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An investigation of alternatives to immune checkpoint inhibitors for advanced urothelial cancer (aUC), with biologic information, is urgently needed. Clinical data for 53 patients who received gemcitabine–paclitaxel therapy (GP) as 2nd-line chemotherapy for aUC refractory to platinum-based chemotherapy were retrospectively reviewed. The efficacy and tolerability of GP were evaluated, and the predictive value of phosphoglycerate kinase 1 (PGK1) immunostained in surgical specimens was investigated for treatment outcomes in 1st- and 2nd-line chemotherapy. GP was associated with an objective response rate of 35.8% and a median overall survival duration of 12.3 months. Multivariate analysis showed that PS2 and 1st- and 2nd-line non-response are independent predictors of worse progression-free survival and that PS2 and 1st-line non-response are independent predictors of worse overall survival. Adverse events were manageable, and no therapy-related deaths occurred. Non-response rates to 1st-line chemotherapy were significantly higher in patients with a high expression of PGK1 in the nucleus than in those with low expression (p = 0.006). Our study demonstrates the efficacy and tolerability of 2nd-line GP for patients with aUC who are refractory to platinum-based chemotherapy. Moreover, PGK1 in the nucleus was predictive values for resistance to platinum-based chemotherapy in aUC.

Early detection of primary bladder cancer (BCa) is vital, because stage and grade have been generally accepted not only as categorical but also as prognostic factors in patients with BCa. The widely accepted screening methods for BCa, cystoscopy and urine cytology, have unsatisfactory diagnostic accuracy, with high rates of false negatives, especially for flat-type BCa with cystoscopy and for low-risk disease with urine cytology. Currently, liquid biopsy has attracted much attention as being compensatory for that limited diagnostic power. In this review, we survey the literature on liquid biopsy for the detection of BCa, focusing on circulating tumor cells (CTCs), urinary cell-free DNA (ucfDNA), and urinary microRNA (umiRNA). In diagnostic terms, CTCs and umiRNA are determined by quantitative analysis, and ucfDNA relies on finding genetic and epigenetic changes. The ideal biomarkers should be highly sensitive in detecting BCa. Currently, CTCs produce an unfavorable result; however, umiRNA and ucfDNA, especially when analyzed using a panel of genes, produce promising results. However, given the small cohort size in most studies, no conclusions can yet be drawn about liquid biopsy’s immediate application to clinical practice. Further large studies to validate the diagnostic value of liquid biopsy for clinical use are mandatory.

To evaluate the prevalence of non-carious cervical lesions (NCCLs) on teeth with or without erosive etiological factors across a broad range of ages of Japanese adults. The study sample consisted of a total of 1108 subjects aged 15 to 89 years in Tokyo, Japan. Two examiners evaluated NCCLs and dental erosion (DE) during a full-mouth examination. Subjects were asked to complete a self-administered daily diet, habits, and health condition questionnaire. Subjects who had frequent acid consumption or gastric reflux and at least one tooth with initial enamel wear were placed in the erosion present (EP) group, and the remainder of subjects were placed in the erosion not present (EN) group. Logistic regression analyses were carried out to identify etiological factors of NCCLs associated with DE. Overall prevalence of NCCLs was 60.2%; the prevalence increased with age. There were no statistical differences in the prevalence of NCCLs between the EP and EN groups, except for the 60–69 years group. Multiple logistic regression analysis showed the frequency of consumption of carbonated soft drinks, citrus juice, and acidic fruits such as oranges; tooth brushing pressure; and bruxism were associated with the presence of NCCLs. There were no statistical differences in the prevalence of NCCLs with or without erosive etiological factors except for the 60–69 years group. NCCL distribution increased with age, and erosive risk factors caused by change in dietary habits might affect the incidence of NCCLs for elders. UMIN000041982

Little data on the preoperative prognostic factors in radical cystectomy (RC) patients have made it difficult to choose the appropriate type of urothelial diversion (UD). This study aimed to investigate the prognostic role of UD, with a subgroup analysis of that of preoperative renal function. From 1990 to 2015, 279 patients underwent RC for bladder cancer at six hospitals affiliated with Kitasato University in Japan. All patients were divided into three groups: cutaneous ureterostomy (CU; n = 54), ileal conduit (IC; n = 139), and orthotopic neobladder (NB; n = 86). Patients were also stratified into three groups based on preoperative estimated glomerular filtration rate (eGFR) (mL/min/1.73 m2): normal eGFR (> 60 mL/min/1.73 m2; n = 149), moderately reduced eGFR (45–60 mL/min/1.73 m2; n = 66), and severely reduced eGFR (

The purpose of this study was to evaluate the effects of two different concentrations of silver diammine fluoride (SDF) on dentin bonding performance. Human mid-coronal dentin was treated with either distilled water (control), 3.8%SDF or 38%SDF for 3 min. A two-step self-etch adhesive and resin composite were applied according to manufacturer's instructions. After thermocycling (TC) at 0, 5,000 and 10,000 cycles, microtensile bond strength (µTBS) testing and morphological assessment of resin-dentin bonding interface were performed. At 0 TC, µTBSs of 3.8% and 38%SDF were significantly reduced (p

This study investigated the influence of application/wash-out times of sodium hypochlorite (NaOCl) and hypochlorous acid (HOCl) on dentin bond strength of one-step self-etch adhesives (1-SEAs). Human coronal dentin discs with a standardized smear layer were pretreated with 6% NaOCl or 100 ppm HOCl for 5 s, 15 s, or 30 s, and washed out with water for 5 s, 15 s or 30 s with or without the application of Clearfil DC Activator (CDA). No pretreatment was used as a control. The discs were bonded with a 1-SEA (Bond Force II or Clearfil Universal Bond Quick) and microtensile bond strength (µTBS) was measured after 24 h. Pretreatment with NaOCl for 15 s and 30 s significantly decreased µTBS (p0.05), irrespective of wash-out time. The application of CDA recovered µTBS but did not outperform the control group. Conversely, pretreatment with HOCl for 15 s and 30 s followed by 30 s wash-out time significantly increased µTBS of 1-SEAs (p0.05), regardless of CDA application.

Background In patients experiencing disease recurrence after radical cystectomy (RC) for bladder cancer, data about the impact of clinicopathologic factors, including salvage treatment using cytotoxic chemotherapy, on the survival are scarce. We investigated the prognostic value of clinicopathologic factors and the treatment effect of salvage cytotoxic chemotherapy (SC) in such patients. Methods In this retrospective study, we evaluated the clinical data for 86 patients who experienced recurrence after RC. Administration of SC or of best supportive care (BSC) was determined in consultation with the urologist in charge and in accordance with each patient’s performance status, wishes for treatment, and renal function. Statistical analyses explored for prognostic factors and evaluated the treatment effect of SC compared with BSC in terms of cancer-specific survival (CSS). Results Multivariate analyses showed that liver metastasis after RC (hazard ratio [HR] 2.13; 95% confidence interval [CI] 1.17 to 3.85; P = 0.01) and locally advanced disease at RC (HR 1.92; 95% CI 1.06 to 3.46; P = 0.03) are independent risk factors for worse CSS in patients experiencing recurrence after RC. In a risk stratification model, patients were assigned to one of two groups based on liver metastasis and locally advanced stage. In the high-risk group, which included 68 patients with 1–2 risk factors, CSS was significantly better for patients receiving SC than for those receiving BSC (median survival duration: 9.4 months vs. 2.4 months, P = 0.005). The therapeutic effect of SC was not related to a history of adjuvant chemotherapy. Conclusions The present study indicated the potential value of 1st-line SC in patients experiencing recurrence after RC even with advanced features, such as liver metastasis after RC and locally advanced disease at RC.

