 years old, this trial assessed comparability of the performance of two PA diagnostic tests: losartan and captopril suppression tests. Methods: A post-hoc subgroup analysis from a prospective cohort was conducted by the TAIPAI (Taiwan Primary Aldosteronism Investigation) group between July 2003 and July 2006. Of the 160 patients in the cohort, 60 patients over 50 years old received captopril and losartan tests to confirm PA. Results: Among the 60 patients over 50 years old, 31 patients had PA confirmed by standardized protocol. The area under the receiver-operating characteristic (ROC) curve for post-captopril aldosterone was significantly less than that for post-losartan plasma aldosterone concentration (PAC) (0.87 vs 0.94, p =0.02). Using the aldosterone-renin ratio (ARR)>35 with PAC>10 ng/dl, the specificity was 82.76% vs 93.1% and the sensitivity was 77.42% vs 87.10% for the captopril and losartan tests, respectively. The equivalence between the two tests were confirmed by the exact McNemar’s test ( p =1.0). Conclusion: The losartan test showed comparable accuracy to confirm PA. Verification of this “elderly-friendly” confirmatory test will be the first step to prepare a specific diagnostic model of PA for the older-aged population.

To provide clinical outcomes of the Resonance metallic ureteral stent in patients with malignant ureteral obstruction, as well as clinical factors predicting stent failure.Cancer patients who have received Resonance stents from July 2009 to March 2012 for ureteral obstruction were included for chart review. Stent failure was detected by clinical symptoms, image studies, and renal function tests. Survival analysis for stent duration was used to estimate patency rate and factors predicting stent failure.A total of 117 stents were inserted successfully into 94 ureteral units in 79 patients. There were no major complications. These stents underwent survival analysis and proportional hazard regression. The median duration for the stents was 5.77 months. In multivariate analysis, age (P=0.043), preoperative serum creatinine level (P=0.0174), and cancer type (P=0.0494) were significant factors associated with stent failure. Cancer treatment before and after stent insertion had no effect on stent duration.Resonance stents are effective and safe in relieving malignant ureteral obstructions. Old age and high serum creatinine level are predictors for stent failure. Stents in patients with lower gastrointestinal cancers have longer functional duration.

To present oncologic results of laparoscopic radical prostatectomy (LRP) monotherapy for men with high-risk, localized prostate cancer, and to find factors associated with a good prognosis via surgery alone.Between 2002 and 2009, 241 men underwent LRP at an Asian tertiary referral center. Among them, we retrospectively identified 85 (35.3%) men who met the D'Amico's high-risk criteria: Prostate-specific antigen level20 ng/mL, Gleason score of 8 to 10, or clinical stage ≥T2c. Perioperative parameters were analyzed against biochemical recurrence (BCR)-free survival.At a median follow-up of 54 months, BCR developed in 28 (34.1%), with an actuarial BCR-free survival rate of 63.3% at 5 years. Pathologically, 37.6% of the men had organ-confined (OC) disease. Positive surgical margins (PSM) were identified in 49.4% of the patients. A favorable pathologic outcome, defined as OC(+)PSM(-), was observed in 24 patients and associated with a 5-year BCR-free survival rate of 87.0%, compared with 100%, 54.0%, and 46.4% in men with OC(+)PSM(+), OC(-)PSM(-) and OC(-)PSM(+) disease (log-rank, P=0.008). The overall positive lymph node rate was 14.1%. Men (65.9%) with only one D'Amico risk factor had a 5-year BCR-free survival rate of 76.9%, compared with 34.6% in men (34.1%) with ≥2 risk factors (log-rank, P0.001).Radical prostatectomy monotherapy performed laparoscopically or robotically appears to be an option for high-risk prostate cancer, especially in men with a single D'Amico risk factor. Men with ≥2 risk factors are more prone for BCR to develop after surgery and may need second-line therapy.

AKI-dialysis patients had a higher incidence of long-term ESRD and mortality than the patients without AKI. The patients who recovered from dialysis were associated with a lower incidence of long-term ESRD and mortality than in the patients who still required dialysis.

