Gustave Roussy Immune score as a prognostic biomarker in patients with platinum-refractory metastatic urothelial carcinoma treated with pembrolizumab: YUSHIMA study.

BACKGROUND: This study aimed to investigate the prognostic value of the Gustave Roussy Immune score (GRIm-score) in platinum-refractory metastatic urothelial carcinoma (UC) treated with pembrolizumab. METHODS: This multicenter retrospective study (YUSHIMA study) evaluated 331 patients with metastatic UC treated with pembrolizumab after platinum-based chemotherapy between January 2018 and June 2023 at 13 institutions. We collected pretreatment variables, including the GRIm-score based on serum albumin, lactate dehydrogenase, and neutrophil-to-lymphocyte ratio. The patients were divided into low and high GRIm-score groups. Prognostic factors for overall survival (OS) and progression-free survival (PFS) were determined using the multivariate Cox proportional hazard model. RESULTS: During the median follow-up period of 7.3 months, 278 (84%) patients showed disease progression, and 223 (67%) died from any cause. Multivariate analysis revealed that the high GRIm-score group was an independent and significant adverse prognostic factor of both OS and PFS (hazard ratio, 1.65 and 1.82, respectively; both p < 0.001) along with Eastern Cooperative Oncology Group Performance Status of ≥ 2 (both p < 0.001), presence of visceral metastasis (both p < 0.001), and hemoglobin of < 9.2 g/dL (p = 0.030 and p = 0.038). C-reactive protein of > 42 mg/L was a significant prognostic factor for OS (p = 0.001). CONCLUSION: The GRIm-score is an independent prognostic marker for survival outcomes in patients with platinum-refractory metastatic UC treated with pembrolizumab.

Risk factors for the long-term persistent genitourinary toxicity after stereotactic body radiation therapy for localized prostate cancer: A single-center, retrospective study of 306 patients.

OBJECTIVES: To identify risk factors for the long-term persistent genitourinary toxicity (GUT) after stereotactic body radiation therapy (SBRT) for localized prostate cancer (PCa). METHODS: A total of 306 patients who underwent SBRT at our institution between March 2017 and April 2022 were retrospectively evaluated. SBRT was performed at 35 Gy in five fractions over 5 or 10 days. Factors related to the long-term persistence of acute GUT after SBRT were analyzed. RESULTS: During the median follow-up period of 39.1 months, 203 (66%) patients experienced any grade of acute GUT, which remained in 78 (26%) patients 6 months after SBRT. Multivariate analysis revealed that age ≥75 years was consistently a significant independent risk factor for any grade of acute GUT 6, 12, and 24 months after SBRT (hazard ratio [HR] 2.31, p = 0.010; HR 2.84, p = 0001; and HR 3.05, p = 0.009, respectively). Older age was not a significant risk factor for the development of grade ≥2 acute GUT. The duration of acute GUT was significantly longer in the older group than in the nonolder group (median duration = 234 vs. 61 days, p < 0.001), and the incidence of persistent GUT was significantly more frequent in the older group beyond 6 months after SBRT. CONCLUSIONS: Older age is a significant independent risk factor for the long-term persistent GUT after SBRT for localized PCa.

Impact of diagnostic ureteral catheterization on intravesical tumour recurrence following radical nephroureterectomy for upper tract urothelial carcinoma.

PURPOSE: To investigate whether even a minimally invasive diagnostic procedure for the upper tract such as ureteral catheterization (UCath) may substantially increase the risk of intravesical recurrence (IVR) in patients with upper tract urothelial carcinoma (UTUC) treated with radical nephroureterectomy (RNU). METHODS: The present, retrospective study enrolled 163 patients undergoing RNU for UTUC between 2010 and 2021 at two, tertiary care hospitals. The primary endpoint was the association between UCath and IVR-free survival (IVRFS). The secondary endpoints were the association of ureterorenoscopy (URS) and URS biopsy (URSBx) with IVRFS. Directed acyclic graph (DAG)-guided multivariable models were used to adjust for potential confounders. RESULTS: Of the 163 patients, 128 (79%), 88 (54%), and 67 (41%) received UCath, URS, and URSBx, respectively. URS was performed concurrently with UCath. During the follow-up period (median: 47 months), IVR developed in 62 patients (5-year IVRFS rate: 52%). A DAG included concurrent bladder cancer, tumour size, hydronephrosis, positive cytology, and multiple UTUCs as potential confounders of the association between UCath and IVR. Both DAG-guided and stepwise multivariable models revealed a significant association between UCath and IVR (hazard ratio: 17.8; P < 0.001). UCath was also associated with shorter IVRFS in a subset of 75 patients who had not received URS (P < 0.001). In contrast, URS and URSBx were not associated with IVR in patients who had received UCath and URS, respectively. CONCLUSION: Any diagnostic manipulations of the upper urinary tract, even a minimally invasive procedure like UCath, could confer a risk of post-RNU IVR in UTUC patients.

