Application of Porcine Kidney-Derived Extracellular Matrix as Coating, Hydrogel, and Scaffold Material for Renal Proximal Tubular Epithelial Cell.

BACKGROUND: Human renal proximal tubular epithelial (RPTE) cell is a very useful tool for kidney-related experiments in vitro/ex vivo. However, only a few primary RPTE cells can be obtained through kidney biopsy, the proliferation rate of primary cell is very low, and the cultured cell properties are easily altered in artificial conditions. Thus, RPTE cell usage is very tricky; we applied porcine kidney-derived extracellular matrix (renal ECM) as coating, hydrogel, and scaffold material to increase cell proliferation and maintain cellular properties providing three-dimensional (3D) niche, which can be a valuable cell delivery vehicle. METHODS: Porcine renal ECM was prepared by decellularization using 1% Triton X-100, solubilized with 0.5 M acetic acid. The final protein concentration was adjusted to 10 µg/µL (pH 7.0). The efficacies as coating, hydrogel, and scaffold materials were analyzed through cell morphology, proliferation rate, renal-associated gene expressions, chemical composition, and microstructure evaluation. The efficacies as a coating material were compared with Matrigel, collagen type 1 (col1), gelatin, fibrinogen, and thrombin. After confirmation of coating effects, the effective concentration range was decided. The efficacies as hydrogel and scaffold materials were compared with hyaluronic acid (HA) and col1, respectively. RESULTS: As the coating material, renal ECM showed a higher cell proliferation rate compared to other materials, except for Matrigel. Renal-associated gene expressions were significantly enhanced in the renal ECM than other materials. Coating effect on cell proliferation was dependent on the renal ECM concentration, and the effective concentration ranged from 30 to 100 µg. As the hydrogel material, renal ECM showed a distinct inner cell network morphology and significantly increased renal-associated gene expressions, compared to HA hydrogel. As the scaffold material, renal ECM showed specific amide peaks, enhanced internal porosity, cell proliferation rate, and renal-associated gene expression compared to the col1 scaffold. CONCLUSIONS: We concluded that renal ECM can be a suitable material for RPTE cell culture and usage. More practically, the coated renal ECM stimulates RPTE cell proliferation, and the hydrogel and scaffold of renal ECM provide useful 3D culture niche and cell delivery vehicles maintaining renal cell properties.

Prognostic Significance of the Neutrophil-to-Lymphocyte Ratio in Patients with Non-Muscle Invasive Bladder Cancer treated with Intravesical Bacillus Calmette-Guérin and the Relationship with the CUETO Scoring Model.

PURPOSE: In this study, we evaluated the predictability of a modified Club Urológico Español de Tratamiento Oncológico (CUETO) scoring model and preoperative neutrophil-to-lymphocyte ratio (NLR) in patients with non-muscle invasive bladder cancer (NMIBC). MATERIALS AND METHODS: From August 2005 to May 2016, a total of 281 patients received intravesical bacillus Calmette-Guérin therapy after transurethral resection of a bladder tumor. The pathologic stage of all patients was Ta or T1. Of 281 patients, 84 (29.9%) experienced recurrence and 14 (5.0%) developed progression. The mean follow-up period was 46 months. The cut-off value for NLRs was 2.29. RESULTS: One hundred-eight patients (38.4%) displayed a high NLR (> 2.29). In Kaplan-Meier curve analysis, a high NLR was associated with lower recurrence-free survival (RFS) (P < .001) and progression-free survival (PFS) (P = .002). CUETO scores were associated with RFS (P < .001), but not with PFS (P = .423). A combination of NLRs and the CUETO risk model correlated with RFS (P < .001) and PFS (P = .002). In multivariate analysis, female gender, concomitant carcinoma in situ (CIS), tumor number >3, recurrent tumors, and a high NLR were independent factors predicting recurrence (all P < .05). Concomitant CIS, recurrent tumors, and a high NLR were independent factors for predicting progression (all P < .05). CONCLUSION: In patients with NMIBC, an NLR >2.29 was identified as a significant factor for predicting tumor recurrence and progression. Inclusion of preoperative NLR enhanced the accuracy of the CUETO model to predict disease progression.

Identification of a novel non-invasive biological marker to overcome the shortcomings of PSA in diagnosis and risk stratification for prostate cancer: Initial prospective study of developmental endothelial locus-1 protein.