To evaluate the microtensile bond strength (µTBS) of a one-step self-etch adhesive (1-SEA) to dentin and its interfacial nanomechanical properties after 8 years of water storage.Flat coronal dentin surfaces of extracted human third molars were bonded with a 1-SEA (Clearfil S3 Bond Plus, CS3+) and built up with a hybrid resin composite (Clearfil AP-X). After storage in water for 24 h or 8 years, non-trimmed stick-shaped specimens were fabricated from the central part of each bonded tooth and subjected to the µTBS test at a crosshead speed of 1.0 mm/min. Failure modes and the morphology of debonded interfaces were analyzed using a scanning electron microscope (SEM). In addition, the elastic modulus (E) and hardness (H) of the adhesive layer and the resin composite were determined by an instrumented nanoindentation test. The acquired µTBS, E, and H data were statistically analyzed using t-tests to examine the effect of storage time (α = 0.05).The 8-year µTBS was slightly lower than that after 24 h, but the difference was not significant (p = 0.123). The SEM observation of debonded surfaces after 8 years revealed extrusions and lacunas. E and H of the adhesive layer and the resin composite significantly decreased over the 8-year water storage (p0.001).Although 8 years of water storage did not decrease the µTBS of CS3+ significantly, the observed failure mode patterns and significantly decreased nanomechanical properties indicated resin degradation of the adhesive and the resin composite.

Bladder cancer is extremely rare in young patients. We reported the clinicopathological outcomes in adolescent and young adult patients with bladder cancer, using age 35 as the cut-off. From 1972 to 2011, 1349 patients were treated with transurethral resection of bladder tumor. Thirty patients were ＜35 years of age and were divided into two groups : ＜30 and ≧30 years. We reviewed the initial symptoms, cystoscopic and pathological findings, and prognosis. Thirteen patients (0.96%) were ＜30 years of age and seventeen (1.3%) were ≧30 of age, with mean follow-up periods of 88.2 and 77.6 months, respectively. The most common complaint was gross hematuria. Most tumors were solitary (26 ; 86.7%) and papillary (29 ; 96.7%). Pathological stages were pTa 15, pT1 10, and pT2 3. Patients with pT2 cancer were ≧30 years of age (p ＝ 0.019). One patient died of bladder cancer. The majority of patients had low-grade, low pathological stage bladder cancer and a good prognosis. However, some pT2 cancers exhibited aggressive behavior.

Objective The influence of light-curing of a one-step self-etch adhesive (1-SEA) prior to the application of different bonding agents (BA) on the micro-tensile bond strength (μTBS) to dentin after 24 h and thermal cycling was investigated. Additionally, the degree of conversion was evaluated using Fourier-transform infrared spectroscopy. Methods Three ion-releasing BAs, BZF-21 (experimental BA), Clearfil SE Protect (CSP), and FL-Bond II (FL-II), were applied subsequently to G-Premio Bond (1-SEA, GPB). Prior to their application, GPB was either light-cured (10 s, 1000 mW/cm2) or remained uncured. GPB was used as a control and Clearfil SE Bond 2 (CSE2) as a gold-standard 2-step reference. After resin-composite build-up and 24-h water storage (24 h), half of the specimens were subjected to 15,000 thermal cycles (TC). Then, the specimens were sectioned into beams and tested under tensile load (1 mm/min). The acquired data were analyzed using a 2-way ANOVA and Student’s t-test with Bonferroni correction, and a two-parameter Weibull analysis, α = 0.05. Results The μTBS of GPB increased significantly in the uncured groups with BZF-21 (24 h: p Significance BZF-21 and CSP improved the μTBS of GPB to dentin both immediately and after TC. Higher μTBSs were obtained when GPB remained uncured prior to BA application.

Bond durability and resistance to acid-base challenge of dentin with dual-cure resin cement have been rarely investigated. The purpose of this study was to evaluate dentin bond strength and observe the adhesive-dentin interface after acid-base challenge using three different dual-cure resin cements.Thirty dentin surfaces from caries-free human premolars were ground and bonded with one of three dual-cure resin cements: PANAVIA V5 (V5), ESTECEM II (E II) and Rely X Ultimate (RXU) and thermocycled for 0, 5,000 and 10,000 cycles. A microtensile bond strength (μTBS) test was undertaken and the interface of the bonded specimens after acid-base challenge was examined by SEM.The μTBS of V5 exhibited a stable bond strength despite thermal cycling while the bond of EII and RXU after 10,000 cycles dropped significantly among all thermal cycle periods (p0.05). An acid-base resistant zone (ABRZ) was observed in all groups, however, the morphology of the bonded interface differed among the tested cements.Bonding durability to dentin and ABRZ morphologies differed among the cements evaluated. PANAVIA V5 cement system with tooth primer provided the most reliable bond strength and was best able to resist the acid-base challenge.

BACKGROUND New biomarkers may help us provide individualized prognosis and allow risk-stratified clinical decision making about radical treatment. OBJECTIVES This study aimed to determine the tumor necrosis factor of receptor superfamily 19 (TROY) expression in urothelial carcinoma and its relationship to clinicopathological findings. METHODS Immunohistochemical staining for TROY was carried out in 136 archival radical cystectomy specimens with immunoreactivity being stratified on a 0-9 scale. Expression scores for TROY were further stratified into negative (score 0) and positive (score 1 or greater). Median age was 65 years, and the median follow-up period was 50.7 months. RESULTS Expression of TROY was significantly associated with the pathological stage (p= 0.019) and expression of nestin (p= 0.013). Log-rank tests indicated that expression of TROY was significantly associated with disease progression and cancer-specific mortality (p= 0.044 and 0.008, respectively). In multivariate Cox regression analysis, lymph node status was the only independent prognostic factor for disease progression and cancer-specific survival. Expression of TROY was a marginal prognostic factor for cancer-specific survival. CONCLUSIONS TROY may therefore be a new molecular marker to aid in identifying and selecting patients undergoing radical cystectomy who could potentially benefit from multimodal treatment.

Purpose The purpose of this study was to evaluate factors related to peristomal moisture-associated skin damage (MASD) in patients who underwent ostomy surgery because of colorectal cancer, and their independence in pouching system changes. Findings were used to determine pre- and postsurgical care for these patients. Design Retrospective review of medical records. Subjects and setting The study setting was an 800-bed hospital in metropolitan Tokyo, Japan. The sample comprised 89 patients (median age: 65 years; male vs female: 58 vs 31) who visited a stoma clinic within 8 weeks of ostomy surgery. Fifty-two subjects had ileostomies and 37 had colostomies; data were collected between January 2008 and July 2014. Methods Data were collected from outpatient and inpatient records. Potential relationships between MASD and independence in pouching system changes were evaluated via univariate tests to identify possible associations, followed by logistic regression analysis. Results Patients living with an ileostomy were more likely to experience peristomal MASD than were patients living with a colostomy (odds ratio [OR] = 3.782; 95% confidence interval [CI]: 1.34-10.64; P = .012). Analysis also found that patients with postsurgical chemotherapy were more than 2.5 times more likely to experience peristomal MASD than patients who did not require postoperative chemotherapy (OR = 2.702; 95% CI: 1.02-7.18; P = .046). We also found that patients 65 years or older were significantly more likely to have difficulty in changing their pouching system than were younger patients (OR = 7.193; 95% CI: 2.21-23.41; P = .001), as were those with diabetes mellitus (OR = 11.842; 95% CI: 2.56-54.77; P = .002). Conclusions Patients undergoing ileostomy and those receiving postoperative chemotherapy are more likely to experience peristomal MASD. Older patients (>65 years) and those with diabetes mellitus are less likely to achieve independence. These findings influenced our management of persons undergoing ostomy surgery for management of colorectal cancer in our clinic. We recommend additional research using a larger and more diverse sample to confirm our findings.