Aristolochic acid (AA), a component of all Aristolochia-based herbal medicines, is a potent nephrotoxin and human carcinogen associated with upper urinary tract urothelial carcinoma (UUC). To investigate the clinical and pathological characteristics of AA-induced UUC, this study included 152 UUC patients, 93 of whom had been exposed to AA based on the presence of aristolactam-DNA adducts in the renal cortex. Gene sequencing was used to identify tumors with A:T-to-T:A transversions in TP53, a mutational signature associated with AA. Cases with both aristolactam-DNA adducts and A:T-to-T:A transversions in TP53 were defined as AA-UUC, whereas patients lacking both of these biomarkers were classified as non-AA-UUC. Cases with either biomarker were classified as possible-AA-UUC. Forty (26%), 60 (40%), and 52 (34%) patients were classified as AA-UUC, possible-AA-UUC and non-AA-UUC, respectively. AA-UUC patients were younger (median ages: 64, 68, 68 years, respectively; p=0.189), predominately female (65%, 42%, 35%, respectively; p=0.011), had more end-stage renal disease (28%, 10%, 12%, respectively; p=0.055), and were infrequent smokers (5%, 22%, 33%, respectively; p=0.07) compared to possible-AA-UUC and non-AA-UUC patients. All 14 patients who developed contralateral UUC had aristolactam-DNA adducts; ten of these also had signature mutations. The contralateral UUC-free survival period was shorter in AA-UUC compared to possible- or non-AA-UUC (p=0.019 and 0.002, respectively), whereas no differences among groups were observed for bladder cancer recurrence. In conclusion, AA-UUC patients tend to be younger and female, and have more advanced renal disease. Notably, AA exposure was associated with an increased risk for developing synchronous bilateral and metachronous contralateral UUC.

There exists a great knowledge gap in terms of long-term effects of various surgical and pharmacological treatments on outcomes among primary aldosteronism (PA) patients. Using a validated algorithm, we extracted longitudinal data for all PA patients diagnosed in 1997–2010 and treated in the Taiwan National Health Insurance. We identified 3362 PA patients for whom the mean length of follow-up was 5.75 years. PA has higher major cardiovascular events (MACE) than essential hypertension (23.3% vs 19.3%, p = 0.015). Results from the Cox model suggest a strong effect of adrenalectomy on lowering mortality (HR = 0.23 with residual hypertension and 0.21 with resolved hypertension). While the need for mineralocorticoid receptor antagonist (MRA) after diagnosis suggests that a defined daily dose (DDD) of MRA between 12.5 and 50 mg may alleviate risk of death in a U-shape pattern. A specificity test identified patients who has aldosterone producing adenoma (HR = 0.50, p = 0.005) also confirmed adrenalectomy attenuated all-cause mortality. Adrenalectomy decreases long-term all-cause mortality independently from PA cure from hypertension. Prescription corresponding to a DDD between 12.5 and 50 mg may decrease mortality for patients needing MRA. It calls for more attention on early diagnosis, early treatment and prescription of appropriate dosage of MRA for PA patients.

