Immunohistological analysis reveals IgG1-dominant immunophenotype of tubulointerstitial nephritis unassociated with IgG4-related diseases.

PURPOSE: Tubulointerstitial nephritis (TIN) has various etiologies, including IgG4-related disease (IgG4-RD), autoimmune diseases, antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), and others. IgG4-positive plasma cell infiltration can occasionally be found in TIN unrelated to IgG4-RD. Therefore, there may be problems with usage of IgG4 immunostaining to differentiate between TIN with and TIN without IgG4-RD. This study aimed to compare the proportion of plasma cells that are positive for each IgG subclass and to clarify the predominant IgG subclass trends and clinical characteristics associated with IgG4-RD and non-IgG4-related interstitial nephritis. METHODS: The study enrolled 44 cases of TIN: 6 of IgG4-RD, 8 of autoimmune disease, 9 of AAV, and 21 of unknown disease group. In addition to clinical characteristics, IgG subclass composition of interstitial plasma cells was evaluated among 4 groups by immunohistochemistry. RESULTS: IgG1 was the predominant IgG subclass in TIN unrelated to IgG4-RD. In the IgG4-RD group, the IgG subclass rate was high in both IgG1 and IgG4. The rate of average IgG4-positive cells was significantly lower in the autoimmune disease group and unknown disease group compared with the IgG4-RD group. CONCLUSION: The present study revealed IgG1-dominant immune profiles of TIN unrelated to IgG4-RD. Further investigation is required to elucidate the clinicopathological differences between IgG1-dominant and IgG4-dominant groups in IgG4-RD.

Toward three-dimensionally ordered nanoporous graphene materials: template synthesis, structure, and applications.

Precise template synthesis will realize three-dimensionally ordered nanoporous graphenes (NPGs) with a spatially controlled seamless graphene structure and fewer edges. These structural features result in superelastic nature, high electrochemical stability, high electrical conductivity, and fast diffusion of gases and ions at the same time. Such innovative 3D graphene materials are conducive to solving energy-related issues for a better future. To further improve the attractive properties of NPGs, we review the template synthesis and its mechanism by chemical vapor deposition of hydrocarbons, analysis of the nanoporous graphene structure, and applications in electrochemical and mechanical devices.

Salvage robot-assisted radical prostatectomy after carbon ion radiotherapy to the prostate.

PURPOSE: This study presents the surgical and oncological outcomes of salvage robot-assisted radical prostatectomy (RARP) after carbon ion radiotherapy at a single institution. METHODS: Patients who underwent salvage RARP for local recurrence after carbon ion radiotherapy at Kyushu University Hospital between 2020 and 2023 were included. A single surgeon performed salvage RARP with extended pelvic lymph node dissection. Clinicopathological characteristics and perioperative and postoperative outcomes were prospectively collected and electronically recorded. RESULTS: Ten cases were included. The preoperative clinical T-stage was T2, except for one case with T3a. The median console time was 171 min (range, 135-226 min). No severe perioperative or postoperative complications were noted. The pathological T-stage was T2, T3a, and T3b in four, four, and two cases, respectively. Biochemical recurrence was observed in one patient at 31.2 months after surgery. For patients with more than 1 year of follow-up, urinary continence recovery with ≤1 pad was achieved in two cases within 1 year, whereas four cases did not recover urinary continence within 1 year. CONCLUSIONS: This case series demonstrated the feasibility of salvage RARP after carbon ion radiotherapy. Although the urinary continence recovery was modest, short-term disease control was favorable.

Hypocalcemia and cardiovascular mortality in cinacalcet users.

