Risk assessment of multi-factorial complications after transrectal ultrasound-guided prostate biopsy: a single institutional retrospective cohort study.

BACKGROUND: Transrectal ultrasound-guided prostate biopsy (TRUSPB) is widely used to diagnose prostate cancer (PCa). The aim of this study was to evaluate the risk of multi-factorial complications (febrile genitourinary tract infection (GUTI), rectal bleeding, and urinary retention) after TRUSPB. METHODS: N = 2053 patients were Japanese patients undergoing transrectal or transperineal TRUSPB for suspicious of PCa. To assess risk of febrile GUTI adequately, the patients were divided into four groups: low-risk patients before starting a rectal culture, low-risk patients after starting a rectal culture, high-risk patients, and patients undergoing transperineal TRUSPB. Furthermore, to identify risk of rectal bleeding and urinary retention, patients were divided into transrectal and transperineal group. RESULTS: Febrile GUTI significantly decreased owing to risk classification. The frequency of rectal bleeding was 1.43% (transrectal: 25/1742), while it did not happen in transperineal group. The patients with rectal bleeding had a significantly lower body mass index (BMI) (P < 0.01). The frequency of urinary retention was 5.57% (transrectal: 97/1742), while it did not happen in transperineal group. The patients with urinary retention had a significantly higher prostate-specific antigen (PSA) (P = 0.01) in transrectal group. CONCLUSIONS: Risk classification, rectal swab culture, and selected antimicrobial prophylaxis for transrectal TRUSPB were extremely effective to reduce the risk of febrile GUTI. Furthermore, lower BMI and higher PSA were novel clinical predictors for rectal bleeding and urinary retention, respectively. When urologists perform transrectal TRUSPB to their patients, they can correctly understand and explain each complication risk to their patients based on these novel risk factors.

Prion protein protects mice from lethal infection with influenza A viruses.

The cellular prion protein, designated PrPC, is a membrane glycoprotein expressed abundantly in brains and to a lesser extent in other tissues. Conformational conversion of PrPC into the amyloidogenic isoform is a key pathogenic event in prion diseases. However, the physiological functions of PrPC remain largely unknown, particularly in non-neuronal tissues. Here, we show that PrPC is expressed in lung epithelial cells, including alveolar type 1 and 2 cells and bronchiolar Clara cells. Compared with wild-type (WT) mice, PrPC-null mice (Prnp0/0) were highly susceptible to influenza A viruses (IAVs), with higher mortality. Infected Prnp0/0 lungs were severely injured, with higher inflammation and higher apoptosis of epithelial cells, and contained higher reactive oxygen species (ROS) than control WT lungs. Treatment with a ROS scavenger or an inhibitor of xanthine oxidase (XO), a major ROS-generating enzyme in IAV-infected lungs, rescued Prnp0/0 mice from the lethal infection with IAV. Moreover, Prnp0/0 mice transgenic for PrP with a deletion of the Cu-binding octapeptide repeat (OR) region, Tg(PrPΔOR)/Prnp0/0 mice, were also highly susceptible to IAV infection. These results indicate that PrPC has a protective role against lethal infection with IAVs through the Cu-binding OR region by reducing ROS in infected lungs. Cu content and the activity of anti-oxidant enzyme Cu/Zn-dependent superoxide dismutase, SOD1, were lower in Prnp0/0 and Tg(PrPΔOR)/Prnp0/0 lungs than in WT lungs. It is thus conceivable that PrPC functions to maintain Cu content and regulate SOD1 through the OR region in lungs, thereby reducing ROS in IAV-infected lungs and eventually protecting them from lethal infection with IAVs. Our current results highlight the role of PrPC in protection against IAV infection, and suggest that PrPC might be a novel target molecule for anti-influenza therapeutics.

Possible "Premotor" Multiple System Atrophy-Cerebellar Form.

