Preoperative smoking and robot-assisted radical cystectomy outcomes & complications in multicenter KORARC database.

To investigate the influence of preoperative smoking history on the survival outcomes and complications in a cohort from a large multicenter database. Many patients who undergo radical cystectomy (RC) have a history of smoking; however, the direct association between preoperative smoking history and survival outcomes and complications in patients with muscle-invasive bladder cancer (MIBC) who undergo robot-assisted radical cystectomy (RARC) remains unexplored. We conducted a retrospective analysis using data from 749 patients in the Korean Robot-Assisted Radical Cystectomy Study Group (KORARC) database, with an average follow-up duration of 30.8 months. The cohort was divided into two groups: smokers (n = 351) and non-smokers (n = 398). Propensity score matching was employed to address differences in sample size and baseline demographics between the two groups (n = 274, each). Comparative analyses included assessments of oncological outcomes and complications. After matching, smoking did not significantly affect the overall complication rate (p = 0.121). Preoperative smoking did not significantly increase the occurrence of complications based on complication type (p = 0.322), nor did it increase the readmission rate (p = 0.076). There were no perioperative death in either group. Furthermore, preoperative smoking history showed no significant impact on overall survival (OS) [hazard ratio (HR) = 0.87, interquartile range (IQR): 0.54-1.42; p = 0.589] and recurrence-free survival (RFS) (HR = 1.12, IQR: 0.83-1.53; p = 0.458) following RARC for MIBC. The extent of preoperative smoking (≤ 10, 10-30, and ≥ 30 pack-years) had no significant influence on OS and RFS in any of the categories (all p > 0.05). Preoperative smoking history did not significantly affect OS, RFS, or complications in patients with MIBC undergoing RARC.

Prediction of Postoperative Creatinine Levels by Artificial Intelligence after Partial Nephrectomy.

Background and Objectives: Multiple factors are associated with postoperative functional outcomes, such as acute kidney injury (AKI), following partial nephrectomy (PN). The pre-, peri-, and postoperative factors are heavily intertwined and change dynamically, making it difficult to predict postoperative renal function. Therefore, we aimed to build an artificial intelligence (AI) model that utilizes perioperative factors to predict residual renal function and incidence of AKI following PN. Methods and Materials: This retrospective study included 785 patients (training set 706, test set 79) from six tertiary referral centers who underwent open or robotic PN. Forty-four perioperative features were used as inputs to train the AI prediction model. XG-Boost and genetic algorithms were used for the final model selection and to determine feature importance. The primary outcome measure was immediate postoperative serum creatinine (Cr) level. The secondary outcome was the incidence of AKI (estimated glomerular filtration rate (eGFR) < 60 mL/h). The average difference between the true and predicted serum Cr levels was considered the mean absolute error (MAE) and was used as a model evaluation parameter. Results: An AI model for predicting immediate postoperative serum Cr levels was selected from 2000 candidates by providing the lowest MAE (0.03 mg/dL). The model-predicted immediate postoperative serum Cr levels correlated closely with the measured values (R2 = 0.9669). The sensitivity and specificity of the model for predicting AKI were 85.5% and 99.7% in the training set, and 100.0% and 100.0% in the test set, respectively. The limitations of this study included its retrospective design. Conclusions: Our AI model successfully predicted accurate serum Cr levels and the likelihood of AKI. The accuracy of our model suggests that personalized guidelines to optimize multidisciplinary plans involving pre- and postoperative care need to be developed.

Single Quantum Dot Selection and Tailor-Made Photonic Device Integration using a Nanoscale-Focus Pinspot.

Among the diverse platforms of quantum light sources, epitaxially grown semiconductor quantum dots (QDs) are one of the most attractive workhorses for realizing quantum photonic technologies owing to their outstanding brightness and scalability. However, the spatial and spectral randomness of most QDs severely hinders the construction of large-scale photonic platforms. In this work, a methodology is presented to deterministically integrate single QDs with tailor-made photonic structures. A nondestructive luminescence picking method termed as nanoscale-focus pinspot (NFP) is applied using helium-ion microscopy to reduce the luminous QD density while retaining the surrounding medium. A single QD emission is only extracted out of the high-density ensemble QDs. Then the tailor-made photonic structure of a circular Bragg reflector (CBR) is designed and deterministically integrated with the selected QD. Given that the microscopy can image with nanoscale resolution and apply NFP in situ, photonic devices can be deterministically fabricated on target QDs. The extraction efficiency of the NFP-selected QD emission is improved by 25 times after the CBR integration. Since the NFP method only controls the luminescence without destroying the medium, it is applicable to various photonic structures such as photonic waveguides or photonic crystal cavities regardless of materials.

