Ferroptosis-Regulated Natural Products and miRNAs and Their Potential Targeting to Ferroptosis and Exosome Biogenesis.

Ferroptosis, which comprises iron-dependent cell death, is crucial in cancer and non-cancer treatments. Exosomes, the extracellular vesicles, may deliver biomolecules to regulate disease progression. The interplay between ferroptosis and exosomes may modulate cancer development but is rarely investigated in natural product treatments and their modulating miRNAs. This review focuses on the ferroptosis-modulating effects of natural products and miRNAs concerning their participation in ferroptosis and exosome biogenesis (secretion and assembly)-related targets in cancer and non-cancer cells. Natural products and miRNAs with ferroptosis-modulating effects were retrieved and organized. Next, a literature search established the connection of a panel of ferroptosis-modulating genes to these ferroptosis-associated natural products. Moreover, ferroptosis-associated miRNAs were inputted into the miRNA database (miRDB) to bioinformatically search the potential targets for the modulation of ferroptosis and exosome biogenesis. Finally, the literature search provided a connection between ferroptosis-modulating miRNAs and natural products. Consequently, the connections from ferroptosis-miRNA-exosome biogenesis to natural product-based anticancer treatments are well-organized. This review sheds light on the research directions for integrating miRNAs and exosome biogenesis into the ferroptosis-modulating therapeutic effects of natural products on cancer and non-cancer diseases.

Protein phosphatase 2A modulation and connection with miRNAs and natural products.

Protein phosphatase 2A (PP2A), a heterotrimeric holoenzyme (scaffolding, catalytic, and regulatory subunits), regulates dephosphorylation for more than half of serine/threonine phosphosites and exhibits diverse cellular functions. Although several studies on natural products and miRNAs have emphasized their impacts on PP2A regulation, their connections lack systemic organization. Moreover, only part of the PP2A family has been investigated. This review focuses on the PP2A-modulating effects of natural products and miRNAs' interactions with potential PP2A targets in cancer and non-cancer cells. PP2A-modulating natural products and miRNAs were retrieved through a literature search. Utilizing the miRDB database, potential PP2A targets of these PP2A-modulating miRNAs for the whole set (17 members) of the PP2A family were retrieved. Finally, PP2A-modulating natural products and miRNAs were linked via a literature search. This review provides systemic directions for assessing natural products and miRNAs relating to the PP2A-modulating functions in cancer and disease treatments.

Lipid Profiles Impact on the Oncologic Outcome of Upper Tract Urothelial Carcinoma.

Background: The prognosis of upper tract urothelial carcinoma (UTUC) varies, with T3/T4 UTUC having less than 50% 5-year survival post-radical nephroureterectomy (RNU). Lipid profiles including cholesterol (CHOL), low-density lipoprotein (LDL), and triglycerides (TGs), and high-density lipoprotein (HDL) have shown correlations with oncologic outcomes in various cancers. We aimed to investigate the prognostic significance of the lipid profiles in UTUC patients who had received RNU. Methods: In this retrospective study, a total of 217 UTUC patients who underwent RNU were analyzed. Prognostic factors for overall survival (OS), cancer-specific survival (CSS), and progression-free survival (PFS) were assessed using Cox proportional hazards regression model and competing risk analysis. Results: The median follow-up duration was 2.36 years. Fifty-one (23.50%) of the patients experienced tumor progression, 16 (7.37%) died from UTUC, and 41 (18.89%) died from all causes during the follow-up period. Multivariate analysis revealed that elevated CHOL, low HDL, and elevated TG were linked to worse OS (P = 0.0188, 0.0002, and 0.0001, respectively). Higher CHOL, LDL, and TG, as well as lower HDL significantly affected PFS (P < 0.001 for all), and elevated CHOL and TG were associated with poorer CSS (P = 0.0033 and 0.0179). A competing risk model indicated that elevated LDL increased the risk of cancer progression (P = 0.407), with CHOL increasing the risk of UTUC-specific mortality (P = 0.0162). Limitations include retrospective design, limited, single-time sampling and relatively small sample size. Conclusions: Lipid profiles were identified as prognostic indicators for UTUC patients post-RNU. It highlights the potential importance of lipid management in improving tumor-related outcomes.

