Multi-System-Level Analysis with RNA-Seq on Pterygium Inflammation Discovers Association between Inflammatory Responses, Oxidative Stress, and Oxidative Phosphorylation.

A pterygium is a common conjunctival degeneration and inflammatory condition. It grows onto the corneal surface or limbus, causing blurred vision and cosmetic issues. Ultraviolet is a well-known risk factor for the development of a pterygium, although its pathogenesis remains unclear, with only limited understanding of its hereditary basis. In this study, we collected RNA-seq from both pterygial tissues and conjunctival tissues (as controls) from six patients (a total of twelve biological samples) and retrieved publicly available data, including eight pterygium samples and eight controls. We investigated the intrinsic gene regulatory mechanisms closely linked to the inflammatory reactions of pterygiums and compared Asian (Korea) and the European (Germany) pterygiums using multiple analysis approaches from different perspectives. The increased expression of antioxidant genes in response to oxidative stress and DNA damage implies an association between these factors and pterygium development. Also, our comparative analysis revealed both similarities and differences between Asian and European pterygiums. The decrease in gene expressions involved in the three primary inflammatory signaling pathways-JAK/STAT, MAPK, and NF-kappa B signaling-suggests a connection between pathway dysfunction and pterygium development. We also observed relatively higher activity of autophagy and antioxidants in the Asian group, while the European group exhibited more pronounced stress responses against oxidative stress. These differences could potentially be necessitated by energy-associated pathways, specifically oxidative phosphorylation.

Aiouea padiformis extract exhibits anti-inflammatory effects by inhibiting the ATPase activity of NLRP3.

Inflammation is implicated as a cause in many diseases. Most of the anti-inflammatory agents in use are synthetic and there is an unmet need for natural substance-derived anti-inflammatory agents with minimal side effects. Aiouea padiformis belongs to the Lauraceae family and is primarily found in tropical regions. While some members of the Aiouea genus are known to possess anti-inflammatory properties, the anti-inflammatory properties of Aiouea padiformis extract (AP) have not been investigated. In this study, we aimed to examine the anti-inflammatory function of AP through the NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome and elucidate the underlying mechanisms. Treatment with AP inhibited the secretion of interleukin-1 beta (IL-1ß) mediated by NLRP3 inflammasome in J774A.1 and THP-1 cells without affecting the viability. In addition, AP treatment did not influence NF-κB signaling, potassium efflux, or intracellular reactive oxygen species (ROS) production-all of which are associated with NLRP3 inflammasome activation. However, intriguingly, AP treatment significantly reduced the ATPase activity of NLRP3, leading to the inhibition of ASC oligomerization and speck formation. Consistent with cellular experiments, the anti-inflammatory property of AP in vivo was also evaluated using an LPS-induced inflammation model in zebrafish, demonstrating that AP hinders NLRP3 inflammasome activation.

Guarea microcarpa C. DC. extract inhibits NLRP3 inflammasome by suppressing its ATPase activity.

