3D hepatic organoid production from human pluripotent stem cells.

Hepatic organoids might provide a golden opportunity for realizing precision medicine in various hepatic diseases. Previously described hepatic organoid protocols from pluripotent stem cells rely on complicated multiple differentiation steps consisting of both 2D and 3D differentiation procedures. Therefore, the spontaneous formation of hepatic organoids from 2D monolayer culture is associated with a low-throughput production, which might hinder the standardization of hepatic organoid production and hamper the translation of this technology to the clinical or industrial setting. Here we describe the stepwise and fully 3D production of hepatic organoids from human pluripotent stem cells. We optimized every differentiation step by screening for optimal concentrations and timing of differentiation signals in each differentiation step. Hepatic organoids are stably expandable without losing their hepatic functionality. Moreover, upon treatment of drugs with known hepatotoxicity, we found hepatic organoids are more sensitive to drug-induced hepatotoxicity compared with 2D hepatocytes differentiated from PSCs, making them highly suitable for in vitro toxicity screening of drug candidates. The standardized fully 3D protocol described in the current study for producing functional hepatic organoids might serve as a novel platform for the industrial and clinical translation of hepatic organoid technology.

Machine learning models for predicting the onset of chronic kidney disease after surgery in patients with renal cell carcinoma.

BACKGROUND: Patients with renal cell carcinoma (RCC) have an elevated risk of chronic kidney disease (CKD) following nephrectomy. Therefore, continuous monitoring and subsequent interventions are necessary. It is recommended to evaluate renal function postoperatively. Therefore, a tool to predict CKD onset is essential for postoperative follow-up and management. METHODS: We constructed a cohort using data from eight tertiary hospitals from the Korean Renal Cell Carcinoma (KORCC) database. A dataset of 4389 patients with RCC was constructed for analysis from the collected data. Nine machine learning (ML) models were used to classify the occurrence and nonoccurrence of CKD after surgery. The final model was selected based on the area under the receiver operating characteristic (AUROC), and the importance of the variables constituting the model was confirmed using the shapley additive explanation (SHAP) value and Kaplan-Meier survival analyses. RESULTS: The gradient boost algorithm was the most effective among the various ML models tested. The gradient boost model demonstrated superior performance with an AUROC of 0.826. The SHAP value confirmed that preoperative eGFR, albumin level, and tumor size had a significant impact on the occurrence of CKD after surgery. CONCLUSIONS: We developed a model to predict CKD onset after surgery in patients with RCC. This predictive model is a quantitative approach to evaluate post-surgical CKD risk in patients with RCC, facilitating improved prognosis through personalized postoperative care.

Machine learning-based prediction model for late recurrence after surgery in patients with renal cell carcinoma.

BACKGROUND: Renal cell carcinoma is characterized by a late recurrence that occurs 5 years after surgery; hence, continuous monitoring and follow-up is necessary. Prognosis of late recurrence of renal cell carcinoma can only be improved if it is detected early and treated appropriately. Therefore, tools for rapid and accurate renal cell carcinoma prediction are essential. METHODS: This study aimed to develop a prediction model for late recurrence after surgery in patients with renal cell carcinoma that can be used as a clinical decision support system for the early detection of late recurrence. We used the KOrean Renal Cell Carcinoma database that contains large-scale cohort data of patients with renal cell carcinoma in Korea. From the collected data, we constructed a dataset of 2956 patients for the analysis. Late recurrence and non-recurrence were classified by applying eight machine learning models, and model performance was evaluated using the area under the receiver operating characteristic curve. RESULTS: Of the eight models, the AdaBoost model showed the highest performance. The developed algorithm showed a sensitivity of 0.673, specificity of 0.807, accuracy of 0.799, area under the receiver operating characteristic curve of 0.740, and F1-score of 0.609. CONCLUSIONS: To the best of our knowledge, we developed the first algorithm to predict the probability of a late recurrence 5 years after surgery. This algorithm may be used by clinicians to identify patients at high risk of late recurrence that require long-term follow-up and to establish patient-specific treatment strategies.

Utility of a Molecular Signature for Predicting Recurrence and Progression in Non-Muscle-Invasive Bladder Cancer Patients: Comparison with the EORTC, CUETO and 2021 EAU Risk Groups.

