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Introduction: Whole-liver radiotherapy (WLRT) is performed for palliative purposes in patients with metastatic liver tumors. However, it remains unclear whether the benefits obtained from WLRT surpass the potential disadvantages of radiotherapy-induced liver disease in such patients, particularly those with severe liver damage. We present the case of a 76-year-old man with diffuse liver metastases from castration-resistant prostate cancer. Case Report: He was diagnosed as having prostate cancer with multiple metastases to the bone, pleura, and para-aortic lymph nodes three years and six months earlier and developed hepatic metastases following a sequence of therapies, including surgical castration, bicalutamide, enzalutamide, and 10 cycles of docetaxel. Despite administering abiraterone acetate for two months, the prostate-specific antigen (PSA) levels increased, and the patient developed symptomatic liver damage, presenting with jaundice, anorexia, and fatigue. His serum total bilirubin (9.5 mg/dL) and liver transaminase (>100 U/L) levels were markedly elevated. The patient received WLRT at 8 Gy in a single fraction for palliative intent. Symptomatic relief was achieved shortly after WLRT, and the total bilirubin and transaminase levels decreased and normalized within two months. Additionally, two months after WLRT, the PSA level decreased from 285 to 23.3 ng/mL, and a robust partial tumor response was observed on computed tomography images. Although the patient died of cancer eight months after WLRT, radiotherapy-induced liver disease was not confirmed during the follow-up period. Conclusion: In the present case, WLRT successfully relieved the symptoms and reversed the liver damage caused by diffuse metastases, and it was considered to contribute to cancer control without adverse events. Thus, WLRT can be a viable option for patients with liver damage induced by diffuse liver metastases.

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 (70 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. 51%, P = 0.007) and systematic (70% vs. 46%, P = 0.005) 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

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).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.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.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.

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.

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 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.

BACKGROUND: The controlling nutritional status (CONUT) score is an objective indicator of general condition from the aspect of nutritional status, calculated from serum albumin, total cholesterol, and total lymphocyte count. The CONUT score is also considered to reflect the degree of tumor-derived chronic inflammation and the host immune status in patients with advanced cancer. OBJECTIVE: To examine the prognostic role of the CONUT score in patients with advanced urothelial carcinoma (aUC) treated with first-line platinum-based chemotherapy. METHODS: Associations of the CONUT score with clinical parameters and overall survival (OS) were investigated retrospectively in 147 patients with aUC receiving first-line platinum-based chemotherapy at a single cancer center from February 2003 to April 2019. RESULTS: The median (range) CONUT score was 1 (0–7). A higher CONUT score was associated with lower hemoglobin (P

(Purpose) Holmium laser enucleation of the prostate (HoLEP) is widely performed in recent years; however, difficulties of surgical techniques and high frequency of postoperative stress urinary incontinence (SUI) remain as significant problems. We determined the predictive factors for de novo SUI after HoLEP. (Patients and methods) A total of 303 patients with benign prostatic hyperplasia who underwent HoLEP were retrospectively evaluated between July 2013 and April 2019. Of these, 109 patients underwent MRI preoperatively. Patients who were unable to answer the questionnaire regarding their SUI because of dementia, those who presented with SUI preoperatively, and those with placed Foley catheter at the time of MRI were excluded. Hence, a total of 83 patients were eligible for the present study. We recorded the MRI findings and clinical variables, including membranous urethral length (MUL), transitional zone (TZ) volume, serum prostate-specific antigen levels, operative time, and presence or absence of SUI. The predictive factors for de novo SUI were determined using multivariable logistic regression analysis. (Results)De novo SUI occurred in 19 (22.9%) patients but disappeared in 16 (84.2%) patients at a mean duration of 14 weeks. The mean MUL was 17.2 mm. Univariate analysis showed that MRI TZ volume >40 mL, MUL ≤17 mm, operative time >100 min, and enucleation time >50 min were associated with de novo SUI. In multivariable logistic regression analysis, MUL ≤17 mm (odds ratio [OR], 23.81; 95% confidence interval [CI], 4.34-447.19; P 100 min (OR, 3.91; 95% CI, 1.20-14.01; P = 0.023) were significantly associated with de novo SUI. (Conclusions) Although de novo SUI occurred occasionally after HoLEP, most of them improved in about 3 months. The MRI measurement of MUL was shown to be a practical tool for predicting de novo SUI after HoLEP.

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.