To investigate the effects of several etching products prior to the application of a one-step self-etch adhesive (1-SEA) or two-step self-etch adhesive (2-SEA) on enamel by microshear bond strength (µSBS) testing and observation of the adhesive-enamel interface.Ground human enamel surfaces were randomly assigned to one of eight groups according to the combination of surface treatments (either no conditioner [NC], ME [Multi Etchant], EC [Enamel Conditioner], or KE [K-etchant Gel]) and adhesive (ADU [Adhese Universal] or SE2 [Clearfil SE Bond 2]). All groups were further divided into two subgroups: 0 or 10,000 thermal cycles (TC). Then, the µSBS test was performed. The adhesive-enamel interface after acid-base challenge and the surface structure after conditioner application were also observed.With 10,000 TCs, there was no statistically significant difference between ME-ADU and NC-ADU. On the other hand, the µSBS of EC-ADU or KE-ADU was significantly higher than that of NC-ADU, while that of ME-SE2 was significantly lower than NC-SE2. There was no significant difference between EC-SE2, NC-SE2, and KE-SE2. Formation of an acid-base resistance zone (ABRZ) was confirmed in all groups. However, funnel-shaped erosion, which indicates interfacial defects, was observed in the NC-ADU, ME-ADU, and ME-SE2 groups.For enamel bonding, application of EC or KE prior to ADU increased the bond strength and created a stable adhesive-enamel interface. On the other hand, SE2 also had stable shear bond strength and interface without the use of conditioners. However, ME decreased the bonding performance of SE2.

The purpose of this multicenter clinical study was to compare the mid-term clinical effectiveness of direct resin composite restorations using one-step or two-step self-etch adhesives (1-SEAs or 2-SEAs). In total, 352 restorations of class I–V cavities and non-carious cervical lesions in vital teeth (1-SEAs; 52 cases, 2-SEAs; 300 cases) were placed at nine university hospitals and evaluated according to the modified USPHS criteria at baseline, and after 1, 2, and 3 years. The recall rates were 86.6% (1 year), 80.1% (2 years), and 62.2% (3 years). Two restorations failed due to fracture during the follow-up, and there was no significant difference in survival rates between 1-SEAs (97.6%) and 2-SEAs (99.4%). However, 2-SEAs exhibited significantly lower occurrences of discoloration, marginal discoloration, fracture, and plaque retention. Moreover, the subjects reported a significantly lower postoperative hypersensitivity and higher overall satisfaction at all evaluation periods if 2-SEAs were used.

The purpose of this study was to investigate the influence of phosphoric acid etching, metal primer or silane coupling agent application on dentin bonding performance of a 2-step self-etch adhesive system. Human dentin surfaces were prepared and divided into four groups depending on the pre-treatment method: no pretreatment (Clearfil SE Bond 2, CONTROL); 40% phosphoric acid (K-Etchant GEL, K); metal primer (Alloy Primer, AP); or silane coupling agent (Porcelain Bond Activator, PB). The specimens were sectioned into beams, separated into 2 subgroups (n=20): no thermocyling or thermocycled (TC), and subjected to a µTBS test and an acid-base challenge for SEM observation. Statistically lower results were observed between K and AP groups, PB and CONTROL, and PB with/without TC (p

Purpose. The potential of UV-mediated photofunctionalization to enhance the resin-based luting agent bonding performance to aged materials was investigated. Methods. Sixty samples of each material were prepared. Yttria-stabilized zirconia (YZr) and Pd-Au alloy (Pd-Au) plates were fabricated and sandblasted. Lithium disilicate glass-ceramic (LDS) was CAD-CAM prepared and ground with #800 SiC paper. Half of the specimens were immersed in machine oil for 24 h to simulate the carbon adsorption. Then, all of the specimens (noncarbon- and carbon-adsorbed) were submitted to UV-mediated photofunctionalization with a 15 W UV-LED (265 nm, 300 mA, 7692 μW/cm2) for 0 (control groups), 5, and 15 min and subjected to contact angle (Ɵ) measurement and bonded using a resin cement (Panavia™ V5, Kuraray Noritake, Japan). The tensile bond strength (TBS) test was performed after 24 h. The Ɵ (°) and TBS (MPa) data were statistically analyzed using two-way ANOVA and Bonferroni correction tests ( α = 0.05 ). Results. In the carbon-adsorbed groups, UV-mediated photofunctionalization for 5 min significantly decreased Ɵ of all materials and increased TBS of YZr, and UV for 15 min significantly increased the TBS of LDS and Pd-Au. In noncarbon-adsorbed groups, UV-photofunctionalization did not significantly change the Ɵ or TBS except YZr specimens UV-photofunctionalized for 15 min. Conclusion. UV-mediated photofunctionalization might have removed the adsorbed hydrocarbon molecules from the materials’ surfaces and enhanced bond strengths of Panavia™ V5 to YZr, LDS, and Pd-Au. Additionally, UV-mediated photofunctionalization improved the overall TBS of YZr. Further investigation on the optimum conditions of UV photofunctionalization on indirect restorative materials should be conducted.

Background Data are scarce regarding intravesical maintenance therapy (MT) with the low-dose bacillus Calmette–Guérin (BCG) Tokyo strain. We investigated the efficacy and safety of MT with a half dose of the Tokyo strain for patients following transurethral resection of nonmuscle invasive bladder cancer (NMIBC). Methods This study retrospectively reviewed clinical data on 78 patients diagnosed with intermediate or high-risk NMIBC followed by either MT (n = 38) or IT alone (n = 40) between January 2012 and March 2018. Statistical analysis was performed to compare recurrence-free survival (RFS) and adverse effects between the two groups. BCG was instilled once weekly for 6 weeks as IT, then once weekly in 2-week for a total of 20 instillations over 3 years. Results Kaplan–Meier analyses showed that patients undergoing MT had significantly better RFS than did those undergoing IT alone (hazard ratio (HR):0.32, 95% confidence interval (CI):0.12–0.89, P = 0.02). The 3-year RFS was 65.0% in the IT group and 89.5% in the MT group. Multivariate analysis showed that MT was associated with a reduced risk of recurrence (HR: 0.32, 95% CI:0.11–0.93, P = 0.03). One MT patient (2.6%) exhibited progression. Conclusions The BCG Tokyo strain showed acceptable efficacy and safety in patients undergoing MT; thus, it is a potential treatment for preventing bladder cancer recurrence.

This longitudinal study aimed to investigate morphologically and quantitatively the progression of non-carious cervical lesions (NCCLs) using a confocal laser scanning microscope (CLSM) and replica models. The samples examined comprised sets of replicas annually obtained from 83 lesions in 16 participants over 3 to 5 years. All lesions were visually categorized as wedge-shaped, saucer-shaped, or mixed-shaped lesions. CLSM images of the replicas were analyzed in terms of axial depth, occlusogingival width (height) in the buccolingual cross-section, and estimated volume using a custom code of the image analysis software to estimate the progression of the NCCLs over time. The morphological characteristics of the NCCLs were also objectively divided into three groups according to the depth to height ratio (D/H ratio). Fisher’s exact test and the Cochran-Armitage trend test were used for statistical analysis. Saucer-shaped lesions progressed mainly in height, whereas wedge-shaped lesions increased both in height and depth. Annual progression in depth and volume significantly increased as the D/H ratio increased. More than half of the NCCLs with a small D/H ratio progressed 50 μm or more in height, whereas none of them progressed more than 50 μm in depth. Annual progression in depth significantly increased as the lesion depth at baseline increased. Progression patterns significantly differed between NCCLs of different shapes. Most NCCLs progressed slowly in depth regardless of their shape. Moreover, NCCLs may progress through active and inactive stages.

Nowadays, the universal adhesives are often used for silane application prior to application of self-adhesive resin cements. The purpose of this study was to evaluate enamel surface roughness and to observe the enamel-adhesive interface after acid-base challenge using three different self-adhesive resin cements combined with universal adhesives.Three self-adhesive resin cements: PANAVIA SA Luting Cement Plus (SA), Calibra Universal (CA) and MaxCem Elite Chroma (MC) which in conjunction with the particular universal adhesives: Clearfil Universal Bond Quick (UQ), PrimeBond Universal (PB) and Optibond Universal (OB) were tested. Thirty enamel surfaces from caries-free human premolars were ground and bonded with the tested self-adhesive resin cements combined with universal adhesives. The surface roughness test (Sa) with or without applying adhesives was performed with 3D-CLSM. The interface of the bonded specimens after acid-base challenge was also examined by SEM.The Sa of OB was significantly higher than those of PB and UQ. There were statistically significant differences among all of the groups (p0.05). An acid-base resistant zone (ABRZ) was observed in all groups, however, formation of the ABRZ was material dependent.OB provided most etching performance to enamel of human premolars and MC group with OB presented durability against acid-base challenge.Nowadays, the combination of self-adhesive resin cement and universal adhesive may be a viable option for a reliable bonding performance and bonding durability in indirect restorative dentistry.

