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Abstract Background Nephroureterectomy with bladder cuff excision is the standard treatment for high-risk upper urinary tract urothelial carcinoma (UTUC). The role of minimally invasive surgery in treating locally advanced UTUC remains controversial. This study aimed to compare the outcomes of open, laparoscopic, and robotic surgeries for managing locally advanced UTUC. Methods We retrospectively reviewed 705 patients with locally advanced UTUC from multiple institutions throughout Taiwan. Perioperative outcomes and oncological outcomes, such as cancer-specific survival, overall survival, disease-free survival and bladder-free survival, were compared between the open, laparoscopic and robotic groups. Results The minimally invasive group had better overall and cancer-specific survival (CSS) rates. The 2-year CSS rates of the open, laparoscopic and robotic groups were 71%, 83%, and 77% respectively (p

Abstract To enhance the accuracy of predicting stone-free rates after retrograde intrarenal surgery, we devised a novel approach to assess the renal infundibulopelvic angle. We conducted a retrospective review of patient records for those who underwent retrograde intrarenal surgery for renal stones between April 2018 and August 2019. Patient demographics, stone characteristics, and perioperative data were recorded. Subsequently, we introduced a modified angle measurement called the pelvic stone angle and evaluated its predictive performance for stone-free rates by comparing it with the traditional method in scoring systems. A total of 43 individuals were included in this study. Notable differences in stone burden and Hounsfield unit measurements were found between stone-free and non-stone-free patients. The pelvic stone angle demonstrated a good model fit when used in scoring systems, performing equally well as the conventional approach. The area under the receiver operating characteristic curve for the R.I.R.S. scoring system using the pelvic stone angle and the conventional approach did not show a significant difference. In conclusion, the predictive ability of the pelvic stone angle for stone-free rates was comparable to the old measurement method. Moreover, scoring systems using the pelvic stone angle exhibited a better model fit than those using the conventional approach.

Purpose:. According to the National Comprehensive Cancer Network guidelines, segmental ureterectomy (SU) of upper tract urothelial carcinoma (UTUC) is a considerable option for selected mid- and distal ureteral urothelial carcinoma (UC). As a UTUC endemic area, Taiwan lacks treatment outcome analysis of SU. Materials and methods:. This study retrospectively reviewed the treatment outcomes of SU for clinically localized UTUCs. Patients with biopsy or washing cytology-confirmed UTUCs who underwent open, laparoscopic, or robot-assisted management with curative intent were retrospectively reviewed for the eligibility of analysis. Cox regression was applied for univariable and multivariable analyses. Results:. A total of 161 patients who underwent SU were reviewed and analyzed. The median follow-up period was 44.5 (interquartile range, 21.6–84.9) months. After SU, 56/161 (34.8%) patients were free of UTUCs after the follow-up, 25/161 (15.5%) patients had local recurrence, and 35/161 (21.7%) had lymph node or distant metastasis. Surgical margin involvement was a risk factor associated with worse cancer-specific survival. Higher bladder recurrence and local recurrence rates were observed with concurrent bladder UC. Lymphovascular invasion and previous radical nephroureterectomy (RNU) for UC were related to higher local recurrence rates. Patients with pathological T3/T4 stage and end-stage renal disease tended to have higher metastasis rates. For the management of local recurrence, 19 patients received salvage RNU and 25 patients had adjuvant chemotherapy. However, 26/161 (16.1%) patients died of UTUCs and 2/161 (1.2%) patients died of surgery-related complications. Conclusion:. SU provides acceptable oncological outcomes if the surgeons select candidates carefully. SU is not recommended if the patient has T3 or higher stage or comorbidity of end-stage renal disease. Concurrent bladder UC is a risk factor for worse bladder recurrence-free survival and local recurrence-free survival. Lymphovascular invasion and previous RNU for UC were related to higher local recurrence rates. After SU, periodic follow-up is mandatory because the local recurrence rate is higher than radical surgery.

Abstract Fundamental principles underlying computation in multi-scale brain networks illustrate how multiple brain areas and their coordinated activity give rise to complex cognitive functions. Whereas brain activity has been studied at the micro- to meso-scale to reveal the connections between the dynamical patterns and the behaviors, investigations of neural population dynamics are mainly limited to single-scale analysis. Our goal is to develop a cross-scale dynamical model for the collective activity of neuronal populations. Here we introduce a bio-inspired deep learning approach, termed NeuroBondGraph Network (NBGNet), to capture cross-scale dynamics that can infer and map the neural data from multiple scales. Our model not only exhibits more than an 11-fold improvement in reconstruction accuracy, but also predicts synchronous neural activity and preserves correlated low-dimensional latent dynamics. We also show that the NBGNet robustly predicts held-out data across a long time scale (2 weeks) without retraining. We further validate the effective connectivity defined from our model by demonstrating that neural connectivity during motor behaviour agrees with the established neuroanatomical hierarchy of motor control in the literature. The NBGNet approach opens the door to revealing a comprehensive understanding of brain computation, where network mechanisms of multi-scale activity are critical.

Purpose: The purpose of this study is to evaluate the rates of pathological complete response (ypT0N0/X) and pathological response (ypT1N0/X or less) in patients with upper tract urothelial cancer who were treated with neo-adjuvant chemotherapy and to examine their impact on oncological outcomes. Methods: This study is a multi-institutional retrospective analysis of patients with high-risk upper tract urothelial cancer who underwent neoadjuvant chemotherapy and radical nephroureterectomy between 2002 and 2021. Logistic regression analyses were used to investigate all clinical parameters for response after neoadjuvant chemotherapy. Cox proportional hazard models were performed to assess the effect of the response on the oncological outcomes. Results: A total of 84 patients with UTUC who received neo-adjuvant chemotherapy were identified. Among them, 44 (52.4%) patients received cisplatin-based chemotherapy, and 22 (26.2%) patients had a carboplatin-based regimen. The pathological complete response rate was 11.6% (n = 10), and the pathological response rate was 42.9% (n = 36). Multifocal tumors or tumors larger than 3 cm significantly reduced the odds of pathological response. In the multivariable Cox proportional hazard model, pathological response was independently associated with better overall survival (HR 0.38, p = 0.024), cancer-specific survival (HR 0.24, p = 0.033), and recurrence-free survival (HR 0.17, p = 0.001), but it was not associated with bladder recurrence-free survival (HR 0.84, p = 0.69). Conclusion: Pathological response after neo-adjuvant chemotherapy and radical nephroureterectomy is strongly associated with patient survival and recurrence, and it might be a good surrogate for evaluating the efficacy of neo-adjuvant chemotherapy in the future.