Michelia compressa-Derived Santamarine Inhibits Oral Cancer Cell Proliferation via Oxidative Stress-Mediated Apoptosis and DNA Damage.

The anti-oral cancer effects of santamarine (SAMA), a Michelia compressa var. compressa-derived natural product, remain unclear. This study investigates the anticancer effects and acting mechanism of SAMA against oral cancer (OC-2 and HSC-3) in parallel with normal (Smulow-Glickman; S-G) cells. SAMA selectively inhibits oral cancer cell viability more than normal cells, reverted by the oxidative stress remover N-acetylcysteine (NAC). The evidence of oxidative stress generation, such as the induction of reactive oxygen species (ROS) and mitochondrial superoxide and the depletion of mitochondrial membrane potential and glutathione, further supports this ROS-dependent selective antiproliferation. SAMA arrests oral cancer cells at the G2/M phase. SAMA triggers apoptosis (annexin V) in oral cancer cells and activates caspases 3, 8, and 9. SAMA enhances two types of DNA damage in oral cancer cells, such as γH2AX and 8-hydroxy-2-deoxyguanosine. Moreover, all of these anticancer mechanisms of SAMA are more highly expressed in oral cancer cells than in normal cells in concentration and time course experiments. These above changes are attenuated by NAC, suggesting that SAMA exerts mechanisms of selective antiproliferation that depend on oxidative stress while maintaining minimal cytotoxicity to normal cells.

Excavatolide C/cisplatin combination induces antiproliferation and drives apoptosis and DNA damage in bladder cancer cells.

Excavatolide C (EXCC), a marine coral-derived compound, exhibits an antiproliferation effect on bladder cancer cells. The present study evaluated the improvement in the antiproliferation ability of EXCC by co-treatment with cisplatin in bladder cancer cells. EXCC/cisplatin (12.5 and 1 µg/mL) showed higher antiproliferation effects on bladder cancer cells than single treatments (EXCC or cisplatin alone) in the 48 h ATP assay. EXCC/cisplatin also enhanced the increase in subG1, annexin V-mediated apoptosis, and activation of poly (ADP-ribose) polymerase (PARP) and several caspases (caspases 3, 8, and 9) compared to the single treatments. Cellular and mitochondrial oxidative stress was enhanced with EXCC/cisplatin compared to the single treatments according to analyses of reactive oxygen species (ROS), mitochondrial superoxide, and mitochondrial membrane potential; in addition, cellular antioxidants, such as glutathione (GSH), and the mRNA expressions of antioxidant signaling genes (catalase and NFE2-like bZIP transcription factor 2) were downregulated. EXCC/cisplatin treatment produced more DNA damage than the single treatments, as indicated by γH2AX and 8-hydroxy-2'-deoxyguanosine levels. Moreover, several DNA repair genes for homologous recombination (HR) and non-homologous end joining (NHEJ) were downregulated in EXCC/cisplatin compared to others. The addition of the GSH precursor N-acetylcysteine, which has ROS scavenging activity, attenuated all EXCC/cisplatin-induced changes. Notably, EXCC/cisplatin showed lower antiproliferation, apoptosis, ROS induction, GSH depletion, and γH2AX DNA damage in normal cells than in bladder cancer cells. Therefore, the co-treatment of EXCC/cisplatin reduces the proliferation of bladder cancer cells via oxidative stress-mediated mechanisms with normal cell safety.

Cumulative sum analysis of the learning curve of laparoendoscopic single-site robot-assisted radical prostatectomy.

