Predictive factors for recurrence and outcomes in T1a renal cell carcinoma: Analysis of the INMARC (International Marker Consortium for Renal Cancer) database.

OBJECTIVE: Stage migration in renal cell carcinoma (RCC) has led to an increasing proportion of diagnosed small renal masses. Emerging knowledge regarding heterogeneity of RCC histologies and consequent impact on prognosis led us to further explore outcomes and predictive factors in surgically-treated T1a RCC. METHODS: The INMARC database was queried for T1aN0M0 RCC. Patients were stratified into groups based on recurrence. Primary outcome was overall survival (OS). Multivariable analyses (MVA) were performed for factors associated with recurrence, cancer-specific (CSM), and all-cause mortality (ACM). Kaplan-Meier analyses (KMA) assessed survival by histology and grade. Subset analysis for time to recurrence was conducted for grade and histologic groups and compared with recent AUA follow-up guidelines [low-risk (AUA-LR), intermediate-risk (AUA-IR), high-risk (AUA-HR), and very-high risk (AUA-VHR) groups]. RESULTS: We analyzed 1,878 patients (median follow-up 35.2 months); 101 (5.4%) developed recurrence. MVA for recurrence demonstrated increasing age (P = 0.026), male sex (P = 0.043), diabetes (P = 0.007), high/unclassified grade (P < 0.001-0.007), and variant histology (P = 0.017) as independent risk factors for increased risk, while papillary (P = 0.016) and chromophobe (P = 0.049) were associated with decreased risk. MVA identified high/unclassified grade (P = 0.003-0.004) and pT3a upstaging (P = 0.043) as predictive factors for worsened risk of CSM while papillary (P = 0.034) was associated with improved risk. MVA for ACM demonstrated increasing age (P < 0.001), non-white (P < 0.001), high-grade (P = 0.022), variant histology (P = 0.049), recurrence (P = 0.004), and eGFR<45 at last follow-up (P < 0.001) to be independent risk factors. KMA comparing clear cell, chromophobe, papillary, and variant RCC revealed significant differences for 5-year CSS (P = 0.018) and RFS (P < 0.001), but not OS (P = 0.34). Median time to recurrence was 23.8 months for low-grade (AUA-LR), 17.3 months for high-grade (AUA-IR), 18 months for pT3a upstaging (AUA-HR), and 12 months for variant histology (AUA-VHR; P < 0.001). CONCLUSION: We noted differential outcomes in T1a RCC based on histology and grade for recurrence and CSM, while renal functional decline in addition to pathological factors and recurrence were predictive for ACM. Our findings support recently promulgated AUA follow-up guidelines for low-grade and variant histology pT1a RCC, but call for consolidation of follow-up protocols for high-grade pT1a and pT3a upstaged patients, with intensification of frequency of imaging follow-up in pT1a high-grade RCC.

Wnt3a promotes differentiation of human bone marrow-derived mesenchymal stem cells into cementoblast-like cells.

Cementum is a calcified, avascular connective tissue that laminates the root of a tooth and plays a pivotal role in the development, homeostasis, and regeneration of a periodontal tissue. As a potential treatment for periodontal tissue defects in the patient with chronic periodontitis, much attention has been paid to tissue engineering combined with mesenchymal stem cells for regenerating periodontal tissues including cementum. However, limited information is available for the molecular factors that have impacts on the differentiation of mesenchymal stem cells into cementoblasts. Here, we focus on the effect of Wnt3a as a potential inducer and tested the effect of this protein in vitro using human bone marrow-derived mesenchymal stem cells. It was found that, when cells were cultured in an osteogenic medium containing Wnt3a, cementoblast-specific genes, such as cementum protein 1 and cementum attachment protein, as well as bone-related genes were significantly upregulated. These results suggest that Wnt3a promotes differentiation of the cells into cementoblast-like cells. Further experiments were carried out using inhibitors to gain deeper insights into molecular mechanisms underlying the observed differentiation. As a result, we conclude that Wnt3a-triggered differentiation into cementoblast-like cells is the consequence of the activation of the canonical Wnt signaling pathway with possible involvement of the non-canonical pathway.

Combined endodontic and periodontal management of a class 3 invasive cervical resorption in a mandibular first molar.

Dental radiography and cone-beam computed tomography revealed the left mandibular first molar in a 68-year-old female patient with Heithersay Class 3 invasive cervical resorption (ICR). The inhibition of ICR progression and environmental improvement in and around the affected tooth through combined endodontic and periodontal treatments led to a favorable clinical outcome.

Brain-Derived Neurotrophic Factor Inhibits Peptidoglycan-Induced Inflammatory Cytokine Expression in Human Dental Pulp Cells.

The aim of this study was to examine the anti-inflammatory effect of brain-derived neurotrophic factor (BDNF) on human dental pulp cells (HDPCs) and identify the intracellular signaling pathway involved. We investigated the effect of BDNF (50 ng/ml) on interleukin (IL)-6 and IL-8 expression in peptidoglycan (PGN)-treated HDPCs. An inhibition assay was performed with MAPK or NF-κB inhibitors to determine the possible signaling pathway. IL-6 and IL-8 mRNA, IL-6 and IL-8 protein, and phosphorylated p38 kinase activity were determined using real-time PCR, ELISA, and Western blot analysis, respectively. BDNF significantly attenuated PGN-induced IL-6 and IL-8 mRNA and protein levels in HDPCs. A p38 inhibitor also inhibited IL-6 and IL-8 mRNA transcription. PGN stimulated phosphorylated p38 kinase activity in HDPCs, which was inhibited by BDNF. Suppression of phosphorylated p38 kinase activity by BDNF in HDPCs inhibited increased IL-6 and IL-8 expression induced by PGN. Our findings suggest that BDNF regulates intracellular signaling molecule activities to exert its anti-inflammatory effect.