ETHNOPHARMACOLOGICAL RELEVANCE: Guarea genus comprises tropical and subtropical terrestrial herbs inhabiting Central and South America. These plants, including Guarea guidonia (L.) Sleumer, have anti-inflammatory, analgesic, antibacterial, antiviral, and immune-enhancing properties. AIM OF THE STUDY: Although various species of the Guarea genus are known for their medicinal properties, comprehensive data on their anti-inflammatory effects remain limited. Therefore, we investigated the NLRP3 inflammasome-inhibiting effects of the Guarea genus in this study. MATERIALS AND METHODS: To evaluate the anti-inflammatory activities of 18 members of the Guarea genus, we treated NLRP3 inflammasome activators with their extracts in LPS-primed J774A.1 and THP-1 cells. Cell viability was determined by water soluble tetrazolium salt (WST) and cytokine production, protein expression, and nuclear fractionation were determined by western blotting. Reactive oxygen species (ROS) production and apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) oligomerization were measured using confocal microscopic analysis. Inflammation-induced zebrafish was used in the in vivo experiments. RESULTS: Among the 18 Guarea members tested, Guarea microcarpa C. DC. extract (GM) exhibited no cytotoxicity and specifically suppressed the activation of the NLRP3 inflammasome, but not of the AIM2 or NLRC4 inflammasomes, by inhibiting the ATPase activity of NLRP3. This was achieved without affecting NF-κB signaling, potassium efflux, or intracellular ROS production, all of which are involved in NLRP3 activation. The reduced ATPase activity of NLRP3 led to decreased ASC oligomerization. Furthermore, GM exhibited anti-inflammatory effects in vivo. Additionally, GM treatment alleviated inflammation at the organismal level in an LPS-induced inflammation model using zebrafish embryos. CONCLUSION: Our results demonstrate the anti-inflammatory effects of GM via suppressing the NLRP3 inflammasome. Therefore, GM can be a potential therapeutic candidate for various inflammatory diseases caused by aberrant NLRP3 inflammasome activation.

Korean Society of Endourology and Robotics (KSER) recommendation on the diagnosis, treatment, and prevention of urolithiasis.

This article provides evidence-based recommendations and expert opinions to aid urologists in making optimal decisions regarding managing urolithiasis in various clinical scenarios. The most frequently asked questions by urologists in their clinical practice have been collected and answered in the form of FAQs; based on the latest evidence and expert opinions. The natural history of urolithiasis is divided into active treatment and silent phases, with the active treatment stage divided into typical and special situations and peri-treatment management. The authors address 28 key questions, offering practical guidance for the proper diagnosis, treatment, and prevention of urolithiasis in clinical practice. This article is expected to be served as a valuable resource for urologists.

Expression of AKT1 Related with Clinicopathological Parameters in Clear Cell Renal Cell Carcinoma.

Pathways such as VEGF, EGF and mTOR are known to be one of the major mechanisms of tumorigenesis including kidney cancer. To identify potential signaling pathway proteins, we performed differential/correlation analyses of mTOR-associated genes from three public datasets. AKT1 protein, one of the PI3K/AKT/mTOR pathways, turned out to be the potential by showing a consistent discrepancy between ccRCC-associated conditions as well as strong correlation with other mTOR-associated genes across the datasets. Then, we analyzed how AKT1 alteration affects clear cell renal cell carcinoma. The pathology of 58 kidney cancer patients was constructed to analyze the relationship between the expression level of AKT1 through immunohistochemical staining and their clinicopathological data. Gender, age and TNM stage did not show significant results. AKT1 is a known oncogene. However, in this study, high expression of AKT1 showed a slight correlation with lower WHO/ISUP grade, longer recurrence-free and progression-free survival rates.

Cystitis Induces Altered CREB Expression Related with Micturition Reflex.

Background and objectives: Bladder stimulation upregulates neurotrophins associated with voiding reflex. Bacterial cystitis can be a stimulant that activates this system, resulting in a pathological state. Phosphorylated responsive element of binding protein (p-CREB) is a pivotal transcriptional factor in the neurotrophin signaling cascade. The goal of our study was to examine the change in expression of p-CREB in dorsal root ganglia (DRG) of rats after uropathogenic Escherichia coli infection of the bladder. Materials and methods: A total of 19 adult female Sprague−Dawley rats were induced with acute E. coli infection (n = 7), chronic E. coli infection (n = 6), or served as controls (n = 6). In each group, the profiles of p-CREB cell were counted in 6−10 sections of each of the DRG collected. DRG cells exhibiting intense nuclear staining were considered to be positive for p-CREB immunoreactivity (p-CREB-IR). Results: Overall, the immunoreactivity of p-CREB was examined in smaller cell profiles with nuclear staining or nuclear and cytoplasmic staining in the DRGs (L1−L6, S1). In the chronic cystitis group, p-CREB-IR in the L1−L6 and S1 DRG was significantly higher than the control group (p < 0.05). Further, p-CREB-IR in the L3−L6 and S1 DRG of the chronic cystitis group was significantly greater than that in the acute cystitis group (p < 0.05). In the control and acute cystitis groups, p-CREB-IR in the L4−L5 DRG was significantly lower than that found in the other DRG sections (p < 0.05). Conclusions: Altogether, acute or chronic E.coli cystitis changed the immunoreactivity of p-CREB in lumbosacral DRG cells. In particular, chronic E. coli infection triggered p-CREB overexpression in L1−L6 and S1 DRG, indicating subsequent pathologic changes.