Inhibition of EZH2 exerts antitumorigenic effects in renal cell carcinoma via LATS1.

The most common type of kidney cancer in adults is renal cell carcinoma (RCC), which accounts for approximately 90% of cases. RCC is a variant disease with numerous subtypes; the most common subtype is clear cell RCC (ccRCC, 75%), followed by papillary RCC (pRCC, 10%) and chromophobe RCC (chRCC, 5%). To identify a genetic target for all subtypes, we analyzed The Cancer Genome Atlas (TCGA) databases of ccRCC, pRCC, and chromophobe RCC. Enhancer of zeste homolog 2 (EZH2), which encodes a methyltransferase, was observed to be significantly upregulated in tumors. The EZH2 inhibitor tazemetostat induced anticancer effects in RCC cells. TCGA analysis revealed that large tumor suppressor kinase 1 (LATS1), a key tumor suppressor of the Hippo pathway, was significantly downregulated in tumors; the expression of LATS1 was increased by tazemetostat. Through additional experiments, we confirmed that LATS1 plays a crucial role in EZH2 inhibition and has a negative association with EZH2. Therefore, we suggest that epigenetic control could be a novel therapeutic strategy for three subtypes of RCC.

Effect of α1D-adrenoceptor blocker for the reduction of ureteral contractions.

PURPOSE: Urolithiasis is a common urinary tract disease with growing prevalence. Alpha1-adrenoceptors (α1-ARs) are abundant in ureteral smooth muscle, distributed with different α1-AR subtypes. α1D-AR is the most widely distributed in the ureter. However, the effect of α1D-AR blockade on ureteric contraction remains unknown. MATERIALS AND METHODS: We dissected smooth muscle tissues (3 mm×3 mm) from the rat bladder and human ureter, tied silk strips on both tissue ends, and measured contraction in an organ bath chamber. Contraction activity in ureteral smooth muscle cells (USMCs) was immunocytochemically examined using primary rat and human USMC cultures. RESULTS: Using the organ bath system, we determined the inhibitory effects of silodosin, tamsulosin, and naftopidil. Naftopidil significantly decreased contractility of rat bladder tissue; similar results were observed in human ureteral tissue. To confirm ex vivo experimental results in vitro , we examined the phosphorylation of myosin light chain (MLC), a marker of contractility, in a primary human USMC culture. The examined drugs decreased phospho-MLC levels in human USMCs; however, naftopidil profoundly increased MLC dephosphorylation. CONCLUSIONS: We studied the effects of naftopidil, an α1D-AR inhibitor, on the ureter. Compared with alpha-blockers, naftopidil significantly relaxed ureteral smooth muscle. Therefore, naftopidil could be an effective therapy for patients with ureteral stones.

Therapeutic Efficacy of YM155 to Regulate an Epigenetic Enzyme in Major Subtypes of RCC.

Renal cell carcinoma (RCC) is the most common type of kidney cancer and includes more than 10 subtypes. Compared to the intensively investigated clear cell RCC (ccRCC), the underlying mechanisms and treatment options of other subtypes, including papillary RCC (pRCC) and chromogenic RCC (chRCC), are limited. In this study, we analyzed the public databases for ccRCC, pRCC, and chRCC and found that BIRC5 was commonly overexpressed in a large cohort of pRCC and chRCC patients as well as ccRCC and was closely related to the progression of RCCs. We investigated the potential of BIRC5 as a therapeutic target for these three types of RCCs. Loss and gain of function studies showed the critical role of BIRC5 in cancer growth. YM155, a BIRC5 inhibitor, induced a potent tumor-suppressive effect in the three types of RCC cells and xenograft models. To determine the mechanism underlying the anti-tumor effects of YM155, we examined epigenetic modifications in the BIRC5 promoter and found that histone H3 lysine 27 acetylation (H3K27Ac) was highly enriched on the promoter region of BIRC5. Chromatin-immunoprecipitation analysis revealed that H3K27Ac enrichment was significantly decreased by YM155. Immunohistochemistry of xenografted tissue showed that overexpression of BIRC5 plays an important role in malignancy in RCC. Furthermore, high expression of P300 was significantly associated with the progression of RCC. Our findings demonstrate the P300-H3K27Ac-BIRC5 cascade in three types of RCC and provide a therapeutic path for future research on RCC.

