Evaluation of histological variants of upper tract urothelial carcinoma as prognostic factor after radical nephroureterectomy.

PURPOSE: To evaluate the impact of variant histology on patients with upper tract urothelial carcinoma (UTUC) survival outcomes. MATERIALS AND METHODS: A total of 519 patients underwent radical nephroureterectomy without neoadjuvant therapy for UTUC at a single institution between May 2003 and December 2019. Multivariate Cox regression analysis evaluated the impact of variant histology on progression-free survival (PFS), cancer-specific survival (CSS), and overall survival (OS). RESULTS: Among 84 patients (16.2%) with variant histology, the most frequent variant type was squamous cell differentiation (64.3%), followed by glandular differentiation (25.0%) and sarcomatoid variant (2.4%). They showed pathologically advanced T stage (for ≥ T3, 59.5% vs 33.3%, p < 0.001), higher tumor grade (96.4% vs 85.7%, p = 0.025), and higher rates of lymph node metastasis (17.9% vs 7.8%, p = 0.015), angiolymphatic invasion (41.7% vs 25.7%, p = 0.003), tumor necrosis (57.1% vs 29.0%, p < 0.001) and positive surgical margin (13.1% vs 5.7%, p = 0.015). On multivariate Cox regression analyses, variant histology was significantly associated with worse PFS (hazard ratio [HR] 2.23; 95% confidence interval [CI] 1.55-3.21; p < 0.001), CSS (HR 2.67; 95% CI 1.35-5.30; p = 0.005) and OS (HR 2.22; 95% CI 1.27-3.88; p = 0.005). In subgroup analysis, no significant survival gains of adjuvant chemotherapy occurred in patients with variant histology. CONCLUSIONS: Variant histology was associated with adverse pathologic features and poor survival outcomes. Our results suggest that patients with variant histology may require a close follow-up schedule and novel adjuvant therapy other than chemotherapy postoperatively.

Computer tomography-based shape of tumor contour and texture of tumor heterogeneity are independent prognostic indicators for clinical T1b-T2 renal cell carcinoma.

PURPOSE: To evaluate association between computer tomography (CT)-based features of renal cell carcinoma (RCC) and survival outcomes. METHODS: Data of 958 patients with clinical T1b-T2 RCC who underwent partial/radical nephrectomy from June 2003 to March 2022 were retrospectively evaluated. CT images of patients were reviewed by two radiologists for texture analysis of tumor heterogeneity and shape analysis of tumor contour. Patients were divided into three groups according to patterns of CT-based features: (1) favorable feature group (n = 117); (2) intermediate feature group (n = 606); and (3) unfavorable feature group (n = 235). Kaplan-Meier survival analysis and multivariate Cox regression analysis were performed to evaluate overall survival (OS), cancer-specific survival (CSS), and recurrence-free survival (RFS). RESULTS: RCCs with unfavorable CT-based feature showed larger size on CT, higher nuclear grade, higher rate of histologic necrosis, and higher rate of capsular invasion than those in the other two groups (all p < 0.001). Unfavorable feature was associated with poorer OS (p = 0.001), CSS (p < 0.001), and RFS (p < 0.001) on Kaplan-Meier analysis. In multivariate analysis, intermediate and unfavorable features were independent predictors for recurrence (hazard ratio [HR] 2.51, 95% confidence interval [CI] 1.09-5.79, p = 0.031 and HR 3.71, 95% CI 1.58-8.73, p = 0.003, respectively), but not for overall death or RCC-specific death. CONCLUSIONS: A combination of irregular tumor contour feature with heterogeneous tumor texture feature on CT is associated with poor RFS in clinical T1b-T2 RCC preoperatively.

Clinical value of prostate health index as an indicator for recommending magnetic resonance imaging in patients with gray-zone prostate-specific antigen level.