Background: Endoscopic management of upper tract urothelial cancer (UTUC) is an important treatment option for low risk UTUC. Although Taiwan is an endemic area for UTUC, endoscopic treatment outcomes in Taiwan are frequently under- reported. Methods: This study retrospectively reviewed the treatment outcomes of endoscopic management for clinically localized UTUC. Patients with biopsy or washing cytology confirmed UTUC who underwent endoscopic or percutaneous management with a curative intent were retrospectively reviewed for eligibility of analysis. Those cases without pre-intervention confirmed UTUC, and metastatic or nodal disease at diagnosis were excluded. Results: In total, 307 patients who underwent endoscopic management were reviewed and 279 cases were eligible for final analysis. With a median follow-up of 44.3 months (inter-quartile range (IQR): 23.4–76.4 months), 117 cases (46.4%) were endoscopic cured after median one session (range:1–8; IQR:1–2) of endoscopic treatment. Those endoscopic cured UTUC was associated with more small-sized tumor, more low-grade biopsied-histology, less concomitant bladder UC and less pre-operative hydronephrosis.In addition, 201(79.7%) cases among 252 cases with confirmed oncological outcome were free of UTUC at the end of follow-up and only 43 (17%) patients had a UTUC related mortality. Salvage RNU offered a better tumor free survival rate (92% vs. 77.5%) than those without salvage RNU in those UTUC refractory to endoscopic management. In multivariable analyses, pre-operative hydronephrosis was the independent risk factor for OS. Multiplicity and concomitant bladder UC were independent risk factors for DFS. Conclusions: We confirmed the consistent safety and efficacy of endoscopic management of clinical localized UTUC in a highly UTUC endemic area like Taiwan. Early salvage RNU is mandatory in those UTUC refractory to endoscopic management in prevention of UTUC related death.

Neural mechanisms and underlying directionality of signaling among brain regions depend on neural dynamics spanning multiple spatiotemporal scales of population activity. Despite recent advances in multimodal measurements of brain activity, there is no broadly accepted multiscale dynamical models for the collective activity represented in neural signals. Here we introduce a neurobiological-driven deep learning model, termed multiscale neural dynamics neural ordinary differential equation (msDyNODE), to describe multiscale brain communications governing cognition and behavior. We demonstrate that msDyNODE successfully captures multiscale activity using both simulations and electrophysiological experiments. The msDyNODE-derived causal interactions between recording locations and scales not only aligned well with the abstraction of the hierarchical neuroanatomy of the mammalian central nervous system but also exhibited behavioral dependences. This work offers a new approach for mechanistic multiscale studies of neural processes.

In this study, Chen et al. introduced a new deep learning-based method termed flimGANE to rapidly generate accurate and high-quality FLIM images even in the photon-starved conditions. flimGANE is particularly useful in fundamental biological research and clinical applications.

Purpose: The surgical treatment for severe benign prostatic hyperplasia is challenging. The aim of our study was to compare the safety and efficacy of monopolar transurethral resection of the prostate (M-TURP) and holmium laser enucleation of the prostate (HOLEP) for prostate size >100 ml. Materials and Methods: We retrospectively evaluated our database of two groups of patients. Thirteen patients underwent M-TURP (group 1), and 27 underwent HOLEP (group 2). Results: The mean prostate size was 163.1 ± 49.0 ml in group 1 and 143.4 ± 40.9 ml in group 2 (P = 0.19). There was no significant difference in resected tissue volume, days of catheter removal, admission days, and postoperative serum hemoglobin between treatment groups. However, in group 1, mean postoperative serum sodium dropped from 137.1 mmol/L to 131.4 mmol/L, which was significantly lower than postoperative serum sodium in group 2 (P < 0.0001). There were more complications in group 1 than group 2, especially for patients undergoing transfusion (76.9% in group 1 and 22.2% in group 2) and with hyponatremia (15.4% in group 1 and 0% in group 2). At 3-month follow-up, the international prostate symptom score, quality of life score, and residual urine volume revealed no significant differences between groups. Conclusion: M-TURP and HOLEP in men with prostate volume greater 100 ml had similar operative time, admission days and postoperative functional outcomes. However, higher transfusion rates and postoperative hyponatremia were noted in the M-TURP group comparing to the HOLEP group.

Abstract Tumor multifocality and location are prognostic factors for upper tract urothelial carcinoma (UTUC). However, confounding effects can appear when these two factors are analyzed together. Therefore, we aimed to investigate the impact of tumor distribution on the outcomes of multifocal UTUC after radical nephroureterectomy. From the 2780 UTUC patients in the Taiwan UTUC Collaboration Group, 685 UTUC cases with multifocal tumors (defined as more than one tumor lesion in unilateral upper urinary tract) were retrospectively included and divided into three groups: multiple renal pelvic tumors, multiple ureteral tumors, and synchronous renal pelvic and ureteral tumors included 164, 152, and 369 patients, respectively. We found the prevalence of carcinoma in situ was the highest in the synchronous group. In multivariate survival analyses, tumor distribution showed no difference in cancer-specific and disease-free survival, but there was a significant difference in bladder recurrence-free survival. The synchronous group had the highest bladder recurrence rate. In summary, tumor distribution did not influence the cancer-specific outcomes of multifocal UTUC, but synchronous lesions led to a higher rate of bladder recurrence than multiple renal pelvic tumors. We believe that the distribution of tumors reflects the degree of malignant involvement within the urinary tract, but has little significance for survival or disease progression.