Background: Reports on the prognostic significance of serum γ-glutamyltransferase (GGT) in men with metastatic castration-resistant prostate cancer (mCRPC) are limited. In addition, GGT expression status in cancer tissues has not been well characterized regardless of cancer types. Methods: This retrospective study included 107 consecutive men with mCRPC receiving docetaxel therapy. The primary endpoints were associations of serum GGT with overall survival (OS) and prostate-specific antigen (PSA) response. The secondary endpoint was an association of serum GGT with progression-free survival (PFS). Additionally, GGT expression status was immunohistochemically semi-quantified using tissue microarrays. Results: A total of 67 (63%) men died during follow-up periods (median 22.5 months for survivors). On multivariable analysis, high Log GGT was independently associated with adverse OS (HR 1.49, p = 0.006) as were low hemoglobin (HR 0.79, p = 0.002) and high PSA (HR 1.40, p &lt, 0.001). In contrast, serum GGT was not significantly associated with PSA response or PFS. Moreover, incorporation of serum GGT into established prognostic models (i.e., Halabi and Smaletz models) increased their C-indices for predicting OS from 0.772 to 0.787 (p = 0.066) and from 0.777 to 0.785 (p = 0.118), respectively. Furthermore, there was a positive correlation between serum and tissue GGT levels (ρ = 0.53, p = 0.003). Conclusions: Serum GGT may be a prognostic biomarker in men with mCRPC receiving docetaxel therapy. GGT overexpression by prostate cancer cells appears to be responsible for the elevation of GGT in the serum.

(Purpose) Holmium laser enucleation of the prostate (HoLEP) is widely performed in recent years; however, difficulties of surgical techniques and high frequency of postoperative stress urinary incontinence (SUI) remain as significant problems. We determined the predictive factors for de novo SUI after HoLEP. (Patients and methods) A total of 303 patients with benign prostatic hyperplasia who underwent HoLEP were retrospectively evaluated between July 2013 and April 2019. Of these, 109 patients underwent MRI preoperatively. Patients who were unable to answer the questionnaire regarding their SUI because of dementia, those who presented with SUI preoperatively, and those with placed Foley catheter at the time of MRI were excluded. Hence, a total of 83 patients were eligible for the present study. We recorded the MRI findings and clinical variables, including membranous urethral length (MUL), transitional zone (TZ) volume, serum prostate-specific antigen levels, operative time, and presence or absence of SUI. The predictive factors for de novo SUI were determined using multivariable logistic regression analysis. (Results)De novo SUI occurred in 19 (22.9%) patients but disappeared in 16 (84.2%) patients at a mean duration of 14 weeks. The mean MUL was 17.2 mm. Univariate analysis showed that MRI TZ volume40 mL, MUL ≤17 mm, operative time100 min, and enucleation time50 min were associated with de novo SUI. In multivariable logistic regression analysis, MUL ≤17 mm (odds ratio [OR], 23.81; 95% confidence interval [CI], 4.34-447.19; P0.0001) and operative time100 min (OR, 3.91; 95% CI, 1.20-14.01; P = 0.023) were significantly associated with de novo SUI. (Conclusions) Although de novo SUI occurred occasionally after HoLEP, most of them improved in about 3 months. The MRI measurement of MUL was shown to be a practical tool for predicting de novo SUI after HoLEP.

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.

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.

Purpose To evaluate the impact of modifications to anatomical apical dissection including a puboprostatic open-collar technique, which visualizes the lateral aspect of the apex and dorsal vein complex (DVC) covering the rhabdosphincter while preserving the puboprostatic collar, on positive surgical margin (PSM) and continence recovery. Methods One-hundred-and-sixty-seven patients underwent gasless single-port retroperitoneoscopic radical prostatectomy using a three-dimensional head-mounted display system. Sequentially modified surgical techniques comprised puboprostatic open-collar technique, sutureless transection of the DVC, retrograde urethral dissection, and anterior reconstruction. The associations of these modifications with PSM and continence recovery were assessed. Results The puboprostatic open-collar technique, sutureless DVC transection, and retrograde urethral dissection were significantly associated with lower apical PSM (P = 0.003, 0.003, and 0.010, respectively). The former two also showed similar associations in 84 patients with anterior apical tumor (P = 0.021 and 0.030, respectively). Among 92 patients undergoing all of these three procedures, overall and apical PSM rates were 13.0% and 3.3%, respectively. Retrograde urethral dissection (odds ratio [OR] 2.73, P = 0.004) together with nerve sparing (OR 2.77, P = 0.003) and anterior apical tumor (OR 0.45, P = 0.017) were independently associated with immediate continence recovery. A multivariable model for 3-month continence recovery included anterior apical tumor (OR 0.28, P = 0.003) and puboprostatic open-collar technique (OR 3.42, P = 0.062). Immediate and 3-month continence recovery rates were 56.3% and 85.4%, respectively, in 103 patients undergoing both the puboprostatic open-collar technique and retrograde urethral dissection. Conclusion Novel anatomical apical dissection utilizing a puboprostatic open-collar technique may favorably impact on both apical surgical margin and continence recovery.