Superior detection of significant prostate cancer by transperineal prostate biopsy using MRI-transrectal ultrasound fusion image guidance over cognitive registration.

BACKGROUND: The BioJet system allows the fusion of magnetic resonance imaging (MRI) images with real-time transrectal ultrasonography to accurately direct biopsy needles to the target lesions. To date, the superiority of targeted biopsy using the BioJet system over cognitive registration remains unknown. METHODS: This retrospective study included 171 biopsy-naïve men with elevated prostate-specific antigen (2.5-20 ng/mL) and MRI-positive lesions; 74 and 97 men underwent a four-core targeted biopsy per MRI-positive target lesion and a 14-core systematic biopsy transperineally using the BioJet system and cognitive registration, respectively. Detection rates of significant cancer, defined as grade group ≥ 2 or maximum cancer length ≥ 5 mm, were compared between the BioJet system and cognitive registration using propensity score matching and a multivariate logistic regression model. RESULTS: After propensity score matching (67 men for each group), the detection rates of significant cancer were significantly higher in the BioJet group than in the cognitive group for both targeted (76% vs. 46%, P = 0.002) and systematic (70% vs. 46%, P = 0.018) biopsy. Multivariate analysis of the entire cohort also showed that the BioJet system was independently associated with significant cancer detection by targeted and systematic biopsy (P < 0.01), along with a higher prostate-specific antigen density and a higher prostate imaging reporting and data system score. CONCLUSIONS: Transperineal prostate biopsy using the BioJet system is superior to cognitive registration in detecting significant cancer for targeted and systematic biopsies.

Preoperative models incorporating the systemic immune-inflammation index for predicting prognosis and muscle invasion in patients with non-metastatic upper tract urothelial carcinoma.

OBJECTIVE: To develop preoperative models as a guide to indications for neoadjuvant chemotherapy (NAC) and regional lymph node dissection (LND) before and at radical nephroureterectomy (RNU), respectively, in patients with non-metastatic upper tract urothelial carcinoma (UTUC) by incorporating the systemic immune-inflammation index (SII). METHODS: This retrospective study enrolled 103 consecutive patients with UTUC undergoing RNU. The SII was calculated as neutrophils × platelets / lymphocytes. Multivariable Cox proportional hazard model was used to develop preoperative models for cancer-specific survival (CSS) and overall survival (OS). A model for predicting muscle invasion was developed using logistic regression analysis. Harrell's concordance-index (c-index) or the area under the receiver operating characteristic curve (AUC) was used to evaluate the accuracy of the models. RESULTS: During follow-up (median: 41 months), 26 and three patients died of UTUC and other causes, respectively. Performance status > 0, clinical tumor (cT) stage ≥ 3, and SII > 520 were independent adverse prognosticators for CSS, and one point was assigned to each prognosticator. Risk score models comprising the sum of the points stratified patients into three risk groups (0, 1, and 2-3; P < 0.001 for CSS and OS) with respective c-indices of 0.843 and 0.820. SII > 677 and ≥ cT3 were independently associated with muscle invasion. A model based on these variables predicted muscle invasion with AUC of 0.804. CONCLUSION: Preoperative SII is significantly associated with worse survival outcomes and muscle invasion in patients with non-metastatic UTUC. Our preoperative predictive models may serve as a guide to indications for NAC and LND.

Prognostic significance of the controlling nutritional status score in patients with metastatic renal cell carcinoma diagnosed before an era of first-line immune-oncology combination therapies.