BACKGROUND: Calcimimetics are widely used in hemodialysis patients and influence serum calcium levels. Although the Kidney Disease: Improving Global Outcomes guidelines argued that low calcium levels induced by calcimimetics may be harmless, large observational studies investigating the association between hypocalcemia and mortality are scarce. We investigated the association between serum calcium levels and cardiovascular mortality in calcimimetics users using the nationwide Japanese registry for dialysis patients. METHODS: In this 9-year prospective cohort study, the baseline data were collected at the end of 2009. We enrolled patients on maintenance hemodialysis or hemodiafiltration. We employed three models (baseline, time-dependent and time-averaged) to conduct Cox proportional hazard regression analyses. RESULTS: Cinacalcet was prescribed to 12.7% (N = 22 853) at baseline. The median observation period was 98 (interquartile range 40-108) months and 108 (interquartile range 59-108) months in the whole cohort (N = 180 136) and in cinacalcet users, respectively. Three-quarters of survivors at the end of 2019 had continued calcimimetic therapy for 10 years, corresponding to a mean annual dropout rate of 2.9%. Hypocalcemia was not associated with cardiovascular mortality in the baseline or time-averaged model. In the time-dependent model, however, the lowest calcium decile (corrected calcium <8.4 mg/dL) was significantly associated with higher cardiovascular mortality than the reference (corrected calcium 8.7-8.9 mg/dL) in both cinacalcet users and all patients [hazard ratio (95% confidence interval) 1.32 (1.00, 1.75) and 1.15 (1.05, 1.26), respectively]. Hypocalcemia was especially associated with sudden death and death due to hemorrhagic stroke, heart failure and ischemic heart disease. Higher rate of fatal and non-fatal cardiovascular events was observed in hypocalcemic patients regardless of cinacalcet usage. CONCLUSIONS: Our findings suggest that transient hypocalcemia was associated with an increased risk of cardiovascular death independent of cinacalcet usage. We should pay attention to hypocalcemia transiently induced by cinacalcet.

Survival benefit of living donor kidney transplantation in patients on hemodialysis.

BACKGROUND: Donors bravely donate their kidneys because they expect that living donor kidney transplantation (LKT) confers benefits to recipients. However, the magnitude of the survival benefit of LKT is uncertain. METHODS: This prospective cohort study used two Japanese nationwide databases for dialysis and kidney transplantation and included 862 LKT recipients and 285,242 hemodialysis (HD) patients in the main model and 5299 LKT recipients and 151,074 HD patients in the supplementary model. We employed time-dependent model in the main model and assessed the hazard ratio and the difference in the restricted mean survival time (RMST) between LKT recipients and HD patients. In the main analysis of the main model (LKT, N = 675; HD, N = 675), we matched LKT recipients with HD patients by age, sex, dialysis vintage, and cause of renal failure and excluded HD patients with dementia or performance status grades 2, 3, or 4. RESULTS: The median observational period was 8.00 (IQR 3.58-8.00) years. LKT was significantly associated with a lower risk of mortality (hazard ratios (95% confidence interval (CI)), 0.50 (0.35-0.72)) and an increase in life expectancy (7-year RMST differences (95% CI), 0.48 (0.35-0.60) years) compared with HD. In subgroup analysis, the survival benefit of LKT was greater in female patients than in male patients in the Cox model; whereas older patients gained longer life expectancy compared with younger patients. CONCLUSIONS: LKT was associated with better survival benefits than HD, and the estimated increase in life expectancy was 0.48 years for 7 years.

Validation of schedules for optimal prostate-specific antigen monitoring after radical prostatectomy.