// Chia-Hui Chang 1, 2 , Ya-Hui Hu 1 , Yao-Chou Tsai 3 , Che-Hsiung Wu 4 , Shuo-Meng Wang 5 , Lian-Yu Lin 6 , Yen-Hung Lin 6 , Fumitoshi Satoh 7 , Kwan-Dun Wu 8 , Vin-Cent Wu 8, 9 1 Division of Endocrinology and Metabolism, Department of Internal Medicine, Taipei Tzu Chi Hospital, The Buddhist Medical Foundation, Hualien, Taiwan 2 Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan 3 Division of Urology, Department of Surgery, Taipei Tzu Chi Hospital, The Buddhist Medical Foundation, Hualien, Taiwan 4 Division of Nephrology, Department of Internal Medicine, Taipei Tzu Chi Hospital, The Buddhist Medical Foundation, Hualien, Taiwan 5 Division of Urology, Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan 6 Division of Cardiology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan 7 Division of Clinical Hypertension, Endocrinology and Metabolism, Tohoku University, Graduate School of Medicine, Sendai, Japan 8 Division of Nephrology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan 9 TAIPAI, Taiwan Primary Aldosteronism Investigation (TAIPAI) Study Group, Taiwan Correspondence to: Vin-Cent Wu, email: q91421028@ntu.edu.tw Keywords: KCNJ5 gene, arterial stiffness, PWV, TAIPAI, CAKS Received: August 24, 2016 Accepted: March 09, 2017 Published: March 16, 2017 ABSTRACT The aim of this study was to show the effect of KCNJ5 mutational status on arterial stiffness in aldosterone-producing adenomas after adrenalectomy. Between February 2008 and January 2010, we prospectively enrolled 108 aldosterone-producing adenoma patients undergoing adrenalectomy. We conducted repeated measurements of pulse wave velocity at baseline, 6 months, and 12 months after adrenalectomy, grouped by KCNJ5 mutational status. Prognostic factors of arterial stiffness and risk for hypertension at 12 months after adrenalectomy were analyzed after propensity score matching in a 1:1 ratio. After matching for age, sex and body mass index, 88 patients were divided equally into KCNJ5-mutant and non-mutant groups. KCNJ5 mutational status was not an independent variable in either the generalized estimating equation model ( p = 0.147) or the percentage change of brachial-ankle pulse wave velocity ( p = 0.106). The generalized additive model smoothing plot showed that aldosterone-producing adenoma patients who carried the KCNJ5 mutation and were aged between 37 and 60 may have a hypertension recovery advantage. According to our observations during a 12-month follow-up after adrenalectomy, KCNJ5 mutational status was not associated with improvement in arterial stiffness.

Primary aldosteronism not only results in hypertension but also stiffer arteries. The time course and factors predicting the reversal of arterial stiffness after treatment are unclear. We prospectively enrolled 102 patients with aldosterone-producing adenoma (APA) from March 2006 to January 2012. We measured the pulse wave velocity (PWV) between brachial-ankle (baPWV) and heart-ankle (haPWV) before, 6 and 12 months after their adrenalectomy. After treatment, the PWV decreased significantly during the first 6 months (both p 0-6mo) and baseline baPWV were significantly associated with the decrease in baPWV at 6 months (ΔbaPWV0-6mo). The associated factors of the change in haPWV at 6 months (ΔhaPWV0-6mo) were baseline haPWV, ΔDBP0-6mo and change in log-transformed plasma renin activity. Our result suggested that reversal of arterial stiffness in APA patients occurred early after adrenalectomy and determined by baseline vascular condition, hemodynamic factors, and humoral factors.

Hemangioblastoma of the kidney is a rare, newly recognized tumor with morphological features similar to its cerebellar counterpart. There have been only 4 cases reported in the literature in English, all of them occurring in middle-aged to elderly patients. Here, we report a case of renal hemangioblastoma in a young adult without clinical evidence of von Hippel-Lindau disease. The tumor was composed of polygonal cells with mildly eosinophilic to clear cytoplasm and a rich vascular network. Immunohistochemical staining revealed a typical profile (positivity for α-inhibin, neuron-specific enolase and S100; negative results for epithelial membrane antigen, HMB-45, and Melan-A), which confirmed the diagnosis. Despite the similarity to renal-cell carcinoma in morphology, hemangioblastoma of the kidney is clinically indolent. Correct recognition of this pathological entity is important to avoid overdiagnosis and unnecessary clinical treatment.

OBJECTIVES: To obtain information about the effect of prolonged aldosterone excess on kidney function. METHODS: We determined kidney function changes defined by cystatin C-based estimations of glomerular filtration rate (CysC-GFR). Pretreatment proteinuria and intrarenal Doppler velocimetric indices in primary aldosteronism were examined and followed after adrenalectomy or spironolactone treatment. RESULTS: This prospective, multicenter study included 130 primary aldosteronism patients (56 men; age, 49.9 ± 13.4 years: 100 with adenoma and 30 with idiopathic hyperaldosteronism) and 73 essential hypertension patients (36 men; age, 51.4 ± 14.8 years) as controls. Patients with primary aldosteronism had higher CysC-GFR (P < 0.05) and heavier proteinuria (0.042) than those with essential hypertension. With primary aldosteronism, a higher aldosterone-renin ratio (odds ratio, OR = 7.85, P = 0.008) was independently related to pretreatment CysC-GFR. The factors related to pretreatment proteinuria included CysC-GFR (OR, -0.006, P = 0.001), plasma aldosterone concentration (OR, 0.004, P = 0.002), and duration of hypertension (OR, 0.016, P = 0.032). Duration of hypertension was also independently correlated with the pretreatment resistive index among primary aldosteronism patients (OR, 0.004, P = 0.035). CysC-GFR (all, P < 0.05), proteinuria (P < 0.001), and resistive index (P < 0.001) decreased 1 year after adrenalectomy but not with spironolactone treatment. CONCLUSION: Our data suggest that prolonged hyperaldosteronism will cause relative kidney hyperfiltration and reversible intrarenal vascular structural changes, which disguise the consequent renal injury, including declining GFR and proteinuria. Adrenalectomy and spironolactone treatment exert different clinical impacts toward kidney damage even with a similar blood pressure-lowering effect.