OBJECTIVE: This prospective study sought to clarify the developmental endothelial locus-1 (Del-1) protein as values of diagnosis and risk stratification of prostate cancer (PCa). DESIGN: From February 2017 to December 2019, a total 458 patients who underwent transrectal ultrasound guided prostate biopsy or surgery of benign prostatic hyperplasia agreed to research of Del-1 protein. We prospectively compared and analyzed the Del-1 protein and prostate specific antigen (PSA) in relation to the patients' demographic and clinicopathological characteristics. RESULTS: Mean age was 68.86±8.55 years. Mean PSA and Del-1 protein was 21.72±89.37, 0.099±0.145, respectively. Two hundred seventy-six (60.3%) patients were diagnosed as PCa. Among them, 181 patients underwent radical prostatectomy (RP). There were significant differences in Del-1 protein between benign and PCa group (0.066±0.131 vs 0.121±0.149, respectively, p<0.001). When we set the cut-off value of del-1 protein as 0.120, in patients with 3≤PSA≤8, positive predictive value and specificity of Del-1 protein (≥0.120) for predicting PCa were 88.9% (56/63) and 93.5% (101/108), respectively. Among 181 patients who underwent RP, there were significant differences in Del-1 protein according to stage (pT2 vs pT3a vs ≥pT3b) (0.113±0.078, 0.171±0.121, 0.227±0.161, respectively, p<0.001) and to Gleason score (6 (3+3) or 7 (3+4) vs 7 (4+3) or 8 (4+4) vs 9 or 10) (0.134±0.103, 0.150±0.109, 0.212±0.178, respectively, P = 0.044). Multivariate analysis showed that PSA, Del-1 protein and high Gleason score (≥9) were the independent prognostic factors for predicting higher pT stage (≥3b). Furthermore, age, PSA and Del-1 protein were independent prognostic factors for predicting significant PCa. CONCLUSION: Patients with PCa showed higher expression of Del-1 protein than benign patients. Del-1 protein increased with the stage and Gleason score of PCa. Collaboration with PSA, Del-1 protein can be a non-invasive useful marker for diagnosis and risk stratification of PCa.

Decrease of Preoperative Serum Albumin-to-Globulin Ratio as a Prognostic Indicator after Radical Cystectomy in Patients with Urothelial Bladder Cancer.

PURPOSE: This study aims to evaluate whether preoperative serum albumin-to-globulin ratio (AGR) could predict the prognosis of patients with urothelial bladder cancer (UBC) after radical cystectomy (RC). MATERIALS AND METHODS: A total of 176 patients with UBC who underwent RC in a tertiary hospital between 2008 and 2019 were retrospectively analyzed. The AGR was calculated as albumin/(total protein - albumin). In addition, the AGR was divided into two groups for the time-dependent receiver operating characteristic curve (ROC) analysis. Survival was estimated using the Kaplan-Meier analysis and compared using the log-rank test. Cox proportional- hazards models were used for multivariate survival analysis. RESULTS: The best cutoff AGR value for metastasis prediction was 1.32 based on the ROC curve analysis. Patients who had lower pretreatment AGR (<1.32) values composed the low-AGR group (n = 57; 32.4%). On the other hand, the remaining patients (n = 119; 67.6%) composed the high-AGR group. The patients in the low-AGR group had more advanced stage tumors compared with the patients in the high-AGR group. The Kaplan-Meier curves revealed that the patients in the low-AGR group had significantly lower rates of metastasis-free survival (MFS) and cancer-specific survival (CSS). The multivariate Cox regression analysis showed that preoperative AGR was an independent prognostic factor for MFS and CSS. CONCLUSION: In this single-institution retrospective study, lower preoperative AGR values demonstrated a poor prognostic effect on MFS and CSS in patients with UBC who underwent RC.

Prognostic impact of perirenal fat stranding on oncologic outcomes in ureteral urothelial carcinoma.

PURPOSE: Perirenal fat stranding (PRFS) is defined as linear areas of soft-tissue attenuation in the perirenal space that can result from ureteral obstruction. We analyzed the prognostic impact of PRFS on outcomes in patients with ureteral urothelial carcinoma (UC). MATERIALS AND METHODS: Overall, 126 patients evaluated preoperatively by computerized tomography (CT) scan and diagnosed with ureteral UC following nephroureterectomy between January 2001 and May 2018 were included. We analyzed associations between oncologic outcomes and secondary signs such as hydronephrosis and PRFS. RESULTS: Overall, 68 patients (54.0%) showed PRFS on preoperative CT scans. The patients' mean age was 66.33±9.49 years. A high pT stage (≥T3) was seen in 47 patients (37.3%) and high-grade tumors were seen in 90 patients (71.4%). Lymphovascular invasion (LVI) was seen in 15 patients (11.9%), and 5 (4.0%) were at the pN1 stage. Multivariate Cox analysis showed that cT stage≥3, PRFS, pT stage≥3, tumor grade, LVI, and pN1 stage were independent prognostic factors of recurrence-free survival (RFS) and cancer-specific survival (CSS) (all p<0.05). CONCLUSIONS: PRFS was found to be an independent prognostic factor for RFS and CSS. PRFS is easily detectable in preoperative CT imaging and may be useful for improving the prediction of oncologic outcomes of ureteral UC. Therefore, PRFS along with other important preoperative CT findings can help urologists give preoperative advice to patients with ureteral UC before surgical management.