Urothelial Cell Carcinoma of the Renal Pelvis Misdiagnosed as Ureteropelvic Junction Obstruction: A Case Report.

Urothelial tumors are typically a disease affecting elderly individuals and are rare in young patients. Moreover, upper urinary tract urothelial carcinoma is extremely rare in the young age group. In this study, we present a case of urothelial cell carcinoma of the renal pelvis and ureter in a young man without risk factors of urothelial carcinoma, which was misdiagnosed as ureteropelvic junction obstruction and treated with a laparoscopic pyeloplasty.

Rapid Recurrence of Giant Multilocular Prostatic Cystadenoma after Laparoscopic Excision for Primary Case: A Case Report.

Giant multilocular prostatic cystadenoma is a rare benign tumor of the prostate gland that presents as a large retroperitoneal pelvic mass. The mass is usually located between the urinary bladder and rectum, and results in obstructive voiding symptoms and a change in bowel habits. Complete surgical excision is the treatment of choice. We present a case of rapid recurrent giant multilocular prostatic cystadenoma after laparoscopic excision for primary case. A previously healthy 54-year-old man presented with acute urinary retention. Prostate MRI showed a large cystic mass approximately 13 cm in size, multiple septa and lobulation in the prostate, and no visible solid lesions. Laparoscopic marsupialization of giant multilocular prostatic cystadenoma cysts was performed. One year later, the patient presented with local recurrence. Repeated laparoscopic complete resection was performed without any complications and further recurrence. Giant multilocular prostatic cystadenoma has the risk of recurrence in case of incomplete resection. Surgical treatment should be performed with the goal of complete removal following the same principles as cancer surgery.

A Case of Incidental Schwannoma Mimicking Necrotic Metastatic Lymph Node from Bladder Cancer.

Background and Objectives: Retroperitoneal schwannoma is a very rare case of schwannoma which commonly occurs in the other part of the body. However, it is difficult to distinguish schwannoma from other tumors before pathological examination because they do not show specific characteristics on imaging study such as ultrasound, computed tomography (CT), and magnetic resonance image (MRI). Case summary: A 60-year-old male showed a retroperitoneal cystic tumor which is found incidentally during evaluation of coexisted bladder tumor. Neurogenic tumor was suspicious for the retroperitoneal tumor through pre-operative imaging study. Finally, a schwannoma was diagnosed by immunohistochemical examination after complete surgical excision laparoscopically. Conclusion: As imaging technology is developed, there may be more chances to differentiate schwannoma from other neoplasm. However, still surgical resection and histopathological examination is feasible for diagnosis of schwannoma.

Tubulocystic Renal Cell Carcinoma Is Not an Indolent Tumor: A Case Report of Recurrences in the Retroperitoneum and Contralateral Kidney.

Tubulocystic renal cell carcinoma (RCC) is a rare subtype of RCC that was recently included in the 2016 World Health Organization classification of tumors of the kidney. Most of these tumors exhibit indolent behavior with low metastatic potential. However, here we report a case of recurrent tubulocystic RCC with aggressive features in the retroperitoneum and contralateral kidney treated with targeted agents and radiofrequency ablation.