We report the case of a 52-year-old Japanese man who, while he had no cerebellar ataxia or parkinsonism, was revealed to have silent cerebellar hypoperfusion/mild cerebellar atrophy and sacral autonomic disorder. His sacral autonomic disorder was urinary retention without marked prostate hyperplasia. Urodynamics-sphincter electromyography revealed detrusor hyperactivity with impaired contraction and neurogenic changes of the sphincter motor unit potentials. Although he did not have a motor disorder, these features suggested possible multiple system atrophy-cerebellar (MSA-C) form. The present case report suggests that neuroimaging helps in diagnosing "premotor" MSA-C form in situ.

Rescuing the aberrant sex development of H3K9 demethylase Jmjd1a-deficient mice by modulating H3K9 methylation balance.

Histone H3 lysine 9 (H3K9) methylation is a hallmark of heterochromatin. H3K9 demethylation is crucial in mouse sex determination; The H3K9 demethylase Jmjd1a deficiency leads to increased H3K9 methylation at the Sry locus in embryonic gonads, thereby compromising Sry expression and causing male-to-female sex reversal. We hypothesized that the H3K9 methylation level at the Sry locus is finely tuned by the balance in activities between the H3K9 demethylase Jmjd1a and an unidentified H3K9 methyltransferase to ensure correct Sry expression. Here we identified the GLP/G9a H3K9 methyltransferase complex as the enzyme catalyzing H3K9 methylation at the Sry locus. Based on this finding, we tried to rescue the sex-reversal phenotype of Jmjd1a-deficient mice by modulating GLP/G9a complex activity. A heterozygous GLP mutation rescued the sex-reversal phenotype of Jmjd1a-deficient mice by restoring Sry expression. The administration of a chemical inhibitor of GLP/G9a enzyme into Jmjd1a-deficient embryos also successfully rescued sex reversal. Our study not only reveals the molecular mechanism underlying the tuning of Sry expression but also provides proof on the principle of therapeutic strategies based on the pharmacological modulation of epigenetic balance.

Prions amplify through degradation of the VPS10P sorting receptor sortilin.

Prion diseases are a group of fatal neurodegenerative disorders caused by prions, which consist mainly of the abnormally folded isoform of prion protein, PrPSc. A pivotal pathogenic event in prion disease is progressive accumulation of prions, or PrPSc, in brains through constitutive conformational conversion of the cellular prion protein, PrPC, into PrPSc. However, the cellular mechanism by which PrPSc is progressively accumulated in prion-infected neurons remains unknown. Here, we show that PrPSc is progressively accumulated in prion-infected cells through degradation of the VPS10P sorting receptor sortilin. We first show that sortilin interacts with PrPC and PrPSc and sorts them to lysosomes for degradation. Consistently, sortilin-knockdown increased PrPSc accumulation in prion-infected cells. In contrast, overexpression of sortilin reduced PrPSc accumulation in prion-infected cells. These results indicate that sortilin negatively regulates PrPSc accumulation in prion-infected cells. The negative role of sortilin in PrPSc accumulation was further confirmed in sortilin-knockout mice infected with prions. The infected mice had accelerated prion disease with early accumulation of PrPSc in their brains. Interestingly, sortilin was reduced in prion-infected cells and mouse brains. Treatment of prion-infected cells with lysosomal inhibitors, but not proteasomal inhibitors, increased the levels of sortilin. Moreover, sortilin was reduced following PrPSc becoming detectable in cells after infection with prions. These results indicate that PrPSc accumulation stimulates sortilin degradation in lysosomes. Taken together, these results show that PrPSc accumulation of itself could impair the sortilin-mediated sorting of PrPC and PrPSc to lysosomes for degradation by stimulating lysosomal degradation of sortilin, eventually leading to progressive accumulation of PrPSc in prion-infected cells.

External validation of two web-based postoperative nomograms predicting the probability of early biochemical recurrence after radical prostatectomy: a retrospective cohort study.