PURPOSE: To evaluate the usefulness of prostate health index (PHI) as an indicator for recommending magnetic resonance imaging (MRI) in patients with prostate-specific antigen (PSA) gray zone level < 10 ng/mL. METHODS: 443 patients who underwent prostate biopsy (PB) after serum PHI test and MRI between April 2019 and December 2022 were enrolled. For patients with visible lesion on MRI with Prostate Imaging Reporting and Data System Score (PI-RADS) ≥ 3, MRI-targeted PB was performed in addition to systematic 12-core PB. RESULTS: The optimal cutoff value of PHI for predicting PI-RADS ≥ 3 lesions was 39.6, which was significantly associated with overall prostate cancer (OR 3.07, p = 0.018) and clinically significant prostate cancer (csPCa) (OR 4.15, p = 0.006) at MRI-targeted PB cores. When MRI was restricted to patients with PHI ≥ 39.6 alone, 28.7% of unnecessary MRI could be saved at the cost of missing 13.6% of csPCa. When omitting MRI for patients with PHI < 39.6 and PSAD < 0.12 ng/mL2, unnecessary MRI could be reduced by 20.1% with the risk of missing 6.2% of csPCa. With addition of systematic PB, 21.0% of patients with negative MRI-targeted PB were diagnosed as csPCa. CONCLUSIONS: For patients in PSA gray zone, PHI of 39.6 might be an indicator for MRI and further MRI-targeted PB in additional to PSAD of 0.12 ng/mL2, reducing 20.1% of unnecessary MRI with the minimal risk of missing 6.2% of csPCa. To maximize csPCa detection, combining both MRI-targeted and systematic PB should be also considered.

Synthesis and anti-prion aggregation activity of acylthiosemicarbazide analogues.

Prions are infectious protein particles known to cause prion diseases. The biochemical entity of the pathogen is the misfolded prion protein (PrPSc) that forms insoluble amyloids to impair brain function. PrPSc interacts with the non-pathogenic, cellular prion protein (PrPC) and facilitates conversion into a nascent misfolded isoform. Several small molecules have been reported to inhibit the aggregation of PrPSc but no pharmacological intervention was well established thus far. We, here, report that acylthiosemicarbazides inhibit the prion aggregation. Compounds 7x and 7y showed almost perfect inhibition (EC50 = 5 µM) in prion aggregation formation assay. The activity was further confirmed by atomic force microscopy, semi-denaturing detergent agarose gel electrophoresis and real-time quaking induced conversion assay (EC50 = 0.9 and 2.8 µM, respectively). These compounds also disaggregated pre-existing aggregates in vitro and one of them decreased the level of PrPSc in cultured cells with permanent prion infection, suggesting their potential as a treatment platform. In conclusion, hydroxy-2-naphthoylthiosemicarbazides can be an excellent scaffold for the discovery of anti-prion therapeutics.

Comparison of Differential Functional Outcomes After Partial Nephrectomy Between Moderate and High Complex Renal Tumor Evaluated with Diethylenetriamine Pentaacetic Acid Scan: A Propensity Score Matched Analysis.

OBJECTIVE: The aim of this study was to compare functional outcomes after partial nephrectomy (PN) between moderate and high complex renal tumors evaluated with a diethylenetriamine pentaacetic acid (DTPA) scan [moderate vs. high: RENAL nephrometry score (RNS) 7-9 vs. 10-12]. METHODS: From January 2004 to December 2019, 471 patients with an RNS of 7-9 (moderate) and 164 patients with an RNS of 10-12 (high) who underwent PN were analyzed for renal function outcomes. The glomerular filtration rate (GFR) was measured using a DTPA scan and calculated the GFR using the Modification of Diet in Renal Disease (MDRD) formula, respectively. Trifecta/pentafecta outcome, recurrence-free survival, and overall survival were compared after propensity score matched analysis (PSMA). RESULTS: After PSMA, 156 cases in each group were matched without significant difference in the preoperative factor. At the postoperative first year, there was no significant difference in the trifecta (p = 0.320), MDRD-based (p = 0.729), or DTPA-based pentafecta achievement rate (p = 0.964) between groups. At postoperative 5 years, DTPA-based total GFR (93.6% vs. 93.8%) and the operated kidney GFR preservation rate (89.9% vs. 81.7%) did not differ significantly (p > 0.05). Kaplan-Meier survival analysis showed no significant differences in survival outcomes (p > 0.05). Significant predictors of de novo chronic kidney disease (CKD) stage 3 or higher at the postoperative first year were age [hazard ratio (HR) 1.10, 95% confidence interval (CI) 1.03-1.17, p = 0.005] and preoperative DTPA-based total GFR (HR 0.94, 95% CI 0.91-0.98, p = 0.001). CONCLUSION: High complex tumors can be treated with PN without significant deterioration in renal function. The postoperative function of the operated kidney was preserved by up to 80% in the long term compared with the preoperative period. However, PN should be selectively performed with caution to avoid the occurrence of postoperative CKD.