Diabetes Mellitus Promotes Smooth Muscle Cell Proliferation in Mouse Ureteral Tissue through the P-ERK/P-JNK/VEGF/PKC Signaling Pathway.

Background and objectives: The aim of our study was to evaluate the role of diabetes mellitus (DM) as a significant factor affecting spontaneous stone expulsion, as suggested by previous research. Materials and methods: We investigated the influence of DM on the ureter using a murine model. The mouse-model arm of this study used 20 15 -week-old mice, including 10 normal (control) mice and 10 DM mice. We measured the proximal, middle and distal ureteral smooth muscle thickness in each mouse and the differences among ureteral sections were analyzed. Mouse ureteral specimens were also analyzed via western blotting to detect relative protein expression of phosphor-extracellular signal regulated kinases (P-ERK), phosphor-C-Jun N-terminal kinase (P-JNK), vascular endothelial growth factor (VEGF), and protein kinase C (PKC), which are representative factors involved in cell regulation. Results: We observed significant hyperproliferation of ureteral smooth muscle in DM mice compared to normal mice, which may provoke reduced peristalsis. The ureteral smooth muscle of DM mice was significantly thicker than that of normal mice in all ureteral tissues: proximal (p = 0.040), mid (p = 0.010), and distal (p = 0.028). The relative protein expression of P-ERK (p = 0.005) and P-JNK (p = 0.001) was higher in the diabetic group compared to the normal group. Additionally, protein expression of VEGF (p = 0.002) and PKC (p = 0.001) were remarkably up-regulated in DM mice. Conclusions: Hyperproliferation of ureteral smooth muscle was observed in DM mice, but not in normal mice. The pathways mediated by P-ERK, P-JNK, VEGF, and PKC may play an important role in pathological ureteral conditions.

Massive retroperitoneal hematoma as an acute complication of retrograde intrarenal surgery: A case report.

BACKGROUND: Retrograde intrarenal surgery (RIRS) has been proven to be a safe and effective treatment modality in large-scale quantitative studies. However, although its safety profile has been established, it also has a potential risk of life-threatening complications. We here describe our experience with a patient who developed a huge periureteral hematoma after RIRS with holmium laser lithotripsy. CASE SUMMARY: A 73-year-old woman visited our center with a complaint of gross hematuria. An enhanced computed tomography (CT) scan revealed a 1.5-cm left renal pelvis stone with hydronephrosis. The patient underwent RIRS. During the surgery, a 12/14-Fr ureteral access sheath was applied and a 6-Fr ureteral catheter was indwelled thereafter. On postoperative day 1, she experienced aggravated left flank pain and left lower-quadrant tenderness without rebound tenderness. A follow-up CT scan was taken, which revealed a huge hematoma in the periureteral space, not in the perirenal space, with suspicious contrast medium extravasation. Immediate angiography was performed; however, it showed no evidence of active bleeding. She was conservatively managed with hydration and antibiotic and nonsteroidal anti-inflammatory drug therapy, and was discharged on postoperative day 7. However, she visited our outpatient department with recurrent left flank pain at 5 d from discharge. Ultrasonography confirmed that the double J-stent was intact. To rule out stent malfunction, the stent was changed. Decreased size of the hematoma was observed in the imaging studies, and conservative management for candiduria was performed for 1 wk. CONCLUSION: Although RIRS is an effective and safe procedure for the management of renal stones, clinicians should be aware of its potential complications.

Programmed Cell Death-Ligand 1 Expression Status in Urothelial Carcinoma According to Clinical and Pathological Factors: A Multi-Institutional Retrospective Study.