The present study aimed to validate and compare the predictive accuracies of the Memorial Sloan Kettering Cancer Center (MSKCC) and Johns Hopkins University (JHU) web-based postoperative nomograms for predicting early biochemical recurrence (BCR) after radical prostatectomy (RP) and to analyze clinicopathological factors to predict early BCR after RP using our dataset. The c-index was 0.72 (95% confidence (CI): 0.61-0.83) for the MSKCC nomogram and 0.71 (95% CI: 0.61-0.81) for the and JHU nomogram, demonstrating fair performance in the Japanese population. Furthermore, we statistically analyzed our 174 patients to elucidate prognostic factors for early BCR within 2 years. Lymphovascular invasion (LVI) including lymphatic vessel invasion (ly) was a significant predictor of early BCR in addition to common variables (pT stage, extraprostatic extension, positive surgical margin and seminal vesicle invasion). LVI, particularly ly, may provide a good predictor of early BCR after RP and improve the accuracy of the nomograms.

Development and external validation of a nomogram to predict high-grade papillary bladder cancer before first-time transurethral resection of the bladder tumor.

BACKGROUND: The aim of this study was to identify the clinical predictors related to the risk of high-grade papillary bladder cancer before first-time transurethral resection of a bladder tumor (TUR-Bt), and to develop and validate a nomogram predicting the risk of high-grade papillary bladder cancer. METHODS: A retrospective clinical study of consecutive patients who underwent first-time TUR-Bt for papillary bladder cancer was performed. Medical records were reviewed uniformly, and the following data were collected: age, sex, episodes of urinary symptoms, tumor size, number of tumors, location of the largest tumor (lateral walls, base, posterior wall, dome, and anterior wall), tumor appearance (papillary or non-papillary, pedunculated or sessile), and urinary cytology. Data from 254 patients (Group A) were used for the development of a nomogram, while data from 170 patients (Group B) were used for its external validation. RESULTS: High-grade papillary bladder cancer was pathologically diagnosed in 51.6 and 74.6% of Group A and Group B patients, respectively. Based on univariable analyses in Group A, macrohematuria, tumor size, multiple tumors, appearance, and positive urinary cytology were selected as variables to incorporate into a nomogram. The AUC value was 0.81 for the internal validation (Group A), and 0.78 for the external validation (Group B). This novel nomogram can predict high-grade papillary bladder cancer accurately. CONCLUSIONS: The present nomogram can help clinicians calculate the probability in patients with bladder cancer before TUR-Bt and decide on earlier intervention and priorities for the treatment of patients diagnosed with bladder cancer.

Development of novel nomograms to predict renal functional outcomes after laparoscopic adrenalectomy in patients with primary aldosteronism.

PURPOSE: Most patients with primary aldosteronism (PA) show a significant decrease in kidney function after surgery. Glomerular hyperfiltration peculiar to PA can mask mild renal failure before surgery. The aim of this retrospective study was to investigate postoperative renal functional outcomes in PA patients from different viewpoints and to develop novel nomograms that can predict renal functional outcomes in PA patients after surgery. METHODS: 130 Japanese PA patients treated by unilateral laparoscopic adrenalectomy were retrospectively surveyed. Pre- and postoperative changes of estimated glomerular filtration rates (eGFRs) and the distribution of eGFR classification were compared. Furthermore, predictors of the following renal functional outcomes were investigated: (I) the percentage decrease >25% in eGFR and (II) the presence of new-onset eGFR <45 ml/min/1.73 m2. Finally, two nomograms that predicted postoperative renal functional outcomes were developed and internally validated. RESULTS: At 6 months, the average decrease in eGFR was 16.7 mL/min/1.73 m2 (corresponding percent decrease: 19.7%). Upstaging of eGFR classification was observed in 54.6% of patients. Age, potassium, plasma aldosterone concentration, and initial eGFR were incorporated into a nomogram predicting a >25% postoperative decrease in eGFR. Duration of hypertension and initial eGFR were incorporated into a nomogram predicting new-onset eGFR <45 ml/min/1.73 m2. The value of the area under the receiver operating characteristics curve for each nomogram was 0.82 and 0.74, respectively. CONCLUSION: The first nomograms that can predict postoperative renal outcomes in PA patients were developed. They will help clinicians calculate the probability of renal dysfunction in PA patients after laparoscopic adrenalectomy.