Background: Radical nephroureterectomy (RNU) is the standard treatment for patients with upper tract urothelial carcinoma (UTUC). However, approximately 25% of patients experience recurrence or metastasis after RNU. This study evaluated the clinical outcome and efficacy of salvage chemotherapy (SC) after recurrence or metastasis. Patients and Methods: Of the 441 nonmetastatic UTUC patients who underwent RNU, 147 patients with recurrent or metastatic lesions were analyzed; patients with bladder cancer recurrence were excluded. Time from disease recurrence or metastasis to cancer-specific survival (CSS) was estimated by the Kaplan-Meier method. Multivariate analyses were performed with the Cox proportional hazards regression model, controlling for the effects of clinicopathological factors. Results: The median time from RNU to disease recurrence or metastasis was 13.2 months. In the recurrent or metastatic sites, 31 cases (21%) were liver. In multivariate analyses, pT stage (≥pT3), time to recurrence (p < 0.001). Conclusion: Two or more risk factors defined the high-risk group for patients with recurrence or metastasis after RNU. SC was associated with improved survival in patients with high-risk UTUC.

The effect of different air-blowing strategies using a prototype of a newly developed clinically applicable warm air-blowing device on the microtensile bond strength (μTBS) of one-step self-etch adhesives (1-SEAs) to human root-canal dentin was evaluated. Post cavities (8 mm depth, 1.5 mm diameter) were prepared and bonded with four 1-SEAs. Air-blowing was performed using normal air (23±1°C) for 10 or 20 s; warm air (60±1°C) for 10 or 20 s; or their combination for 10 s (5 s normal, 5 s warm) or 20 s (10 s normal, 10 s warm). After filling with corresponding core materials and 24-h water storage, μTBS test was performed. For three of the 1-SEAs, combined air-blowing for 20 s significantly increased μTBS compared to other air-blowing strategies (p

Background Wide-spectrum antibiotics have been favored to treat acute uncomplicated cystitis (AUC) for a long time, leading to the emergence of multi-drug resistant bacteria. We hypothesize that narrow-spectrum antibiotics might mitigate the issue and aim to investigate the clinical efficacy of cefaclor in patients with AUC. Methods We retrospectively reviewed the clinical data of female outpatients with AUC treated with cefaclor and evaluated the safety and clinical efficacy. Clinical cure was defined as the elimination of clinical symptom under 4 white blood cells (WBCs) per high power field on microscopy. Results Overall, 223 women with AUC were enrolled. Escherichia coli was the dominant pathogen (n = 160; 68.6%), followed by Klebsiella species and E. coli-extended spectrum β-lactamase (ESBL) (n = 19; 8.1% and n = 18; 7.7%). Overall success rate was 94.0% (n = 219) and susceptibility rate of cefazolin was 84.1%, which was close to that of levofloxacin (82.9%). Ampicillin showed the lowest rate of 63.7% with a significantly greater resistance rate of 35.3% among all antibiotics (P n = 24) or 93.3% (n = 14). The rate in patients with resistance to both antibiotics was 60.0% (n = 9), and the pathogens in the other 40.0% (n = 6) of patients with treatment failure were E. coli-ESBL. Conclusion Cefaclor showed excellent efficacy in AUC patients, even in those with in vitro resistance to cefazolin or levofloxacin. Cefaclor may be considered as a first-line option in patients with AUC and a second-line option for those with levofloxacin treatment failure.

Purpose The use of warm air-blowing to evaporate solvents of one-step self-etch adhesive systems (1-SEAs) has been reported to be a useful method. The purpose of this study was to evaluate the effect of warm air-blowing on root canal dentin. Methods Four 1-SEAs (Clearfil Bond SE ONE, Unifil Core EM self-etch bond, Estelink, BeautiDualbond EX) were used. Each 1-SEA was applied to root canal dentin according to the manufacturers' instructions. After the adhesives were applied, solvent was evaporated using either normal air (23±1°C) or warm air (80±1°C) for 20s, and resin composite was placed in the post spaces. The air from the dryer, which could be used in normal- or hot-air-mode, was applied at a distance of 5cm above the root canal cavity in the direction of tooth axis. The temperature of the stream of air from the dryer in the hot-air-mode was 80±1°C, and in the normal mode, 23±1°C. After water storage of the specimens for 24h, the μTBS were evaluated at the coronal and apical regions. The μTBSs were statistically analyzed using three-way ANOVA and Student's t-test with Bonferroni correction ( α =0.05). Results The warm air-blowing significantly increased the μTBS of all 1-SEAs at the apical regions, and also significantly increased the μTBS of two adhesives (Estelink and BeautiDualBond EX) at coronal regions. Conclusions The μTBS of 1-SEAs to root canal dentin was improved by using warm air-blowing.

AIM To investigate the association of perioperative estimated glomerular filtration rate (eGFR) with prognosis in patients with upper urinary tract urothoelial caicinoma (UTUC). METHODS A total of 433 patients underwent radical nephroureterectomy with excision of the bladder cuff (RNU) at six hospitals affiliated with Kitasato University in Japan. Patients were divided into three groups each in terms of preoperative eGFR: normal eGFR (>60 mL/min/1.73 m2 ; n = 172), moderately reduced eGFR (45-60 mL/min/1.73 m2 ; n = 147) and severely reduced eGFR ( 30% decreased; n = 129). Statistical analyses were performed to investigate the association between perioperative eGFR and prognosis. RESULTS Patients in the preoperative normal and moderately reduced eGFR group had significantly better progression-free survival (PFS) and cancer-specific survival (CSS) than those in the severely reduced eGFR group (both; P

Aim To evaluate the impact of body mass index (BMI) on the oncological outcomes of urothelial carcinoma (UC) patients. Patients and methods We retrospectively analyzed data from 818 patients with upper tract urothelial cancer (UTUC) and bladder cancer (BC) who were treated with radical nephroureterectomy (RNU) or radical cystectomy (RC) between 1990 and 2015 at six different institutions in Japan. Patients with distant metastasis at diagnosis and those who received neoadjuvant therapies were excluded, leaving 727 eligible patients (UTUC: n = 441; BC: n = 286). Patients were classified into four groups according to World Health Organization BMI criteria: underweight (BMI 30 kg/m2 ). Results Overweight UTUC and BC patients achieved significantly better cancer-specific survival (CSS) than the other three groups. However, obese UTUC and BC patients had significantly worse CSS than the other three groups (UTUC: P = 0.031; BC: P = 0.0019). Multivariate analysis of BC patients demonstrated that obesity was an independent predictor of unfavorable CSS (hazard ratio [HR] = 7.47; P = 0.002) and that being underweight was an independent predictor of favorable CSS (HR = 0.37; P = 0.029). However, BMI was not a prognostic factor for CSS in UTUC patients according to multivariate analysis. Conclusions Obesity was an independent predictor of BC patients requiring RC. Conversely, being underweight was associated with a favorable prognosis for BC patients. However, BMI was not an independent prognostic factor in patients with upper urinary tract cancer.