OBJECTIVE: To explore the prognostic role of the controlling nutritional status score in patients with metastatic renal cell carcinoma. METHODS: We retrospectively analyzed 107 patients with metastatic renal cell carcinoma who received their diagnosis between 2007 and 2018 and were treated with or without a first-line interferon or tyrosine kinase inhibitor at a single cancer center. The controlling nutritional status score was based on values for albumin, lymphocyte count and total cholesterol at the metastatic renal cell carcinoma diagnosis. Association of the controlling nutritional status score and clinical variables, including the Memorial Sloan-Kettering Cancer Center and the International Metastatic Renal Cell Carcinoma Database Consortium risk classifications, with overall survival was examined using the Cox proportional hazard model. Predictive accuracy of the prognostic factors was assessed using Harrell's concordance index. RESULTS: First-line interferon and tyrosine kinase inhibitor were given to 48 (45%) and 41 (38%) patients, respectively, and 28 (26%) and 33 (31%) patients underwent cytoreductive nephrectomy and metastasectomy, respectively. During follow-up (median: 36.3 months), 64 patients died. The median controlling nutritional status score was 2 (range: 0-8). A controlling nutritional status score ≥ 2 was significantly associated with shorter overall survival (P < 0.01) independently of the Memorial Sloan-Kettering Cancer Center and International Metastatic Renal Cell Carcinoma Database Consortium risk classifications. Integration of the controlling nutritional status score into the Memorial Sloan-Kettering Cancer Center and International Metastatic Renal Cell Carcinoma Database Consortium risk classifications improved concordance index from 0.702 to 0.770 and from 0.698 to 0.749, respectively. CONCLUSION: The controlling nutritional status score may serve as a prognostic biomarker objectively reflecting the general physical condition of patients with metastatic renal cell carcinoma treated with or without first-line interferon or tyrosine kinase inhibitor in terms of nutritional and immuno-inflammatory status.

Gelatin Methacryloyl-Riboflavin (GelMA-RF) Hydrogels for Bone Regeneration.

Gelatin methacryloyl (GelMA) is a versatile biomaterial that has been used in various biomedical fields. UV light is commonly used to photocrosslink such materials; however, its use has raised several biosafety concerns. We investigated the mechanical and biological properties of a visible-wavelength (VW)-light-crosslinked gelatin-based hydrogel to evaluate its viability as a scaffold for bone regeneration in bone-destructive disease treatment. Irgacure2959 or riboflavin was added as a photoinitiator to create GelMA solutions. GelMA solutions were poured into a mold and exposed to either UV or VW light. KUSA-A1 cell-laden GelMA hydrogels were crosslinked and then cultured. Mechanical characterization revealed that the stiffness range of GelMA-RF hydrogel was suitable for osteoblast differentiation. KUSA-A1 cells encapsulated in GelMA hydrogels photopolymerized with VW light displayed significantly higher cell viability than cells encapsulated in hydrogels photopolymerized with UV light. We also show that the expression of osteogenesis-related genes at a late stage of osteoblast differentiation in osteoblasts encapsulated in GelMA-RF hydrogel was markedly increased under osteoblast differentiation-inducing conditions. The GelMA-RF hydrogel served as an excellent scaffold for the encapsulation of osteoblasts. GelMA-RF hydrogel-encapsulated osteoblasts have the potential not only to help regenerate bone mass but also to treat complex bone defects associated with bone-destructive diseases such as periodontitis.

DWI as an Imaging Biomarker for Bladder Cancer.

OBJECTIVE: DWI has been increasingly applied in the management of bladder cancer. In this article, we discuss the role of DWI as an imaging biomarker for bladder cancer. CONCLUSION: The DWI signal is derived from the motion of water molecules, which represents the physiologic characteristics of the tissue of interest. The emerging evidence highlights the utility of DWI for bladder cancer detection and characterization. DWI is a potentially useful tool to individualize treatment strategies.

Role of poly(ADP-ribose) polymerase activation in the pathogenesis of periodontitis in diabetes.