Kidney impairment is noted in primary aldosteronism (PA), and probably initiated by glomerular hyperfiltration.A prospectively defined survey was conducted on 602 patients who were suspected of PA in the multiple-center Taiwan Primary Aldosteronism Investigation (TAIPAI) database. Estimated glomerular filtration rate (eGFR) was calculated and followed up at 1 yr after treatment.The diagnosis of PA was confirmed in 330 patients. Among them 17% of these patients had kidney impairment (eGFR60 ml/min/1.73 m²). Patients with PA had a higher prevalence of estimated hyperfiltration than those with essential hypertension (EH) (14.5% vs. 7.0%, p=0.005). The eGFR independently predicted PA (OR, 1.017) in the propensity-adjusted multivariate logistic model. In PA, plasma renin activity and lower serum potassium (p=0.018) was correlated with kidney impairment (p=0.001), while this relationship was not significant in patients with EH. Either unilateral adrenalectomy or treatment of spironolactone for PA patients caused a decrease of eGFR (p0.001). Pre-operative hypokalemia (p=0.013) and the long latency of hypertension (p=0.016) could enhance the significant decrease of eGFR after adrenalectomy.Patients with aldosteronism had relative estimated hyperfiltration than patients with EH. Calculation of eGFR may increase the specificity in identifying patients with PA. Our findings demonstrate the correlation of serum potassium and renin with estimated hyperfiltration in PA and their relationship to kidney damage. These results provide a high priority for future renal protective strategies and methods for the early diagnosis and prompt treatment of PA.

Eur J Clin Invest 2011; 41 (7): 743–750 Abstract Background Primary aldosteronism (PA) is associated a worse cardiovascular outcome than essential hypertension. Hypokalemia, which is one major characteristic of PA, can affect both cardiac structure and function. The goal of this study is to evaluate the influence of serum potassium level on left ventricular (LV) mass and function in PA patients. Materials and methods We prospectively analysed 85 PA patients from October 2006 to September 2008 and 27 essential hypertension patients as the control group (group 1). Thirty-two patients with serum potassium

Objective: To present the initial experience of laparoendoscopic single-site (LESS) nephroureterectomy via the transperitoneal approach using the Alexis wound retractor and bladder cuff resection by endoloop. Methods: Two patients received LESS nephroureterectomies and bladder cuffs resection with homemade single ports, which were created by using an Alexis wound retractor as an access platform through a 4-cm incision. Distal ureters were resected through the same incision with endoloop. No additional ports were used and both procedures were completed successfully. Results: Both LESS procedures were completed successfully without traditional laparoscopic conversion or complication. LESS nephreoureterectomy with bladder cuff excision was performed in 165 and 325 minutes with estimated blood loss of 30 and 65 mL, respectively. Patients were discharged on postoperative days 3 and 7, respectively. Conclusions: The initial results demonstrated that LESS technique of nephroureterectomy and bladder cuff resection with endoloop is a safe and feasible procedure for urothelial carcinoma of upper urinary tract.