The Effect of Curcuma phaeocaulis Valeton (Zingiberaceae) Extract on Prion Propagation in Cell-Based and Animal Models.

Prion diseases are neurodegenerative disorders in humans and animals for which no therapies are currently available. Here, we report that Curcuma phaeocaulis Valeton (Zingiberaceae) (CpV) extract was partly effective in decreasing prion aggregation and propagation in both in vitro and in vivo models. CpV extract inhibited self-aggregation of recombinant prion protein (PrP) in a test tube assay and decreased the accumulation of scrapie PrP (PrPSc) in ScN2a cells, a cultured neuroblastoma cell line with chronic prion infection, in a concentration-dependent manner. CpV extract also modified the course of the disease in mice inoculated with mouse-adapted scrapie prions, completely preventing the onset of prion disease in three of eight mice. Biochemical and neuropathological analyses revealed a statistically significant reduction in PrPSc accumulation, spongiosis, astrogliosis, and microglia activation in the brains of mice that avoided disease onset. Furthermore, PrPSc accumulation in the spleen of mice was also reduced. CpV extract precluded prion infection in cultured cells as demonstrated by the modified standard scrapie cell assay. This study suggests that CpV extract could contribute to investigating the modulation of prion propagation.

Evaluation of functional outcome of bilateral kidney tumors after sequential surgery.

BACKGROUND: There are limited data concerning patients treated with sequential bilateral kidney surgery. Current guidelines still lack an optimal surgical sequencing approach. We evaluated renal functional outcomes after sequential partial nephrectomy (PN) and radical nephrectomy (RN) in patients with bilateral renal cell carcinoma (RCC). METHODS: A propensity score matched cohort of 267 patients (synchronous bilateral RCCs, N = 44 [88 lesions]; metachronous bilateral, N = 45 [90 lesions]; unilateral, N = 178) from two tertiary institutions were retrospectively analyzed. Synchronous bilateral RCCs were defined as diagnosis concomitantly or within 3 months of former tumor. Renal functional outcomes were defined as estimated glomerular filtration rate (eGFR) changes and de novo chronic kidney disease (CKD, stage ≥3) after surgery. Renal functional outcomes and clinical factors predicting de novo CKD were assessed using descriptive statistics and Cox regression analysis. RESULTS: In subgroup of bilateral RCCs, patients underwent sequential PN (N = 48), PN followed by RN (N = 8), or RN followed by PN (N = 25). Final postoperative estimated glomerular filtration rates (eGFRs) were 79.4, 41.4, and 61.2 ml/minute/1.73 m2, respectively (p = 0.003). There were significant differences in eGFR decline from baseline and de novo chronic kidney disease (CKD stage ≥ III) among groups, with PN followed by RN group showing the worst functional outcomes (all p <  0.05). Moreover, sequential PN subgroup in bilateral RCC showed significantly higher rate of de novo CKD than unilateral RCC group (13.8% vs. 6.9%, p = 0.016). On multivariate analysis, hypertension (p = 0.010) and surgery sequence (PN followed by RN, p <  0.001) were significant predictors of de novo CKD. CONCLUSIONS: The surgery sequence should be prudently determined in bilateral renal tumors. PN followed by RN showed a negative impact on renal functional preservation. Nephron-sparing surgery should be considered for all amenable bilateral RCCs.

Personalised three-dimensional printed transparent kidney model for robot-assisted partial nephrectomy in patients with complex renal tumours (R.E.N.A.L. nephrometry score ≥7): a prospective case-matched study.