To evaluate the utility of different risk assessments in non-muscle-invasive bladder cancer (NMIBC) patients, a total of 178 NMIBC patients from Chungbuk National University Hospital (CBNUH) were enrolled, and the predictive value of the molecular signature-based subtype predictor (MSP888) and risk calculators based on clinicopathological factors (EORTC, CUETO and 2021 EAU risk scores) was compared. Of the 178 patients, 49 were newly analyzed by the RNA-sequencing, and their MSP888 subtype was evaluated. The ability of the EORTC, MSP888 and two molecular subtyping systems of bladder cancer (Lund and UROMOL subtypes) to predict progression of 460 NMIBC patients from the UROMOL project was assessed. Cox regression analyses showed that the MSP888 was an independent predictor of NMIBC progression in the CBNUH cohort (p = 0.043). Particularly in patients without an intravesical BCG immunotherapy, MSP888 significantly linked with risk of disease recurrence and progression (both p < 0.05). However, the EORTC, CUETO and 2021 EAU risk scores showed disappointing results with respect to estimating the NMIBC prognosis. In the UROMOL cohort, the MSP888, Lund and UROMOL subtypes demonstrated a similar capacity to predict NMIBC progression (all p < 0.05). Conclusively, the MSP888 is favorable for stratifying patients to facilitate optimal treatment.

Effect of pre-operative internal obturator muscle mass index in MRI on biochemical recurrence of prostate cancer patients after radical prostatectomy: a multi-center study.

BACKGROUND: Recent reports show that the pre-operative or post-operative skeletal mass index (sarcopenia) affects survival rates for various cancers; however, the link between prostate cancer survival and sarcopenia is unclear. Therefore, this study examined the effect of the pre-operative internal obturator muscle (IOM) mass index on biochemical recurrence (BCR) of prostate cancer (PCa) patients who underwent radical prostatectomy. METHODS: In total, 222 patients, who underwent open, laparoscopic, or robot-assisted radical prostatectomy at seven centers in 2011 and were followed up for 5 years, were enrolled. BCR was examined in the context of pre-operative IOM mass index and BMI. RESULTS: The mean age of the patients was 67.82 ± 6.23 years, and the mean pre-operative prostate-specific antigen (PSA) level was 11.61 ± 13.22 ng/ml. There was no significant difference in baseline characteristics between the low and high IOM mass index groups (p > 0.05). Age, pre-op PSA level, ECE, and T-stage were associated with BCR (p = 0.049, p < 0.001, p = 0.001, p = 0.004, respectively). BMI, prostate volume, Gleason score, resection margin, N-stage, M-stage and IOM mass index was not associated with BCR (p > 0.05). CONCLUSIONS: Pre-operative IOM mass index was not associated with BCR; however, long-term follow-up is necessary to evaluate cancer-specific and overall survival of PCa patients.

Prognostic Value of BUB1 for Predicting Non-Muscle-Invasive Bladder Cancer Progression.

Non-muscle-invasive bladder cancer (NMIBC) is a common disease with a high recurrence rate requiring lifetime surveillance. Although NMIBC is not life-threatening, it can progress to muscle-invasive bladder cancer (MIBC), a lethal form of the disease. The management of the two diseases differs, and patients with MIBC require aggressive treatments such as chemotherapy and radical cystectomy. NMIBC patients at a high risk of progression benefit from early immediate cystectomy. Thus, identifying concordant markers for accurate risk stratification is critical to predict the prognosis of NMIBC. Candidate genetic biomarkers associated with NMIBC prognosis were screened by RNA-sequencing of 24 tissue samples, including 16 NMIBC and eight normal controls, and by microarray analysis (GSE13507). Lastly, we selected and investigated a mitotic checkpoint serine/threonine kinase, BUB1, that regulates chromosome segregation during the cell cycle. BUB1 gene expression was tested in 86 NMIBC samples and 15 controls by real-time qPCR. The performance of BUB1 as a prognostic biomarker for NMIBC was validated in the internal Chungbuk cohort (GSE13507) and the external UROMOL cohort (E-MTAB-4321). BUB1 expression was higher in NMIBC patients than in normal controls (p < 0.05), and the overexpression of BUB1 was correlated with NMIBC progression (log-rank test, p = 0.007). In in vitro analyses, BUB1 promoted the proliferation of bladder cancer cells by accelerating the G2/M transition of the cell cycle. Conclusively, BUB1 modulates the G2/M transition to promote the proliferation of bladder cancer cells, suggesting that it could serve as a prognostic marker in NMIBC.