Effects of prion protein devoid of the N-terminal residues 25-50 on prion pathogenesis in mice.

The N-terminal polybasic region of the normal prion protein, PrPC, which encompasses residues 23-31, is important for prion pathogenesis by affecting conversion of PrPC into the pathogenic isoform, PrPSc. We previously reported transgenic mice expressing PrP with residues 25-50 deleted in the PrP-null background, designated as Tg(PrP∆preOR)/Prnp 0/0 mice. Here, we produced two new lines of Tg(PrP∆preOR)/Prnp 0/0 mice, each expressing the mutant protein, PrP∆preOR, 1.1 and 1.6 times more than PrPC in wild-type mice, and subsequently intracerebrally inoculated RML and 22L prions into them. The lower expresser showed slightly reduced susceptibility to RML prions but not to 22L prions. The higher expresser exhibited enhanced susceptibility to both prions. No prion transmission barrier was created in Tg(PrP∆preOR)/Prnp 0/0 mice against full-length PrPSc. PrPSc∆preOR accumulated in the brains of infected Tg(PrP∆preOR)/Prnp 0/0 mice less than PrPSc in control wild-type mice, although lower in RML-infected Tg(PrP∆preOR)/Prnp 0/0 mice than in 22L-infected mice. Prion infectivity in infected Tg(PrP∆preOR)/Prnp 0/0 mice was also lower than that in wild-type mice. These results indicate that deletion of residues 25-50 only slightly affects prion susceptibility, the conversion of PrPC into PrPSc, and prion infectivity in a strain-specific way. PrP∆preOR retains residues 23-24 and lacks residues 25-31 in the polybasic region. It is thus conceivable that residues 23-24 rather than 25-31 are important for the polybasic region to support prion pathogenesis. However, other investigators have reported that residues 27-31 not 23-24 are important to support prion pathogenesis. Taken together, the polybasic region might support prion pathogenesis through multiple sites including residues 23-24 and 27-31.

Clinical predictors for high-grade bladder cancer before first-time transurethral resection of the bladder tumor: a retrospective cohort study.

The aim of this study was to identify the clinical predictors related to the risk of high-grade bladder cancer before first-time transurethral resection of the bladder tumor (TUR-Bt) and to externally validate the accuracy of Shapur's nomogram predicting the risk of high-grade bladder cancer in Japanese patients. As a result, episode of gross hematuria (odds ratio: 2.68, P = 0.02), larger tumor size (odds ratio: 1.89, P < 0.01) and positive urinary cytology (odds ratio: 8.34, P < 0.01) were found to be significant predictors for high-grade bladder cancer. Furthermore, the nomogram showed a high predictive accuracy in our Japanese population (area under the curve: 0.79). Clinicians will be able to predict high-grade bladder cancer using the common factors in Shapur's study and ours, such as tumor size and urinary cytology, and gross hematuria as the additional factor first identified here to decide priorities for the treatment of patients diagnosed with bladder cancer.

Effect of androgen deprivation therapy on arterial stiffness and serum lipid profile changes in patients with prostate cancer: a prospective study of initial 6-month follow-up.