A chairside tool for quantitative analysis of dental caries would improve clinical dental inspections. The wireless caries sensing tool with dental-explorer size has been developed comparing two sensing methods, Raman reading and pH reading for evaluating dental caries. The Raman spectra at 575 cm−1 and 960 cm−1 for in inorganic compounds, as well as 1450 cm−1 and 2940 cm−1 for organic compounds reinforced and supported the pH results. An Iridium/Iridium oxide (Ir/IrOx) pH sensing probe and wireless pH sensor (comprising an ESP8266 ESP-01 wireless module and ADS1115 analog digital converter) has been developed to quantitatively evaluate dental caries. All the operations of the wireless pH sensor were performed with a developed LabVIEW-based real-time data monitoring program. The slope and the linear fitting regression value (R2) of the wireless pH sensor using seven standards were −54.9 mV/pH and 0.999, respectively, showing high accuracy and stability for the pH measurements. The pH on the dental caries surface was measured with the wireless pH sensor, and the pH mapping results in the non-caries and caries areas were 6.9 and 5.7, respectively. The developed wireless pH sensor would be useful to understand the condition of dental caries and support dentists’ inspection to remove only the caries part while keeping the non-caries structure.

Objective: Several prognostic factors for biochemical recurrence after radical prostatectomy have been reported, including initial prostate-specific antigen level, Gleason score, positive surgical margin, and seminal vesicle invasion. Here we investigate whether Gleason pattern 5 is a predictor for biochemical recurrence. Methods: This retrospective study included 168 patients who underwent laparoscopic radical prostatectomy from 2006 to 2015. The relationship between biochemical recurrence after laparoscopic radical prostatectomy and the presence of Gleason pattern 5, even as a tertiary pattern, was investigated. Biochemical recurrence was defined when the prostate-specific antigen level rose to >0.2 ng/ml after having decreased to

No definitive evidence exists regarding the clinical significance of histologic variants (HV) in upper urinary tract cancer. We investigated the impact of HV on prognosis in patients with upper urinary tract cancer following radical surgery. We retrospectively analyzed 451 patients with upper urinary tract cancer who underwent radical nephroureterectomy at six affiliated hospitals from 1990 to 2015. Patients with distant metastatic disease prior to surgery and those who received neoadjuvant chemotherapy were excluded, leaving 441 eligible patients. Patients were classified into two groups: pure urothelial carcinoma (UC) and HV. The clinicopathological variables of each group were examined using Kaplan–Meier plots and proportional Cox hazard ratios (HR) to compare the oncological outcomes between the two groups. HV included 37 patients (8%). Compared with the pure UC patients, HV patients had significantly worse recurrence-free survival (RFS) and cancer-specific survival (CSS; RFS p = 0.0002, CSS p = 0.0001). Multivariate analysis for RFS revealed HV were independent predictors (HR 1.92; p = 0.026), but the association did not remain significant for CSS. There was no significant difference in CSS between the adjuvant chemotherapy (AC) group and the non-AC group for all HV patients, except in patients with ≥ pT3 tumor or positive lymph node status where the AC group had significantly favorable CSS. HV in upper urinary tract cancer are independent predictors for RFS, but not for CSS. AC improved CSS for HV patients with ≥ pT3 tumor or positive lymph node status.

To investigate the efficacy of different ceramic surface cleaning methods after saliva contamination on the resin bond strength to lithium disilicate ceramics.300 e.max CAD blocks (Ivoclar Vivadent) were polished with 600-grit silicon carbide paper and divided into five groups with or without human saliva contamination and according to the surface treatment performed (n = 10); control: no pretreatment; MP: Monobond Plus; PA+MP: 37% phosphoric acid (PA) followed by MP; HF+MP: 5% hydrofluoric acid (HF) followed by MP; MEP: Monobond EtchPrime. The specimens were bonded with one of three resin cements: Variolink Esthetic DC (VE), Multilink Automix (MA) and Speed CEM (SC). After 24-h water storage, tensile bond strength (TBS) was measured. The ceramic surfaces after pretreatment were analyzed using x-ray photoelectron spectroscopy (XPS).XPS analysis showed similar elemental distributions between saliva contamination vs no saliva in PA, HF, and MEP. The TBSs were significantly influenced by surface treatments (p0.05). HF+MP and MEP showed statistically non-significantly different bond strengths to saliva-contaminated HF+MP and MEP, but were different from MP and saliva-contaminated MP. The TBSs after 24 h were significantly higher in HF+MP and MEP groups with VE. HF+MP and MEP did not show statistically significant differences among any groups with or without saliva contamination.Surface treatments with PA or HF followed by silane or by MEP alone were effective in removing saliva contamination and enhancing the resin bond strength.

To investigate the effect of different etching products used prior to the application of universal self-etching adhesive on dentin bonding.The etching products Multi Etchant (ME), Enamel Conditioner (EC), and K-etchant GEL (KE) were used as pre-treatments prior to the application of the one-bottle self-etching adhesive Adhese Universal (AU). Ground human dentin surfaces were randomly divided into four treatment groups: 1. control (CT; AU without con-ditioner); 2. ME; 3. EC; 4. KE. Microtensile bond strength (µTBS) tests with a thermocycling challenge (0-TC or 10,000-TC) were carried out and the morphological attributes of the adhesive-dentin interface were observed after an acid-base challenge using SEM to observe the acid-base resistant zone (ABRZ).The KE group had a statistically significantly lower µTBS than did the ME and EC groups at 0-TC, and than the CT, ME, and EC groups at 10,000-TC (p0.05). An ABRZ was observed in all groups but had partially disappeared in KE. A funnel-shaped area of erosion was also observed at the junction of the dentin and bonding layer in the CT, ME, and EC groups, while the hybrid layer was thicker in the KE group with no evidence of erosion.The application of ME or EC did not reduce the microtensile bond strength and resulted in ABRZ formation, while the ABRZ was partially reduced in the KE group.

Objectives Checkpoint inhibitors have led to a paradigm shift in urothelial carcinoma (UC) treatment. However, the relationship between PD-L1 expression status and oncological outcomes in UC patients remains uncertain. Here, we investigated the prognostic value of PD-L1 expression status in patients with UC of the bladder (UCB) who underwent radical cystectomy (RC). Materials and methods We retrospectively analyzed pathological specimens from 97 UCB patients treated with RC from 1990 to 2015 at Kitasato University Hospital. Immunohistochemical staining using SP263 was performed to evaluate PD-L1 expression in tumor cells (TCs) and tumor-infiltrating lymphocytes (TILs). Kaplan-Meier plots and proportional Cox hazard ratios were examined to assess the relationship between PD-L1 expression and clinicopathological parameters and survival outcomes. Results Of the 97 specimens, 19.5% contained PD-L1-positive TCs, and 35.0% contained PD-L1-positive TILs. Regarding clinicopathological factors, PD-L1-positive TCs and TILs were significantly associated with high-grade tumors (TCs, P = 0.01; TILs, P = 0.003). Kaplan-Meier analyses showed that PD-L1-positive TCs were not correlated with survival rates. However, PD-L1-positive TILs were significantly associated with better recurrence-free survival (RFS; P = 0.03) and better cancer-specific survival (CSS; P = 0.02). Univariate analysis, but not multivariate analysis, CSS indicated that PD-L1-positive TILs were significant predictors of patient prognoses. Multivariate analysis showed that PD-L1-positive TILs independently predicted CSS in patients without lymph node metastasis (pN0). Conclusion Positive PD-L1 expression is associated with high-grade tumors. PD-L1-positive TILs are independent predictors of favorable survival outcomes in surgically resected UCB patients at stage pN0.

To evaluate the roles of MDP and NaF in the bonding resin of a two-step self-etch adhesive (2-SEA) on enamel bonding performance.The experimental 2-SEAs were composed of an MDP-containing self-etching primer and four different bonding resins which were MDP- and NaF-free (00), MDP-containing and NaF-free (M0), MDP-free and NaF-containing (0F), and MDP- and NaF-containing (MF) adhesives. Microshear bond strength (µSBS) to enamel and ultimate tensile strength (UTS) of the adhesive resin were determined. The morphological characteristics of the adhesive-enamel interface after acid-base challenge were observed using SEM to evaluate the acid-base resistant zone (ABRZ).No decrease in μSBS was observed even after thermocycling (TC) in 00, 0F and MF. However, the μSBS of M0 significantly decreased after TC. The UTS of M0 significantly decreased after 1- and 180-day storage in water. SEM observations indicated that ABRZ was present in all groups. However, formation of erosion beneath the ABRZ was observed in M0 and 00, whereas formation of a slope without erosion was observed at the bottom of the ABRZ in MF.In the experimental 2-SEAs, the addition of MDP alone to the adhesive resin did not contribute to an improvement in enamel bonding durability and interfacial morphology, whereas the addition of NaF in the adhesive resin demonstrated an enhancement of the bonding durability and improvement of acid resistance at the bonded interface.