Ginsenoside Rh2 sensitizes the anti-cancer effects of sunitinib by inducing cell cycle arrest in renal cell carcinoma.

Sunitinib, a VEGF blockade, is used to treat clear cell renal cell carcinoma (ccRCC). However, the anti-cancer treatment effects of sunitinib do not last long in ccRCC patients. Ginsenoside, a natural medicine extracted from ginseng, has been studied in cancer treatment and shown to have anti-tumor effects and low toxicity. We assessed cell viability and cell cycle analysis in ccRCC cell lines after treatment with ginsenoside and sunitinib. DNA damage was evaluated by measuring 8-OHdG levels and comet assay. ROS levels, reflecting the cause of oxidative stress, were also measured. Ginsenoside significantly enhanced the inhibition of cell viability by sunitinib, a result that was also confirmed in the xenograft model. In cell cycle analysis, combination treatment of ginsenoside and sunitinib enhanced G2M arrest in comparison with single-treatment groups. In addition, DNA damage was increased by ginsenoside and sunitinib according to the comet assay, and the level of 8-OHdG, which reflects oxidative DNA damage, also increased. We verified that ginsenoside enhances the efficacy of sunitinib to inhibit the proliferation of ccRCC cells via induction of oxidative DNA damage. The combination therapy of sunitinib and ginsenoside suggested the possibility of effectively treating ccRCC patients.

SWIR imaging using PbS QD photodiode array sensors.

We fabricated a 1 × 10 PbS QD photodiode array with multiple stacked QD layers with high-resolution patterning using a customized photolithographic process. The array showed the average responsivity of 5.54 × 10-3 A/W and 1.20 × 10-2 A/W at 0 V and -1 V under 1310- nm short-wavelength infrared (SWIR) illumination. The standard deviation of the pixel responsivity was under 10%, confirming the uniformity of the fabrication process. The response time was 2.2 ± 0.13 ms, and the bandwidth was 159.1 Hz. A prototype 1310-nm SWIR imager demonstrated that the QD photodiode-based SWIR image sensor is a cost-effective and practical alternative for III-V SWIR image sensors.

Anti-adhesion agent to prevent of post-operative adhesion and fibrosis after vasectomy: a study using a rat model.

Background: Post-vasectomy pain syndrome (PVPS) is difficult to treat. Direct damage to the vas deferens, inflammation, compression of nerves through fibrotic adhesions, and congestion of the epididymis are known to cause PVPS. The purpose of this study was to evaluate whether the application of anti-adhesion agents after vasectomy can reduce the degree of adhesion and fibrosis in a rat model. Methods: In the study, 11 Sprague-Dawley rats (22 vas deferens) from each group were evaluated. In the experimental group, surgery was terminated after applying the anti-adhesion agent; this was not applied in the control group. After 14 days of vasectomy, the scrotum was dissected to evaluate the degree of gross adhesion at the vasectomy site. Histological examination of the surrounding tissues, including the vas deferens and the spermatic cord, was also performed. Results: Adhesions were not observed in 72.73% (16/22) rats from the experimental group, in which the anti-adhesion agent was applied; in contrast, the incidence of adhesions in the control group was 100%. There was a statistically significant relationship between the distribution of grades for adhesion and anti-adhesion agent (chi-square, P<0.001). On classification of fibrosis and inflammation, application of the anti-adhesion agent was significantly associated with lower grade inflammation and fibrosis compared to that of the control group (chi-square, P=0.001). The rate of intact muscle structure was 90.91% (20/22) in the experimental group, and 36.36% (8/22) in the control group, and the application of the anti-adhesion agent demonstrated significant association with preservation of intact muscle structure (chi-square, P<0.001). Conclusions: The application of an anti-adhesion agent after vasectomy prevented the development of adhesion, fibrosis, and inflammation reaction and further reduced structural destruction.

Synergic Effect of Metformin and Everolimus on Mitochondrial Dynamics of Renal Cell Carcinoma.