OBJECTIVES: To evaluate the effectiveness of a three-dimensional (3D) printed transparent kidney model as a surgical navigator for robot-assisted partial nephrectomy (RPN) in patients with complex renal tumours, defined by a R.E.N.A.L. (Radius, Exophytic/Endophytic, Nearness, Anterior/Posterior, Location) nephrometry score of ≥7. PATIENTS AND METHODS: A total of 80 patients who underwent RPN were included in the present prospective case-matched study (case group [n = 40, application of 3D-printed transparent kidney model during RPN] vs matching group [n = 40, routine protocol]). The RPNs were performed by a single experienced surgeon. The RPN procedure consisted of six steps: (i) preparation of the renal hilar vessel for clamping, (ii) tumour detection and dissection, (iii) robotic ultrasonography, (iv) tumour resection, (v) calyx repair and haemostasis, and (vi) renorrhaphy. The time for each step, console time, and warm ischaemia time were compared between the two groups as a surrogate marker for surgical effectiveness. RESULTS: Both groups were well-balanced for all baseline characteristics. The use of the model reduced the console time by ~20% compared to the matched group (64.6 vs 78.5 min, P = 0.001). On multivariate logistic regression analysis, tumour radius (P < 0.001) and application of the model (P = 0.009) were identified as significant predictors of a console time of ≤70 min. CONCLUSION: We established the usefulness of a personalised 3D-printed transparent kidney model for more effective RPNs. Use of the 3D-printed transparent kidney model reduced the operative time even for complex renal tumours and would be expected to broaden the indications for PN.

Metastatic renal cell carcinoma to the pancreas: Clinical features and treatment outcome.

BACKGROUND AND OBJECTIVES: Metastatic renal cell carcinoma to the pancreas (PM-RCC) is infrequent; we sought to describe the characteristics of PM-RCC and analyze the outcome following treatment. METHODS: Data of 3107 mRCC patients treated between 1992 and 2007 from the Korean Renal Cancer Study Group database were obtained to identify 300 (9.7%) PM-RCC patients. Characteristics and survival were analyzed and compared to the rest of the mRCC, according to the timing of metastasis and surgical treatments received. RESULTS: PM-RCC was younger at initial diagnosis (55.0 vs. 58.2 years), more frequently in women (30.3% vs. 22.3%), and metachronous (65.3% vs. 41.9%) with a longer disease-free period (82.0 vs. 33.0 months). Overall survival (OS) was significantly better in PM-RCC but pancreas metastasectomy was associated with improved OS only among metachronous PM-RCC. In the 132 metachronous PM-RCC with pancreas metastasectomy, median recurrence-free survival was 17.2 months and we found Heng risk group (hazard ratio [HR] = 2.384, 95% confidence interval [CI] = 1.213-4.684), younger age (HR = 0.965, 95% CI = 0.945-0.987), shorter interval to pancreas metastasis (HR = 0.993, 95% CI = 0.986-0.999), and Eastern Cooperative Oncology Group performance status to be predictive of early progression following pancreas metastasectomy. CONCLUSION: Compared to the other mRCC, PM-RCC demonstrated a favorable prognosis. Pancreas metastasectomy was associated with prolonged survival in the metachronous PM-RCC with a long progression-free period.

Favorable intermediate risk prostate cancer with biopsy Gleason score of 6.

BACKGROUND: To identify potential prognostic factors among patients with favorable intermediate risk prostate cancer with a biopsy Gleason score 6. METHODS: From 2003 to 2019, favorable intermediate risk patients who underwent radical prostatectomy were included in this study. All patients were evaluated preoperatively with MRI. Using PI-RADS scores, patients were divided into two groups, and clinic-pathological outcomes were compared. The impact of preoperative factors on significant pathologic Gleason score upgrading (≥ 4 + 3) and biochemical recurrence were assessed via multivariate analysis. Subgroup analysis was performed in patients with PI-RADS ≤ 2. RESULTS: Among the 239 patients, 116 (48.5%) were MRI-negative (PI-RADS ≤ 3) and 123 (51.5%) were MRI-positive (PI-RADS > 3). Six patients in the MRI-negative group (5.2%) were characterized as requiring significant pathologic Gleason score upgrading compared with 34 patients (27.6%) in the MRI-positive group (p < 0.001). PI-RADS score was shown to be a significant predictor of significant pathologic Gleason score upgrading (OR = 6.246, p < 0.001) and biochemical recurrence (HR = 2.595, p = 0.043). 10-years biochemical recurrence-free survival was estimated to be 84.4% and 72.6% in the MRI-negative and MRI-positive groups (p = 0.035). In the 79 patients with PI-RADS ≤ 2, tumor length in biopsy cores was identified as a significant predictor of pathologic Gleason score (OR = 11.336, p = 0.014). CONCLUSIONS: Among the patients with favorable intermediate risk prostate cancer with a biopsy Gleason score 6, preoperative MRI was capable of predicting significant pathologic Gleason score upgrading and biochemical recurrence. Especially, the patients with PI-RADS ≤ 2 and low biopsy tumor length could be a potential candidate to active surveillance.