A Molecular Signature Determines the Prognostic and Therapeutic Subtype of Non-Muscle-Invasive Bladder Cancer Responsive to Intravesical Bacillus Calmette-Guérin Therapy.

Non-muscle-invasive bladder cancer (NMIBC) is clinically heterogeneous; thus, many patients fail to respond to treatment and relapse. Here, we identified a molecular signature that is both prognostic and predictive for NMIBC heterogeneity and responses to Bacillus Calmette-Guérin (BCG) therapy. Transcriptomic profiling of 948 NMIBC patients identified a signature-based subtype predictor, MSP888, along with three distinct molecular subtypes: DP.BCG+ (related to progression and response to BCG treatment), REC.BCG+ (related to recurrence and response to BCG treatment), and EP (equivocal prognosis). Patients with the DP.BCG+ subtype showed worse progression-free survival but responded to BCG treatment, whereas those with the REC.BCG+ subtype showed worse recurrence-free survival but responded to BCG treatment. Multivariate analyses revealed that MSP888 showed independent clinical utility for predicting NMIBC prognosis (each p = 0.001 for progression and recurrence, respectively). Comparative analysis of this classifier and previously established molecular subtypes (i.e., Lund taxonomy and UROMOL class) revealed that a great proportion of patients were similar between subtypes; however, the MSP888 predictor better differentiated biological activity or responsiveness to BCG treatment. Our data increase our understanding of the mechanisms underlying the poor prognosis of NMIBC and the effectiveness of BCG therapy, which should improve clinical practice and complement other diagnostic tools.

Single-layer metamaterial bolometer for sensitive detection of low-power terahertz waves at room temperature.

This study demonstrates a metamaterial bolometer that can detect terahertz (THz) waves by measuring variations in electrical resistance. A metamaterial pattern for enhanced THz waves absorption and a composite material with a high temperature coefficient of resistance (TCR) are incorporated into a single layer of the bolometer chip to realize a compact and highly sensitive device. To detect the temperature change caused by the absorption of the THz waves, a polydimethylsiloxane mixed with carbon black microparticles is used. The thermosensitive composite has TCR ranging from 1.88%/K to 3.11%/K at room temperature (22.2-23.8°C). In addition, a microscale metamaterial without a backside reflector is designed to enable the measurement of the resistance and to enhance the sensitivity of the bolometer. The proposed configuration effectively improves thermal response of the chip as well as the absorption of the THz waves. It was confirmed that the irradiated THz waves can be detected via the increment in the electrical resistance. The resistance change caused by the absorption of the THz waves is detectable in spite of the changes in resistance originating from the background thermal noise. The proposed metamaterial bolometer could be applied to detect chemical or biological molecules that have fingerprints in the THz band by measuring the variation of the resistance without using the complex and bulky THz time-domain spectroscopy system.

A Low Geriatric Nutritional Risk Index is Associated with Aggressive Pathologic Characteristics and Poor Survival after Nephrectomy in Clear Renal Cell Carcinoma: A Multicenter Retrospective Study.

Purpose: To investigated the prognostic significance of the geriatric nutritional risk index (GNRI) in patients with surgically treated clear cell renal cell carcinoma (ccRCC).Patients and methods: We retrospectively selected 4,591 consecutive patients with surgically treated ccRCC from a multi-institutional Korean collaboration between 1988 and 2015. The clinical significance of the GNRI as a continuous and categorical variable was determined.Results: Preoperative low GNRI was significantly associated with older age, low body mass index, presence of diabetes, poor performance status, and presence of symptoms at diagnosis, as well as pathologic features such as aggressive tumor characteristics including large tumor size, advanced stage, high nuclear grade, lymphovascular invasion, sarcomatous differentiation, and tumor necrosis. A low GNRI was significantly associated with a short recurrence-free survival (RFS) in localized (pT1-2N0M0) ccRCC and cancer-specific survival (CSS) in the entire cohort, and with short RFS and CSS in the subgroup analysis according to age categories (≤65 and >65 years). Multivariate Cox regression analysis showed that preoperative GNRI, as a continuous or categorical variable, was an independent predictor of RFS and CSS.Conclusion: Malnutrition as assessed by the preoperative GNRI is associated with aggressive tumor characteristics and poor survival in patients with surgically treated ccRCC.