BACKGROUND: Early detection of biochemical recurrence (BCR) after radical prostatectomy (RP) is crucial for early treatment and improving survival outcomes. The optimal prostate-specific antigen (PSA) monitoring remains unclear, and several models have been proposed. We aimed to externally validate four models for optimal PSA monitoring after RP and propose modifications to improve them. METHODS: We reviewed the clinicopathological data of 896 patients who underwent robot-assisted RP between 2009 and 2022. We examined all PSA values and estimated the PSA value for four monitoring schedules at each time point in the virtual follow-up. We defined the ideal PSA for BCR detection between 0.2 and 0.4 ng/mL. RESULTS: During the median follow-up of 21.4 months, 128 (14.3%) patients presented BCR. The original and modified Keio models, National Cancer Center Hospital model, and American Urological Association/American Society for Radiation Oncology model detected BCR in 14 (10.9%), three (2.3%), 12 (9.4%), and 11 (8.6%) patients with PSA >0.4 ng/mL. Most patients experienced BCR detected with PSA >0.4 ng/mL during the first year postoperative. The modification of interval within 6 months postoperative avoided BCR detection with PSA >0.4 ng/mL within the first year postoperative in 8/9 (88.9%), 1/2 (50.0%), 5/6 (83.3%), and 4/4 (100%) for the original and modified Keio models, National Cancer Center Hospital model, and American Urological Association/American Society for Radiation Oncology model, respectively. CONCLUSION: We validated four models for PSA monitoring after RP to detect BCR and suggested modifications to avoid detections out of the desired range of PSA. These modifications could help to establish an optimal PSA monitoring schedule after RP.

Association of abnormalities in electrocardiography and ultrasonic echocardiography with the occurrence of cardiovascular disease in patients with advanced chronic kidney disease.

BACKGROUND: In patients with chronic kidney disease (CKD), the incidence of cardiovascular disease (CVD) increases with disease progression. CVD screening tests in those with CKD were researched to determine whether abnormalities observed in electrocardiography (ECG) and ultrasonic echocardiography (UCG) were risk factors associated with the development of CVD. METHODS: This study included 604 patients with CKD G4 and G5, for whom both ECG and UCG were performed. They were divided into four groups: those without ECG- and UCG-indicated abnormalities (group A, n = 333), with only ECG abnormalities (group B, n = 106), with only UCG abnormalities (group C, n = 75), and with both ECG and UCG abnormalities (group D, n = 90). Multivariate analysis using Cox regression analysis of the occurrence of CVD was performed during a follow-up period. RESULTS: During the observation period, 124 patients had clinical events. Among them, 45 patients (13.5%) were in Group A, 25 patients (23.6%) in Group B, 19 patients (25.3%) in Group C, and 35 patients (38.9%) in Group D, respectively. CVD event occurrence was highest in Group D. The results of the multivariate analysis also showed that the CVD event rates were significantly higher in Group C (HR: 2.96, P = < .001) and D (HR: 4.22, P < .001) than in Group A. CONCLUSION: In patients with advanced CKD, there was a significant correlation of ECG and UCG abnormalities with CVD events. Additionally, those having both types of abnormalities may have a higher risk of coronary artery disease than other groups.

Current status and future perspective of immunotherapy for renal cell carcinoma.

In the last decade, the standard treatment for advanced renal cell carcinoma (RCC) has evolved, mainly driven by the development and approval of immune checkpoint inhibitors (ICIs). Currently, ICI monotherapy and ICI-based combinations with tyrosine kinase inhibitors and targeted therapies against mammalian target of rapamycin or vascular endothelial growth factor have become new standard treatments for first-line and subsequent-line therapies. ICIs play an important role as an adjuvant postoperative therapy, and this field is the subject of active research. Furthermore, ongoing randomized controlled trials are investigating the clinical value of more intense treatments by combining multiple effective treatments for RCC. Additionally, novel biomarkers for prognosis have been investigated. This study reviews the current evidence on immunotherapy as a treatment for RCC patients, randomized controlled trials, and ongoing studies including RCC patients and recent findings, and discusses future perspectives.

Surface defect healing in annealing from nanoporous carbons to nanoporous graphenes.