Background A common pharmacologic test for the diagnosis of primary aldosteronism (PA) is the administration of captopril to determine whether an abnormal plasma aldosterone concentration (PAC) to plasma renin activity (PRA) ratio(ARR) persists, although active renin concentration (ARC) may offer advantages with regard to processing and standardization. Methods A prospective, head-to-head study was conducted between Feb 2008 and Dec 2008. One hundred and fourteen patients enrolled and received captopril to aid in the diagnosis of PA in the TAIPAI intervention. Results Fifty-one patients were diagnosed with PA. Post-captopril ARC was significantly correlated with PRA. The area under the receiver operating characteristic curve of the post-captopril ARR was not different in PRA vs ARC measurements. When post-captopril ARC-based ARR (ARRARC) > 35.5 as the cut-off value, we obtained sensitivity of 75.0% and specificity of 86.4% to differentiate PA from essential hypertension. Conclusions The correlation of individual PRA and ARC after administration of captopril was excellent; especially at the lower PRA levels. Post-captopril ARRARC values used to diagnose PA are not different from post-captopril PRA-based (ARRPRA) values in patients without kidney, liver and heart failures. Primary aldosteronism can be diagnosed with a post-captopril cut-off value of ARRARC > 35.5 pmol/ng.

Study Type – Therapy (case series) Level of Evidence 4 OBJECTIVE To investigate the effect of renal function on the stone-free rate (SFR) of proximal ureteric stones (PUS) after extracorporeal shock wave lithotripsy (ESWL), as urinary obstruction caused by PUS can impair renal function, and elevated serum creatinine levels are associated with decreased ureteric stone passage. PATIENTS AND METHODS From January 2005 to December 2007, 1534 patients had ESWL for urolithiasis, 319 having ESWL in situ for PUS; they were reviewed retrospectively. Patients requiring simultaneous treatment of kidney stones, placement of a double pigtail stent, or percutaneous pigtail nephrostomy tube were excluded. We divided patients into groups by chronic kidney disease (CKD) stage according to the estimated glomerular filtration rate (eGFR) of ≥60 and 7 mm were significant predictors affecting the SFR after one session of ESWL for PUS.

Background Autonomous secretion of aldosterone in patients with primary aldosteronism increases glomerular filtration rate and causes kidney damage. The influence of a mild decrease in kidney function on residual hypertension after adrenalectomy is unexplored. Study Design Nonconcurrent prospective study. Setting & Participants The study was based on the Taiwan Primary Aldosteronism Investigation (TAIPAI) database. 150 patients (61 men; overall mean age, 47.2 ± 11.6 years) with a diagnosis of aldosterone-producing adenoma had undergone unilateral adrenalectomy at National Taiwan University Hospital from July 1999 to January 2007. Predictor Presurgery estimated glomerular filtration rate (eGFR). Outcomes & Measurements Residual hypertension after adrenalectomy, defined either as less than 75% of recorded blood pressure measurements with systolic blood pressure less than 140 mm Hg and diastolic blood pressure less than 90 mm Hg or requiring antihypertensive medications during the first year after surgery. Results Before surgery, 27 (18%), 72 (48%), and 51 (34%) patients had moderately to severely decreased ( 2 ), mildly decreased (60 ≤ eGFR 2 ), or nondecreased eGFR (≥90 mL/min/1.73 m 2 ), respectively. After surgery, 16 (59.3%), 29 (40.3%), and 10 (19.3%) patients in each category had postsurgery residual hypertension. Compared with patients without decreased eGFR before surgery, adjusted odds ratios for postsurgery residual hypertension were 2.7 (95% confidence interval, 1.03 to 7.0; P = 0.04) and 2.8 (95% confidence interval, 1.05 to 9.3) for mildly and moderately to severely decreased eGFR, respectively. Limitations Arbitrary definition for residual hypertension. Conclusions Two-thirds of patients with aldosterone-producing adenoma were cured of hypertension by means of unilateral adrenalectomy. Kidney function impairment, even mild, appears to be associated with a high incidence of postsurgery residual hypertension.