Targeted therapy response in early versus late recurrence of renal cell carcinoma after surgical treatment: A propensity score-matched study using the Korean Renal Cancer Study Group database.

OBJECTIVES: To investigate the clinicopathological features and outcomes of targeted therapy in patients with recurrence of renal cell carcinoma in <5 years or ≥5 years after the surgical treatment for renal cell carcinoma. METHODS: Patients with metastatic renal cell carcinoma treated with targeted therapy in a multicenter database were retrospectively characterized according to time from surgery to recurrence. Early recurrence was defined as recurrence within 5 years after surgery, and late recurrence was defined as occurring ≥5 years after surgery. The propensity scores for recurrence status were calculated, and patients with late recurrence were matched to patients with early recurrence at a 1:3 ratio. The oncological outcomes of targeted therapy in both groups were compared. RESULTS: Among 716 patients, 512 (71.5%) experienced early recurrence and 204 (28.5%) experienced late recurrence. The patients with late recurrence presented with younger age at surgery, lower tumor stages and Fuhrman grade, and fewer sarcomatoid features and lymphovascular invasion (all P < 0.005). All differences in clinicopathological characteristics before targeted therapy disappeared after matching. Patients with late recurrence had significantly longer median overall survival (56 months vs 36 months; P < 0.0001) and median first-line progression-free survival (12 months vs 8 months; P = 0.031). The early recurrence status was a significantly worse predictor for overall survival and first-line progression-free survival (hazard ratio 1.30, P = 0.007; and hazard ratio 1.76, P < 0.001, respectively). CONCLUSIONS: Late recurrence might have prognostic value in terms of oncological outcomes in metastatic renal cell carcinoma treated with targeted therapy.

Clinical and pathologic characteristics of familial prostate cancer in Asian population.

BACKGROUND: We investigated prevalence of familial and hereditary prostate cancer (PCa) in Asian population, and compared clinical characteristics between familial and sporadic disease. METHODS: Pedigrees of 1102 patients who were treated for PCa were prospectively acquired. Clinical and pathologic characteristics and biochemical recurrence (BCR)-free survival were compared between familial PCa and sporadic PCa in patients who underwent radical prostatectomy (RP; n = 751). RESULTS: The prevalence of familial, first-degree familial, and hereditary PCa was found to be 8.4%, 6.7%, and 0.9%, respectively; similar result was obtained in patients who underwent RP (8.4%, 6.4%, and 0.9%). Patients with familial PCa were significantly younger than those with sporadic PCa (63.3 vs 65.6 years; P = .015). However, preoperative variables (prostate-specific antigen, clinical stage, biopsy Gleason score [GS], and percentage of positive biopsy cores) and postoperative variables (surgical GS, upgrading rate, pathologic stage, and percentage of tumor volume) did not correlate with family history (P range: .114-.982). Kaplan-Meier analysis of 5-year BCR-free survival revealed no significant difference between sporadic (82.7%), familial (89.4%; P = .594), and first-degree familial (87.1%; P = .774) PCa. Analysis of p53, Bcl-2, Ki67, and other immunohistochemistry biomarkers revealed that only increasing p53 expression and first-degree familial PCa approached significance (P = .059). CONCLUSION: The prevalence of familial PCa was somewhat lower in the Asian population than in other ethnic groups. Clinical and pathologic variables and selected histologic biomarker abnormalities were not significantly different in patients with and without a family history of PCa. BCR-free survival following RP was also unaffected by family history.