BACKGROUND: Radical prostatectomy has become the gold standard for treating localized prostate cancer. Improvement in the single-site technique and surgeon's skill reduces not only the hospital duration but also the number of wounds. Realizing the learning curve for a new procedure can prevent unnecessary mistakes. OBJECTIVE: To analyze the learning curve of extraperitoneal laparoendoscopic single-site robot-assisted radical prostatectomy (LESS-RaRP). METHODS: We retrospectively evaluated 160 patients diagnosed with prostate cancer during June 2016 to December 2020 who underwent extraperitoneal LESS-RaRP. Calculated cumulative sum analysis (CUSUM) was used to evaluate the learning curves for the extraperitoneal setting time, robotic console time, total operation time, and blood loss. The operative and functional outcomes were also assessed. RESULTS: The learning curve of the total operation time was observed in 79 cases. For the extraperitoneal setting and robotic console times, the learning curve was observed in 87 and 76 cases, respectively. The learning curve for blood loss was observed in 36 cases. No in-hospital mortality or respiratory failure was observed. CONCLUSION: Extraperitoneal LESS-RaRP using the da Vinci Si system is safe and feasible. Approximately 80 patients are required to achieve a stable and consistent operative time. A learning curve for blood loss was observed after 36 cases.

Antibladder Cancer Effects of Excavatolide C by Inducing Oxidative Stress, Apoptosis, and DNA Damage In Vitro.

Excavatolide C (EXCC) is a bioactive compound derived from the gorgonian octocoral Briareum excavatum, and its anticancer effects are rarely addressed, particularly for bladder cancer. This investigation aimed to explore the potential impacts of EXCC on inhibiting the proliferation of three kinds of bladder cancer cells (5637, BFTC905, and T24). EXCC inhibits bladder cancer cell proliferation based on 48 h ATP assay. This antiproliferation function is validated to be oxidative stress dependent. Cellular and mitochondrial oxidative stresses were upregulated by EXCC, accompanied by depleting glutathione and mitochondrial membrane potential. These antiproliferation and oxidative stress events were suppressed by N-acetylcysteine (NAC), indicating that EXCC has an oxidative stress-regulating function for antiproliferation of bladder cancer cells. Oxidative stress-related responses such as apoptosis, caspase activation, and DNA damage were upregulated by EXCC and reverted by NAC. Taken together, the antiproliferation function of EXCC provides a potential treatment against bladder cancer cells via oxidative stress modulation.

Prognostic value of renal function for upper tract urothelial carcinoma who underwent radical nephroureterectomy: Sex differences.

BACKGROUND/PURPOSE: Upper tract urothelial carcinoma (UTUC) is a relatively rare type of urothelial carcinoma. Additionally, only few reports have examined the sex differences in patients with UTUC. Therefore, the present study aimed to identify the sex factors affecting renal function in patients with UTUC who underwent radical nephroureterectomy (RNU). METHODS: Patients who underwent RNU for non-metastatic UTUC between 2000 and 2013 were retrospectively reviewed and divided into two groups by sex. The Kaplan-Meier method was applied to evaluate the effects of sex on survival, whereas for the other clinicopathological parameters, hazard ratios were evaluated using the Cox regression model. The analyses were also performed in patients with different chronic kidney disease (CKD) stages. RESULTS: A total of 368 patients were included, 147 men and 221 women. Female patients had a higher rate of anemia, advanced CKD stage, and dialysis. Male patients predominantly had a higher rate of smoking. The Kaplan-Meier analysis revealed no differences between sexes on recurrence-free survival (RFS) and cancer-specific survival (CSS). Multivariate analysis confirmed that ureteral tumors, advanced pathological tumor stage, and adjuvant chemotherapy indicated significantly worse survival outcomes in both sexes. However, only female patients with advanced CKD showed poorer RFS. After adjusting for renal function, the analysis found men had worse RFS. CONCLUSION: The female sex is significantly associated with a higher prevalence of advanced CKD stage, and dialysis among patients with UTUC who underwent RNU in our institute. Sex differences in renal function needs to be considered when evaluating survival.

Prognostic Factors for Contralateral Recurrence of Upper Tract Urothelial Carcinoma after Nephroureterectomy: A Large Multiregional Study.