Fluorescent light-up aptamers (FLAPs) are well-performed biosensors for cellular imaging and the detection of different targets of interest, including RNA, non-nucleic acid molecules, metal ions, and so on. They could be easily designed and emit a strong fluorescence signal once bound to specified fluorogens. Recently, one unique aptamer called Mango-II has been discovered to possess a strong affinity and excellent fluorescent properties with fluorogens TO1-Biotin and TO3-Biotin. To explore the binding mechanisms, computational simulations have been performed to obtain structural and thermodynamic information about FLAPs at atomic resolution. AMOEBA polarizable force field, with the capability of handling the highly charged and flexible RNA system, was utilized for the simulation of Mango-II with TO1-Biotin and TO3-Biotin in this work. The calculated binding free energy using published crystal structures is in excellent agreement with the experimental values. Given the challenges in modeling complex RNA dynamics, our work demonstrates that MD simulation with a polarizable force field is valuable for understanding aptamer-fluorogen binding and potentially designing new aptamers or fluorogens with better performance.

Abstract Introduction Inflammation and infection are causative factors of benign prostatic hyperplasia (BPH). Urine is not sterile, and urine microbiota identified by DNA sequencing can play an important role in the development of BPH and can influence the severity of lower urinary tract symptoms (LUTS). Materials and methods We collected mid-stream voided urine samples from BPH patients and control participants and stored them in a freezer at − 80 °C. All enrolled participants were requested to provide information about their clinical characteristics and complete the International Prostate Symptom Score (IPSS) questionnaire. Each step of the procedure, including the extraction of the genomic DNA from the urine samples; the amplification by polymerase chain reaction (PCR); PCR product quantification, mixing, and purification; DNA library preparation; and sequencing was performed with quality control (QC) measures. Alpha diversity was indicative of the species complexity within individual urine samples, and beta diversity analysis was used to evaluate the differences among the samples in terms of species complexity. Pearson’s correlation analysis was performed to calculate the relationship between the clinical characteristics of the participants and the microbiota species in the urine samples. Results We enrolled 77 BPH patients and 30 control participants who reported no recent antibiotic usage. Old age, high IPSS and poor quality of life were observed in the participants of the BPH group. No significant differences were observed in the alpha diversity of the samples. In the beta diversity analysis, there was a significant difference between the microbiota in the samples of the BPH and control groups according to ANOSIM statistical analysis. On comparing the groups, the ten bacterial genera present in the samples of the BPH group in descending order of abundance were: Sphingomonas, Bacteroides, Lactobacillus, Streptococcus, Alcaligenes, Prevotella, Ruminococcaceae UCG-014, Escherichia_Shigella, Akkermansia, and Parabacteroides. Spearman’s correlation analysis revealed that urine samples showing the presence of the bacterial genera Haemophilus, Staphylococcus, Dolosigranulum, Listeria, Phascolarctobacterium, Enhydrobacter, Bacillus, [Ruminococcus]torques, Faecalibacterium, and Finegoldia correlated with a high IPSS, and severe storage and voiding symptoms (P

Abstract Our aim was to analyze the clinical and survival differences among patients who underwent the two main treatment modalities, endoscopic ablation and radical nephroureterectomy. This study examined all patients who had undergone endoscopic management and RNU between Jul. 1988 and Mar. 2019 from the Taiwan UTUC registry. The inclusion criteria were low stage UTUC in RNU and all cases in endoscopic managed UTUC with a curative intent. The demographic and clinical characteristics were included for analysis. In total, 84 cases in the endoscopic group and 272 cases in the RNU group were enrolled for final analysis. The median follow-up period were 33.5 and 42.0 months in endoscopic and RNU group, respectively (p = 0.082). Comparison of Kaplan–Meier estimated survival curves between groups, the endoscopic group was associated with similar overall survival (OS), cancer specific survival (CSS), and intravesical recurrence free survival (IVRS) but demonstrated inferior disease free survival (DFS) (p = 0.188 for OS, p = 0.493 for CSS and p

PurposeWe aimed to evaluate the impact of preoperative local symptoms on prognosis after radical nephroureterectomy in patients with upper tract urothelial carcinoma (UTUC).MethodsThis retrospective study consisted of 2,662 UTUC patients treated at 15 institutions in Taiwan from 1988 to 2019. Clinicopathological data were retrospectively collected for analysis by the Taiwan UTUC Collaboration Group. The Kaplan-Meier method was used to calculate overall survival (OS), cancer-specific survival (CSS), disease-free survival (DFS), and bladder recurrence-free survival (BRFS). The prognostic value of preoperative local symptoms in OS, CSS, DFS, and BRFS was investigated using Cox proportional hazards models.ResultsThe median follow-up was 36.6 months. Among 2,662 patients, 2,130 (80.0%) presented with hematuria and 398 (15.0%) had symptomatic hydronephrosis at diagnosis. Hematuria was associated with less symptomatic hydronephrosis (p

PurposeThis study aimed to compare the oncological outcomes of patients with upper tract urothelial carcinoma (UTUC) without clinical lymph node metastasis (cN0) undergoing lymph node dissection (LND) during radical nephroureterectomy (NU).MethodsFrom the updated data of the Taiwan UTUC Collaboration Group, a total of 2726 UTUC patients were identified. We only include patients with ≥ pT2 stage and enrolled 658 patients. The Kaplan–Meier estimator and Cox proportional hazards model were used to analyze overall survival (OS), cancer-specific survival (CSS), disease-free survival (DFS), and bladder recurrence-free survival (BRFS) in LND (+) and LND (−) groups.ResultsA total of 658 patients were included and 463 patients without receiving LND and 195 patients receiving LND. From both univariate and multivariate survival analysis, there are no significant difference between LND (+) and LND (-) group in survival rate. In LND (+) group, 18.5% patients have pathological LN metastasis. After analyzing pN+ subgroup, it revealed worse CSS (p = 0.010) and DFS (p < 0.001) compared with pN0 patients.ConclusionsWe found no significant survival benefit related to LND in cN0 stage, ≥ pT2 stage UTUC, irrespective of the number of LNs removed, although pN+ affected cancer prognosis. However, from the result of pN (+) subgroup of LND (+) cohort analysis, it may be reasonable to not perform LND in patients with cT2N0 stage due to low positive predictive value of pN (+). In addition, performing LND may be considered for ureter cancer, which tends to cause lymphatic and hematogenous tumor spreading. Further large prospective studies are needed to validate our findings.

