Shih-Chieh Jeff Chueh

Risk of Fracture in Primary Aldosteronism: A Population‐Based Cohort Study

Primary aldosteronism (PA) is associated with increased urinary calcium excretion and osteoporosis prevalence. We studied the long‐term effect of hyperaldosterone on fracture risk and possible risk mitigation via treatments, by comparing PA patients and their essential hypertension (EH) counterparts extracted by propensity score match. We used a longitudinal population database from the Taiwan National Health Insurance, and used a validated algorithm to identify PA patients diagnosed in 1997–2010. Our sample included 2533 PA patients, including 921 patients with aldosterone‐producing adenoma (APA). Our methods for assessing excessive fracture risk included multivariable Cox regression and the competing risk regression. The incidence rate of fracture at any site was 14.4 per 1000 person‐years for PA, and 11.2 per 1000 person‐years for APA. In contrast, the incidence rate of fracture at any site was 8.3 per 1000 person‐years in EH controls for PA, and 6.5 per 1000 person‐years in EH controls for APA. Mineralocorticoid receptor antagonist (MRA) treatment might be associated with higher risk of osteoporotic fracture in the whole female PA cohort (subdistribution hazard ratio [SHR] = 2.12, p = 0.008) as well as female APA patients (SHR = 1.15, p = 0.049). As to fracture at any site, MRA treatment was also associated with higher risk; the SHR was 1.88 (p < 0.001) in the whole female PA cohort, and 2.17 (p = 0.019) in female APA patients. PA is tightly associated with higher risk of bone fracture, even in the case where the competing risk of death was controlled. Particularly, female PA patients treated with MRA were confronted with significantly higher risk in bone fracture than their EH controls.

The prevalence of CTNNB1 mutations in primary aldosteronism and consequences for clinical outcomes

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.

Long term outcome of Aldosteronism after target treatments.

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 need for receptor antagonist (MRA) 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.

Laparoendoscopic single-site (LESS) retroperitoneal partial adrenalectomy using a custom-made single-access platform and standard laparoscopic instruments: Technical considerations and surgical outcomes

BACKGROUND We previously reported our initial experience with laparoendoscopic single-site (LESS) retroperitoneal partial adrenalectomy using a custom-made single-port device and conventional straight laparoscopic instruments. METHODS Between December 2010 and February 2012, LESS retroperitoneal partial adrenalectomies were performed in 11 patients. Six patients had aldosterone-producing adenomas (APAs) and five patients had nonfunctioning tumors. A single-port access was created with an Alexis wound retractor (Applied Medical, Rancho Santa Margarita, CA, USA) through an incision of 2-3 cm beneath the tip of the 12th rib. All procedures were performed with straight laparoscopic instruments. RESULTS All LESS procedures were successfully completed without conversion to traditional laparoscopic conversion. The tumors ranged from 1 cm to 4.7 cm (mean, 2.3 cm). The operative time was 71-257 minutes (mean, 121 minutes). Most patients (n = 8) had minimal blood loss; the other three patients had a blood loss of 150 mL, 100 mL, and 100 mL. The mean hospital stay was 3 days (range, 1-6 days). There were no perioperative or postoperative complications. Pathological examinations revealed negative surgical margins in all specimens. All patients with Conns syndrome had an improvement in blood pressure and normalization of plasma renin activity and serum aldosterone levels; all patients were free of potassium supplementation. CONCLUSION Our results clearly demonstrate that LESS retroperitoneal partial adrenalectomy can be performed safely and effectively using a custom-made single-access platform and standard laparoscopic instruments.

Oncologic Outcomes of Asian Men with Clinically Localized Prostate Cancer after Extraperitoneal Laparoscopic Radical Prostatectomy: A Single-Institution Experience

Purpose. To evaluate the midterm oncologic results of extraperitoneal laparoscopic radical prostatectomy (EPLRP) for Asian men with localized prostate cancer. Methods. Between 2004 and 2009, 218 men underwent EPLRP at an Asian tertiary hospital. The mean preoperative prostate-specific antigen (PSA) was 15.5 ng/ml and mean Gleason score was 6.6. Stage distributions were cT1a-b in 21 cases, cT1c in 139, cT2 in 48 and cT3 in 10. Disease recurrence was defined as PSA ≥ 0.2 ng/mL in 2 consecutive measurements or initiation of secondary therapy. Results. Postoperative pathological stage was pT2a-b in 33 patients, pT2cN0 in 10, pT3a in 27, pT3b in 36, pT4 in 9 and pN1 in 10. Positive surgical margins occurred in 14.6% and 48.6% for pT2 and pT3 diseases, respectively (P < .001). The overall PSA recurrence-free survival at 3 and 5 years was 82.1% and 74.5%. By the pathological stages, 3-year recurrence-free survival was 92.4% (pT2), 81.1% (pT3a), 62.6% (pT3b-4) and 55.6% (pN1), respectively (P < .001). Conclusions. EPLRP is curative even for some locally advanced prostate cancers in a midterm follow-up. Even at an Asian center of low volume of radical prostatectomy EPLRP still provides oncologic outcomes similar to that of high volume centers.