This study aimed to examine the prognostic significance of preoperative inflammation-associated blood cell markers in the metachronous contralateral recurrence of upper tract urothelial carcinoma (UTUC). Patients with nonmetastatic UTUC treated in Taiwan and the U.S. between 1990 and 2017 were included. The Kaplan-Meier method was used to calculate the contralateral recurrence rate, and multivariate logistic regression was performed to study the association of blood cell markers and clinicopathological characteristics with contralateral recurrence. Overall, a total of 1039 patients were included in this study, 52 of whom (5.0%) developed metachronous recurrence of the contralateral side. Kaplan-Meier analysis indicated that a history of bladder cancer (p = 0.006), multiple tumors (p = 0.016), advanced chronic kidney disease (CKD; p < 0.001), elevated serum white blood cell (WBC) count (p < 0.001), and decreased hemoglobin levels (p = 0.001) significantly reduced the contralateral recurrence-free survival. Multivariate analysis showed that multiple tumors (hazard ratio (HR), 1.87; p = 0.030), advanced CKD (HR, 2.63; p = 0.002) and increased WBC count (HR, 2.60; p = 0.001) were independent risk factors for higher contralateral recurrence rate. Notably, advanced CKD was a significant factor regardless of the patient's region. In summary, multiple tumors, advanced CKD and elevated serum WBC count are independent predictors of contralateral recurrence in patients with UTUC. It is recommended that patients with these adverse characteristics be closely followed up to monitor the opposite upper urinary tract.

The Predictive Value of Systemic Immune-Inflammation Index on Bladder Recurrence on Upper Tract Urothelial Carcinoma Outcomes after Radical Nephroureterectomy.

BACKGROUND: This study aimed to assess the prognostic significance of pre-treatment lymphocyte-related systemic inflammatory biomarkers in upper tract urothelial carcinoma (UTUC) patients. METHODS: This study included non-metastatic UTUC patients treated at our hospital between 2001 and 2013. The receiver operating characteristic curve was used to obtain the optimal neutrophile-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), and systemic immune-inflammation index (SII). Multivariate logistic regression was performed to investigate the relationship between NLR, PLR, and SII and clinical pathologic characteristics. The Kaplan-Meier method was used to calculate the metastasis-free survival (MFS), cancer-specific survival (CSS), and bladder recurrence-free survival (BRFS), and the log-rank test was used to compare the survival rate. RESULTS: Overall, 376 patients were included in the current study. An elevated SII was associated with symptomatic hydronephrosis, bladder cancer history, advanced pathologic tumor stage, lymph node invasion, adjuvant chemotherapy and concomitant carcinoma in situ (CIS); high NLR was associated with older age, symptomatic hydronephrosis, hemodialysis status, anemia, multifocal tumor, advanced pathologic tumor stage, and adjuvant chemotherapy; and high PLR was associated with older age, anemia, advanced pathologic tumor stage, and adjuvant chemotherapy. The Kaplan-Meier analysis indicated that patients exhibiting higher NLR, PLR, and SII showed significantly poor MFS and CSS rates. Only high SII showed significantly worse BRFS rates. CONCLUSIONS: The NLR, PLR, and SII were independent predictive factors for both MFS and CSS in UTUC patients. Among the factors, only elevated SII can predict bladder recurrence. Therefore, the patients might need close bladder monitoring during the follow-up.

Nepenthes Extract Induces Selective Killing, Necrosis, and Apoptosis in Oral Cancer Cells.