PurposeThis study aimed to compare the oncological outcomes and surgical complications of patients with upper tract urothelial carcinoma (UTUC) treated with different minimally invasive techniques for nephroureterectomy.MethodsFrom the updated data of the Taiwan UTUC Collaboration Group, a total of 3,333 UTUC patients were identified. After excluding ineligible cases, we retrospectively included 1,340 patients from 15 institutions who received hand-assisted laparoscopic nephroureterectomy (HALNU), laparoscopic nephroureterectomy (LNU) or robotic nephroureterectomy (RNU) between 2001 and 2021. Kaplan-Meier estimator and Cox proportional hazards model were used to analyze the survival outcomes, and binary logistic regression model was selected to compare the risks of postoperative complications of different surgical approaches.ResultsAmong the enrolled patients, 741, 458 and 141 patients received HALNU, LNU and RNU, respectively. Compared with RNU (41.1%) and LNU (32.5%), the rate of lymph node dissection in HALNU was the lowest (17.4%). In both Kaplan-Meier and univariate analysis, the type of surgery was significantly associated with overall and cancer-specific survival. The statistical significance of surgical methods on survival outcomes remained in multivariate analysis, where patients undergoing HALNU appeared to have the worst overall (p = 0.007) and cancer-specific (p = 0.047) survival rates among the three groups. In all analyses, the surgical approach was not related to bladder recurrence. In addition, HALNU was significantly associated with longer hospital stay (p = 0.002), and had the highest risk of major Clavien-Dindo complications (p = 0.011), paralytic ileus (p = 0.012), and postoperative end-stage renal disease (p

Abstract CSN6 is a subunit of the constitutive photomorphogenesis 9 (COP9) signalosome (CSN). CSN is involved in cellular and developmental processes such as signal transduction, transcriptional activation, cell cycle control, and tumorigenesis. CSN6 is highly expressed in several human cancers, including colorectal cancer, and breast cancer. However, no previous research has elaborated on the relationship between CSN6 expression and survival in patients with upper tract urothelial carcinoma (UTUC). Therefore, the purpose of this study is to evaluate the clinical significance of CSN6 in UTUC. CSN6 expression in 89 patients with UTUC enrolled in this study was examined using immunohistochemistry. The associations between CSN6 expression and clinicopathological variables were analyzed. CSN6 expression was significantly correlated with patients with high pathological stage (P = .006), male gender (P = .025), and high serum creatinine levels (P = .014). In univariate and multivariable analysis, high CSN6 expression was associated with a higher bladder recurrence (P = .005) and poor cancer‐specific survival (P = .001) for UTUC. In conclusion, CSN6 expression is a potential biomarker for predicting cancer recurrence and clinical survival in UTUC. Further research is necessary to investigate its role in the progression of UTUC.

Zerumbone is a natural product isolated from the pinecone or shampoo ginger, Zingiber zerumbet (L.) Smith, which has a wide range of pharmacological activities, including anti-inflammatory effects. However, the effects of zerumbone on activation of the NLRP3 inflammasome in macrophages have not been examined. This study aimed to examine the effects of zerumbone on LPS-induced inflammatory responses and NLRP3 inflammasome activation using murine J774A.1 cells, murine peritoneal macrophages, and murine bone marrow-derived macrophages. Cells were treated with zerumbone following LPS or LPS/ATP treatment. Production of nitric oxide (NO) was measured by Griess reagent assay. The levels of IL-6, TNF-α, and IL-1β secretion were analyzed by ELISA. Western blotting analysis was performed to determine the expression of inducible NO synthase (iNOS), COX-2, MAPKs, and NLRP3 inflammasome-associated proteins. The activity of NF-κB was determined by a promoter reporter assay. The assembly of NLRP3 was examined by immunofluorescence staining and observed by confocal laser microscopy. Our experimental results indicated that zerumbone inhibited the production of NO, PGE2 and IL-6, suppressed the expression of iNOS and COX-2, repressed the phosphorylation of ERK, and decreased the activity of NF-κB in LPS-activated J774A.1 cells. In addition, zerumbone suppressed the production of IL-1β and inhibited the activity of NLRP3 inflammasome in LPS/ATP- and LPS/nigericin-activated J774A.1 cells. On the other hand, we also found that zerumbone repressed the production of NO and proinflammatory cytokines in LPS-activated murine peritoneal macrophages and bone marrow-derived macrophages. In conclusion, our experimental results demonstrate that zerumbone effectively attenuates the LPS-induced inflammatory response in macrophages both in vitro and ex vivo by suppressing the activation of the ERK-MAPK and NF-κB signaling pathways as well as blocking the activation of the NLRP3 inflammasome. These results imply that zerumbone may be beneficial for treating sepsis and inflammasome-related diseases.

Background We aimed to identify prognostic biomarkers of upper tract urothelial carcinomas (UTUCs), including microRNAs (miRNAs) and genes which account for only 5% to 10% of all urothelial carcinomas (UCs). In Taiwan, this figure is markedly higher, where it can reach up to 30% of UC cases. Materials and Methods Using next-generation sequencing (NGS), we analyzed two pairs of renal pelvis tumors and adjacent normal urothelial tissues to screen miRNAs and messenger RNAs. By combining bioinformatics analysis from miRmap, Gene Expression Omnibus (GEO), and Oncomine and Ingenuity® Pathway Analysis databases, we identified candidate genes. To search for upstream miRNAs with exact target binding sites, we used miRmap, TargetScan, and miRDB to enforce evidence. Then, we clarified gene and protein expression through an in vitro study using western blot analysis and quantitative real-time reverse transcriptase-PCR. Results Interactions between selected target genes obtained using the NGS and miRmap methods were assessed through a Venn diagram analysis. Six potential genes, namely, PDE5A, RECK, ZEB2, NCALD, PLCXD3 and CYBRD1 showed significant differences. Further analysis of gene expression from the GEO dataset indicated lower expression of PDE5A, RECK, ZEB2, and CYBRD1 in bladder cancer tissue than in normal bladder mucosa, which indicated that PDE5A, RECK, ZEB2, and CYBRD1 may act as tumor suppressors in UTUC. In addition, we compared the expression of these genes in various UC cell lines (RT4, BFTC905, J82, T24, UMUC3, 5637, BFTC 909, UMUC14) and found decreased expression of PDE5A in muscle-invasive UC cells compared with the RT4 cell line. Furthermore, by using paired UTUC and normal tissues from 20 patients, lower PDE5A expression was also demonstrated in tumor specimens. Conclusions Our findings suggest these candidate genes may play some roles in UTUC progression. We propose that these markers may be potential targets clarified by in vitro and in vivo experiments. PDE5A also potentially presents tumor suppressor genes, as identified by comparing the expression between normal and tumor specimens.