Significant Mendelian genetic contribution to pediatric mild-to-moderate hearing loss and its comprehensive diagnostic approach.

PURPOSE: Timely diagnosis and identification of etiology of pediatric mild-to-moderate sensorineural hearing loss (SNHL) are both medically and socioeconomically important. However, the exact etiologic spectrum remains uncertain. We aimed to establish a genetic etiological spectrum, including copy-number variations (CNVs) and efficient genetic testing pipeline, of this defect. METHODS: A cohort of prospectively recruited pediatric patients with mild-to-moderate nonsyndromic SNHL from 2014 through 2018 (n = 110) was established. Exome sequencing, multiplex ligation-dependent probe amplification (MLPA), and nested customized polymerase chain reaction (PCR) for exclusion of a pseudogene, STRCP, from a subset (n = 83) of the cohort, were performed. Semen analysis was also performed to determine infertility (n = 2). RESULTS: Genetic etiology was confirmed in nearly two-thirds (52/83 = 62.7%) of subjects, with STRC-related deafness (n = 29, 34.9%) being the most prevalent, followed by MPZL2-related deafness (n = 9, 10.8%). This strikingly high proportion of Mendelian genetic contribution was due particularly to the frequent detection of CNVs involving STRC in one-third (27/83) of our subjects. We also questioned the association of homozygous continuous gene deletion of STRC and CATSPER2 with deafness-infertility syndrome (MIM61102). CONCLUSION: Approximately two-thirds of sporadic pediatric mild-to-moderate SNHL have a clear Mendelian genetic etiology, and one-third is associated with CNVs involving STRC. Based on this, we propose a new guideline for molecular diagnosis of these children.

Effect of personalized extracorporeal biofeedback device for pelvic floor muscle training on urinary incontinence after robot-assisted radical prostatectomy: A randomized controlled trial.

AIMS: To investigate the effectiveness of a novel personalized extracorporeal biofeedback device (Anykegel) for pelvic floor muscle training (PFMT) on the recovery of postprostatectomy urinary incontinence (PPI) after robot-assisted laparoscopic radical prostatectomy (RARP) through a randomized controlled trial. METHODS: A total of 84 patients who underwent RARP were randomized either to the intervention group (42) (receiving biofeedback-PFMT using a novel device in addition to verbal and written instruction) or to the control group (42). Patients were evaluated 1, 2, and 3 months after surgery. Incontinence severity was measured by the 24-hour pad test. The International Prostate Symptom Score (IPSS) and the International Index of Erectile Function (IIEF-5) questionnaire were also assessed. RESULTS: The intervention group showed a significantly smaller volume of urine loss at the 1-month follow-up than the control group on a 24-hour pad test (71.0 g vs 120.8 g; P = .028). However, from the 2-month follow-up visit, no significant differences were observed between the two groups. In addition, in the 1-month follow-up data of the IPSS-total score, the intervention group demonstrated significantly favorable changes from baseline with improved scores compared to the control group (0.25 ± 9.15 vs -3.81 ± 8.98; P = .046). Regarding the IIEF-5 score changes, no significant differences were reported throughout the study periods. CONCLUSIONS: The personalized extracorporeal biofeedback device for PFMT offers a significant positive effect on the recovery of PPI after RARP, especially in the early postoperative period. Furthermore, patients can be offered more convenience through performing the regular exercise at any place with ease.

Self-Assembling Peptides and Their Application in the Treatment of Diseases.

Self-assembling peptides are biomedical materials with unique structures that are formed in response to various environmental conditions. Governed by their physicochemical characteristics, the peptides can form a variety of structures with greater reactivity than conventional non-biological materials. The structural divergence of self-assembling peptides allows for various functional possibilities; when assembled, they can be used as scaffolds for cell and tissue regeneration, and vehicles for drug delivery, conferring controlled release, stability, and targeting, and avoiding side effects of drugs. These peptides can also be used as drugs themselves. In this review, we describe the basic structure and characteristics of self-assembling peptides and the various factors that affect the formation of peptide-based structures. We also summarize the applications of self-assembling peptides in the treatment of various diseases, including cancer. Furthermore, the in-cell self-assembly of peptides, termed reverse self-assembly, is discussed as a novel paradigm for self-assembling peptide-based nanovehicles and nanomedicines.