Ethyl acetate Nepenthes extract (EANT) from Nepenthes thorellii × (ventricosa × maxima) shows antiproliferation and apoptosis but not necrosis in breast cancer cells, but this has not been investigated in oral cancer cells. In the present study, EANT shows no cytotoxicity to normal oral cells but exhibits selective killing to six oral cancer cell lines. They were suppressed by pretreatment of the antioxidant inhibitor N-acetylcysteine (NAC), demonstrating that EANT-induced cell death was mediated by oxidative stress. Concerning high sensitivity to EANT, Ca9-22 and CAL 27 oral cancer cells were chosen for exploring detailed selective killing mechanisms. EANT triggers a mixture of necrosis and apoptosis as determined by annexin V/7-aminoactinmycin D analysis. Still, they show differential switches from necrosis at a low (10 µg/mL) concentration to apoptosis at high (25 µg/mL) concentration of EANT in oral cancer cells. NAC induces necrosis but suppresses annexin V-detected apoptosis in oral cancer cells. Necrostatin 1 (NEC1), a necroptosis inhibitor, moderately suppresses necrosis but induces apoptosis at 10 µg/mL EANT. In contrast, Z-VAD-FMK, a pancaspase inhibitor, slightly causes necrosis but suppresses apoptosis at 10 µg/mL EANT. Furthermore, the flow cytometry-detected pancaspase activity is dose-responsively increased but is suppressed by NAC and ZVAD, although not for NEC1 in oral cancer cells. EANT causes several oxidative stress events such as reactive oxygen species, mitochondrial superoxide, and mitochondrial membrane depolarization. In response to oxidative stresses, the mRNA for antioxidant signaling, such as nuclear factor erythroid 2-like 2 (NFE2L2), catalase (CAT), heme oxygenase 1 (HMOX1), and thioredoxin (TXN), are overexpressed in oral cancer cells. Moreover, EANT also triggers DNA damage, as detected by γH2AX and 8-oxo-2'-deoxyguanosine adducts. The dependence of oxidative stress is validated by the evidence that NAC pretreatment reverts the changes of cellular and mitochondrial stress and DNA damage. Therefore, EANT exhibits antiproliferation involving an oxidative stress-dependent necrosis/apoptosis switch and DNA damage in oral cancer cells.

Withaferin A Triggers Apoptosis and DNA Damage in Bladder Cancer J82 Cells through Oxidative Stress.

Withaferin A (WFA), the Indian ginseng bioactive compound, exhibits an antiproliferation effect on several kinds of cancer, but it was rarely reported in bladder cancer cells. This study aims to assess the anticancer effect and mechanism of WFA in bladder cancer cells. WFA shows antiproliferation to bladder cancer J82 cells based on the finding of the MTS assay. WFA disturbs cell cycle progression associated with subG1 accumulation in J82 cells. Furthermore, WFA triggers apoptosis as determined by flow cytometry assays using annexin V/7-aminoactinomycin D and pancaspase detection. Western blotting also supports WFA-induced apoptosis by increasing cleavage of caspases 3, 8, and 9 and poly ADP-ribose polymerase. Mechanistically, WFA triggers oxidative stress-association changes, such as the generation of reactive oxygen species and mitochondrial superoxide and diminishment of the mitochondrial membrane potential, in J82 cells. In response to oxidative stresses, mRNA for antioxidant signaling, such as nuclear factor erythroid 2-like 2 (NFE2L2), catalase (CAT), superoxide dismutase 1 (SOD1), thioredoxin (TXN), glutathione-disulfide reductase (GSR), quinone dehydrogenase 1 (NQO1), and heme oxygenase 1 (HMOX1), are overexpressed in J82 cells. In addition, WFA causes DNA strand breaks and oxidative DNA damages. Moreover, the ROS scavenger N-acetylcysteine reverts all tested WFA-modulating effects. In conclusion, WFA possesses anti-bladder cancer effects by inducing antiproliferation, apoptosis, and DNA damage in an oxidative stress-dependent manner.

A retrospective study on sex difference in patients with urolithiasis: who is more vulnerable to chronic kidney disease?