Nanoporous graphene (NPG) materials have the pronounced electrochemical stability of the seamless graphene structures developed over the 3D space. We revisited the Raman spectra of nanoporous carbons (NPCs) synthesized using θ-/γ-Al2O3 templates and NPGs converted from NPCs by annealing at 1800 °C to identify the type and density of defects. We found that both the NPCs and NPGs mostly consist of single-layered graphene with a few single vacancies and Stone-Wales defects. The density of vacancy defect per hexagon in the graphene sheet is estimated to be 10-2 for NPCs, while the annealing reduced the value to 10-3-10-4 for NPGs. This supports the outstanding chemical and electrochemical stability of the novel porous carbon materials.

Associations of calcium, phosphate and intact parathyroid hormone levels with mortality, residual kidney function and technical failure among patients on peritoneal dialysis.

Background: Associations of calcium, phosphate and intact parathyroid hormone (iPTH) levels with outcomes may be different between patients on peritoneal dialysis (PD) and hemodialysis (HD). The aim of the study is to evaluate these associations among PD patients. Methods: In this prospective cohort study on the Japan Renal Data Registry, adults on PD at the end of 2009 were included. The observation period was until the end of 2018 and the data were censored at the time of transplantation or transition to HD. Exposures were time-averaged or time-dependent albumin-corrected calcium (cCa), phosphate and iPTH levels. Outcomes were all-cause and cardiovascular mortality, transition to HD and urine output. Data were analyzed using Cox regression models or linear mixed-effects models and the results were shown as cubic spline curves. Results: Among 7393 patients, 590 deaths and 211 cardiovascular deaths were observed during a median follow-up of 3.0 years. Higher cCa and phosphate levels were associated with higher mortality. Lower cCa levels were associated with a faster decline, whereas lower phosphate was associated with a slower decline in urine output. Lower phosphate and iPTH levels were associated with a lower incidence of transition to HD. Conclusions: Among PD patients, the observed associations of cCa, phosphate and iPTH with mortality, residual kidney function and technical failure suggest that avoiding high cCa, phosphate and iPTH levels might improve outcomes.

Donor Evaluation of Living Kidney Transplantation in the Aging Society.

BACKGROUND: Because of the lack of organ donation, living kidney transplantation (LKT) is increasing worldwide. Recently, the number of elderly donors has been increasing, and the patients with end-stage kidney diseases are older than those in the previous decades. Due to the advanced ages, their glomerular filtration rates (GFR) decrease, and the comorbidities such as hypertension, diabetic condition, and obesity are common. The clinicians now have to give their unwilling consent to the LKT from the donors with expanded criteria. SUMMARY: For the secure selection of donors, proper GFR measuring is essential. Although directly measured GFR (mGFR) was recommended in the guidelines, estimated GFR (eGFR) is used at the initial evaluation of donor renal function clinically. Many equations calculating eGFR have been published so far. In the selection of eGFR equations, the smaller difference between mGFR and eGFR and the closer relationship to the prevalence rates of comorbidities are requisite points. Therefore, we compared the specificity of the various eGFR equations. The eGFR calculated from the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation showed approximate reliability with minimal difference between mGFR and eGFR and the closer relationships to the prevalence rates of comorbidities. KEY MESSAGE: The CKD-EPI-eGFR presented optimal performance in the donor renal function evaluation. Therefore, eGFR from the CKD-EPI equation is highly recommended in evaluating renal function in LKT donors.

Improved urinary continence recovery after robot-assisted radical prostatectomy with lateral pelvic fascia preservation.

The novel technique of lateral pelvic fascia preservation (LPFP) in robot-assisted radical prostatectomy (RARP) has been reported to improve urinary continence recovery. We aimed to investigate surgical and oncological outcomes after RARP using the LPFP technique and compare them with conventional RARP. This study included patients who underwent RARP with and without the LPFP technique. Time to urinary continence recovery was compared between the LPFP and non-LPFP groups using univariate, multivariate, and propensity-score matched analysis. Perioperative and postoperative outcomes were compared between the two groups using univariate analysis. We included 139 patients who underwent RARP, 68 in the LPFP group and 71 in the non-LPFP group. The LPFP technique was associated with a shorter time to urinary continence recovery, a shorter operative time and lower estimated blood loss. Surgical and oncological outcomes, including complications, pathological T-stage, surgical margin status, and biochemical recurrence-free survival, were comparable between the two groups. This study demonstrated that the LPFP technique improves urinary continence recovery and operative times without compromising surgical and oncological outcomes. The use of this technique in patients with clinically localized prostate cancer is recommended.