Renal cell carcinoma (RCC) frequently recurs or metastasizes after surgical resection. Everolimus, an mTOR inhibitor, is used as a second-line treatment, but the response of RCC to everolimus is insufficient. Metformin is an antidiabetic drug; recent reports have indicated its anti-cancer effects in various cancers, and it is known to have synergistic effects with other drugs. We investigated the possibility of coadministering everolimus and metformin as an effective treatment for RCC. RCC cells treated with a combination of the two drugs showed significantly inhibited cell viability, cell migration, and invasion, and increased apoptosis compared to those treated with each drug alone. An anti-cancer synergistic effect was also confirmed in the xenograft model. Transcriptome analysis for identifying the underlying mechanism of the combined treatment showed the downregulation of mitochondrial fusion genes and upregulation of mitochondrial fission genes by the combination treatment. Changes in mitochondrial dynamics following the combination treatment were observed using LysoTracker, LysoSensor, and JC-1 staining. In conclusion, the combination of everolimus and metformin inhibited RCC growth by disrupting mitochondrial dynamics. Therefore, we suggest that a treatment combining metformin and everolimus disrupts mitochondrial dynamics in RCC, and may be a novel strategy for RCC treatment.

Predicting factor analysis of postoperative complications after robot-assisted radical cystectomy: Multicenter KORARC database study.

OBJECTIVES: To evaluate postoperative complications following robot-assisted radical cystectomy in patients diagnosed with bladder cancer and reveal if there are predictors for postoperative complications. METHODS: Prospectively collected medical records of 730 robot-assisted radical cystectomy patients between 2007/04 and 2019/05 in 13 tertiary referral centers were reviewed. Perioperative outcomes were compared between two groups by postoperative complications (complication vs non-complication). We assessed recurrence-free survival, cancer-specific survival, and overall survival between groups. Regression analyses were implemented to identify factors associated with postoperative complications. RESULTS: Any total and high-grade complication (Clavien-Dindo grade ≥3) rates were 57.8% and 21.1%, respectively. Patients in complication group had significantly higher proportion of diabetes mellitus (P = 0.048), chronic kidney disease (P = 0.011), dyslipidemia (P < 0.001), longer operation time (P = 0.001), more estimated blood loss (P = 0.001), and larger intraoperative fluid volume (P < 0.001). There was a significant difference in cancer-specific survival (log-rank P = 0.038, median cancer-specific survival: both groups not reached). Dyslipidemia (odds ratio 2.59, P = 0.002) and intraoperative fluid volume (odds ratio 1.0002, P = 0.040) were significantly associated with high-grade postoperative complications. Diabetes mellitus (odds ratio 1.97, P = 0.028), chronic kidney disease (odds ratio 1.89, P = 0.046), dyslipidemia (odds ratio 5.94, P = 0.007), and intraoperative fluid volume (odds ratio 1.0002, P = 0.009) were significantly associated with any postoperative complications. CONCLUSIONS: Patients with diabetes mellitus, chronic kidney disease, dyslipidemia, or a relatively large intraoperatively infused fluid volume are more likely to develop postoperative complications. Patients with postoperative complications might have a possibility of lower cancer-specific survival rate.

Gender-related outcomes in robot-assisted radical cystectomy: A multi-institutional study.

PURPOSE: Robot-assisted radical cystectomy (RARC) optimizes patient recovery and has outcomes comparable with those of open surgery. This study aimed to compare the perioperative and oncologic outcomes of RARC in female and male patients. MATERIALS AND METHODS: A retrospective cohort study of the Korean Robot-Assisted Radical Cystectomy Study Group database from 2007 to 2019 identified 749 patients (111 females and 638 males). Female were matched 1:1 to male by propensity score matching using a logistic regression. We compared perioperative outcomes, oncologic outcomes, and complications between the two groups. RESULTS: The female group had comparable perioperative outcomes to the male group in terms of operation time, lymph node yield, positive surgical margin, blood transfusion rate, and hospitalization days. Complication rate and grade were not significantly different between the two groups. The most common complication was infection in female and gastrointestinal complications in male. We compared the 5-year overall, disease-specific, and recurrence-free survival of female and male: 58.2% vs. 68.0% (p=0.495), 75.7% vs. 79.3% (p=0.645), and 40.8% vs. 53.5% (p=0.913), respectively. On multivariable analysis, T stage (>T2), postoperative complications, and positive surgical margin were prognostic factors of poor outcome. Sex was not an independent predictor of the three survivals. CONCLUSIONS: The current study suggests that RARC in female has comparable perioperative and oncologic outcomes to those in male. The complication rate of RARC in female was comparable to that in male, but the type of complications differed by sex.