AIM: The aetiology of progressive periodontitis in diabetes has not yet been elucidated. We previously demonstrated that nitrosative stress is increased in diabetic rats with periodontitis. Nitrosative stress induces poly(ADP-ribose) polymerase (PARP) activation. Here, we demonstrated the involvement of PARP activation in diabetic periodontitis and detailed the therapeutic effects of PARP inhibitor. MATERIALS AND METHODS: Experimental periodontitis was induced by placing a nylon thread ligature. Half of the normal and diabetic rats received the PARP inhibitor, 1,5-isoquinolinediol, for 2 weeks. Gingival PARP activation was detected by immunostaining for poly(ADP-ribose). Periodontitis was evaluated by gingival inflammatory cell infiltration, inflammatory gene expressions and micro-CT analyses. RESULTS: Although both periodontitis and the presence of diabetes increased PARP activation in the gingiva, diabetic rats with periodontitis had the highest activation of PARP. Diabetic rats with periodontitis also showed significant increases in monocyte/macrophage invasion into the gingiva, inflammatory gene expressions, nitrotyrosine-positive cells in the gingiva and alveolar bone loss, all of which were suppressed by treatment with the PARP inhibitor. CONCLUSIONS: These results indicate the involvement of PARP activation in the pathogenesis and aggravation of periodontal disease in diabetes and suggest the therapeutic potential of PARP inhibition for treating periodontal disease, especially in patients with diabetes.

Serum Amyloid A Promotes E-Selectin Expression via Toll-Like Receptor 2 in Human Aortic Endothelial Cells.

Periodontitis is a chronic inflammatory disease that affects the periodontium. Recent studies suggest an association between periodontal and cardiovascular diseases. However, the detailed molecular mechanism is unknown. A previous study has demonstrated that experimental periodontitis induces serum amyloid A (SAA) in the liver and peripheral blood of ApoE-deficient mice as an atherosclerosis model. SAA is an acute-phase protein that affects systemic inflammation. The aim of this study is to investigate the atherosclerosis-onset mechanism using human aortic endothelial cells (HAECs) stimulated by SAA in vitro. Atherosclerosis PCR array and qPCR analyses showed upregulation of adhesion molecules such as intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and E-selectin in HAECs upon SAA stimulation. In addition, the results demonstrated that Toll-like receptor, TLR2, could serve as an important receptor of SAA in HAECs. Furthermore, small interfering RNA (siRNA) against TLR2 inhibited the upregulation of adhesion molecules in HAECs stimulated by SAA. Our results suggest that SAA stimulates the expression of adhesion molecules via TLR2. SAA could be an important molecule for atherosclerosis induced by periodontal disease.

Predictive risk factors of postoperative urinary incontinence following holmium laser enucleation of the prostate during the initial learning period.

PURPOSE: To determine the predictive factors for postoperative urinary incontinence (UI) following holmium laser enucleation of the prostate (HoLEP) during the initial learning period. PATIENTS AND METHODS: We evaluated 127 patients with benign prostatic hyperplasia who underwent HoLEP between January 2011 and December 2013. We recorded clinical variables, including blood loss, serum prostate-specific antigen levels, and the presence or absence of UI. Blood loss was estimated as a decline in postoperative hemoglobina levels. The predictive factors for postoperative UI were determined using a multivariable logistic regression analysis. RESULTS: Postoperative UI occurred in 31 patients (24.4%), but it cured in 29 patients (93.5%) after a mean duration of 12 weeks. Enucleation time >100 min (p=0.043) and blood loss >2.5g/dL (p=0.032) were identified as significant and independent risk factors for postoperative UI. CONCLUSIONS: Longer enucleation time and increased blood loss were independent predictors of postoperative UI in patients who underwent HoLEP during the initial learning period. Surgeons in training should take care to perform speedy enucleation maneuver with hemostasis.

Continued administration of antithrombotic agents during transperineal prostate biopsy.

PURPOSE: To determine the safety of continued administration of antithrombotic agents during transperineal (TP) prostate biopsy. PATIENTS AND METHODS: A total of 811 men who underwent transrectal ultrasound (TRUS)-guided TP biopsy from January 2008 to June 2012 at our two institutions were retrospectively analyzed. Among these 811 men, 672 received no antithrombotic agents (group I), 103 received and continued administration of antithrombotic agents (group II), and 36 interrupted administration of antithrombotic agents (group III). Overall complications were graded and hemorrhagic complications were compared (group I with group II) using propensity score matching (PSM) analysis. RESULTS: An overall complication rate of 4.6% was recorded. Hemorrhagic complications occurred in 1.8% and they were virtually identical in all the three groups, and no severe hemorrhagic complications occurred. One patient in group III required intensive care unit admission for cerebral infarction. PSM analysis revealed no statistical difference between groups I and II with regard to the incidence of gross hematuria, perineal hematoma, and rectal bleeding. Multiple regression analysis revealed that hemorrhagic complications were associated with lower body mass index (<21 kg/m2, P=0.0058), but not with administration of antithrombotic agents. CONCLUSIONS: Continued administration of antithrombotic agents does not increase the risk of hemorrhagic complications; these agents are well tolerated during TP biopsy.