Intraoperative allogeneic blood transfusion is associated with adverse oncological outcomes in patients with surgically treated non-metastatic clear cell renal cell carcinoma.

BACKGROUND: The objective of this study was to provide more definitive information about the prognostic impact of perioperative blood transfusion (PBT) on patients with surgically treated renal cell carcinoma (RCC). METHODS: A database of 4019 patients with clear cell RCC, all of whom underwent radical or partial nephrectomy as primary therapy as part of a multi-institutional Korean collaboration between 1988 and 2015, was analyzed retrospectively. PBT was defined as transfusion of allogeneic red blood cells during surgery or postsurgical period. Receipt of a PBT, as well as the amount and time of blood transfusion (BT), was compared. RESULTS: Overall, 335 (8.3%) patients received a PBT: 84 received postoperative BT, 202 received intraoperative BT, and 49 received both intraoperative and postoperative BT. Patients receiving a PBT had a poor preoperative immuno-nutritional status, and aggressive tumor characteristics. Multivariate analyses identified PBT as an independent predictor of recurrence-free survival and cancer-specific survival. Prognostic impact of PBT was restricted to those with locally advanced stage (pT3-4), and who underwent radical nephrectomy. Among patients who received a PBT, intraoperative (but not postoperative) BT was a prognostic factor for survival. Among patients who received intraoperative BT, those receiving three or more transfusion units had a significantly worse survival. CONCLUSION: Receipt of a PBT was an independent predictor of RFS and CSS in patients with surgically treated RCC, specifically locally advanced disease. Regarding the prognostic impact of timing or dose of PBT on survival, intraoperative BT and ≥ 3 pRBC units were associated with adverse oncological outcomes.

Prognostic Impact of Nutritional Status Assessed by the Controlling Nutritional Status (CONUT) Score in Patients with Surgically Treated Renal Cell Carcinoma.

PURPOSE: The prognostic role of the controlling nutritional status (CONUT) score in renal cell carcinoma (RCC) has not been evaluated. The aim of the current study was to clarify the prognostic significance of the CONUT score in Korean patients with surgically treated RCC. MATERIALS AND METHODS: A database of 1,881 patients with surgically treated RCC from a multiinstitutional Korean collaboration between 1999 and 2015 was analyzed. The preoperative CONUT score was calculated from serum albumin, total cholesterol concentrations, and total lymphocyte count. Clinicopathological variables and survival rates were compared between the CONUT score groups. RESULTS: A high CONUT score was associated with older age, lower body mass index, lower preoperative prognostic nutritional index, and presence of diabetes or hypertension (each P < 0.001). Regarding pathologic features, a high CONUT score was associated with aggressive tumor characteristics including large tumor size, advanced stage, high nuclear grade, lymphovascular invasion, and sarcomatous differentiation (each P < 0.001). Multivariate Cox regression analysis indicated that a high CONUT score (≥ 2) was an independent predictor of cancer-specific mortality (hazard ratio, 1.892; 95% CI: 1.118-3.201; P = 0.018). CONCLUSION: The CONUT score, an easily measurable immune-nutritional biomarker, may provide useful prognostic information in patients with surgically treated RCC.

Age-dependent prognostic value of body mass index for non-metastatic clear cell renal cell carcinoma: A large multicenter retrospective analysis.