In response to a variety of stresses, mammalian cells activate the inflammasome for targeted caspase-dependent pyroptosis. The research community has recently begun to deduce that the activation of inflammasome is instigated by several known oncogenic stresses and metabolic perturbations; nevertheless, the role of inflammasomes in the context of cancer biology is less understood. In manipulating the expression of inflammasome, researchers have found that NLRP3 serves as a deterministic player in conducting tumor fate decisions. Understanding the mechanistic underpinning of pro-tumorigenic and anti-tumorigenic pathways might elucidate novel therapeutic onco-targets, thereby providing new opportunities to manipulate inflammasome in augmenting the anti-tumorigenic activity to prevent tumor expansion and achieve metastatic control. Accordingly, this review aims to decode the complexity of NLRP3, whereby summarizing and clustering findings into cancer hallmarks and tissue contexts may expedite consensus and underscore the potential of the inflammasome in drug translation.

Abstract Background To clarify if diagnostic ureteroscopy (URS) before radical nephroureterectomy for patients with upper tract urothelial carcinoma (UTUC) will increase the risk of intravesical recurrence. Methods From retrospective review of cohort at our institution, 502 patients with UTUC who underwent radical nephroureterectomy with bladder cuff excision were enrolled from 1990 to 2013. Cox proportional hazards model was used to analyze the overall survival (OS), disease-free survival (DFS), metastasis-free survival (MFS), and intravesical recurrence-free survival (IVRFS). The log-rank test was used for comparing survival curves. All potential risk factors were included in the multivariate Cox proportional hazards model to recognize independent predictors. From NHI database, we included patients of UTUC without bladder cancer history using population-based database in Taiwan from 1996 to 2013. In total, 3079 URS and 2634 non-URS patients with UTUC were identified. Univariate and multivariate Cox proportional hazards regressions were performed to measure the risk of IVRFS and all-cause mortality. Results From our database, the comparison of clinicopathological characteristics in UTUC patients between with URS biopsy group (URS+) (n = 206, 41%) and without URS biopsy group (URS−) (n = 296, 59%) was insignificantly different excluding surgical method. URS biopsy is not associated with worse OS (p = 0.720), DFS (p = 0.294), MFS (p = 0.808), and IVRFS (p = 0.560) by multivariate analysis. Only bladder cancer history is an independent significant factor to predict IVR (p

Aims: Laparoendoscopic single-site (LESS) adrenalectomy has become a feasible choice for adrenal lesions and can substitute for conventional open adrenalectomy. This report shares our surgical experience and describes the characteristics of adrenal tumors after LESS retroperitoneal adrenalectomy. Subjects and Methods: Between January 2010 and August 2016, 123 patients underwent an LESS adrenalectomy by retroperitoneal approach in our hospital. We retrospectively reviewed the records of these patients and analyzed the characteristics of adrenal tumors. The incision is below the 12th rib in the posterior axillary line and is about 2.3–3.2 cm in length. A 5 mm 30° rigid laparoscope and other conventional laparoscopic instruments are manipulated through a commercial port. No postoperative drain is placed. Results: Among 123 patients, the mean operative time was 114.1 ± 31.1 min, and mean blood loss was 65.1 ± 68.7 ml. Mean hospital stay was 5.4 ± 1.2 days. The postoperative course was uneventful without complications. Among all adrenal tumors undergoing surgery, Conn's disease is the most common (68.3% Conn's disease, 19.5% nonfunctioning, 4.9% Cushing's disease, 3.3% pheochromocytoma, and 0.8% malignancy). We found that left-side adrenal tumors (64.2%) were more common than right-side tumors (35.8%). Conclusions: Our experience shows that retroperitoneal LESS adrenalectomy is promising. Conn's disease accounts for more than half of adrenal tumors undergoing surgery. In the future, further comparative study is warranted to define the role of LESS in adrenal surgery.

Zearalenone (ZEA) is a mycotoxin that has several adverse effects on most mammalian species. However, the effects of ZEA on macrophage-mediated innate immunity during infection have not been examined. In the present study, bacterial lipopolysaccharides (LPS) were used to induce the activation of macrophages and evaluate the effects of ZEA on the inflammatory responses and inflammation-associated signaling pathways. The experimental results indicated that ZEA suppressed LPS-activated inflammatory responses by macrophages including attenuating the production of proinflammatory mediators (nitric oxide (NO) and prostaglandin E2 (PGE2)), decreased the secretion of proinflammatory cytokines (tumor necrosis factor (TNF)-α, interleukin (IL)-1β and IL-6), inhibited the activation of c-Jun amino-terminal kinase (JNK), p38 and nuclear factor-κB (NF-κB) signaling pathways, and repressed the nucleotide-binding and oligomerization domain (NOD)-, leucine-rich repeat (LRR)- and pyrin domain-containing protein 3 (NLRP3) inflammasome activation. These results indicated that mycotoxin ZEA attenuates macrophage-mediated innate immunity upon LPS stimulation, suggesting that the intake of mycotoxin ZEA-contaminated food might result in decreasing innate immunity, which has a higher risk of adverse effects during infection.

Abstract In addition to testosterone (T), the emerging role of sex hormone-binding globulin (SHBG) in pathogenesis of metabolic syndrome (MetS) has been noted recently. However, reports of associations with serum adipocytokine levels are still limited. Therefore, we conducted this study to evaluate whether serum T and SHBG levels are independent predictors for the risk of MetS that are associated with adiponectin and leptin levels in 614 Taiwanese men over 40 years old collected from a free health screening. Subjects in the lowest quartile of TT and SHBG levels are exposed to a 1.58 and 3.22 times risk of developing MetS, as compared to those in the highest quartile of TT and SHBG levels. However, SHBG retains its significance independent of TT as a MetS risk predictor, but not vice versa. In addition, SHBG was significantly correlated with both adiponectin and leptin levels even after adjusting for TT levels. In conclusion, SHBG served as a major predictor for the risk of MetS and was correlated with serum adiponectin and leptin levels that are independent of T. Further studies are needed to elucidate the true role of SHBG in the pathogenesis of MetS and possible mechanisms associated with serum adiponectin and leptin levels.