Comparison of Testosterone Level of Seminal Vesicle Fluid in Patients With Prostate Cancer Versus Other Malignancies.

BACKGROUND/AIM: Testosterone is essential for prostate cancer development and growth. This study aimed to investigate the relationship between testosterone in seminal vesicles and prostate cancer incidence and its malignant phenotype. PATIENTS AND METHODS: After obtaining institutional review board approval, seminal vesicle fluid samples were collected from patients who underwent prostatectomy or cystectomy. Pathological review demonstrated that 26 patients had benign prostate tissue and 149 had prostate cancer. First, testosterone levels in seminal vesicle fluid from benign prostate and prostate cancer samples were compared. Next, the relationship between pathological stage, International Society of Urological Pathology (ISUP) score, and testosterone concentrations in seminal vesicle fluid in the prostate cancer group were examined. RESULTS: Testosterone in seminal vesicles was significantly higher in the prostate cancer group [median (range), 1.94 (0.17-4.32) ng/ml] than in the benign prostate group (mainly bladder cancer) [1.45 (0.60-2.78) ng/ml] (p=0.001). Testosterone in seminal vesicles showed no difference in relation to pathological stage (pT2 vs. pT3) or ISUP score (12 vs. 345) (p=0.480 and p=0.964, respectively). Neoadjuvant chemotherapy for other cancers (e.g., bladder or rectal cancer) significantly reduced testosterone in seminal vesicles (p=0.013). Multivariate regression analysis revealed that testosterone in seminal vesicles was significantly correlated with prostate cancer, and not with neoadjuvant chemotherapy (p=0.023, p=0.457, respectively). CONCLUSION: Testosterone in seminal vesicles may contribute to prostate cancer incidence, but has no relationship with pathological grading.

Investigation of bone mineral density and the changes by enzyme replacement therapy in patients with Fabry disease.

BACKGROUND: Fabry disease (FD) is an inherited disorder that causes organ dysfunction. However, only a few studies have reported on bone mineral density (BMD) in FD patients, and the relationship between BMD and clinical factors such as globotriaosylsphingosine (lyso-Gb3) remains unclear. Therefore, the current study sought to investigate BMD in FD patients, the relationship between BMD and lyso-Gb3, and the effects of enzyme replacement therapy (ERT) on changes in BMD and lyso-Gb3. METHODS: This single-center, observational study included 15 patients who visited our facility for FD between January 2008 and June 2021. We assessed BMD and clinical characteristics in study patients, including plasma lyso-Gb3 levels, and examined the relationship between BMD and plasma lyso-Gb3 levels, and changes in BMD after starting ERT. RESULTS: Male patients' BMD had reduced, whereas female patients' BMD was preserved. Male patients had significantly higher plasma lyso-Gb3 levels than female patients. Moreover, plasma lyso-Gb3 levels were found to be significantly related to the lumbar spine and femoral BMD. These were strongly linked with plasma lyso-Gb3 levels in male patients, whereas no strong link was observed in female patients. Furthermore, BMD significantly increased only in male patients although plasma lyso-Gb3 levels significantly decreased by ERT in all patients. CONCLUSION: BMD decreased possibly due to Gb3 accumulation, and ERT could increase BMD in male FD patients.

Renal protective effects of astragalus root in rat models of chronic kidney disease.