Background To assess whether angiotensin-II receptor blockers (ARBs) offer any additional advantage in confirming the diagnosis of primary aldosteronism (PA) and their use in the differentiation of PA subtypes. Methods A prospective, cohort, head-to-head study was conducted between July 2003 and July 2006. A total of 135 patients received captopril and losartan tests to confirm the diagnosis of PA in the TAIPAI (Taiwan Primary Aldosteronism Investigation) intervention. Results In total, 71 patients were diagnosed with PA. The area under the receiver-operating characteristic (ROC) curve of the postcaptopril plasma aldosterone concentration (PAC) was significantly less than that of the postlosartan PAC (0.744 vs. 0.829, P = 0.038). Using an aldosterone-renin ratio (ARR, ng/dl per ng/ml/h) >35 with a PAC >10 ng/dl, the specificity was 89.1% vs. 93.8% and the sensitivity was 66.2% vs. 84.5 % for the captopril test vs. the losartan test, respectively. With respect to the losartan test, the accuracy was 88.9%, the agreement was good (k = 0.778), and there was no disagreement with the McNemar test (P = 0.118). Losartan had the advantage of a better negative predictive value to exclude PA when patients were referred with a serum potassium (SK) level 60 was the cutoff value, the positive predictive value was 82% with a negative predictive value of 57% in distinguishing aldosterone-producing adenomas (APAs) from idiopathic hyperaldosteronism (IHA). Conclusions The postlosartan ARR and PAC were shown to have better accuracy for the diagnosis of PA than the captopril test. With a postlosartan ARR >60, APAs can be adequately differentiated from IHA.

Laparoscopic adrenalectomy is the standard treatment for patients with aldosterone producing adenoma (APA). Tthe comparative effectiveness between laparoscopic total and partial adrenalectomy remains controversial, however. In this study, we compared the clinical outcomes for the two procedures.We analyzed the patients with unilateral APA undergoing laparoscopic total or partial adrenalectomy during the period 2008 to 2011. All surgical procedures were performed transperitoneally. We compared the perioperative and postoperative parameters between two procedures. Clinical outcomes including serum aldosterone, renin, and potassium levels, and systolic and diastolic blood pressure (DBP) were assessed and compared at 1 year after operation.A total of 63 cases (16 partial and 47 total adrenalectomies) were included. There were no differences with regard to age, sex, hypertension duration, and tumor size as well as preoperative blood pressure, serum aldosterone, rennin, and potassium levels between the two groups. The perioperative and postoperative outcomes such as operative time, hospital stay, blood loss, and complications were similar between the two groups. The clinical outcomes at 1-year follow-up including serum aldosterone, renin, and potassium levels and blood pressure significantly improved in both groups.Laparoscopic partial adrenalectomy is technically feasible and yields similar perioperative, postoperative, and 1-year clinical outcomes to those of total adrenalectomy for the treatment of patients with unilateral APA. A prospective randomized study with a larger sample size is needed to further prove the cost and effectiveness of the two procedures.

A 53-year-old man who underwent successful kidney transplantation for stage 5 chronic kidney disease presented to our clinic with intermittent painless gross hematuria. Urachal adenocarcinoma, stage III A by Sheldon system, was diagnosed after serial histopathologic and radiological studies. The patient was treated with extended partial cystectomy, en bloc resection of urachus and umbilicus, pelvic lymphadenectomy, and ileocystoplasty. There were no complications seen in this patient. Neither urachal adenocarcinoma recurrence, metastasis, nor de novo uroileal cancer developed during 48-month follow-up. His reconstructed bladder functioned efficiently, without compromising the transplanted kidney function. Our case demonstrated that conservative surgery and augmentation ileocystoplasty could be offered to kidney transplant recipients with localized urachal carcinoma.

Objectives.To investigate the prognostic factors for bladder recurrence after radical nephroureterectomy (RNU) in patients with upper urinary tract urothelial carcinoma (UUT-UC).Methods.From 1994 to 2012, 695 patients with UUT-UC treated with RNU were enrolled in National Taiwan University Medical Center. Among them, 532 patients with no prior bladder UC history were recruited for analysis. We assessed the impact of potentially prognostic factors on bladder recurrence after RNU.Results.The median follow-up period was 47.8 months. In the Cox model, ureteral involvement and diabetes mellitus (DM) were significantly associated with a higher bladder recurrence rate in the multivariate analysis (hazard ratio [HR]: 1.838;P=0.003and HR: 1.821;P=0.010, resp.). In the Kaplan-Meier analysis, DM patients with concomitant ureteral UC experienced about a threefold increased risk of bladder recurrence as compared to those without both factors (HR: 3.222;P<0.001). Patients with either of the two risk factors experienced about a twofold increased risk as compared to those without both factors (with DM, HR: 2.184,P=0.024; with ureteral involvement, HR: 2.006,P=0.003).Conclusions.Ureteral involvement and DM are significantly related to bladder recurrence after RNU in patients with UUT-UC.