Objective: Laparoendoscopic single-site surgery (LESS) is a new laparoscopy development that avoids the use of multiple ports and minimizes morbidity. Combined with retroperitoneoscopy, LESS is suitable for adrenalectomy. We compared open, conventional laparoscopic, and LESS-retroperitoneoscopic adrenalectomy (LESS-RA) surgeries for adrenal tumor removal. Furthermore, we analyzed the conventional retroperitoneoscopic adrenalectomy (CRA) and LESS-RA outcomes. Materials and Methods: We examined 178 patients who underwent adrenalectomy: 43 by open surgery, 72 by conventional laparoscopy, and 63 by LESS-RA. We analyzed the outcomes of operative time, estimated blood loss (EBL), complications, postoperative convalescence, time to resuming oral intake, analgesics on demand, and hospital stay. Results: We found that the open surgery group had a significantly greater mean EBL than the conventional laparoscopy or LESS-RA group (353.1±313.6 mL vs. 62.3±76.9 mL vs. 60.9±64.3 mL, respectively; p

Objective: A urethral stricture is the narrowing of the urethra caused by scar formation. The etiologies include infection, trauma with total urethral disruption, and iatrogenic procedures. The impact of urethral stricture diseases is very high. Several kinds of endoscopic procedures have become available for managing the disease. Among them, complete obliteration of the urethra during endoscopic procedures remains a challenge for surgeons. We describe a modified procedure in which laser urethrotomy was guided under the light source from an antegrade flexible cystoscope for treating a short completely obliterated urethra. This procedure is indicated if the obliterated segment is less than 10 mm because longer strictures may increase the chance of extra false lumen formation and bleeding. Materials and Methods: Forty-three male patients who underwent optical urethrotomy for urethral strictures at Kaohsiung Municipal Ta-Tung Hospital (Kaohsiung, Taiwan) between March 2013 and January 2015 were induced in the study. Five of these patients were diagnosed as having complete urethral obliteration. Results: In all five patients with a completely obliterated urethra, retrograde laser incision was performed successfully. Three patients had total bulbar urethral obstruction and two had penile obstruction. All patients experienced improved urination after the procedure. Conclusion: Our preliminary data showed that our modified method for treating a completely obliterated urethra yielded satisfactory results. Long-term follow-up and large-scale studies should be conducted to better examine technique efficacy; however, our current results regarding the simple modification of endoscopic urethrotomy seem promising.

The importance of blood cell markers in patients with malignant tumors has been studied, but there are few studies on the prognostic value of hemoglobin-to-red cell distribution width ratio (HRR) in cancer. This is the first study to investigate the effect of preoperative HRR on patients with upper tract urothelial carcinoma (UTUC). Our retrospective cohort study included 730 UTUC patients who underwent nephroureterectomy from 2000 to 2019. Clinicopathological parameters were compared according to HRR levels, and the relationship between blood cell markers (HRR, white blood cell [WBC] count, platelet count) and prognosis was evaluated using Kaplan–Meier method and Cox regression model. We found that patients with HRR ≤ 1.05 tended to have worse renal function, higher pathological stages, and more high-grade tumors. In univariate analysis, HRR ≤ 1.05, WBC > 8.65 × 103 cells/μL and platelets >309 × 103 cells/μL were associated with poor progression-free survival (PFS), cancer-specific survival (CSS), and overall survival (OS). Multivariate analysis demonstrated that HRR ≤ 1.05 and WBC > 8.65 × 103 cells/μL were independent prognostic factors for predicting deterioration of PFS, CSS, and OS. In conclusion, HRR and WBC are easy to obtain in clinical practice and are useful indicators to provide prognostic information before surgery for UTUC.

Piplartine (or Piperlongumine) is a natural alkaloid isolated from Piper longum L., which has been proposed to exhibit various biological properties such as anti-inflammatory effects; however, the effect of piplartine on sepsis has not been examined. This study was performed to examine the anti-inflammatory activities of piplartine in vitro, ex vivo and in vivo using murine J774A.1 macrophage cell line, peritoneal macrophages, bone marrow-derived macrophages and an animal sepsis model. The results demonstrated that piplartine suppresses iNOS and COX-2 expression, reduces PGE2, TNF-α and IL-6 production, decreases the phosphorylation of MAPKs and NF-κB and attenuates NF-κB activity by LPS-activated macrophages. Piplartine also inhibits IL-1β production and suppresses NLRP3 inflammasome activation by LPS/ATP- and LPS/nigericin-activated macrophages. Moreover, piplartine reduces the production of nitric oxide (NO) and TNF-α, IL-6 and IL-1β, decreases LPS-induced tissue damage, attenuates infiltration of inflammatory cells and enhances the survival rate. Collectively, these results demonstrate piplartine exhibits anti-inflammatory activities in LPS-induced inflammation and sepsis and suggest that piplartine might have benefits for sepsis treatment.

Upper tract urothelial carcinomas are tumors derived from urothelium along the urinary tract. Currently, there are no reliable biomarkers for their diagnosis or for prediction of tumor progression outcomes. It has a high incidence in Taiwanese populations at specific locations with exposure histories, and occurs relatively more frequent in the ureter than in the pyelocaliceal cavities. Radical nephroureterectomy with bladder cuff excision is the gold standard treatment for adequate local tumor control and better long-term survival. Despite optimal surgical treatment, the patient outcomes are still not satisfactory. An improved understanding of the biomolecular predictors is urgently needed to plan neoadjuvant/adjuvant therapy and proper follow-up strategies. In this study, a literature search was carried out through the PubMed database using the key words “upper tract urothelial carcinoma,” “prognostic factors,” and “outcome” from January 1985 to August 2015. The results showed that several preoperative clinical characteristics (such as chronic kidney disease, female sex, synchronous urothelial carcinoma of the bladder, and tumor location) and molecular markers (such as glutathione S-transferase, p53 protein, cyclooxygenase-2, TG-interacting factor, nuclear factor-kB, osteopontin, and hypoxia-inducible factor-1α) could serve as candidate biomarkers for the early detection of progression to upper tract urothelial carcinomas. Additional investigations of these results are required to resolve the gene combinations precisely and personalize the management of upper tract urothelial carcinomas.