Epidemiologic study of bladder and urethral injury in Korea: A nationwide population-based study.

PURPOSE: We aimed to analyze the characteristics and management of bladder and urethral injuries in Korea by use of the National Health Insurance Service (NHIS) database. MATERIALS AND METHODS: Data from the NHIS database representative of all cases of Korean bladder injury (n=4,631) and urethral injury (n=17,858) reported between 2012 and 2016 were analyzed. We used the International Classification of Diseases, 10th revision, clinical modification codes to identify the diagnoses. RESULTS: A total of 491 males (1.97/100,000) and 590 females (2.39/100,000) experienced bladder injury in 2012, and 449 males (1.76/100,000) and 624 females (2.47/100,000) in 2016. The risk of bladder injury was higher in female than in male (hazard ratio [HR], 1.267; p<0.001). The annual incidence of bladder injury did not increase (HR, 0.992; p=0.409). A total of 2,886 (62.3%) patients were managed with conservative treatment, and 1,745 (37.7%) patients underwent surgical treatment. A total of 4,114 males (16.5/100,000) and 285 females (1.2/100,000) had urethral injury in 2012, while 4,465 males (17.5/100,000) and 303 females (1.2/100,000) had urethral injury in 2016. The incidence of urethral injury is increasing annually (HR, 1.010; p=0.036). CONCLUSIONS: The incidence of urethral injury increased continuously over the years studied, whereas that of bladder injury remained unchanged in Korea. The incidence of bladder injury was higher in females, and more than 90% of total urethral injuries were reported in males. This is the first study to evaluate the epidemiology of bladder and urethral injury using a nationwide population database.

Signaling Role of Adipocyte Leptin in Prostate Cell Proliferation Induced by Trichomonas vaginalis.

Leptin is a type of adipokine mainly produced by adipocytes and reported to be overproduced in prostate cancer. However, it is not known whether it stimulates the proliferation of prostate cells. In this study, we investigated whether benign prostatic hyperplasia epithelial cells (BPH-1 cells) infected with Trichomonas vaginalis induced the proliferation of prostate cells via a leptin signaling pathway. To investigate the effect of crosstalk between adipocyte leptin and inflamed epithelial cell in proliferation of prostate cells, adipocytes 3T3-L1 cells were incubated in conditioned medium of BPH-1 cells infected with T. vaginalis (T. vaginalis-conditioned medium, TCM), and then the adipocyte-conditioned medium (ATCM) was identified to cause proliferation of prostate cells. BPH-1 cells incubated with live T. vaginalis released pro-inflammatory cytokines, and conditioned medium of these cells caused migration of adipocytes. When prostate stromal cells and BPH-1 cells were incubated with adipocyte conditioned medium containing leptin, their growth rates increased as did expression of the leptin receptor (known as OBR) and signaling molecules such as JAK2/STAT3, Notch and survivin. Moreover, blocking the OBR reduced this proliferation and the expression of leptin signaling molecules in response to ATCM. In conclusion, our findings show that inflamed BPH-1 cells infected with T. vaginalis induce the proliferation of prostate cells through leptin-OBR signaling. Therefore, it is likely that T. vaginalis contributes to prostate enlargement in BPH via adipocyte leptin released as a result of inflammation of the prostate.

Effect of intraoperative fluid volume on postoperative ileus after robot-assisted radical cystectomy.

This study aimed to investigate the effect of intraoperative fluid volume on the postoperative ileus (POI) recovery period. A retrospective review of the Korean robot-assisted radical cystectomy database identified 718 patients who underwent robot-assisted radical cystectomy (RARC). Regression analyses were performed to identify the associations between the amount of intraoperative fluid administration (crystalloid/colloid/total), POI period (time to flatus/bowel movements), and length of hospital stay (LOS) after adjusting for covariates. In addition, we analyzed the risk factors for gastrointestinal complications and prolonged POI using a logistic regression model. An increasing volume of the administered crystalloid/total fluid was associated with prolonged POI (crystalloid R2 = 0.0725 and P < 0.0001; total amount R2 = 0.0812 and P < 0.0001), and the total fluid volume was positively associated with the LOS (R2 = 0.099 and P < 0.0001). The crystalloid amount was a risk factor for prolonged POI (P < 0.001; odds ratio, 1.361; 95% confidence interval, 1.133-1.641; P < 0.001). In the context of RARC, increased intravenous fluids are associated with prolonged POI and longer LOS.