Periodontitis is one of the diabetic complications due to its high morbidity and severity in patients with diabetes. The prevention of periodontitis is especially important in diabetic patients because the relationship between diabetes and periodontitis is bidirectional. Here, we evaluated the impacts of glucagon-like peptide-1 (GLP-1) receptor agonist liraglutide on the amelioration of periodontitis. Five-wk-old Male Sprague–Dawley (SD) rats ( n = 30 ) were divided into 3 groups: normal, periodontitis, and periodontitis with liraglutide treatment groups. Periodontitis was induced by ligature around the maxillary second molar in SD rats. Half of the rats were administered liraglutide for 2 weeks. Periodontitis was evaluated by histological staining, gene expressions of inflammatory cytokines in gingiva, and microcomputed tomography. Periodontitis increased inflammatory cell infiltration, macrophage accumulation, and gene expressions of tumor necrosis factor-α and inducible nitric oxide synthase in the gingiva, all of which were ameliorated by liraglutide. Liraglutide decreased M1 macrophages but did not affect M2 macrophages in periodontitis. Moreover, ligature-induced alveolar bone resorption was ameliorated by liraglutide. Liraglutide treatment also reduced osteoclasts on the alveolar bone surface. These results highlight the beyond glucose-lowering effects of liraglutide on the treatment of periodontitis.

OBJECTIVE Increasing age is a potential risk factor for periodontal tissue breakdown, which may be affected by commensal flora. The aim of this study evaluated age-related changes in CD4+ T cells, C-C chemokine ligand 5 (CCL5), interleukin (IL)-17A, and receptor activator of nuclear factor-kappa B ligand (RANKL) expression using germ-free (GF) and conventionally reared (SPF) mice. DESIGN GF and SPF mice at 8 (n = 6/group) and 22 weeks old (n = 6/group) were used. Immunohistochemical analyses were performed to determine the effects of aging on protein expression in periodontal tissues. Age-related changes in alveolar bone were quantified using micro-CT analysis. RESULTS SPF mice, but not GF mice, showed an age-related increase in alveolar bone loss (P

The purpose of this study is to develop a method for quantifying the fluidity of flowable resin composites using determinations of yield stress. Five commercially available composites (AliteFlo LV, Flow-it ALC, Venus flow, Tetric N-flow, Revolution Formula2) were investigated. Yield stress values were obtained by plotting shear stresses for a range of shear rates, followed by fitting of Casson fluid models to flow curve data and extrapolation to the stress axis. To confirm that yield stress reflected fluidity, apparent viscosity at the lower shear rate (0.2 s-1) was calculated from flow curves. Yield stresses ranged from 5.4 to 43.1 Pa, and were found to capture differences in the fluidity of composites that were not captured by viscosity measurement at the low shear rate. Yield stress is directly proportional to fluidity, and could serve as a simple and precise indicator for selecting flowable resin composites for use in various clinical applications.

Periodontal disease which consists of gingivitis and periodontitis is one of the diabetic complications due to the high prevalence and the severity. Periodontitis is a chronic inflammation by the infection of Gram-negative bacteria in the periodontal pocket, following the destruction of periodontal tissue. On the other hand, many researches have shown extrapancreatic functions of glucagon-like peptide-1 (GLP-1), including the anti-inflammatory action and the suppression of indirectly bone resorption. In this study, we focused on the therapeutic effects of GLP-1 on periodontitis. Experimental periodontitis was induced by placing a nylon thread ligatureat the cervical portion of the maxillary second molar in Sprague-Dawley rats. Half of the rats were administered GLP-1 receptor agonist, Liraglutide (0.4mg/kg/day). Two weeks after the ligation, periodontitis was evaluated by histological examinations (H-E staining and the immunostaining) and mRNA expressions of inflammatory cytokines. Alveolar bone loss was evaluated by the distance at maximal bone resorption site from cement-enamel junction (CEJ) to the alveolar bone crest, and the bone micro-architecture parameters, using micro-CT and analytical software. We also investigated the anti-inflammatory effects of GLP-1 on monocytes using THP-1 cells. The mRNA expressions of TNF-α, iNOS and Mac1 in gingiva and alveolar bone resorption were significantly increased in the periodontitis rats. Liraglutide significantly suppressed the periodontitis-related inflammatory cytokine expressions and alveolar bone resorption. The part of the bone micro-architecture parameters in periodontitis rats deteriorate, which was not affected by Liraglutide. In vitro study revealed that GLP-1 significantly inhibited lipopolysaccharide-induced TNF-α mRNA expression in THP-1 cells in a dose-dependent manner. In conclusion, GLP-1 may be effective in the treatment of periodontal disease mainly through the suppression of gingival inflammation. Disclosure N. Sawada: None. K. Naruse: None. T. Matsubara: None. N. Nakamura: None. M. Miyabe: None. M. Ito: None. Y. Suzuki: None. K. Adachi: None. S. Kobayashi: None. T. Kikuchi: None. A. Mitani: None. T. Toriumi: None. M. Mizutani: None. M. Honda: None.