BACKGROUND: Urolithiasis is considered a vital public health issue with a substantial burden on kidney function. Additionally, only few reports focused on the gender difference in patients with urolithiasis. Therefore, this study aimed to compare the clinical characteristics of sex difference and their potential risk for chronic kidney disease (CKD) in patients with urolithiasis. METHODS: Patients diagnosed with stone disease from 2013 to 2018 were retrospectively reviewed and divided into two groups by gender. Clinical demographic characteristics, stone location, stone composition, urine chemistries, and renal function were investigated. Univariate and multivariate analyses were used to assess the relationship and potential risk of CKD between sex groups. RESULTS: A total of 1802 patients were included: 1312 from men and 490 from women. Female patients had a higher rate of hypertension, diabetes, and dyslipidemia. Male patients predominantly had calcium-containing stones, especially calcium oxalate stone, uric acid stone, and struvite stone. Carbonate apatite stone was more frequently found in women. Complex surgeries such as percutaneous nephrolithotomy (PCNL) and ureteroscopic lithotripsy (URSL) were more frequently performed in women than that in men. Multivariate analysis confirmed that age > 60 years (odds ratios [ORs] = 6.36; 95% confidence interval [CI], 3.8-10.8), female sex (ORs = 5.31; 95% CI 3.3-8.4), uric acid stone (ORs = 3.55; 95% CI 2.0-6.4), hypertension (OR = 7.20; 95% CI 3.8-13.7), and diabetes (OR = 7.06; 95% CI 3.1-16.2) were independent predictors of poor prognoses in CKD. CONCLUSIONS: The female gender is significantly associated with a higher prevalence of CKD among patients with urolithiasis. Therefore, women with stone disease may need close renal function monitoring during follow-up.

Extraperitoneal Robotic Laparo-Endoscopic Single-Site Plus1-Port Radical Prostatectomy Using the da Vinci Single-Site Platform.

Currently, over 80% of radical prostatectomies have been performed with the da Vinci Surgical System. In order to improve the aesthetic outlook and decrease the morbidity of the operation, the new da Vinci Single Port (SP) system was developed in 2018. However, one major problem is the SP system is still not available in most countries. We aim to present our initial experience and show the safety and feasibility of the single-site robotic-assisted radical prostatectomy (LESS-RP) using the da Vinci Single-Site platform. From June 2017 to January 2020, 120 patients with localized prostate cancer (stage T1-T3b) at Kaohsiung Medical University Hospital were included in this study. We describe our technique and report our initial results of LESS-RP using the da Vinci Si robotic system. Preoperative, intraoperative and postoperative patient variables were recorded. Prostate-specific antigen (PSA)-free survival was also analyzed. A total of 120 patients were enrolled in the study. The median age of patients was 68 years (IQR 63-71), with a median body mass index of 25 kg/m2 (IQR 23-27). The median PSA value before operation was 10.7 ng/mL (IQR 7.9-21.1). The median setup time for creat-ing the extraperitoneal space and ports document was 25 min (IQR 18-34). The median robotic console time and operation time were 135 min (IQR 110-161) and 225 min (IQR 197-274), respectively. Median blood loss was 365 mL (IQR 200-600). There were 11 (9.2%) patients who experienced complications (Clavien-Dindo classification Gr II). The me-dian catheter duration was 8 days (IQR 7-9), with a median of 10 days (IQR 7-11) of hospital stay. The PSA free-survival rate was 86% at a median 19 months (IQR 6-28) of follow up. Robotic radical prostatectomy using the da Vinci Single-Site platform system is safe and feasible, with acceptable outcomes.

Interethnic differences in the impact of body mass index on upper tract urothelial carcinoma following radical nephroureterectomy.