Primary aldosteronism (PA), characterized by an excessive production of aldosterone, affects 5−13 % of patients with hypertension. Accurate strategies are needed for the timely diagnosis of PA to allow curability and prevention of excessive cardiovascular events and related damage. This study aimed to evaluate the usefulness of semiquantification of 131I-6β-iodomethyl-norcholesterol (NP-59) single photon emission computed tomography (SPECT)/CT in differentiating aldosterone-producing adenoma (APA) from idiopathic adrenal hyperplasia (IAH) and in predicting clinical outcomes after adrenalectomy. We retrospectively reviewed 49 PA patients who had undergone adrenalectomy after NP-59 SPECT/CT within 1 year. A conventional visual scale (VS) and two semiquantitative parameters generated from SPECT/CT, adrenal to liver ratio (ALR) and lesion to contralateral ratio of bilateral adrenal glands (CON), with cutoff values calculated by receiver-operating characteristic (ROC) analysis, were compared with pathology results and postsurgical outcomes to determine the accuracy. An ALR cutoff of 1.84 and a CON cutoff of 1.15 showed an ability to distinguish adenoma from hyperplasia similar to VS (p = 0.2592 and 0.1908, respectively). An ALR cutoff of 2.28 and a CON cutoff of 1.11 yielded the highest sensitivity and specificity to predict postsurgical outcomes, and an ALR of 2.28 had an ability superior to VS (p = 0.0215), while a CON of 1.11 did not (p = 0.1015). Patients with either ALR or CON greater than the cutoff had a high probability of positive postsurgical outcomes (n = 36/38), while patients with both ALR and CON less than the cutoff had a low probability of positive postsurgical outcomes (n = 2/11). Semiquantification of NP-59 scintigraphy has an ability similar to VS in differentiating APA from IAH, but an excellent ability to predict postsurgical outcomes of adrenalectomy. An ALR or CON greater than the cutoff strongly suggests benefits from adrenalectomy, and both ALR and CON less than the cutoff implies a reduced chance of improvement in postsurgical outcome.

Introduction Both end-stage renal disease (ESRD) and urothelial cancer (UC) are associated with the consumption of Chinese herbal products containing aristolochic acid (AA) by the general population. The objective of this study was to determine the risk of UC associated with AA-related Chinese herbal products among ESRD patients. Methods We conducted a cohort study using the National Health Insurance reimbursement database to enroll all ESRD patients in Taiwan from 1998–2002. Cox regression models were constructed and hazard ratios and confidence intervals were estimated after controlling for potential confounders, including age, sex, residence in region with endemic black foot disease, urinary tract infection, and use of non-steroidal anti-inflammatory drugs and acetaminophen. Results A total of 38,995 ESRD patients were included in the final analysis, and 320 patients developed UC after ESRD. Having been prescribed Mu Tong that was adulterated with Guan Mu Tong (Aristolochia manshuriensis) before 2004, or an estimated consumption of more than 1–100 mg of aristolochic acid, were both associated with an increased risk of UC in the multivariable analyses. Analgesic consumption of more than 150 pills was also associated with an increased risk of UC, although there was little correlation between the two risk factors. Conclusion Consumption of aristolochic acid-related Chinese herbal products was associated with an increased risk of developing UC in ESRD patients. Regular follow-up screening for UC in ESRD patients who have consumed Chinese herbal products is thus necessary.