Objectives: The prevalence of both chronic kidney disease (CKD) and upper tract urothelial carcinoma (UTUC) in Taiwan is unusually high, and we aimed to investigate the impact of preoperative renal function on UTUC after radical nephroureterectomy. Materials and methods: Between 2000 and 2013, 248 UTUC patients were enrolled in this retrospective study after excluding patients who had concomitant muscle-invasive bladder cancer, whose tumor metastasized at initial presentation, and who received perioperative chemotherapy or radiotherapy. The significance of CKD on overall survival (OS), cancer-specific survival (CSS), and bladder recurrence-free survival (BRFS) was evaluated by Cox proportional hazard model. Results: The median follow-up time was 45.41 months. Overall 5-year OS, CSS, and BRFS rates were 78.27%, 87.81%, and 70.42%, respectively. Aging, late-stage CKD, and nonorgan-confined primary tumor stage were independent predictors for OS after adjustment. Nonorgan-confined primary tumor stage and lymph node involvement were two independent predictors for CSS after adjustment. Concomitant bladder tumor was the only significant predictor for BRFS after adjustment. Conclusion: Patients with late-stage CKD had a higher risk of having poor OS. Patients with concomitant bladder tumor had a greater risk of having bladder cancer recurrence despite primary tumor stage. Concomitant bladder tumor, however, had no effect on OS and CSS in this study.

DNA-templated few-atom silver nanoclusters (DNA/Ag NCs) are a new class of organic/inorganic composite nanomaterials whose fluorescence emission can be tuned throughout the visible and near-IR range by simply programming the template sequences. Compared to organic dyes, DNA/Ag NCs can be brighter and more photostable. Compared to quantum dots, DNA/Ag NCs are smaller, less prone to blinking on long timescales, and do not have a toxic core. The preparation of DNA/Ag NCs is simple and there is no need to remove excess precursors as these precursors are non-fluorescent. Our recent discovery of the fluorogenic and color switching properties of DNA/Ag NCs have led to the invention of new molecular probes, termed NanoCluster Beacons (NCBs), for DNA detection, with the capability to differentiate single-nucleotide polymorphisms by emission colors. NCBs are inexpensive, easy to prepare, and compatible with commercial DNA synthesizers. Many other groups have also explored and taken advantage of the environment sensitivities of DNA/Ag NCs in creating new tools for DNA/RNA detection and single-nucleotide polymorphism identification. In this review, we summarize the recent trends in the use of DNA/Ag NCs for developing DNA/RNA sensors.

Radical surgery (RS) with adjuvant chemotherapy (AC) or radiotherapy has been conventionally used for patients with advanced urothelial carcinoma (AUC). Recent research has indicated that systemic neoadjuvant chemotherapy (NC) with RS yields better outcomes than RS alone for patients with locally advanced bladder cancer. However, there are no reports indicating whether NC or AC would be beneficial for patients with AUC. The present study compared the survival rate for AUC patients receiving NC or AC. A retrospective analysis was conducted using data for 64 patients with AUC who underwent RS and systemic chemotherapy at our institution between March 2002 and March 2011. Of the 64 patients, 30 received NC before RS and 34 received RS followed by systemic AC. Pathologic stages (p=0.002), grades (p=0.018) and lymphovascular invasion (p=0.047) were significantly lower in the patients who received NC first than in those who received RC first. Furthermore, analysis of the surgical specimens revealed that 26.7% of patients who received NC before RS had complete remission. There were no significant differences in demographic data, surgical complications, and chemotoxicity between the two patient groups. The progression-free survival (PFS) and overall survival (OS) of patients who received initial NC were significantly better than those of patients who received initial RC (p=0.002 and 0.018, respectively). Our results indicate that NC administration before RS significantly improved the PFS and OS of AUC patients, without increasing surgical complications and chemotoxicity. Further prospectively controlled trials need to be conducted to confirm the effectiveness of NC for AUC patients.

The incidence of upper tract urothelial cancer (UTUC) has gradually increased over the past 30 years. Although most reports have shown that UTUC occurs more frequently in men than in women, women have been found to have a worse prognosis than men. In Taiwan, a high incidence of UTUC has been reported, with an unusual minor predominance of female cases. The purpose of this study was to determine the influence of gender on the outcome of patients with UTUC after nephroureterectomy and bladder cuff excision. From January 1990 to December 2007, 301 patients diagnosed with UTUC were admitted at our institution. A retrospective analysis of the effect of gender on the clinical outcome was performed. We compared the 5-year bladder recurrence-free, progression-free, and disease-specific survival rates. While we did not observe any differences between men and women in bladder recurrence-free, progression-free, or disease-specific survival rates, we found that female patients had a significantly higher percentage of contralateral recurrence than the males (5.9% vs. 0.8%, p = 0.019).

Laparoscopic radical prostatectomy (LRP) is a demanding procedure that requires surgical skill, a long learning curve and significant laparoscopic expertise. We report herein our initial experience with 41 laparoscopic radical prostatectomies to assess all perioperative complications in our initial 5-year experience. We reviewed retrospectively the case records of 41 patients who underwent laparoscopic radical prostatectomy for clinically localized prostate cancer from 2005 to 2010 at our institution. All abnormal symptoms were developed during the 30 days after the operation. Complications were noted as well as their severity according to the Clavien grading system. No conversion to open surgery was necessary in all cases. The median postoperative hospital stay was 10 days (range 9–16). The median duration of bladder catheterization was 8 days (range 7–35). There was no case of multiple-organ dysfunction or death. Minor complications constituted 82.6% of all complications. The incidence of severe complications was 17.4%. LRP displayed some advantages over open surgery in the perioperative period. Our complication rates were significantly higher than those indicated in the series previously reported. We found that most complications occurred in the first 30 patients who underwent LRP. We suggest that the surgeons should pay more attention to the difficulties of the procedure.