Apparent diffusion coefficient value reflects invasive and proliferative potential of bladder cancer.

PURPOSE: To elucidate a role of apparent diffusion coefficient (ADC) value as a biomarker of bladder cancer, we investigated its associations with Ki-67 labeling index (LI) along with classical clinicopathological prognosticators. MATERIALS AND METHODS: Diffusion-weighted MRI (DW-MRI) at 1.5 Tesla using b-values of 0, 500, 1000, and 2000 s/mm(2) was prospectively taken before transurethral resection by 132 bladder cancer patients. ADC value of index tumors was measured and compared with clinicopathological prognosticators including Ki-67 LI. RESULTS: ADC value was significantly lower in tumors with higher Ki-67 LIs, sessile tumors (versus papillary), larger tumors, higher grade disease, and higher T stage disease. ADC value inversely correlated with Ki-67 LI (ρ = -0.57; P < 0.0001). On multiple regression analysis, T stage and Ki-67 LI significantly correlated with ADC value. The Akaike information criterion confirms these two parameters constitute the best model for determining ADC value. Similarly, T stage and ADC value significantly correlated with Ki-67 LI and these two parameters composed the best model for predicting Ki-67 LI. CONCLUSION: ADC value would reflect T stage and Ki-67 LI, representing invasive and proliferative potential, respectively. ADC value is likely to serve as a biomarker reflecting aggressiveness of bladder cancer.

Enhanced bioactivity of polyvinylidene chloride films using argon ion bombardment for guided bone regeneration.

Polyvinylidene chloride (PVDC) is a long chain carbon synthetic polymer. The objective of this study was to improve the bioactivity of PVDC films through surface modification using argon (Ar) ion bombardment to create Ar-modified PVDC films (Ar-PVDC) to address the clinical problems of guided bone regeneration (GBR), which is technique-sensitive, and low bone regenerative ability. First, the effects of Ar ion bombardment, a low temperature plasma etching technique widely used in industry, on PVDC film wettability, surface chemistry, and morphology were confirmed. Next, fibroblast-like and osteoblast-like cell attachment and proliferation on Ar-PVDC were assessed. As a preclinical in vivo study, Ar-PVDC was used to cover a critical-sized bone defect on rat calvaria and osteoconductivity was evaluated by micro-computed tomography analysis and histological examinations. We found that the contact angle of PVDC film decreased by 50° because of the production of -OH groups on the PVDC film surface, though surface morphological was unchanged at 30 min after Ar ion bombardment. We demonstrated that cell attachment increased by about 40% and proliferation by more than 140% because of increased wettability, and 2.4 times greater bone regeneration was observed at week 3 with Ar-PVDC compared with untreated PVDC films. These results suggest that Ar ion bombardment modification of PVDC surfaces improves osteoconductivity, indicating its potential to increase bone deposition during GBR.

Apparent diffusion coefficient as a prognostic biomarker of upper urinary tract cancer: a preliminary report.

OBJECTIVES: To investigate the role of apparent diffusion coefficient (ADC) as a biomarker reflecting the aggressiveness of upper urinary tract urothelial cell carcinoma (UUT-UCC). METHODS: Thirty-four consecutive patients treated with nephroureterectomy for non-metastatic disease were prospectively enrolled in this study. ADC was compared with clinicopathological variables including Ki-67 labelling index (LI) and cancer-specific survival (CSS). RESULTS: The overall 3-year CSS rate was 82 % (median follow-up, 36 months). ADC was significantly lower in grade 3 disease than in grades 1-2 disease (P = 0.011) and significantly and inversely correlated with Ki-67 LI (ρ = -0.59, P = 0.0002). Low ADCs (<1.10 × 10(-3) mm(2)/s) were significantly associated with shorter CSS (P = 0.039). Multivariate analysis of preoperative variables identified ADC and MRI-based clinical T stage as independent indicators of shorter CSS; the patients were stratified into high-risk (8 patients with low ADC and at least clinical T3) and low-risk (26 patients with high ADC or not more than clinical T2) groups with 3-year CSS rates of 43 % and 93 % (P = 0.0003). CONCLUSIONS: Our preliminary data suggest the potential role of ADC as a quantitative biomarker reflecting the aggressiveness of UUT-UCC. ADC might be useful for preoperative risk stratification of UUT-UCC patients. KEY POINTS: • Diffusion-weighted MRI offers new information about the aggressiveness of urinary tract cancers. • The apparent diffusion coefficient acts as a quantitative biomarker for upper urinary tract cancers. • ADC inversely correlates with immunohistochemical and histological grading of UUT-UCC. • ADC offers a prognosis for UUT-UCC patients treated with nephroureterectomy.