PURPOSE: Inconsistent prognostic implications of body mass index (BMI) in upper tract urothelial carcinoma (UTUC) have been reported across different ethnicities. In this study, we aimed to analyze the oncologic role of BMI in Asian and Caucasian patients with UTUC. METHODS: We retrospectively collected data from 648 Asian Taiwanese and 213 Caucasian American patients who underwent radical nephroureterectomy for UTUC. We compared clinicopathologic features among groups categorized by different BMI. Kaplan-Meier method and Cox regression model were used to examine the impact of BMI on recurrence and survival by ethnicity. RESULTS: According to ethnicity-specific criteria, overweight and obesity were found in 151 (23.2%) and 215 (33.2%) Asians, and 79 (37.1%) and 78 (36.6%) Caucasians, respectively. No significant association between BMI and disease characteristics was detected in both ethnicities. On multivariate analysis, overweight and obese Asians had significantly lower recurrence than those with normal weight (HR 0.631, 95% CI 0.413-0.966; HR 0.695, 95% CI 0.493-0.981, respectively), and obesity was an independent prognostic factor for favorable cancer-specific and overall survival (HR 0.521, 95% CI 0.342-0.794; HR 0.545, 95% CI 0.386-0.769, respectively). There was no significant difference in outcomes among normal, overweight and obese Caucasians, but obese patients had a relatively poorer 5-year RFS, CSS, and OS rates of 52.8%, 60.5%, and 47.2%, compared to 54.9%, 69.1%, and 54.9% for normal weight patients. CONCLUSION: Higher BMI was associated with improved outcomes in Asian patients with UTUC. Interethnic differences could influence preoperative counseling or prediction modeling in patients with UTUC.

Prognostic Significance of Primary Tumor Location in Upper Tract Urothelial Carcinoma Treated with Nephroureterectomy: A Retrospective, Multi-Center Cohort Study in Taiwan.

We sought to examine the effect of tumor location on the prognosis of patients with upper tract urothelial carcinoma (UTUC) treated with radical nephroureterectomy (RNU). This retrospective study came from the Taiwan UTUC Collaboration Group, which consisted of 2658 patients at 15 institutions in Taiwan from 1988 to 2019. Patients with kidney-sparing management, both renal pelvic and ureteral tumors, as well as patients lacking complete data were excluded; the remaining 1436 patients were divided into two groups: renal pelvic tumor (RPT) and ureteral tumor (UT), with 842 and 594 patients, respectively. RPT was associated with more aggressive pathological features, including higher pathological T stage (p < 0.001) and the presence of lymphovascular invasion (p = 0.002), whereas patients with UT often had synchronous bladder tumor (p < 0.001), and were more likely to bear multiple lesions (p = 0.001). Our multivariate analysis revealed that UT was a worse prognostic factor compared with RPT (overall survival: HR 1.408, 95% CI 1.121-1.767, p = 0.003; cancer-specific survival: HR 1.562, 95% CI 1.169-2.085, p = 0.003; disease-free survival: HR 1.363, 95% CI 1.095-1.697, p = 0.006; bladder-recurrence-free survival: HR 1.411, 95% CI 1.141-1.747, p = 0.002, respectively). Based on our findings, UT appeared to be more malignant and had a worse prognosis than RPT.

Single-Site Sutureless Partial Nephrectomy for Small Exophytic Renal Tumors.

Partial nephrectomy (PN) is the standard procedure for most patients with localized renal cancer. Laparoscopy has become the preferred surgical approach to target this cancer, but the steep learning curve with laparoscopic PN (LPN) remains a concern. In LPN intracorporeal suturing, the operation time is further extended even under robot assistance, a step which prolongs warm ischemic time. Herein, we shared our experience to reduce the warm ischemia time, which allows surgeons to perform LPN more easily by using a combination of hemostatic agents to safely control parenchymal bleeding. Between 2015 and 2018, we enrolled 52 patients who underwent LPN in our hospital. Single-site sutureless LPN and traditional suture methods were performed in 33 and 19 patients, respectively. Preoperative, intra-operative, and postoperative variables were recorded. Renal function was evaluated by estimated glomerular filtration rate (eGFR) pre- and postoperatively. The average warm ischemia time (sutureless vs. suture group; 11.8 ± 3.9 vs. 21.2 ± 7.2 min, p < 0.001) and the operation time (167.9 ± 37.5 vs. 193.7 ± 42.5 min, p = 0.035) were significantly shorter in the sutureless group. In the sutureless group, only 2 patients suffered from massive urinary leakage (>200 mL/day) from the Jackson Pratt drainage tube, but the leakage spontaneously decreased within 7 days after surgery. eGFR and serum hemoglobin were not found to be significantly different pre- and postoperatively. All tumors were removed without a positive surgical margin. All patients were alive without recurrent tumors at mean postoperative follow-ups of 29.3 ± 12.2 months. Single-site sutureless LPN is a feasible surgical method for most patients with small exophytic renal cancer with excellent cosmetic results without affecting oncological results.