Drug repurposing screening identifies bortezomib and panobinostat as drugs targeting cancer associated fibroblasts (CAFs) by synergistic induction of apoptosis.

Cancer associated fibroblasts (CAFs) are the most abundant components of cancer-microenvironment. They play important roles in cancer initiation, progression, and metastasis. In addition, CAFs can confer drug-resistance to cancer cells. Considering their pro-tumorigenic roles, it is recommended to remove CAFs to prevent cancer recurrence after chemotherapy. Despite their clinical significance, few anti-CAF drugs have been developed. The objective of this study was to find a drug that could suppress the viability of patient-derived CAFs through repurposed screening of 51 drugs that were in clinical trials or received FDA approval. As a result, bortezomib (BTZ), carfilzomib (CFZ), and panobinostat (PST) were identified as anti-CAF drug candidates. It was confirmed that BTZ and PST could decrease the viability of various patients derived CAFs through inducing of caspase-3 mediated apoptosis. Interestingly, combination therapy with BTZ and PST showed better efficacy of inhibiting CAFs than single treatment. The synergistic effect between BTZ and PST on viability of CAFs was observed both in vitro CAF culture and in vivo mouse model. Furthermore, combination therapy with BTZ/PST and conventional anticancer compound docetaxel strongly inhibited tumor growth in xenografts of mouse breast cancer cells with mouse CAFs. In conclusion, our present study revealed that BTZ and PST could significantly reduce the viability of CAFs. Therefore, a combination therapy with BTZ/PST and anticancer drugs might be considered as a new rational for the development of anticancer therapy.

Outcomes of pathologic stage T3a renal cell carcinoma up-staged from small renal tumor: emphasis on partial nephrectomy.

BACKGROUND: The prognosis of patients with pathologic stage T3a renal cell carcinoma (RCC) that is up-staged from a small renal tumor remains controversial. We evaluated the prognosis of patients with RCC who were up-staged from clinical stage T1 to pathologic stage T3a. METHODS: We retrospectively reviewed the data of 3431 patients who were surgically treated for clinical stage T1 RCC. The survival outcomes were compared using Kaplan-Meier and Cox proportional analyses. RESULTS: Among the clinical stage T1 patients, 215 (6.3%) were finally up-staged to pathologic stage T3a. Patient age (HR 1.302, 95% CI 1.018-1.046, p <  0.001), tumor diameter (HR 1.686, 95% CI 1.551-1.834, p <  0.001), and hilar location (HR 1.765, 95% CI 1.147-2.715, p = 0.010) were significantly associated with upstaging. Kaplan-Meier analyses showed significantly shorter recurrence-free, cancer-specific and overall survivals (all p <  0.001) in patients who were up-staged. Multivariate Cox analyses revealed pathologic upstaging as an independent predictor of shorter recurrence-free (HR 2.195, 95% CI 1.459-3.300, p <  0.001), cancer-specific (HR 2.238, 95% CI 1.252-4.003, p = 0.007), and overall survivals (HR 1.632, 95% CI 1.029-2.588, p = 0.037). Subgroup analysis of pathologic stage T3a showed no significant difference in survival of the partial nephrectomy group when compared to the radical nephrectomy group (all p > 0.5). CONCLUSIONS: Patients up-staged from clinical stage T1 to pathologic stage T3a RCC showed shorter survival outcomes than those without upstaging. However, partial nephrectomy, compared with radical nephrectomy, showed comparable outcomes in patients who were up-staged.

Impact of warm ischaemia time on postoperative renal function after partial nephrectomy for clinical T1 renal cell carcinoma: a propensity score-matched study.