BACKGROUND: To explore arterial stiffness during the administration of androgen deprivation therapy (ADT) in patients with prostate cancer (PCa), a new indicator, the cardio-ankle vascular index (CAVI), and serum lipid profile changes were monitored. METHODS: A prospective study assessed the changes in arterial stiffness using the CAVI and clinical laboratory variables among 58 men with prostate cancer treated with ADT for 6 months. Furthermore, patients who had a high risk of developing arterial stiffness after ADT were investigated. RESULTS: The whole cohort had no significant increase in arterial stiffness within 6 months after ADT, but 55.2 % of patients had an increased CAVI. Serum levels of total cholesterol, high-density-lipoprotein cholesterol (HDL-C), and low-density-lipoprotein cholesterol (LDL-C) increased significantly at 1 month after the start of ADT and maintained high values thereafter. At baseline, HDL-C was lower and LDL-C and LDL-C/HDL-C were higher in the group with than without an increased CAVI after 6 months of ADT administration. CONCLUSIONS: Although the whole cohort did not show a significant change in arterial stiffness with ADT, some patients showed an increased arterial stiffness monitored with the CAVI. The balance between LDL-C and HDL-C, or LDL-C/HDL-C, might have an impact on the development of arterial stiffness after ADT administration. Thus, clinicians might be able to monitor PCa patients who have a high risk of development of arterial stiffness after ADT administration by referring to LDL-C/HDL-C levels.

External validation and comparison of two nomograms predicting the probability of Gleason sum upgrading between biopsy and radical prostatectomy pathology in two patient populations: a retrospective cohort study.

The aim of this study is to validate and compare the predictive accuracy of two nomograms predicting the probability of Gleason sum upgrading between biopsy and radical prostatectomy pathology among representative patients with prostate cancer. We previously developed a nomogram, as did Chun et al. In this validation study, patients originated from two centers: Toho University Sakura Medical Center (n = 214) and Chibaken Saiseikai Narashino Hospital (n = 216). We assessed predictive accuracy using area under the curve values and constructed calibration plots to grasp the tendency for each institution. Both nomograms showed a high predictive accuracy in each institution, although the constructed calibration plots of the two nomograms underestimated the actual probability in Toho University Sakura Medical Center. Clinicians need to use calibration plots for each institution to correctly understand the tendency of each nomogram for their patients, even if each nomogram has a good predictive accuracy.

[CLINICOPATHOLOGICAL STUDY OF PROSTATE BIOPSY IN PATIENTS RECEIVING DUTASTERIDE FOR BENIGN PROSTATIC HYPERPLASIA].

OBJECTIVE: Dutasteride is a 5-alpha reductase inhibitor used to treat benign prostatic hyperplasia. Dutasteride lowers prostate-specific antigen (PSA) levels, which may lead to delays in the diagnosis and treatment of prostate cancer (PCa). This study investigated patients who underwent prostate biopsy (PBx) while receiving dutasteride to investigate whether this agent affects the diagnosis and treatment of PCa. PATIENTS AND METHODS: PBx was performed on six patients receiving dutasteride for > 3 months at our medical institutions between January 2010 and June 2013. No patients underwent PBx before dutasteride administration. We performed PBx both for patients with high initial PSA levels and for those with elevated PSA levels with or without initial PSA decline after dutasteride administration. We also investigated clinicopathological findings. RESULTS: Mean age at the start of administration was 69.5 ± 5.9 years (range, 59-77 years), mean duration of administration was 14.1 ± 7.4 months (range, 4.0-23.5 months), mean prostate volume at the start of administration was 70.4 ± 30.7 ml (range, 18.8-104.6 ml), and mean PSA level at the start of administration was 7.7 ± 3.3 ng/ml (range, 4.9-14.2 ng/ml). PSA density was 0.098 ± 0.045 ng/ml/cm3 (range, 0.042-0.181 ng/ml/cm3), and PSA level at PBx was 5.4 ± 2.7 ng/ml (range, 2.5-10.7 ng/ml). We detected three PCa patients, and clinical stage in each case was cT1cN0M0. Radical retropubic prostatectomy was performed in two cases, and androgen-deprivation therapy was performed in one case. CONCLUSION: All PCa were detected in the early clinical stage. No delays in detection or treatment of PCa were seen in any cases. Careful observation of PSA levels is simple and useful for detecting PCa in patients under dutasteride administration.

Structural basis for the different stability and activity between the Cdk5 complexes with p35 and p39 activators.