BACKGROUND: Astragalus root is a commonly used herb in traditional Chinese medicine. Although renoprotective effects have been reported in some clinical and experimental studies, the details remain unknown. METHODS: We used 5/6 nephrectomized rats as chronic kidney disease (CKD) models. At 10 weeks, they were divided into four groups, namely, CKD, low-dose astragalus (AR400), high-dose astragalus (AR800), and sham groups. At 14 weeks, they were sacrificed for the evaluation of blood, urine, mRNA expression in the kidney, and renal histopathology. RESULTS: Kidney dysfunction was significantly improved following astragalus administration (creatinine clearance: sham group; 3.8 ± 0.3 mL/min, CKD group; 1.5 ± 0.1 mL/min, AR400 group; 2.5 ± 0.3 mL/min, AR800 group; 2.7 ± 0.1 mL/min). Blood pressure, urinary albumin, and urinary NGAL levels were significantly lower in the astragalus-treated groups than those in the CKD group. Excretion of urinary 8-OHdG, an oxidative stress marker, and intrarenal oxidative stress were lower in the astragalus-treated groups than those in the CKD group. Furthermore, the mRNA expression of NADPH p22 phox, NADPH p47 phox, Nox4, renin, angiotensin II type 1 receptor, and angiotensinogen in the kidney was lower in the astragalus-treated groups compared with the CKD group. CONCLUSION: This study suggests that astragalus root slowed CKD progression, possibly through the suppression of oxidative stress and the renin-angiotensin system.

Effect of Bisphosphonate and Active Vitamin D Analog on Glucocorticoid-induced Osteoporosis in Patients with IgA Nephropathy: A Retrospective Observational Study.

Few studies on glucocorticoid (GC)-induced osteoporosis exist in IgA nephropathy (IgAN). Here we aimed to compare the effects of bisphosphonate (Bis) and active vitamin D analog (Vit. D) in maintaining bone mineral density (BMD) in patients with IgAN. This study is a retrospective observational one. Between April 2007 and December 2014, a total of 127 patients with IgAN received GC treatment at Kobe University Hospital. Among them, we measured the BMD of 48 patients with a mean age of approximately 30 years, before and after GC treatment. The %ΔBMD of the lumber spine increased in the Bis group (1.6% ± 2.3%), but decreased in the Vit. D group (-3.3% ± 3.6%). The %ΔBMD of the two groups differed significantly (p < 0.05). Although the %ΔBMD of the femoral neck showed the same tendency, the difference between two groups was not significant. Bis was significantly superior to Vit. D in maintaining the BMD of lumbar spine bones. Even in young patients with IgAN, Bis is recommended to prevent the reduction of BMD during GC treatment.

Fusion-targeted biopsy significantly improves prostate cancer detection in biopsy-naïve men.

OBJECTIVE: The precise diagnosis of prostate cancer (PC) is crucial to avoid underdiagnosis, overdiagnosis, and overtreatment. We aimed to compare clinically significant PC (csPC) detection between MRI/ultrasound fusion-targeted prostate (TBx) compared to systematic biopsy (SBx) in biopsy-naïve Japanese men. METHODS: We included patients with suspect PC due to elevated PSA level or abnormal digital rectal examination, or both. csPC was defined as International Society Urological Pathology (ISUP) grade group ≥2 (csPC-A) and ISUP grade group ≥3 (csPC-B). RESULTS: This study included 143 patients. Overall PC detection was 66.4% for SBx and 67.8% for MRI-TBx. MRI-TBx presented a significantly higher rate of csPC detection (csPC-A 67.1% vs. 58.7%, p = 0.04, and csPC-B 49.6% vs. 39.9%, p < 0.001) and significantly lower detection of non-csPC-A (0.6% vs. 6.7%). Importantly, MRI-TBx missed 4.9% (7/143) of csPC-A and only 0.7% (1/143) of csPC-B. On the other hand, SBx alone missed 13.3% (19/143) of csPC-A and 4.2% (6/143) of csPC-B. CONCLUSION: MRI-TBx significantly outperformed 12-cores SBx for csPC detection and decreased non-csPC detection in biopsy-naive men. Performing MRI-TBx without SBx would have missed some csPC, supporting that MRI-TBx synergizes with SBx to increase csPC detection.