Background The prognostic value of histologic variants (HV) after radical cystectomy (RC) remains controversial. We evaluated the clinicopathological features and prognosis in patients with pure urothelial carcinoma (UC) and HV following RC. Methods From 1990 to 2015, 286 patients with bladder cancer were treated with RC at six Kitasato University-affiliated hospitals. All patients were divided into two groups: pure UC and HV, which contained pure variants and mixed-type UC with variant pattern. A comparison of patient characteristics between the two groups was made to assess the clinicopathological features, and statistical analyses were performed to investigate prognosis in the two groups. Results Of the 286 patients, 226 (79%) had pure UC, while 60 (21%) had HV. Of all HV, pure variants accounted for 45% (n = 27). The prevalence of lymph node involvement, locally advanced stage (≥ pT3), positive soft tissue surgical margin and lymphovascular invasion were significantly higher in patients with HV than in those with pure UC. Patients with HV showed worse disease-free survival and cancer-specific survival than those with pure UC (P = 0.009 and 0.003, respectively). In multivariate analysis, HV and lymph node involvement were independent predictors of worse disease-free survival (P = 0.017 and 0.001, respectively). HV, locally advanced stage, lymph node involvement, and positive soft tissue surgical margin were also confirmed as independent predictors of worse cancer-specific survival (P = 0.011, 0.012, 0.003 and 0.010, respectively.). Conclusions HV was associated with greater biological aggressiveness and worse prognosis than pure UC.

To evaluate the effect of selective phosphoric acid etching on enamel using "no-wait" self-etching adhesives.Clearfil Universal Bond Quick (UBQ, Kuraray Noritake) or G-Premio BOND (GPB, GC) was applied to ground human enamel surfaces. The adhesives were used in 3 modes: no-waiting self-etching mode (UBQ-0 or GPB-0), 10-s self-etching mode (UBQ-10 or GPB-10), and the selective-etch mode with phosphoric acid etching (UBQ-PA or GPB-PA). After an acid-base challenge, the morphological attributes of the interface were examined using scanning electron microscopy (SEM) to characterize the acid-base resistant zone (ABRZ). Microshear bond strength (µSBS) testing to enamel and ultimate tensile strength (UTS) of the adhesive resin were carried out.ABRZ formation was confirmed in all groups. UBQ-PA and GPB-PA created thicker ABRZ with no funnel-shaped erosion beneath the adhesive-enamel interface. µSBS of UBQ-PA was significantly higher than UBQ-0 and UBQ-10 (p0.05). However, there were no statistically signficant differences in µSBS among GPB-0, GPB-10, and GPB-PA. For the UTS, UBQ was significantly higher than GPB.Selective phosphoric acid etching created a stable adhesive-enamel interface. The no-waiting self-etching concept adhesive led to a thinner ABRZ. The results of µSBS suggest that phosphoric acid etching effects on enamel are material dependent.

Objectives Ultra-high-speed (UHS) videography was used to visualize the fracture phenomena at the resin–dentin interface during micro-tensile bond strength (μTBS) test. We also investigated whether UHS videography is applicable for failure-mode analysis. Methods Ten human mid-coronal dentin surfaces were bonded using Clearfil SE Bond either in self-etching (SE) or etch-and-rinse (ER) mode. After 24-h water storage, the samples were cut into beams for μTBS test and tested at a cross-head speed of 1 mm/min. The fracture phenomena at the bonded interface were captured using a complementary metal–oxide–semiconductor digital UHS camera at 299,166 frames per second. The failure modes were classified using UHS videography, followed by scanning electron microscopy (SEM) analysis. The failure-mode distributions determined by UHS videography and SEM analysis were statistically analyzed using Fisher’s exact test with Bonferroni correction. Results The crack-propagation speed exceeded 1,500 km/h. No significant difference was found between the SEM and UHS videography failure-mode distributions in the SE mode. A significant difference appeared between them in the ER mode. Significant differences in the incidence of cohesive failures within the adhesive and at the adhesive–composite interface between the SE and ER modes were identified by both SEM and UHS videography. Significance UHS videography enabled visualization of the fracture dynamics at the resin– dentin interfaces under tensile load. However, the resolution at such high frame rate was insufficient to classify the failure mode as precisely as that of SEM. Nevertheless, UHS videography can provide more detailed information about the fracture origin and propagation.

To assess the remineralization capacity of carious, non-carious, and combined white spot lesions (WSLs) using the ICDAS and SS-OCT.This clinical trial was based on a quasi-experimental design. Forty-two healthy subjects (median age 26.6 years), who visited university hospital and had at least one WSL with an ICDAS score of 2 or 1, were recruited. The subjects chewed a non-blind sugar-free gum containing bioavailable calcium and fluoride for 3 months. The remineralization capacities of carious and non-carious 121 WSLs were assessed using ICDAS by two calibrated non-blind examiners and optical boundary depth (BD) by SS-OCT at a monthly recall. The outcome variables, transitions of ICDAS score, mean BD, and mean BD recovery rate (RR%), were statistically analyzed using the chi-square test, two way-repeated measures ANOVA, and Wilcoxon rank sum test, respectively (alpha = 0.05).Based on the visual inspection, OCT images at the baseline, 72 WSLs were purely carious, 20 were non-carious (developmental) lesions, while 29 were combined (carious-developmental). The responses of WSLs over time showed to be highly variable. There was a significant difference in transitions of ICDAS scores after 3 months between carious and non-carious WSLs (p 0.05) and non-carious and combined WSLs (p 0.05). Carious and combined WSLs underwent significant changes in the mean BD between baseline (161.8 ± 56.8 μm) and 2 months (130.7 ± 57.4 μm) or 3 months (119.1 ± 57.5 μm) (p 0.05), while there was no significant difference between baseline (132.2 ± 26.2 μm) and 2 months (122.8 ± 24.1 μm) or 3 months (119.8 ± 22.6 μm) in non-carious WSLs (p 0.05). There was a significant difference in mean RR% after 2 and 3 months between carious and non-carious WSLs (p 0.05).The remineralization capacity of WSL was variable among the cases and subjects, and depended on the WSLs history, etiology (carious, non-carious, or combined lesion) and structure (histological pattern).Carious WSLs showed the highest remineralization potential.

The purpose of this study was to evaluate the role of 10-methacryloyloxydecyl dihydrogen phosphate (MDP) contained in the bonding resin of a two-step self-etch adhesive system. An experimental adhesive (M0) containing MDP only in the primer, but not in the bonding resin was prepared. Clearfil SE Bond (MM) and M0 were compared in terms of microtensile bond strength to dentin, ultimate tensile strength of the bonding resin, and dentin-resin bonding interface morphology under SEM and TEM. The immediate µTBS values of MM significantly decreased after thermal cycles while M0 were stable even after 10,000 cycles. In the SEM observations, formation of erosion was observed beneath the acid-base resistant zone only in M0. The results suggested that MDP in the bonding resin of the two-step self-etching system; 1) improved the immediate bond strength, but caused reduction in long-term bond durability; 2) offered the advantages of acid-base resistance at the ABRZ forefront area.

A 59-year-old woman was referred to our hospital with the finding of an incidentaloma in her right kidney. Computed tomographyand magnetic resonance imaging showed a solid tumor, approximately8 cm in diameter, at the lower pole of the right kidney. Partial nephrectomy was performed without a renal vessel clamp. Histopathologically, fibroblast-like spindle cells were proliferating with rich collagenous fibers, and tumor cells were infiltrated into the renal parenchyma. The tumor cells were stained positive with CD34, CD99, and bcl-2. The tumor was diagnosed as solitaryfibrous tumor originating from the kidney based on these histopathological findings. The patient was followed 3 years after surgery with neither recurrence nor metastasis.