Assessment of liver function in thioacetamide-induced rat acute liver injury using an empirical mathematical model and dynamic contrast-enhanced MRI with Gd-EOB-DTPA.

PURPOSE: To evaluate thioacetamide (TAA)-induced acute liver injury in rats using an empirical mathematical model (EMM) and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) with gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA). MATERIALS AND METHODS: Eighteen rats were divided into three groups (normal control [n = 6], TAA [140] [n = 6], and TAA [280] groups [n = 6]). The rats of the TAA (140) and TAA (280) groups were intravenously injected with 140 and 280 mg/kg body weight (BW) of TAA, respectively, while those of the normal control group were intravenously injected with the same volume of saline. DCE-MRI studies were performed using Gd-EOB-DTPA (0.025 mmol Gd/kg; 0.1 mL/kg BW) as the contrast agent 48 hours after TAA or saline injection. After the DCE-MRI study, blood was sampled and serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were measured. We calculated the rate of contrast uptake (α), the rate of contrast washout (ß), the elimination half-life of relative enhancement (RE) (T(1/2)), the maximum RE (RE(max)), and the time to (RE(max)) (T(max)) from time-signal intensity curves using EMM. RESULTS: The RE(max) values in the TAA (140) groups and TAA (280) groups were significantly smaller than that in the normal control group. The T(max) value in the TAA (280) group was significantly greater than that in the normal control group. The ß value in the TAA (280) group was significantly smaller than those in the normal control and TAA (140) groups, whereas there were no significant differences in ß among groups. The T(1/2) value in the TAA (280) group was significantly greater than those in the normal control and TAA (140) groups. The RE(max), T(max), ß, and T(1/2) values significantly correlated with AST and ALT. CONCLUSION: The EMM is useful for evaluating TAA-induced acute liver injury using DCE-MRI with Gd-EOB-DTPA.

Adverse Prognostic Impact of Diagnostic Ureterorenoscopy in a Subset of Patients with High-Risk Upper Tract Urothelial Carcinoma Treated with Radical Nephroureterectomy.

Background: We hypothesized that diagnostic ureterorenoscopy (URS) may adversely affect prognosis in a subset of patients with high-risk upper tract urothelial carcinoma (UTUC) undergoing radical nephroureterectomy (RNU). Methods: The present retrospective study included 143 patients with UTUC treated between 2010 and 2021 at two tertiary care hospitals, of whom 79 received URS prior to RNU. Subgroups were stratified by clinicopathological variables relevant to prognosis. The primary endpoint was to evaluate the prognostic impact of URS on overall survival (OS) and progression-free survival (PFS) after RNU. Results: During follow-up (median 54 months for survivors), 32 cases of all-cause mortality and 40 cases of progression were recorded. No significant difference was found in OS or PFS between patients with and without URS. Subgroup analysis demonstrated that URS was significantly associated with worse OS (p < 0.001) and PFS (p = 0.008) in 29 patients with non-papillary and ≥pT3 UTUC. Importantly, URS did not have any adverse effects on prognosis in 62 patients with papillary and ≤pT2 UTUC (p = 0.005). Conclusions: URS may adversely affect prognosis of UTUC patients, specifically non-papillary and ≥pT3 disease. URS may better be avoided in patients with high-risk UTUC features unless URS is necessary to diagnose UTUC. This study also corroborates the oncological safety of URS in those with low-risk UTUC.

Gingival epithelial cell-derived microvesicles activate mineralization in gingival fibroblasts.