Purpose: To investigate programmed cell death-ligand 1 (PD-L1) expression status and the clinical and pathological factors related to its expression in urothelial carcinoma (UC) patients. Materials and Methods: Data from 761 UC patients who underwent testing for PD-L1 expression using the VENTANA (SP-142 immunohistochemistry assay) for measuring PD-L1 expression according to the manufacturer's protocol between February 2016 and July 2019 were retrospectively reviewed. Patients were categorized into three groups based on the percentage of tumor area covered by PD-L1-expressing tumor-infiltrating immune cells (ICs) as follows: IC0 (<1%), IC1 (≥1% and <5%), and IC2/3 (≥5%). Positive PD-L1 expression was defined as IC2/3 (≥5%). The factors related to positive PD-L1 expression were assessed by using unadjusted and adjusted logistic regression analyses. Results: In the entire cohort, 213 (28%) patients showed positive PD-L1 expression. Final adjusted regression analyses for positive PD-L1 expression revealed that several factors, including intravesical BCG prior to PD-L1 testing (odds ratio [OR] 0.57, 95% confidence interval [CI] 0.37-0.96), advanced tumor stage (stage III/IV) (OR 2.04, 95% CI 1.41-2.93), and high tumor grade (OR 5.31, 95% CI 2.38-11.83) were significantly associated with positive PD-L1 expression. Conclusions: This study showed that the PD-L1 expression is associated with several clinical and pathological factors for the first time in a real-world setting. Further follow-up clinical trials should consider adjusting these factors, including intravesical BCG treatment, tumor stage and grade to clarify the utility of PD-L1 as a biomarker.

Differences between Risk Factors for Sepsis and Septic Shock in Obstructive Urolithiasis.

BACKGROUND: Complicated acute pyelonephritis (APN) is a life-threatening condition that requires immediate intervention. This study examined the characteristics of APN occurring as a complication of ureteral stone. METHODS: We retrospectively reviewed 85 patients diagnosed with APN complicated by ureteral stone between December 2006 and July 2017 at our institution. Patients with concomitant renal stone, multiple ureteral stones, ureteral strictures, ureteral cancer, and urogenital anomalies, including vesicoureteral reflux were excluded. Clinical characteristics including age, sex, underlying disease, medical history, stone characteristics, initial laboratory data, and the procedure used to correct urinary obstruction were summarized, and the risk factors associated with sepsis and septic shock were analyzed. RESULTS: Sepsis was diagnosed at initial presentation in 62 patients, 17 of whom suffered from septic shock. Disease-related death did not occur in any patient. Previous history of stone (P = 0.015), leukocytosis (P < 0.001), elevated C-reactive protein levels (P = 0.006), and low albumin (P = 0.038) were significant risk factors for progression to sepsis. The absence of hypertension (P = 0.047), thrombocytopenia (P = 0.006), decreased erythrocyte sedimentation rate (ESR) (P = 0.003), elevated blood urea nitrogen (P = 0.016), and positive blood culture (P = 0.018) were significant predictors for progression to septic shock. Multivariate analysis revealed that previous history of stone (P = 0.015) was an independent risk factor for sepsis, while the absence of hypertension (P = 0.047), thrombocytopenia (P = 0.013), and decreased ESR (P = 0.009) were risk factors for shock. CONCLUSION: The risk factors associated with the progression from APN to sepsis differed from those associated with the progression from sepsis to septic shock. Various factors should be considered while selecting treatment options based on the severity of APN associated with ureteral stone. It should be managed with aggressive treatment and close observation, especially in the presence of risk factors.

Aggressive Paraganglioma of the Urinary Bladder with Local Recurrence and Pelvic Metastasis.

Many pheochromocytoma and extra-adrenal paraganglioma are benign, but some are malignant. Pheochromocytoma of the Adrenal gland Scaled Score analyzed the histological characteristics of the tumor. Tumors with a Pheochromocytoma of the Adrenal gland Scaled Score of 4 or higher have a higher risk of recurrence. This pattern is thought to be applicable to paraganglioma as well, and to future patient follow-up efforts. We report a recurrent and metastatic paraganglioma of the urinary bladder.

Lump type crossed fused renal ectopia with bilateral vesicoureteral reflux: A case report.