Background No definitive evidence exists regarding use of adjuvant chemotherapy (AC) for high-risk cases after radical nephroureterectomy (RNU), and the benefit of AC remains controversial. The aims of this study were to evaluate the efficacy of AC in patients with upper tract urothelial carcinoma (UTUC) and to determine those who qualified for AC. Patients and Methods From 1990 to 2015, 449 patients with nonmetastatic UTUC underwent RNU at 6 Kitasato University-affiliated hospitals. Eight patients who received neoadjuvant chemotherapy were excluded from this study. One hundred patients (23%) received platinum-based AC for a median of 3 courses. Disease-free survival and cancer-specific survival (CSS) were estimated using the Kaplan–Meier method. Multivariate analyses were performed with the Cox proportional hazards regression model, controlling for the effects of clinicopathological factors. Results The median age was 69 years, and the median follow-up period was 35.7 months. In multivariate analyses, factors independently predictive of poorer survival included pT stage (≥pT3), lymph node status (pN+), tumor grade (Grade 3), lymphovascular invasion, and soft tissue surgical margin. For the risk stratification model, patients were categorized into 3 groups on the basis of these 5 risk factors. In the high-risk group (at least 3 risk factors, 83 patients), 41 patients (49%) were treated with AC, and the 5-year CSS rate was higher in the AC group compared with the non-AC group (P = .02). Conclusion Having more than 3 risk factors defined the high-risk group among UTUC patients after RNU. AC was associated with improved CSS in patients with high-risk UTUC.

Background We evaluated a five-tiered Gleason grade groups arising from the 2014 International Society of Urological Pathology consensus conference on prognostic prediction in clinical stage T3a (extracapsular invasion) and T3b (seminal vesicle involvement) prostate cancer undergoing high-dose-rate brachytherapy (HDR-BT). Methods From November 2003 to December 2012, 283 patients with stage T3 prostate cancer received HDR-BT and external beam radiation therapy (EBRT) with long-term androgen deprivation therapy (ADT). Of these, 203 (72%) and 80 (28%) patients had stage T3a and T3b disease, respectively. The mean dose to 90% of the planning target volume was 7.5 Gy/fraction of HDR-BT. After five fractions, EBRT with 10 fractions of 3 Gy was administered. All patients first underwent ≥6 months of neoadjuvant ADT, and adjuvant ADT continued for 36 months. Median follow-up was 74 months from the start of radiotherapy. Results The 10-year biochemical recurrence (BCR) -free rate for stage T3a and T3b disease was 79% and 64%, respectively (P = 0.0083). The 10-year cancer-specific survival (CSS) rate for stage T3a and T3b was 96% and 91%, respectively (P = 0.0305). Although grade groups ≥4 were independent predictors for BCR in cT3a patients (P = 0.0270), they failed to significantly predict prostate cancer-specific mortality (PCSM) among cT3a patients. Among cT3b patients, grade group 5 was a significant predictor of both BCR (P = 0.0017) and PCSM (P = 0.0233). Among stage T3a patients, no significant difference existed in 10-year CSS between grade groups 5 and 4 (94% vs 97%, P = 0.3960). In contrast, grade group 5 had a significantly worse outcome in 10-year CSS than grade group 4 among stage T3b patients (74% vs 100%, P = 0.0350). Conclusions Stage T3a patients with grade groups 4/5 and stage T3b with grade group 4 had fairly low PCSM risk. Approximately one of four patients among stage T3b patients with grade group 5 showed PCSM after combined HDR-BT and EBRT with long-term ADT. Stage T3b patients with grade group 5 may have a greater risk for PCSM.

Objectives To analyze the frequency of incidental prostate cancer (PC) at radical cystoprostatectomy (RC) for urothelial carcinoma of the bladder (UCB) and its association with survival outcomes in an international cohort. Patients and methods In this retrospective study, we included 2114 who underwent RC and lymphadenectomy for UCB between 1976 and 2012 male patients from seven institutions. Univariable and multivariable Cox regression models addressed the association of incidental PC with cancer-specific mortality and overall mortality after RC. Results Overall, incidental PC was found in 513 (24.3%) patients with the lowest frequency in a Japanese center (23/164, 11.2%) and the highest frequency in a North American center (122/325, 37.5%), respectively (p < 0.001). Within a median follow up of 27 months (IQR: 50 months), 20 patients (3.9%) were diagnosed with biochemical recurrence (BCR) and none of the patients died of PC. PC pathological tumor stage was more advanced in patients experiencing BCR (p < 0.001). In multivariable Cox regression analyses adjusted for standard clinicopathologic features, incidental PC was not associated with cancer-specific (HR: 1.11, 95% CI: 0.91–1.35, p = 0.30) or overall mortality (HR: 1.06, 95% CI: 0.83–1.35, p = 0.65). Conclusions Incidental PC at RC for UCB is a frequent event. However, the majority of PC cases are well-differentiated and organ-confined. Presence of incidental PC shows significant geographic differences. The risk of BCR after incidental PC is low and incidental PC is not associated with survival in UCB patients treated with RC.

Resection of metastatic lesions (metastasectomy) is performed for highly selected patients with metastatic urothelial carcinoma (mUC). This study aimed to identify the clinicopathologic factors associated with oncologic outcome for patients who underwent metastasectomy for mUC. This analysis included 37 UC patients who underwent metastasectomy with curative intent at nine Japanese hospitals. The primary end point was cancer-specific survival. The Kaplan–Meier method with the log-rank test and the multivariable Cox proportional hazards model addressed the relationship between clinical characteristics and survival. Metastasectomy was performed for pulmonary (n = 23), nodal (n = 7), and other (n = 7) metastases. The median survival time was 35.4 months (interquartile range [IQR] 15.5, not reached) from the detection of metastasis and 34.3 months (IQR 13.1, not reached) from metastasectomy. The 5-year cancer-specific survival rate after detection of metastasis was 39.7%. In the multivariate analysis, the time from primary surgery to detection of metastasis (time-to-recurrence [TTR]) of 15 months or longer (hazard ratio [HR] 0.23; p = 0.0063), no symptoms of recurrence (HR 0.23; p = 0.0126), and serum C-reactive protein (CRP) levels lower than than 0.5 mg/dl (HR 0.24; p = 0.0052) were significantly associated with better survival. Long-term survival could be achieved for some patients with mUC who underwent metastasectomy. Lung and lymph nodes were predominant sites for metastasectomy. Symptoms, TTR, and CRP value were identified as associated with survival and should be taken into account when metastasectomy is considered.

Background The impact of gender on the staging and prognosis of urothelial carcinoma of the bladder (UCB) is insufficiently understood. Objective To assess gender-specific differences in pathologic factors and survival of UCB patients treated with radical cystectomy (RC). Design, setting, and participants Data from 8102 patients treated with RC (6497 men [80%] and 1605 women [20%]) for UCB between 1971 and 2012 were analyzed. Outcome measurements and statistical analysis Multivariable competing-risk regression analyses were performed to evaluate the relationship of gender on disease recurrence (DR) and cancer-specific mortality (CSM). We also tested the interaction of gender and tumor stage, nodal status, and lymphovascular invasion (LVI). Results and limitations Female patients were older at the time of RC ( p =0.033) and had higher rates of pathologic stage T3/T4 disease ( p p =0.022 and p =0.11, respectively). Female gender was an independent predictor for CSM ( p =0.004). We did not find a significant interaction between gender and stage, nodal metastasis, or LVI (all p values >0.05). Conclusions We found female gender to be associated with a higher risk of CSM following RC. However, these findings do not appear to be explained by gender differences in pathologic stage, nodal status, or LVI. This gender disparity may be due to differences in care and/or the biology of UCB.