Soft tissue calcification occurs in many parts of the body, including the gingival tissue. Epithelial cell-derived MVs can control many functions in fibroblasts but their role in regulating mineralization has not been explored. We hypothesized that microvesicles (MVs) derived from gingival epithelial cells could regulate calcification of gingival fibroblast cultures in osteogenic environment. Human gingival fibroblasts (HGFs) were cultured in osteogenic differentiation medium with or without human gingival epithelial cell-derived MV stimulation. Mineralization of the cultures, localization of the MVs and mineral deposits in the HGF cultures were assessed. Gene expression changes associated with MV exposure were analyzed using gene expression profiling and real-time qPCR. Within a week of exposure, epithelial MVs stimulated robust mineralization of HGF cultures that was further enhanced by four weeks. The MVs taken up by the HGF's did not calcify themselves but induced intracellular accumulation of minerals. HGF gene expression profiling after short exposure to MVs demonstrated relative dominance of inflammation-related genes that showed increases in gene expression. In later cultures, OSX, BSP and MMPs were significantly upregulated by the MVs. These results suggest for the first time that epithelial cells maybe associated with the ectopic mineralization process often observed in the soft tissues.

Controlling Nutritional Status (CONUT) Score and Sarcopenia as Mutually Independent Prognostic Biomarkers in Advanced Urothelial Carcinoma.

Background: While the controlling nutritional status (CONUT) score and sarcopenia are objective indices of different aspects of a patient's general condition, few studies have comprehensively examined their mutual relationship in patients with advanced cancer. Methods: This retrospective study included 200 Japanese patients with advanced urothelial carcinoma (aUC). Sarcopenia was diagnosed using Prado's definition. The CONUT score and sarcopenia were examined for their possible association, and their prognostic value was analyzed. Results: The CONUT score and sarcopenia were not significantly associated. While sarcopenia occurred in 168 patients (84%), more than half of them had normal or only slightly impaired nutritional status, as indicated by a CONUT score of 0−2. During follow-up (median: 13.3 months), 149 patients died. The CONUT score and sarcopenia were independent prognostic factors (hazard ratio 1.22 and 2.23, respectively; both p < 0.001), whereas performance status was not. Incorporating the CONUT score, sarcopenia, and both into Bajorin's and Apolo's prognostic models increased their concordance index as follows: 0.612 for Bajorin's original model to 0.653 (+the CONUT score), 0.631 (+sarcopenia), and 0.665 (+both), and 0.634 for Apolo's original model to 0.655 (+the CONUT score), 0.653 (+ sarcopenia), and 0.668 (+both). Conclusion: The CONUT score and sarcopenia were mutually independent in terms of their prognostic value in patients with aUC. These objective indices of a patient's general condition may help in decision-making when considering treatment for patients with aUC.

Diagnostic performance of diffusion-weighted magnetic resonance imaging in bladder cancer: potential utility of apparent diffusion coefficient values as a biomarker to predict clinical aggressiveness.

OBJECTIVES: The diagnostic performance of diffusion-weighted magnetic resonance imaging (DW-MRI) in bladder cancer and the potential role of apparent diffusion coefficient (ADC) values in predicting pathological bladder cancer phenotypes associated with clinical aggressiveness were investigated. METHODS: One hundred and four bladder cancer patients underwent DW-MRI and T2-weighted magnetic resonance imaging (T2W-MRI) before transurethral resection. The image sets were reviewed by two independent radiologists. ADC values were measured in 121 eligible tumours. RESULTS: In detecting patients with bladder cancer, DW-MRI exhibited high sensitivity equivalent to that of T2W-MRI (>90%). Interobserver agreement was excellent for DW-MRI (κ score, 0.88) though moderate for T2W-MRI (0.67). ADC values were significantly lower in high-grade (vs. low-grade, P < 0.0001) and high-stage (T2 vs. T1 vs. Ta, P < 0.0001) tumours. At a cut-off ADC value determined by partition analysis, clinically aggressive phenotypes including muscle-invasive bladder cancer (MIBC) and high-grade T1 disease were differentiated from less aggressive phenotypes with a sensitivity of 88%, a specificity of 85% and an accuracy of 87%. CONCLUSION: DW-MRI exhibits high diagnostic performance in bladder cancer with excellent objectivity. The ADC value could potentially serve as a biomarker to predict clinical aggressiveness in bladder cancer.