Cyclin-dependent kinase 5 (Cdk5) is a brain-specific membrane-bound protein kinase that is activated by binding to the p35 or p39 activator. Previous studies have focused on p35-Cdk5, and little is known regarding p39-Cdk5. The lack of functional understanding of p39-Cdk5 is due, in part, to the labile property of p39-Cdk5, which dissociates and loses kinase activity in nonionic detergent conditions. Here we investigated the structural basis for the instability of p39-Cdk5. p39 and p35 contain N-terminal p10 regions and C-terminal Cdk5 activation domains (AD). Although p35 and p39 show higher homology in the C-terminal AD than the N-terminal region, the difference in stability is derived from the C-terminal AD. Based on the crystal structures of the p25 (p35 C-terminal region including AD)-Cdk5 complex, we simulated the three-dimensional structure of the p39 AD-Cdk5 complex and found differences in the hydrogen bond network between Cdk5 and its activators. Three amino acids of p35, Asp-259, Asn-266, and Ser-270, which are involved in hydrogen bond formation with Cdk5, are changed to Gln, Gln, and Pro in p39. Because these three amino acids in p39 do not participate in hydrogen bond formation, we predicted that the number of hydrogen bonds between p39 and Cdk5 was reduced compared with p35 and Cdk5. Using substitution mutants, we experimentally validated that the difference in the hydrogen bond network contributes to the different properties between Cdk5 and its activators.

TGF-ß type II receptor expression in thymic epithelial cells inhibits the development of Hassall's corpuscles in mice.

Hassall's corpuscles are concentric clusters of keratinized epithelial cells located within the thymic medulla of humans and guinea pigs but are scant in mouse and rat. They are considered to be the terminally differentiated stages of medullary thymic epithelial cells (mTECs) but the mechanisms of their origin are unclear. We have previously deleted the TGF-ß type II receptor (TGFßRII) specifically in mouse TECs and reported that these mice have mitigated thymic involution and exhibit earlier reconstitution post-irradiation. In this study, we analyzed the differentiation of mTECs in the TGFßRII-knockout mice. Interestingly, the TGFßRII-knockout mice display enhanced development of Hassall's corpuscles. The expression of Aire, stromal-cell-derived factor 1 and thymic stromal lymphopoietin in the thymi of the TGFßRII-knockout mice was similar to that previously reported for the human thymus. In addition, the putative epithelial progenitor markers MTS20 and MTS24 labeled Hassall's corpuscles in normal mice, but the extent and intensity of this staining were greatly enhanced in Hassall's corpuscles of the TGFßRII-knockout mice. The phosphorylated forms of ERK and JNK were also found in Hassall's corpuscles of the TGFßRII-knockout mice. Taken together, we suggest that TGFßRII-mediated signaling in TECs inhibits their development into Hassall's corpuscles in mice.

Tolterodine activates the prefrontal cortex during bladder filling in OAB patients: a real-time NIRS-urodynamics study.

AIMS: Studies of overactive bladder (OAB) have shown urothelial/suburothelial changes and increased bladder afferents, while in the brain the frontal micturition area that normally suppresses the bladder is deactivated. It has been unclear whether anticholinergic medication could reverse this suppression. To address this question, we performed a real-time NIRS (near-infrared spectroscopy)-urodynamic study in OAB patients before and after the administration of an anticholinergic agent, tolterodine. METHODS: We recruited 13 OAB patients in our outpatient clinic (9 males, 4 female; mean age 73 years). Before and after the administration of 4 mg/day tolterodine for 3 months, all patients completed the OAB-symptom scale and a NIRS-urodynamics examination. Cerebral changes in the oxy-hemoglobin concentration (oxy-Hb) were sampled. Concentration changes in oxy-Hb were calculated based on a modified Beer-Lambert approach. RESULTS: Tolterodine significantly reduced the OAB patients' nighttime frequency (P < 0.05) and increased their first-sensation volume (290-359 ml, P < 0.01). The number of patients with detrusor overactivity did not lessen significantly (11-9). The real-time NIRS-urodynamic study showed that, during slow bladder filling between start and bladder capacity, tolterodine significantly activated the right frontal micturition area of the OAB patients (P < 0.05). The activation was prominent in Brodmann's area 8, 9, 10 of the prefrontal cortex. CONCLUSIONS: Tolterodine reduced bladder sensation together with a significant activation of the frontal micturition area of OAB patients, particularly Brodmann's area 8, 9, 10 of the right prefrontal cortex. This activation seems to be a secondary phenomenon, since tolterodine does not easily penetrate the blood-brain barrier.