Susceptibility of the Index Urinary Tract Infection to Prophylactic Antibiotics Is a Predictive Factor of Breakthrough Urinary Tract Infection in Children with Primary Vesicoureteral Reflux Receiving Continuous Antibiotic Prophylaxis.

BACKGROUND: Few studies have reported on breakthrough urinary tract infection (UTI) associated with the susceptibility of index UTI to prophylactic antibiotics in children with primary vesicoureteral reflux (VUR) receiving continuous antibiotic prophylaxis (CAP). We assessed the impact of the susceptibility of index UTI to prophylactic antibiotics in breakthrough UTIs in children with primary VUR receiving CAP. METHODS: We retrospectively reviewed the medical records of 81 children with primary VUR who were diagnosed after febrile or symptomatic UTI and subsequently received trimethoprim-sulfamethoxazole (TMP-SMX) as CAP between January 2010 and December 2013. We allocated children to a susceptible group or a resistant group based on the susceptibility of index UTI to TMP-SMX. We evaluated patient demographics and clinical outcomes after CAP according to the susceptibility of index UTI to TMP-SMX. Multivariate analysis was used to identify the predictive factors for breakthrough UTI. RESULTS: Of the 81 children, 42 were classified into the susceptible group and 39 into the resistant group. The proportion of breakthrough UTI was 31.0% (13/42) in the susceptible group and 53.8% (21/39) in the resistant group (P = 0.037). Progression of renal scarring was observed in 0% of children in the susceptible group and 15% in the resistant group (P = 0.053). Multivariate analysis showed that TMP-SMX resistance and initial renal scarring were significant predictors of breakthrough UTI. CONCLUSION: Susceptibility of index UTI to prophylactic antibiotics is a risk factor of breakthrough UTI and is associated with poor clinical outcomes in children with primary VUR receiving CAP.

Predictive factors for adrenal metastasis in extra-adrenal malignancy patients with solitary adrenal mass.

BACKGROUND AND OBJECTIVES: The adrenal gland is a frequent site for metastasis, and a solitary adrenal mass is often observed during staging workup or imaging follow-up in patients with extra-adrenal malignancy. To create an appropriate management plan, it is essential to distinguish between benign adrenal lesions and metastasis in patients with extra-adrenal cancer having solitary adrenal masses. Therefore, here we evaluated the predictive factors for adrenal metastasis in patients with extra-adrenal malignancy having solitary adrenal mass. MATERIALS AND METHODS: From September 2003 to June 2016, we retrospectively reviewed patients with extra-adrenal malignancy having solitary adrenal mass on a cancer staging workup or follow-up study who subsequently underwent adrenalectomy at our institution. All patients underwent preoperative functional studies; those with positive results were excluded from this study. Characteristics of oncology patients with adrenal mass including age, sex, body mass index, smoking, mass location, mass size, hypertension, diabetes mellitus, precontrast Hounsfield unit (HU), and synchronous or metachronous adrenal mass based on the time of the extra-adrenal cancer diagnosis were analyzed. RESULTS: Of the total 68 patients with extra-adrenal cancer having solitary adrenal mass, 22 had pathologically confirmed adrenal metastasis. Primary cancers consisted of hepatocellular cell carcinoma (n = 7), renal cell carcinoma (n = 7), lung cancer (n = 4), colon cancer (n = 3), and breast cancer (n = 1). On multivariate analysis, a higher precontrast HU (P = 0.001, odds ratio [OR] = 1.105, 95% confidence interval [CI] = 1.042-1.172), male sex ( P = 0.019, OR = 9.782, 95% CI = 1.462-65.461), and metachronous adrenal mass ( P = 0.007, OR = 11.090, 95% CI = 1.937-63.490) were observed as predictive factors for adrenal metastasis in patients with extra-adrenal cancer having solitary adrenal mass. The cut-off value of precontrast HU to distinguish between metastasis and benign lesions was 36.2 (sensitivity = 81.8%; specificity = 91.3%). CONCLUSION: High precontrast HU (> 36), male sex, and metachronous adrenal mass are predictive factors for adrenal metastasis in patients with extra-adrenal malignancy having solitary adrenal mass.