Clinical Implication of Consistently Strict Phosphate Control for Coronary and Valvular Calcification in Incident Patients Undergoing Hemodialysis.

AIMS: Serum phosphate control is crucial for the progression of vascular and valvular calcifications. Strict phosphate control is recently suggested; however, there is a lack of convincing evidence. Therefore, we explored the effects of strict phosphate control on vascular and valvular calcifications in incident patients undergoing hemodialysis. METHODS: A total of 64 patients undergoing hemodialysis from our previous randomized controlled trial were included in this study. Coronary artery calcification score (CACS) and cardiac valvular calcification score (CVCS) were evaluated using computed tomography and ultrasound cardiography at baseline and 18 months after the initiation of hemodialysis. The absolute changes in CACS (ΔCACS) and CVCS (ΔCVCS) and the percent change in CACS (%ΔCACS) and CVCS (%ΔCVCS) were calculated. Serum phosphate level was measured at 6, 12, and 18 months after the initiation of hemodialysis. Moreover, phosphate control status was evaluated using the area under the curve (AUC) by the amount of time spent with a serum phosphate level of ≥ 4.5 mg/dL and the extent to which this threshold exceeded over the observation period. RESULTS: ΔCACS, %ΔCACS, ΔCVCS, and %ΔCVCS were significantly lower in the low AUC group than in the high AUC group. ΔCACS and %ΔCACS were also significantly lower. ΔCVCS and %ΔCVCS tended to be lower in patients whose serum phosphate level never exceeded 4.5 mg/dL than in those whose serum phosphate level continuously exceeded 4.5 mg/dL. AUC significantly correlated with ΔCACS and ΔCVCS. CONCLUSION: Consistently strict phosphate control may slow the progression of coronary and valvular calcifications in incident patients undergoing hemodialysis.

Correlation between extended pelvic lymph node dissection and urinary incontinence at early phase after robot-assisted radical prostatectomy.

OBJECTIVES: To investigate the impact of extended pelvic lymph node dissection (ePLND) on urinary incontinence (UI) at early post-surgery robot-assisted radical prostatectomy (RARP). METHODS: Patients who underwent RARP without cavernous nerve sparing were included between 2014 and 2019. Patient data were obtained prospectively. The associations between ePLND and postoperative urinary continence were defined as a maximum of one daily pad use. International prostate symptom score (IPSS) was examined. Expression of synaptophysin and tyrosine hydroxylase (TH) in perilymph node adipose tissue (PLA) was evaluated by immunohistochemistry. RESULTS: In total, 186 and 163 patients underwent RARP with and without ePLND. Urinary continence rate at 1 month postoperatively among patients with ePLND was lower than those without ePLND (24.1% vs. 35.1%, p < 0.05), however, not significantly different at 3, 6, and 12 months after RARP (57.4 vs. 62.6%, 73.1 vs. 74.2%, and 83.0 vs. 81.2%, respectively). Total and voiding plus postvoiding IPSS scores at 1 month were higher in patients with ePLND than in those without ePLND (14.5 ± 0.5 vs. 13.6 ± 0.6, 7.0 ± 0.3 vs. 6.2 ± 0.4, respectively, p < 0.05). In univariate and multivariate analyses, larger prostate volume and ePLND were factors associated with an increased UI rate. Among patients who underwent ePLND, synaptophysin and TH-positive nerve fibers were detected in PLA. CONCLUSIONS: Detection of synaptophysin and TH-immunopositive nerves suggested denervation of sympathetic and peripheral nerves caused by ePLND might be associated with a higher UI rate and poor urinary symptoms at an early stage after RARP.