BACKGROUND AND OBJECTIVES: The prognostic value of obesity is unestablished for renal cell carcinoma. We assessed the age-dependent prognostic value of body mass index (BMI) in a large multicenter cohort of patients with non-metastatic clear cell renal cell carcinoma (nm-cRCC). METHODS: This study evaluated 2092 patients with nm-cRCC who underwent surgery with curative intent at five Korean institutions between 2001 and 2014. RESULTS: There was no significant difference in BMI between the young (<45 years) and older patients (≥45 years) (P = 0.398). Among older patients, high BMI (≥25 kg/m2 ) was associated with better 5-year rates of recurrence-free survival (RFS) and cancer-specific survival (CSS) (P = 0.003 and 0.004, respectively), and multivariate analysis confirmed that high BMI was independently associated with better RFS and CSS (RFS hazard ratio [HR]: 0.617, P = 0.005; CSS HR: 0.588, P = 0.024). However, among young patients, there were no significant BMI-related differences in the 5-year RFS and CSS rates (P = 0.457 and 0.420, respectively), and high BMI was not independently associated with RFS or CSS (P = 0.822 and 0.749, respectively). CONCLUSIONS: Among patients with nm-cRCC, high BMI was associated with a favorable prognosis among older patients but not among young patients. Therefore, the relationship between obesity and nm-cRCC prognosis might vary according to age.

Low preoperative serum cholesterol level is associated with aggressive pathologic features and poor cancer-specific survival in patients with surgically treated renal cell carcinoma.

BACKGROUND: The prognostic implications of preoperative serum total cholesterol (TC) level in patients with renal cell carcinoma (RCC) remain poorly understood. We investigated the prognostic role of preoperative serum TC in patients with surgically treated RCC from a large, multi-institutional Korean collaboration. PATIENTS AND METHODS: A database of 3064 patients with RCC who underwent radical or partial nephrectomy between 1999 and 2011 at eight academic centers was analyzed. Preoperative serum TC levels were measured in fasting blood samples. RESULTS: Low preoperative serum TC level was associated with aggressive tumor characteristics, including large tumor size, advanced stage, high nuclear grade, lymph node involvement, and sarcomatous differentiation (all P < 0.001). Low TC level was associated with poor recurrence-free or cancer-specific survival (CSS) in the entire cohort, whereas the significance of the association changed after stratification by disease stage and histologic subtype. Multivariate Cox regression analysis showed that preoperative TC, as a continuous or categorical variable, was an independent predictor of CSS. CONCLUSIONS: Preoperative low serum TC level was associated with aggressive tumor characteristics and poor CSS in patients with surgically treated RCC. Preoperative TC may provide additional guidance regarding the choice of therapeutic strategies to improve prognosis.

CDC6 mRNA Expression Is Associated with the Aggressiveness of Prostate Cancer.

BACKGROUND: Cell division cycle 6 (CDC6) is an essential regulator of DNA replication and plays important roles in the activation and maintenance of the checkpoint mechanisms in the cell cycle. CDC6 has been associated with oncogenic activities in human cancers; however, the clinical significance of CDC6 in prostate cancer (PCa) remains unclear. Therefore, we investigated whether the CDC6 mRNA expression level is a diagnostic and prognostic marker in PCa. METHODS: The study subjects included 121 PCa patients and 66 age-matched benign prostatic hyperplasia (BPH) patients. CDC6 expression was evaluated using real-time polymerase chain reaction and immunohistochemical (IH) staining, and then compared according to the clinicopathological characteristics of PCa. RESULTS: CDC6 mRNA expression was significantly higher in PCa tissues than in BPH control tissues (P = 0.005). In addition, CDC6 expression was significantly higher in patients with elevated prostate-specific antigen (PSA) levels (> 20 ng/mL), a high Gleason score, and advanced stage than in those with low PSA levels, a low Gleason score, and earlier stage, respectively. Multivariate logistic regression analysis showed that high expression of CDC6 was significantly associated with advanced stage (≥ T3b) (odds ratio [OR], 3.005; confidence interval [CI], 1.212-7.450; P = 0.018) and metastasis (OR, 4.192; CI, 1.079-16.286; P = 0.038). Intense IH staining for CDC6 was significantly associated with a high Gleason score and advanced tumor stage including lymph node metastasis stage (linear-by-linear association, P = 0.044 and P = 0.003, respectively). CONCLUSION: CDC6 expression is associated with aggressive clinicopathological characteristics in PCa. CDC6 may be a potential diagnostic and prognostic marker in PCa patients.

Change in Prostate Specific Antigen Concentration in Men with Prostate Specific Antigen Less than 2.5 ng/ml Taking Low Dose Finasteride or Dutasteride for Male Androgenetic Alopecia.