Development of a novel nomogram to predict hypertension cure after laparoscopic adrenalectomy in patients with primary aldosteronism.

BACKGROUND: Primary aldosteronism is the most common curable cause of secondary hypertension. Despite resection, however, many patients with primary aldosteronism continue to require antihypertensive drugs to control their blood pressure. Although many patients with primary aldosteronism want to know the postoperative probability of hypertension cure before surgery, there are no predictive models calculating its probability. We therefore developed a nomogram to predict hypertension cure in patients with primary aldosteronism after laparoscopic adrenalectomy. METHODS: We retrospectively surveyed 132 Japanese patients with primary aldosteronism who were treated by unilateral laparoscopic adrenalectomy. Hypertension cure was defined as normal blood pressure (<140/90 mmHg) without antihypertensive drugs 6 months postoperatively. We developed a novel nomogram that postoperatively predicted cured hypertension in 105 (80 %) randomly selected patients and validated it with the remaining 27 (20 %). RESULTS: At 6 months, blood pressure had normalized in 42 % of patients without antihypertensive drugs. Duration of hypertension, preoperative number of antihypertensive drug classes, age, and sex were incorporated into a novel nomogram as independent predictors of hypertension cure. The value of the area under the receiver operating characteristics curve for this nomogram was 0.83-which was significantly higher than that of the Aldosteronoma Resolution Score-on internal validation. CONCLUSIONS: We developed the first nomogram that can accurately predict postoperative hypertension cure in patients with primary aldosteronism. This nomogram can help clinicians calculate the probability of postoperative hypertension cure in patients with primary aldosteronism and objectively inform them of their hypertension outcome before laparoscopic adrenalectomy.

Bladder function of patients with Parkinson's disease.

Bladder function of patients with Parkinson's disease alters significantly: the majority of patients have overactive bladder (urinary urgency/frequency) with little or no post-void residuals. This seems to be the result of an altered brain-bladder relationship, as in Parkinson's disease, the frontal-basal ganglia D1 dopaminergic circuit that normally suppresses the micturition reflex is altered. The pathophysiology of the bladder dysfunction in Parkinson's disease differs from that in multiple system atrophy; therefore, it might also aid in differential diagnosis. The effects of levodopa, the major drug to treat motor dysfunction, on the bladder in Parkinson's disease vary significantly; therefore, add-on therapy is often required. Anticholinergic drugs are the first-line treatment, with particular care for cognitive function in elderly patients. The second-line treatment includes serotonergics drug, desmopressin and others. Newer modalities include deep brain stimulation that improves the bladder in Parkinson's disease; and botulinum toxin is promising, particularly in difficult cases. These treatments might be beneficial in maximizing the patients' quality of life.

Is overactive bladder a brain disease? The pathophysiological role of cerebral white matter in the elderly.

Small-vessel disease of the brain affecting the deep white matter characteristically manifests with neurological syndromes, such as vascular dementia and vascular parkinsonism. There is, however, compelling evidence to suggest that white matter disease can cause overactive bladder and incontinence, and in some patients these might be the initial manifestation. As white matter disease increases significantly with age, and preferentially affects the prefrontal deep white matter, white matter disease becomes an anatomical substrate in the brain etiology of overactive bladder. Treatment entails the management of small-vessel disease risk factors and anticholinergic drugs that do not easily penetrate the blood-brain barrier, to improve bladder control. In short, when caring for elderly overactive-bladder patients, we should look at both the brain and the bladder.