OBJECTIVES: To analyse the effect of prolonged warm ischaemia time (WIT) on long-term renal function after partial nephrectomy (PN), as controversy still exists as to whether prolonged WIT adversely affects the incidence of chronic kidney disease (CKD) after PN. PATIENTS AND METHODS: We reviewed data from 1816 patients who underwent PN for a clinical T1 renal tumour. The propensity scores for prolonged WIT were calculated with the shorter WIT group (<30 min) matched to the longer WIT group (≥30 min) in a 2:1 ratio. Multivariate analysis was used to determine independent predictors for occurrence of postoperative CKD [defined as an estimated glomerular filtration rate (eGFR) of <60 mL/min/1.73 m2 ] and major renal function deterioration (MRFD; defined as an eGFR decrease of ≥25% postoperatively). RESULTS: After propensity score matching, there was no significant difference in CKD-free survival between the two WIT groups (P = 0.787). Furthermore, longer WIT did not show any significant associations with postoperative CKD-free survival [hazard ratio (HR) 1.002, 95% confidence interval (CI) 0.989-1.015; P = 0.765) and MRFD-free survival (HR 1.014, 95% CI 1.000-1.028; P = 0.055). From further subgroup analyses using more specific WIT thresholds (≤20, 21-30, 31-40, 41-50, ≥50 min) and status of preoperative CKD, no significant differences were noted in CKD and MRFD-free survival amongst the subgroups (all P > 0.05). CONCLUSIONS: Prolonged WIT was not associated with increased incidence of CKD or MRFD after PN.

Personalized 3D kidney model produced by rapid prototyping method and its usefulness in clinical applications.

BACKGROUND: Three-dimensional (3D) printing has been introduced as a novel technique to produce 3D objects. We tried to evaluate the clinical usefulness of 3D-printed renal model in performing partial nephrectomy (PN) and also in the education of medical students. MATERIALS AND METHODS: We prospectively produced personalized renal models using 3D-printing methods from preoperative computed tomography (CT) images in a total of 10 patients. Two different groups (urologist and student group) appraised the clinical usefulness of 3D-renal models by answering questionnaires. RESULTS: After application of 3D renal models, the urologist group gave highly positive responses in asking clinical usefulness of 3D-model among PN (understanding personal anatomy: 8.9 / 10, preoperative surgical planning: 8.2 / 10, intraoperative tumor localization: 8.4 / 10, plan for further utilization in future: 8.3 / 10, clinical usefulness in complete endophytic mass: 9.5 / 10). The student group located each renal tumor correctly in 47.3% when they solely interpreted the CT images. After the introduction of 3D-models, the rate of correct answers was significantly elevated to 70.0% (p < 0.001). The subjective difficulty level in localizing renal tumor was also significantly low (52% versus 27%, p < 0.001) when they utilized 3D-models. CONCLUSION: The personalized 3D renal model was revealed to significantly enhance the understanding of correct renal anatomy in patients with renal tumors in both urologist and student groups. These models can be useful for establishing the perioperative planning and also education program for medical students.

Preoperative cholesterol level as a new independent predictive factor of survival in patients with metastatic renal cell carcinoma treated with cyto-reductive nephrectomy.

BACKGROUND: The obesity and lipid metabolism were previously proposed to be related with the clinical outcomes of metastatic renal cell carcinoma (mRCC). We tried to investigate the relationship between preoperative cholesterol level (PCL) and survival outcomes in patients with mRCC. METHODS: We analysed the data of 244 patients initially treated with cyto-reductive nephrectomy after being diagnosed with mRCC. Patients were stratified into two groups according to the PCL cut-off level of 170 mg/dL. The postoperative survival rates were compared using Kaplan-Meier analysis and the possible predictors of patients' cancer-specific survival (CSS) and overall survival (OS) were tested using multivariate Cox-proportional hazard models. RESULTS: The low cholesterol group showed significantly worse postoperative CSS (p = 0.013) and OS (p = 0.009) than the high cholesterol group. On multivariate analysis, low PCL was revealed as an independent predictor of worse CSS (hazard ratio [HR], 2.162; 95% CI, 1.221-3.829; p = 0.008) and OS (HR, 2.013; 95% CI, 1.206-3.361; p = 0.007). Subsequent subgroup analysis showed that these results were maintained in the clear cell subgroup but not in the non-clear cell subgroup. CONCLUSION: Decreased PCL was significantly correlated with worse survival outcomes in patients with mRCC treated with cytoreductive nephrectomy. The underlined mechanism is still uncharted and requires further investigation.