The aim of this study was to evaluate the clinical outcomes of radical cystectomy (RC) and concurrent chemoradiotherapy (CRT) with methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) in patients with locally advanced bladder cancer (BC). From December 2000 to February 2012, 72 patients with locally advanced BC (T3-4a, N0 or N+, M0) received either RC or CRT. RC with bilateral pelvic lymph node dissection including the common iliac region as the standard procedure. Patients in the CRT group received one cycle of MVAC followed by radiotherapy with a half dose of MVAC and then two more cycles of MVAC. Standard fractionation at a daily dose of 1.8-2.0 Gy was used, with a median total dose of 50 Gy (range, 45-60 Gy). The 3-year progression-free survival (PFS) rates in the RC and CRT groups were 56.2% and 25.6%, respectively (p=-0.015) and the 3-year overall survival (OS) rates were 63.5% and 48.1% (p=0.272). Multivariate Cox proportional hazards regression analysis with application of a propensity score indicated that RC was a significant predictor of PFS (p=0.033) but not of OS (p=0.291). Among patients with locally advanced BC, PFS was significantly prolonged in the RC group compared with the CRT group. However, RC was not a significant predictor of OS. Although the sample size in this study was small, the results suggest that patient background and postoperative quality of life should be considered when choosing treatment strategy for locally advanced BC.

The purpose of this study was to report the outcomes of high-dose-rate (HDR) brachytherapy and hypofractionated external beam radiotherapy (EBRT) combined with long-term androgen deprivation therapy (ADT) for National Comprehensive Cancer Network (NCCN) criteria-defined high-risk (HR) and very high-risk (VHR) prostate cancer. Data from 178 HR (n = 96, 54%) and VHR (n = 82, 46%) prostate cancer patients who underwent (192)Ir-HDR brachytherapy and hypofractionated EBRT with long-term ADT between 2003 and 2008 were retrospectively analyzed. The mean dose to 90% of the planning target volume was 6.3 Gy/fraction of HDR brachytherapy. After five fractions of HDR treatment, EBRT with 10 fractions of 3 Gy was administered. All patients initially underwent ≥ 6 months of neoadjuvant ADT, and adjuvant ADT was continued for 36 months after EBRT. The median follow-up was 61 months (range, 25-94 months) from the start of radiotherapy. The 5-year biochemical non-evidence of disease, freedom from clinical failure and overall survival rates were 90.6% (HR, 97.8%; VHR, 81.9%), 95.2% (HR, 97.7%; VHR, 92.1%), and 96.9% (HR, 100%; VHR, 93.3%), respectively. The highest Radiation Therapy Oncology Group-defined late genitourinary toxicities were Grade 2 in 7.3% of patients and Grade 3 in 9.6%. The highest late gastrointestinal toxicities were Grade 2 in 2.8% of patients and Grade 3 in 0%. Although the 5-year outcome of this tri-modality approach seems favorable, further follow-up is necessary to validate clinical and survival advantages of this intensive approach compared with the standard EBRT approach.

The use of virtual reality simulation (VRS) is a new teaching modality in dentistry, and there is scope for further research evaluating its use under different educational programs. The purpose of this study was to evaluate how VRS with or without instructor feedback influenced students' learning and skills related to porcelain fused to metal (PFM) crown preparation. In this study, forty-three dental students in their fifth year of study at Tokyo Medical and Dental University, Tokyo, Japan, were randomly divided into three groups: the first group used VRS (DentSim) with the instructor's feedback (DSF) (n=15), the second group used VRS without the instructor's feedback (DS) (n=15), and the third group neither used features of VRS (NDS) (n=13) nor received the instructor's feedback. All the students performed PFM crown preparation under the same setup once a week for four weeks. Total scores, preparation time, and twelve evaluation items were compared among the three groups and four experiments. The total scores of students in the DSF and DS groups were significantly higher than those in the NDS group. The presence of the instructor did not result in significant difference when VRS was used for training, while it shortened the preparation time at early stages. The results of this study suggested that the use of the VRS system improved student training for PFM crown preparation.

This study aimed to investigate the effect of fluoride concentration in adhesives on morphology of acid-base resistant zone (ABRZ). Seven experimental adhesives with different concentrations of NaF (0 wt%; F0 to 100 wt%: F100) were prepared based on the formulation of a commercially available adhesive (Clearfil Protect Bond, F100). The resin-dentin interface of the bonded specimen was subjected to demineralizing solution and NaOCl, sectioned, polished and argon-ion etched for SEM observation. Fluoride release from each adhesive was measured using an ion-selective electrode. Fluoride ion release from the adhesive linearly increased with higher NaF concentration. The ABRZ area increased significantly with higher NaF concentration except for F0, F10, and F20 (p

Objectives To investigate the intratumoral heterogeneity of BAP1 and PBRM1 expression at the primary site and metastatic sites and to evaluate whether BAP1 and PBRM1 expression in metastatic sites of clear cell renal cell carcinoma (ccRCC) has prognostic value. Methods and materials We collected paired samples from the primary site and the first metastatic site in 41 patients with ccRCC. Immunohistochemistry analyses were performed for the expression of BAP1 and PBRM1 proteins. We retrospectively analyzed the associations between the expression of BAP1 and PBRM1 and overall survival (OS). Results The most common first metastatic sites were lung (68.3%) and lymph node (12.2%). BAP1 protein expression was negative in 8 (19.5%) primary sites and in 11 (26.8%) metastatic sites. PBRM1 protein expression was negative in 9 (22.0%) primary sites and in 11 (26.8%) metastatic sites. The incidences of intratumoral heterogeneity for BAP1 and PBRM1 protein expression in primary/metastatic sites were 9.8%/2.4% and 24.4%/7.3%, respectively. The concordance rates between primary and metastatic sites for BAP1 and PBRM1 protein expression were 82.9% and 63.4%, respectively. Median OS from the first occurrence of metastasis in patients with BAP1-positive and BAP1-negative metastatic sites were 97 months (95% CI: 58–136) and 51 months (95% CI: 13–82), respectively (P = 0.0077). Median OS in patients with PBRM1-positive and PBRM1-negative metastatic sites were 82 (95% CI: 42–97) and 120 (95% CI: 52–120) months, respectively (P = 0.25). Conclusion Intratumoral heterogeneity of BAP1 protein expression is more frequent in primary tumor than in metastatic sites. The loss of BAP1 protein expression in metastatic sites predicts poor prognosis in patients with ccRCC.

Purpose We aimed to identify prognostic clinicopathological factors and to create a nomogram able to predict overall survival (OS) in recurrent urothelial carcinoma of the bladder (UCB) after radical cystectomy (RC). Materials and methods Among 1,087 patients with UCB who had undergone RC at our 11 institutions between 1990 and 2010, 306 patients who subsequently developed distant metastasis or local recurrence or both were identified. Clinical data were collected with medical record review. Univariate and multivariate Cox regression models addressed OS after recurrence. A nomogram predicting postrecurrence OS was constructed based on Cox proportional hazards model, without using postrecurrence factors (systemic chemotherapy and resection of metastasis). The performance of the nomogram was internally validated by assessing concordance index and calibration plots. Results Of the 306 patients, 268 died during follow-up with a median survival of 7 months (95% CI: 5.8–8.5). Postrecurrence chemotherapy was administered in 119 patients (38.9%). Multivariable analysis identified 9 independent predictors for OS; period of time from RC to recurrence (time-to-recurrence), symptomatic recurrence, liver metastasis, hemoglobin level, serum alkaline phosphatase level, serum lactate dehydrogenase level, serum C-reactive protein level, postrecurrence chemotherapy, and resection of metastasis. A nomogram was formed with the following 5 variables to predict OS: time-to-recurrence, symptomatic recurrence, liver metastasis, albumin level, and alkaline phosphatase level. Concordance index rate was 0.75 (95% CI: 0.72–0.78) by internal validation using Bootstraps with 1,000 resamples. Calibration plots showed that the nomogram fitted well. Conclusions We identified 9 clinicopathological factors as independent OS predictors in postcystectomy recurrence of UCB. We also created a validated nomogram with 5 variables that efficiently stratified those patients regardless of eligibility for chemotherapy. The nomogram would be useful for acquiring relevant prognostic information and for stratifying patients for clinical trials.