Case detection and diagnosis of primary aldosteronism – The consensus of Taiwan Society of Aldosteronism

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.

The value of losartan suppression test in the confirmatory diagnosis of primary aldosteronism in patients over 50 years old

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.

The benefits of pulsatile machine perfusion of standard criteria deceased donor kidneys at a geographically remote transplant center.

Benefits of pulsatile machine perfusion (pumping) of standard criteria donor (SCD) kidneys are unclear. Our center is located 4½ hours from our Organ Procurement Organization. We evaluated outcomes of pumping SCD kidneys under such circumstances by conducting a retrospective examination of all SCD kidneys transplanted between January 2007 and March 2012, comparing kidneys pumped (28 [group 1]) versus standard cold storage (77 [group 2]). Group 1 had fewer delayed graft function (DGF, 3.57% vs. 23.38%, p = 0.02) and slow graft function (SGF, 7.14% vs. 24.68%; p = 0.047) and faster serum creatinine recovery curve (p < 0.001) than group 2. Having a kidney pumped decreases the incidence (odds ratio [OR], 0.059) of DGF, SGF, or primary nonfunction. Group 1 were quicker to reach an estimated glomerular filtration rate (eGFR) >30 ml/min (OR, 4.186; confidence interval [CI], [2.448–7.157]) or an eGFR >60 ml/min (OR, 2.669; CI [1.255–5.679]). Pumping the SCD kidneys in a geographically remote transplant center tended to be better than those preserved in cold storage. However, except recovery curve of serum creatinine during the first postoperative month, other parameters failed to reach statistical significance in the post hoc examination of the contemporary groups. Prospective paired kidney study is required to scrutinize this finding.

Bladder migration of Hem-o-Lok clips after laparoscopic radical nephroureterectomy and bladder cuff excision.

The Hem-o-Lok clips are widely used in various laparoscopic operations because of its easy application and secure clamping. The Hem-o-Lok clips were adopted to ligate bladder cuff during bladder cuff excision because of its advantages. We report 2 cases of bladder migration of Hem-o-Lok clips after laparoscopic nephroureterectomy and bladder cuff excision. The clips were found during routine follow-up cystoscopy and were removed by cystoscopic procedure. We described the case presentation, treatment, and the alternative method to avoid such shortcomings.

Outcome Prediction of Acute Kidney Injury Biomarkers at Initiation of Dialysis in Critical Units

The ideal circumstances for whether and when to start RRT remain unclear. The outcome predictive ability of acute kidney injury (AKI) biomarkers measuring at dialysis initializing need more validation. This prospective, multi-center observational cohort study enrolled 257 patients with AKI undergoing renal replacement therapy (RRT) shortly after admission. At the start of RRT, blood and urine samples were collected for relevant biomarker measurement. RRT dependence and all-cause mortality were recorded up to 90 days after discharge. Areas under the receiver operator characteristic (AUROC) curves and a multivariate generalized additive model were applied to predict outcomes. One hundred and thirty-five (52.5%) patients died within 90 days of hospital discharge. Plasma c-terminal FGF-23 (cFGF-23) had the best discriminative ability (AUROC, 0.687) as compared with intact FGF-23 (iFGF-23) (AUROC, 0.504), creatinine-adjusted urine neutrophil gelatinase-associated lipocalin (AUROC, 0.599), and adjusted urine cFGF-23 (AUROC, 0.653) regardless whether patients were alive or not on day 90. Plasma cFGF-23 levels above 2050 RU/mL were independently associated with higher 90-day mortality (HR 1.76, p = 0.020). Higher cFGF-23 levels predicted less weaning from dialysis in survivors (HR, 0.62, p = 0.032), taking mortality as a competing risk. Adding cFGF-23 measurement to the AKI risk predicting score significantly improved risk stratification and 90-day mortality prediction (total net reclassification improvement = 0.148; p = 0.002). In patients with AKI who required RRT, increased plasma cFGF-23 levels correlated with higher 90-day overall mortality after discharge and predicted worse kidney recovery in survivors. When coupled to the AKI risk predicting score, cFGF-23 significantly improved mortality risk prediction. This observation adds evidence that cFGF-23 could be used as an optimal timing biomarker to initiate RRT.