PURPOSE: In this retrospective cohort study we assessed the effect on prostate specific antigen concentration of low dose finasteride or dutasteride treatment for male androgenetic alopecia in men with baseline serum prostate specific antigen less than 2.5 ng/ml. MATERIALS AND METHODS: The cohort consisted of 1,379 consecutive male patients who were treated for androgenetic alopecia with finasteride 1.25 mg daily or dutasteride 0.5 mg every 3 days in 2002 to 2012 and who underwent prostate specific antigen measurements at baseline and at least once thereafter. Patients in whom baseline or followup prostate specific antigen after prescription exceeded 2.5 ng/ml were excluded from study to rule out men with a higher likelihood of prostate cancer. Patients were stratified according to age, baseline prostate specific antigen, medication type and treatment duration. RESULTS: Overall low dose 5α-reductase inhibitor treatment reduced prostate specific antigen by 27.8% relative to baseline. Of the patients 1,094 (79.3%) showed prostate specific antigen decreases (average 40.8%). In the remaining 285 patients (20.7%) prostate specific antigen was stable or increased (average 24.2% increase). Closer analysis largely showed that only men with baseline prostate specific antigen 0.5 ng/ml or greater had a treatment related prostate specific antigen reduction. On multivariate logistic analysis low baseline prostate specific antigen was significantly associated with stable/increased prostate specific antigen. Low dose dutasteride and finasteride reduced prostate specific antigen to similar degrees (31.1% and 25.1%, respectively). A marked prostate specific antigen decrease of 26.0% was observed even after short-term treatment (3 to 6 months). CONCLUSIONS: Dutasteride and finasteride reduced prostate specific antigen to similar degrees. This effect was observed soon after commencing treatment. In patients with low baseline prostate specific antigen the levels could remain stable or even increase. These findings are limited to men with baseline prostate specific antigen less than 2.5 ng/ml.

Design method for broadband free-space electromagnetic cloak based on isotropic material for size reduction and enhanced invisibility.

A design method is proposed that not only improves the invisibility of but also minimizes the size of a two-dimensional (2D) free-space electromagnetic cloak based on the quasi-conformal mapping (QCM) technique. The refractive index profile of the cloak based on the QCM is optimally scaled to minimize performance deterioration due to the imperfect isotropy of the cloak medium. Moreover, the method can be applied to compensate for the performance degradation due to size reduction. Based on the proposed method, as much as a 78.3% reduction in size is demonstrated. Enhancement of invisibility is evidenced by a 71% reduction in the normalized scattering cross section (SCS) at 10 GHz. Performance enhancement and miniaturization are achieved simultaneously with the extremely simple proposed method, making it one of the most practical cloaks reported thus far. Finally, experimental results over a broad bandwidth as well as for a wide range of incident angles are provided for cloaks fabricated using a 3D printer, which validate the effectiveness of the proposed method of cloak design.

Surgical margin does not influence recurrence rate in pT1 clear cell renal cell carcinoma after partial nephrectomy: A multicenter study.

PURPOSE: To assess the risk factors of positive surgical margins (PSM) and the influence of margin status on recurrence in pT1 clear cell renal cell carcinoma (RCC) following partial nephrectomy (PN). MATERIALS AND METHODS: Patients (1,831) with pathologically confirmed stage T1 clear cell RCC were retrospectively analyzed following PN at eight institutions in Korea between 1999 and 2011. Demographics, operative data, pathological margin status, and site of recurrence were analyzed. RESULTS: Resection margins were positive in 31 patients (1.7% of the cohort) on final pathology. None of the clinicopathological parameters were significantly related to the marginal status (all P > 0.05). During a median follow-up of 32.5 months, local recurrences were observed in 0.4% of negative surgical margins. There was no local recurrence in any of the cases with PSM. Distant recurrences developed in 1.7% of negative surgical margins and 3.2% of PSM. There were no significant differences in recurrence-free survival by margin status (P = 0.566). CONCLUSIONS: Our multi-institutional data suggest that marginal status does not influence tumor recurrence risk in pT1 clear cell RCC after PN. Careful surveillance seems to be a sufficient strategy in this clinical scenario. J. Surg. Oncol. 2016;114:70-74. © 2016 Wiley Periodicals, Inc.

Preoperative Chronic Kidney Disease Status is an Independent Prognostic Factor in Patients with Renal Cell Carcinoma.