Oncologic Outcomes of Intracorporeal vs Extracorporeal Urinary Diversion After Robot-Assisted Radical Cystectomy: A Multi-Institutional Korean Study.

Background: We aimed to compare the oncologic outcomes of intracorporeal urinary diversion (ICUD) and extracorporeal urinary diversion (ECUD) following robot-assisted radical cystectomy (RARC) in patients diagnosed with bladder cancer. Materials and Methods: Medical records of 730 patients who underwent RARC between April 2007 and May 2019 in 11 tertiary referral centers were retrospectively reviewed. We assessed recurrence-free survival (RFS), cancer-specific survival (CSS), and overall survival (OS) in the two groups using the Kaplan-Meier method. Cox regression models were used to identify factors associated with RFS, CSS, and OS. Results: Among 591 patients, neobladder diversion was performed more frequently in the ICUD group (70.8% vs 52.5%, p = 0.001). The median follow-up duration was shorter in the ICUD group than in the ECUD group (16 vs 26 months, p < 0.001). The rates of overall recurrence (36.5% vs 25.5%, p = 0.013) and pelvic recurrence (12.1% vs 5.9%, p = 0.031) were higher in the ECUD group. However, no differences in 5-year RFS (43.2% vs 58.4%, p = 0.516), CSS (79.3% vs 89.7%, p = 0.392), and OS (74.3% vs 81.4%, p = 0.411) were noted between the two groups. Multivariable analysis revealed that when compared to ICUD, ECUD was not associated with RFS (hazard ratio [HR], 0.982; p = 0.920), CSS (HR, 0.568; p = 0.126), and OS (HR, 0.642; p = 0.124). Conclusion: Although there was a difference in recurrence rate between the two groups, multivariable analysis indicated that the diversion technique after RARC did not affect the oncologic outcomes. Large prospective studies with long-term follow-up are warranted to verify the oncologic outcomes of ICUD and ECUD following RARC.

Oncological outcome according to attainment of pentafecta after robot-assisted radical cystectomy in patients with bladder cancer included in the multicentre KORARC database.

OBJECTIVES: To investigate the oncological significance of a robot-assisted radical cystectomy (RARC)-related pentafecta in patients with bladder cancer. PATIENTS AND METHODS: Using the KORARC database, which includes data from 12 centres, data from 730 patients who underwent RARC between April 2007 and May 2019 were prospectively collected and retrospectively analysed. Pentafecta was achieved if patients met all of the following criteria: (i) negative soft tissue surgical margin; (ii) ≥16 lymph nodes removed; (iii) no major complications (Clavien-Dindo grade 3-5) within 90 days; (iv) no clinical recurrence within the first 12 months; and (v) no ureteroenteric stricture. Patients were divided into two groups according to pentafecta attainment, and a comparison of overall survival (OS) and cancer-specific survival (CSS) using multivariate Cox proportional analysis was then carried out. RESULTS: Of the 730 patients included in this analysis, 208 (28.5%) attained the RARC pentafecta; the remaining 522 (71.5%) did not. The mean age of the patients was 64.67 years, 85.1% were men, 53.6% received a conduit, 37.7% received orthotopic neobladders and the total complication rate was 57.8%. Those who attained the pentafecta received more neobladders (P = 0.039), were more likely to be treated with the intracorporeal technique (P < 0.001), had longer operating times (P = 0.020) and had longer console time (P = 0.021) compared with those who did not attain the pentafecta. Over a mean of 31.1 months of follow-up, the pentafecta attainment group had significantly higher OS and CSS rates compared with the non-attainment group (10-year OS 70.4% vs 58.1%, respectively [P = 0.016]; 10-year CSS 87.8% vs 70.0%, respectively [P = 0.036]). Multivariate analysis showed that the RARC pentafecta was a significant predictor of overall mortality (hazard ratio 0.561; P = 0.038). CONCLUSIONS: Patients who attained the RARC pentafecta had significantly better survival outcomes compared with those who did not. These criteria could be used to standardize assessment of the surgical quality of RARC. In the future, a similar study using an independent cohort is warranted to confirm our results.

Visceral Adiposity as a Significant Predictor of Sunitinib-Induced Dose-Limiting Toxicities and Survival in Patients with Metastatic Clear Cell Renal Cell Carcinoma.