BACKGROUND: Crossed fused renal ectopia is a rare congenital anomaly of the ascent of the kidney. This anomaly may be observed as a solitary kidney during initial evaluation. A solitary kidney must be evaluated for associated anomalies such as duplication, horseshoe kidney, or crossed renal ectopia. CASE SUMMARY: An anomaly was observed in a 9-mo-old male child who was subsequently diagnosed with crossed fused renal ectopia and vesicoureteral reflux (VUR). In this condition, recurrent febrile urinary tract infection can be a serious problem, and can easily cause renal damage due to relatively short ureters and high pressure in the kidney. CONCLUSION: To prevent urosepsis and preserve renal function, early diagnosis and proper management including surgical correction should be considered for the management of renal ectopia with VUR.

Trends in Testicular Injury in Korea, 1986-2015.

The objectives of this study were to investigate patients treated for scrotal trauma at our institute for the last three decades to describe our experience with an emphasis on the etiologies and ultrasonographic findings in these patients. We reviewed medical records of patients who underwent scrotal ultrasonography for evaluation of testicular trauma at our institutes from 1986 to 2015. Trends regarding the etiology of scrotal trauma were evaluated during each decade. The echo pattern and contour definition of the testicular parenchyma and the pattern of hematoma development were recorded to evaluate radiographic findings of testicular injury. The correlation between ultrasonographic and intraoperative findings was assessed. A total of 115 patients were analyzed. Most patients (92.2%) presented with blunt trauma. The most common etiology of testicular trauma was assault during the first and second decades, while injury related to a fall was most common during the third decade. Of the 77 patients (67.0%) who underwent urgent exploration, 46 patients (59.7%) had testicular rupture. Loss of contour definition, heterogeneous echo pattern of the testicular parenchyma, and testicular hematoma showed a moderate to strong degree of correlation with testicular rupture (Spearman correlation co-efficient: 0.5-0.8). Over the past 30 years, the etiology of testicular injury changed from assault to falls or athletic injury and the severity of injury has decreased. Our findings demonstrate the importance of ultrasonography for determining an appropriate management strategy in scrotal trauma. Surgical exploration should be considered in patients with abnormal ultrasonographic findings.

Analysis of factors affecting spontaneous expulsion of ureteral stones that may predict unfavorable outcomes during watchful waiting periods: What is the influence of diabetes mellitus on the ureter?

PURPOSE: The aim of our study was to evaluate the association of several factors with spontaneous stone expulsion, including ureteral stone characteristics (size, location, hydronephrosis, perinephric stranding), types of medications prescribed (α-blocker, low-dose steroid), and other possible demographic and health-history factors (gender, age, serum creatinine, underlying diabetes mellitus [DM], and hypertension). MATERIALS AND METHODS: A total of 366 patients with ureteral stones were enrolled. All patients underwent watchful waiting without any invasive procedures. Initial diagnoses of ureteral stones were confirmed by computed tomography scans, which were taken at approximately 1-month intervals to check for stone expulsion. Univariate and multivariate analyses were conducted to identify significant factors that contributed to stone expulsion. RESULTS: Among 366 patients, 335 patients (91.5%) experienced spontaneous stone passage during a mean follow-up period of 2.95±2.62 weeks. The patients were divided into two groups depending on the success of spontaneous stone passage. Univariate analyses revealed that stone location (p=0.003), stone size (p=0.021), and underlying DM (p<0.001) were significant predictors of stone passage. Multivariate analyses confirmed that stone size (p=0.010), stone location (p=0.008), and underlying DM (p=0.003) were independent predictive factors affecting stone passage. CONCLUSIONS: Stone size, location, and underlying DM were confirmed to be significant predictive factors for spontaneous passage of ureteral stones. Urologists should consider active procedures, such as shock wave lithotripsy or ureteroscopy, rather than conservative management in patients presenting with proximally located stones, large ureteral stones, or underlying DM.