PURPOSE: Preoperative chronic kidney disease (CKD) status may affect disease outcomes in patients with renal cell carcinoma (RCC). This study evaluated the influence of preoperative CKD status on clinicopathological features and prognosis in patients with RCC. METHODS: Between 1999 and 2011, a total of 1855 patients underwent radical nephrectomy at various centers throughout Korea. Of these patients, 1655 had an estimated glomerular filtration rate (eGFR) ≥60 ml/min/1.73 m(2) (non-CKD group) and 200 patients had an eGFR ≥30 but <60 ml/min/1.73 m(2) (CKD group). To reduce the effects of selection bias and potential confounding factors, 600 patients in the non-CKD group were selected by propensity-score matching. RESULTS: The median age of all patients was 57.3 years (range 20-94 years) and the median follow-up was 35.0 months (range 1-154 months). Comparisons of the propensity-score-matched cohorts showed that T and N stages were more advanced and tumor size was larger in the CKD group than in the non-CKD group (p < 0.05 each). Kaplan-Meier analyses showed that recurrence-free survival, cancer-specific survival (CSS), and overall survival (OS) were significantly lower in the CKD group (p < 0.01 each). Multivariate regression analysis showed that preoperative CKD status was an independent predictor of CSS and OS in patients with RCC (p < 0.05 each). CONCLUSIONS: Preoperative CKD may be associated with more aggressive features and poorer prognosis in patients with RCC. RCC patients with preoperative CKD should be carefully and frequently followed-up after nephrectomy.

Lower Levels of Human MOB3B Are Associated with Prostate Cancer Susceptibility and Aggressive Clinicopathological Characteristics.

Mps one binder (MOB) proteins are integral components of signaling pathways that control important cellular processes, such as mitotic exit, centrosome duplication, apoptosis, and cell proliferation. However, the biochemical and cellular functions of the human MOB (hMOB) protein family remain largely unknown. The present study investigated the association between hMOB3B expression and clinicopathological characteristics of prostate cancer (PCa).Study subjects included 137 PCa patients and 137 age-matched benign prostatic hyperplasia (BPH) patients. hMOB3B expression was estimated using real-time PCR and compared with clinicopathological parameters of PCa. hMOB3B mRNA expression was significantly lower in PCa tissues than in BPH control tissues (P<0.001). According to receiver operating characteristics curve analysis, the sensitivity of hMOB3B expression for PCa diagnosis was 84.7%, with a specificity of 86% (AUC=0.910; 95% CI=0.869-0.941; P<0.001). hMOB3B expression was significantly lower in patients with elevated prostate specific antigen (PSA) levels (≥10 ng/mL), a Gleason score≥8, and metastatic disease (any T, N+/M+) than in those with low PSA levels, a low Gleason score, and non-metastatic disease (each P<0.05). In conclusion, low levels of hMOB3B are closely associated with aggressive clinicopathologic features in patients with PCa. Our results suggest that hMOB3B may act as a tumor suppressor in human PCa.

Effect of renal insufficiency on stone recurrence in patients with urolithiasis.

The study was designed to assess the relationship between glomerular filtration rate (GFR) and urinary stone-forming constituents, and to assess the effect of renal insufficiency on stone recurrence risk in first stone formers (SF). Baseline serum creatinine levels were obtained, and renal insufficiency was defined as creatinine clearance ≤60 mL/min (Cockroft-Gault). This retrospective case-control study consists of 342 first SF; 171 SF with normal renal function were selected with 1:1 propensity scores matched to 171 SF with renal insufficiency. Urinary metabolic evaluation was compared to renal function. GFR was positively correlated with urinary calcium, uric acid, and citrate excretion. Subjects with renal insufficiency had significantly lower urinary calcium, uric acid, and citrate excretion than those with normal renal function, but not urine volume. With regard to urinary metabolic abnormalities, similar results were obtained. SF with renal insufficiency had lower calcium oxalate supersaturation indexes and stone recurrence rates than SF with normal renal function. Kaplan-Meier curves showed similar results. In conclusion, GFR correlates positively with urinary excretion of stone-forming constituents in SF. This finding implies that renal insufficiency is not a risk factor for stone recurrence.