Sunitinib is a first-line treatment for metastatic renal cell carcinoma (mRCC). Little is known about the predictive factors of sunitinib-induced dose-limiting toxicity (DLT) in Asian populations. We investigated whether body composition predicts sunitinib-induced DLT. We retrospectively reviewed sunitinib-treated Korean patients with clear cell mRCC from eight institutions. Body composition was measured using computed tomography. DLT was defined as any adverse event leading to dose reduction or treatment discontinuation. Univariate analysis was used to compare body composition indices, and logistic regression analyses were performed for factors predicting early DLT. Overall, 111/311 (32.5%) of patients experienced DLT. Significant differences were observed in the subcutaneous adipose tissue index (SATI; p = 0.001) and visceral adipose tissue index (VATI; p < 0.001) between patients with and without DLT. Multivariate analyses revealed that VATI (odds ratio: 1.013; p = 0.029) was significantly associated with early DLT. Additionally, 20% of patients who had a body mass index (BMI) greater than 23 kg/m2 and a low VATI experienced DLT, whereas 34.3% of the remaining groups had DLT (p = 0.034). Significant differences were observed for median progression-free survival (13.0 vs. 26.0 months, respectively; p = 0.006) between patients with low and high VATI. Visceral adiposity was a significant predictor of sunitinib-associated DLT and survival. Patients with a low VATI and a BMI greater than 23 kg/m2 experienced lower DLTs.

Carbon monoxide-releasing molecule-3: Amelioration of renal ischemia reperfusion injury in a rat model.

Purpose: Despite the role of carbon monoxide in ameliorating ischemia-reperfusion injury (IRI), its use in the clinical setting is restricted owing to its toxicity. Herein, we investigated the in vivo effects of carbon monoxide-releasing molecule-3 (CORM-3) on IRI. Materials and Methods: Fifteen rats were equally and randomly divided into three groups: sham (right nephrectomy), control (right nephrectomy and left renal ischemia), and CORM-3 (right nephrectomy and CORM-3 injection before left renal ischemia). Kidney tissues and blood samples collected from sacrificed rats were evaluated to determine the renoprotective effect and mechanism of CORM-3. Results: Concentrations of serum creatinine and kidney injury molecule-1 in the CORM-3 group were significantly lower than in the control group after 75 minutes of IRI (1.2 vs. 2.4 mg/dL, p=0.01, and 292 vs. 550 pg/mL, p<0.001, respectively). Furthermore, the CORM-3 group exhibited a higher portion of normal tubules and glomeruli. TUNEL staining revealed fewer apoptotic renal tubular cells in the CORM-3 group than in the control group. The expression of 960 genes in the CORM-3 group was also altered. Pretreatment with CORM-3 before renal IRI produced a significant renoprotective effect. Fifteen of the altered genes were found to be involved in the peroxisome proliferator-activated receptors signaling pathway, and the difference in the expression of these genes between the CORM-3 and control groups was statistically significant (p<0.001). Conclusions: CORM-3 ameliorates IRI by decreasing apoptosis and may be a novel strategy for protection against renal warm IRI.

Clinicopathological Significance of MTUS1 Expression in Patients With Renal Cell Carcinoma.

BACKGROUND/AIM: Microtubule-associated tumor suppressor 1 (MTUS1) is a novel tumor suppressor involved in proliferation and migration, and down-regulation of MTUS1 is associated with the poor prognosis of several cancers. We evaluated the clinicopathological significance of MTUS1 expression in renal cell carcinoma (RCC). PATIENTS AND METHODS: We assessed MTUS1 expression by immunohistochemical staining of tissue microarrays from 249 cases of RCC. We analyzed the correlation of MTUS1 expression and clinicopathological characteristics. Additionally, we used public databases and performed bioinformatics analysis. RESULTS: We investigated The Cancer Genome Atlas databases and identified that MTUS1 mRNA expression was significantly lower in RCC tissues than in normal tissues. Loss of MTUS1 expression was correlated with high WHO/ISUP nuclear grade, lymphovascular invasion, renal vein thrombus, and high pT stage in patients with RCC. Although there was no statistically significant correlation between MTUS1 expression and patients' prognosis in our cohort, MTUS1 overexpression was significantly correlated with a favorable prognosis in public data. CONCLUSION: Loss of MTUS1 expression in RCC might be a potential biomarker for predicting clinical outcome.