Background/Purpose End-stage renal disease (ESRD) may increase the likelihood of malignancy. The aim of this study is to evaluate the characteristics of increased urothelial cancer (UC) risk in patients with ESRD in Taiwan by a population-based study. Methods The standardized incidence ratios (SIRs) for UC among a registered cohort of ESRD in Taiwan during 1997–2002 were calculated using reimbursement data obtained from the Bureau of National Health Insurance (NHI), with the incidence rates of UC in the general population as the reference. Results During the study period we identified 58,739 patients with ESRD, 20,939 patients with UC, and 1305 patients with ERSD and UC. Among the 1305 patients with both diseases, 687 developed UC after ESRD had been diagnosed. Using the general population as the reference group, SIRs were 12.9 [95% confidence interval (CI)]: 12.0–13.9) for all UC cases, 13.9 (95% CI: 12.4–15.0) for bladder cancer, 11.9 (95% CI: 8.6–16.0) for renal cell carcinoma, and 11.6 (95% CI: 10.1–13.1) for upper tract urothelial cancer. Conclusion Patients with ESRD are at increased risk for UC in Taiwan, especially women age 50 years and younger. Early and lifelong surveillance of UC is recommended after diagnosis of ESRD.

To provide short-term result of the metallic ureteral stent in patients with malignant ureteral obstruction and identify radiological findings predicting stent failure. The records of all patients with non-urological malignant diseases who have received metallic ureteral stents from July 2009 to March 2012 for ureteral obstruction were reviewed. Stent failure was detected by clinical symptoms and imaging studies. Survival analysis was used to estimate patency rates and factors predicting stent failure. A total of 74 patients with 130 attempts of stent insertion were included. A total of 113 (86.9 %) stents were inserted successfully and 103 (91.2 %) achieved primary patency. After excluding cases without sufficient imaging data, 94 stents were included in the survival analysis. The median functional duration of the 94 stents was 6.2 months (range 3–476 days). Obstruction in abdominal ureter (p = 0.0279) and lymphatic metastasis around ureter (p = 0.0398) were risk factors for stent failure. The median functional durations of the stents for abdominal and pelvic obstructions were 4.5 months (range 3–263 days) and 6.5 months (range 4–476 days), respectively. The median durations of the stents with and without lymphatic metastasis were 5.3 months (range 4–398 days) and 7.8 months (range 31–476 days), respectively. Metallic ureteral stents are effective and safe in relieving ureteral obstructions resulting from non-urological malignancies, and abdominal ureteral obstruction and lymphatic metastasis around ureter were associated with shorter functional duration.

We retrospectively evaluated the efficacy of prophylaxis with pipemidic acid and levofloxacin in transrectal ultrasound guided prostate biopsy (TRUSP-Bx). From January 2002 to December 2004, patients receiving oral pipemidic acid 500 mg twice daily for three days with or without a preoperative intravenous cefazolin 1 gm injection comprised group A. Between January 2005 and December 2009, patients receiving oral levofloxacin 500 mg one hour before biopsy comprised group B. We calculated the annual febrile urinary tract infection (fUTI) rates. Patients’ characteristics, including age, prophylactic antibiotics, biopsy core numbers, pathologic results, PSA, and the spectrums and susceptibility of pathogens, were also evaluated. A total of 1313 (35.5%) patients belonged to group A, while 2381 (64.5%) patients belonged to group B. Seventy-three patients experienced postoperative infectious complications. There was a significant difference in the fUTI rate between groups A and B (3.7% versus 1.0%,P<0.001). The yearly fUTI rates varied from 0.6 to 3.9% between 2002 and 2009. Of the 73 patients with fUTI, those receiving levofloxacin prophylaxis were more likely to harbor fluoroquinolone-resistant pathogens (P<0.001).E. coliwas the most common pathogen in both groups. Levofloxacin remains effective and appears superior to pipemidic acid based prophylaxis.

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Objective To investigate the association between aldosterone and cardiac diastolic dysfunction. Design and methods We prospectively enrolled 20 patients with primary aldosteronism (PA) and 22 patients with essential hypertension (EH). Plasma aldosterone concentration, plasma renin activity, and 24-h urine aldosterone level were measured. Echocardiography, including tissue Doppler image recordings, was performed. Results PA patients had a significantly higher left ventricular (LV) mass index and worse LV diastolic function than those in EH patients. Among various measures of aldosterone, log-transformed 24-h urine aldosterone level had the most consistent correlation with diastolic function. Conclusions Aldosterone is strongly associated with LV diastolic dysfunction. Twenty-four hour urine aldosterone is a good indicator to evaluate the impact of aldosterone on LV diastolic function.