Villous adenomas are common in the gastrointestinal tract but are rare in the urinary tract. Villous adenomas of the urinary tract are identified mostly in the urinary bladder in the current published literature in English. There are only scattered individual case reports showing villous adenoma in the other parts of the urinary tract such as the urethra, ureter, and renal pelvis. Here, we report a fourth case of villous adenoma in the renal pelvis with manifestation of mucus-filled kidney (muconephrosis). A 54-year-old male patient presented with acute urinary retention with mucinuria initially and he finally received nephrectomy. No obvious evidence of recurrence has been noted in the 1-year follow-up.

Ureteral obstruction secondary to endometriosis is relatively uncommon. We present a 49-year-old female (gravida 3, para 2, abortion 1), who was identified as suffering from right hydronephrosis while undergoing her regular health examination. Retrograde pyelography demonstrated a partial obstruction of the right ureter in the distal third. She underwent ureteroscopy and biopsy to remove a right ureteral tumor. Histological examination confirmed ureteral endometriosis. During follow-up at the obstetrics and gynecology outpatient department, an abdominal echo was detected that revealed a right endometrioma (size, 7.5 × 4.8 × 5.5 cm) on the ovary. As a result, a total hysterectomy and bilateral salpingo-oophorectomy was performed. Although the patient had right residual hydronephrosis, the creatinine level improved to 1.2 mg/dL during follow-up.

Schwannoma of the adrenal gland is extremely rare. Here, we report a 49-year-old patient with an adrenal tumor noted incidentally by abdominal ultrasonography while undergoing regular health examination. Retroperitoneal laparoscopic adrenalectomy was performed and the schwannoma was diagnosed by histologic findings and immunohistochemistry. Five months after surgery, the patient remained well and without evidence of recurrence or metastasis.

A 66-year-old man, with a history of gastric signet ring cell carcinoma, was admitted due to intermittent dull pain in the left lower abdomen for 3 months. Left ureteral obstruction with suspicious tumor encasement and hydronephrosis was found on imaging studies. Endoscopic ureteral biopsy revealed infiltrating high-grade urothelial carcinoma. As a result, he underwent left nephroureterectomy and bladder cuff excision. Unexpectedly, metastatic carcinoma of the left ureter from the stomach was the final diagnosis after comparison of the permanent sections of the two specimens. Unfortunately, acute disseminated intravascular coagulation developed and the patient died of disease complications 16 days after the operation, even with intensive care. The details of this rare condition are reported herein with a review of the medical literature.

The purpose of this study was to determine the influence of metabolic syndrome (MS) and serum testosterone in patients with erectile dysfunction (ED) and their possible association. A total of 103 men with ED were enrolled. The International Index of Erectile Function (IIEF) questionnaire was used to assess erectile condition. MS was defined according to the criteria formulated by the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) and the International Diabetes Federation (IDF). The mean age of the study population was 57.5 ± 10.7 years, with an average IIEF of 14.7 ± 6.7. The age and prevalence of MS using the NCEP ATP III criteria, but not the IDF criteria, were significantly different between mild and moderate/severe ED patients (p = 0.031 and 0.009, respectively). The percentage of hypertension (78.6% vs. 36.2%; p < 0.001) and raised fasting glucose levels (46.4% vs. 19.1%; p = 0.004) were significantly higher in the moderate/severe ED group, and both differences remained significant in multivariate analysis (p = 0.001 and 0.042, respectively). In addition, serum testosterone levels were significantly lower in ED patients with MS (p = 0.002). In summary, the presence of MS is associated with more severe ED. Among the components of MS, elevated blood pressure and fasting blood glucose were independent risk factors. NCEP ATP III criteria seem to correlate better with the degree of ED than the IDF definition. Our results also indicate that MS is associated with a lower testosterone level in patients with ED.

The simultaneous occurrence of renal collecting duct (Bellini duct) carcinoma and bladder urothelial carcinoma is very rare. A 68-year-old female patient with bladder urothelial carcinoma first received transurethral resection of the tumor. Left side nephrouretectomy and transurethral resection of the intramural ureter were performed 8 months later under the diagnosis of concomitant renal pelvic urothelial carcinoma. However, the final pathologic examination revealed collecting duct carcinoma. The patient received systemic chemotherapy after surgery, but distant metastasis was noted 6 months later. Here, we report a rare case of combined renal collecting duct carcinoma and bladder urothelial carcinoma confirmed by pathologic examination and immunohistochemical staining.

Actinomycosis is a rare, chronic suppurative infection caused by the Gram-positive anaerobic filamentous bacterium, Actinomyces Israeli. In most cases, the diagnosis is made postoperatively because of its unusual clinical presentation. Abdominal actinomycosis is the second most common site of the disease and may mimic abdominal cancer, inflammatory bowel disease or diverticulitis. The abdominal-pelvic form of this disease mostly results from the prolonged use of an intrauterine device. We report a rare case of combined intra- and extra-abdominal actinomycosis mimicking urachal tumor that was diagnosed by computed tomography, which presented as two tender abdominal palpable masses following long-term intrauterine device use. The disease was confirmed by postoperative histopathologic examination, which revealed sulfur granules microscopically, and was successfully treated by complete surgical resection following a period of appropriate antibiotic treatment.

The occurrence of metastasis to the head and neck region in renal cell carcinoma is extremely rare. An 80-year-old man presented with a soft nodule in the left parietal calvarium and was admitted to our hospital. Biopsy of the nodule showed nests of clear tumor cells, suggesting metastatic renal cell carcinoma. Computed tomography of the abdomen revealed a well-defined hypervas-cular tumor, measuring around 7×7×8 cm, exophytic from the lower pole of the right kidney. Since there were no other systemic metastases, right nephrectomy and complete resection of the skull lesion were performed. No adjunctive therapy was given postoperatively After 22 months of follow-up, the patient was well and without evidence of disease.

Spermatoceles are usually asymptomatic and often found incidentally during physical examination. We report a case of giant spermatocele that mimicked a hydrocele. A 55-year-old man suffered from right scrotal enlargement for several years. As the heavy sensation and scrotal soreness worsened in recent months, he came to our outpatient clinic for help. Hydrocele was suspected due to transilluminating appearance of the scrotal content. Surgical exploration was arranged and a giant spermatocele was found. Total excision of the spermatocele was performed and the patient recovered well. The specimen was sent for pathology and spermatocele with spermatozoa was noted.