Interrelationship of environmental melamine exposure, biomarkers of oxidative stress and early kidney injury.

Melamine contamination has remained pervasive in the environment even after the 2008 toxic milk scandal. Exposure to chronic low dosages of melamine is known to induce renal tubular damage, increasing the risk of stone formation and early kidney injury. This damage may come about via increased oxidative stress, but no studies of this possibility have been performed in humans. We conducted two human studies in 80 workers from melamine tableware factories (melamine workers) and 309 adult patients with calcium urolithiasis (stone patients) to evaluate the relationships between urinary melamine levels and two urinary biomarkers of oxidative stress, 8-oxo-2'-deoxyguanosine (8-OHdG) and malondialdehyde (MDA). Both human studies showed urinary melamine levels to be significantly and positively correlated with urinary 8-OHdG and MDA, indicating melamine exposure can increase oxidative stress. Additionally, we used structure equation modeling to evaluate relative contribution of type of melamine-induced oxidative stress on renal tubular injury and found that MDA mediated 36 %-53 % of the total effect of melamine on a biomarker of renal tubular injury, N-Acetyl-ß-d Glucosaminidase (NAG). In conclusion, our findings suggest exposure to low-dose melamine can increase oxidative stress and increase the risk of early damage to kidneys in humans.

Role of Microtubule-Associated Protein 1b in Urothelial Carcinoma: Overexpression Predicts Poor Prognosis.

We sought to examine the relationship between microtubule-associated proteins (MAPs) and the prognosis of urothelial carcinoma by assessing the microtubule bundle formation genes using a reappraisal transcriptome dataset of urothelial carcinoma (GSE31684). The result revealed that microtubule-associated protein 1b (MAP1B) is the most significant upregulated gene related to cancer progression. Real-time reverse-transcription polymerase chain reaction was used to measure MAP1B transcription levels in urothelial carcinoma of the upper tract (UTUC) and the bladder (UBUC). Immunohistochemistry was conducted to detect MAP1B protein expression in 340 UTUC and 295 UBUC cases. Correlations of MAP1B expression with clinicopathological status, disease-specific survival, and metastasis-free survival were completed. To assess the oncogenic functions of MAP1B, the RTCC1 and J82 cell lines were stably silenced against their endogenous MAP1B expression. Study findings indicated that MAP1B overexpression was associated with adverse clinical features and could independently predict unfavorable prognostic effects, indicating its theranostic value in urothelial carcinoma.

Urolithiasis increases the risk of subsequent onset of osteoporosis.

Urolithiasis and osteoporosis are two different pathological entities, but are both important public health issues in older patients. Moreover, the two diseases may share some similar pathogenesis pathway. Currently, few studies focus on the relationship between urolithiasis and osteoporosis. Furthermore, whether the common mobilities influence the long-term osteoporosis rate in urolithiasis patients has never been studied. In the present study, we used the Taiwan National Health Insurance Database (LHID 2000) compiled by the NHI from 1996 to 2013 to determine whether urolithiasis influenced long-term osteoporosis; controls were matched for age, sex, and other comorbidities (including hypertension, diabetes mellitus, dyslipidemia, liver disease, and cardiovascular disease). We included a total of 91,254 patients, including 22,575 patients with urolithiasis and 68,679 control patients. There was a significant difference between the incidence of osteoporosis between the urolithiasis and control groups (adjusted hazard ratio 1.34, 95% CI 1.19-1.79, p < 0.001) during the follow up. The incidence rate of osteoporosis during the follow-up period was 8.87 per 1000 person-years in the urolithiasis group and 6.37 per 1000 person-years in the control group. Based on our results, it is evident that urolithiasis significantly increases the subsequent osteoporosis rate. Though the clinical mechanisms are not fully understood, patients who have a history of urolithiasis may need regular follow-up assessment of bone marrow density.