Tumor location in bladder neck has reported to be a prognostic factor for non-muscle-invasive bladder cancer (NMIBC). We investigated the impact of bladder neck involvement (BNI) on recurrence in NMIBC using time-dependent covariate analysis.We enrolled 585 Japanese patients who underwent transurethral resection for bladder tumors at a single center from 2000 to 2016 and were pathologically diagnosed with Ta and T1 NMIBC. Each patient at each recurrence was assigned to a separate time-dependent stratum with its own baseline hazard function according to the Prentice-Williams-Peterson gap time model for analyzing recurrent events.Over a median follow-up period of 41.3 months (interquartile range, 18.0-82.3 months), 253 (43.2%) patients experienced a total of 475 recurrences. Among the 1001 total transurethral resection procedures, BNI was observed in 122 (12.2%) cases. The 3-year cumulative recurrence rates of patients with and without BNI were 62.5% and 46.3%, respectively. Multivariable analysis revealed that number of tumors ≥ 4 (sub-hazard ratio [SHR], 1.48; P = .004), intravesical bacillus Calmette-Guérin therapy (SHR, 0.44; P .001), and BNI (SHR, 1.59; P = .004) were all independent predictors of recurrence. Assigning 1 point for each of these 3 predictive factors, the resulting scores enabled us to classify patients into 3 prognostic groups that were clearly stratified according to recurrence.Our time-dependent covariate analysis shows that BNI is a significant risk factor for recurrence in NMIBC. Our prognostic model incorporating BNI is an easy means of estimating recurrence risk and determining optimal management for individual patients.

We experienced the giant seminoma with 18×10×10cm sized and about 2.6kg weight of 25year old patient. We intensively examined the histological tissue type distributions in this giant seminoma. Most of the tumor consisted of seminoma components. In addition, the tumor included the very small fragments of yolk sac tumor and embryonal carcinoma component at the root part of the seminoma mass. This shows that intensive histological examination may contribute to the finding of other embryonic component of the large seminoma. This may show that leaving the seminoma growing may generate the other embryonic tumor component, not always big enough to find out in a routine procedure, during the growth, in the different way from the original mixed cell germ tumor.

Background Few studies have examined epithelial attachment to zirconia and the proliferative ability of epithelial cells on zirconia surfaces. Purpose To evaluate the adhesion properties of zirconia materials for epithelial cell attachment and compare this with titanium and alumina. Materials and Methods Human oral epithelial cells were cultured on smooth-surfaced specimens of commercially pure titanium (cpTi), ceria-stabilized zirconia/alumina nano-composite (P-NANOZR), yttria-stabilized zirconia (Cercon), and alumina oxide (inCoris AL). The cell morphology, the cell viability and mRNA of integrin β4, laminin γ2, catenin δ2, and E-cadherin were evaluated by SEM, Cell-Counting Kit-8, and real-time PCR, respectively. Results Morphology of cells attached to specimens was similar among all groups. The viable cell numbers on Cercon and inCoris AL after 24 hours culture were significantly higher than for cpTi. Integrin β4, laminin γ2, and catenin δ2 mRNA expression was not different among all groups. However, at 3 and 24 hours after incubation, E-cadherin mRNA expression in the P-NANOZR group was significantly higher than for cpTi. Conclusion Zirconia may support binding of epithelial cells through hemidesmosomes comparable with titanium. Furthermore, P-NANOZR may impart resistance to exogenous stimuli through strong intercellular contacts with peri-implant mucosal cells when used as an abutment and implant superstructure.

Purpose To evaluate associations of Ki-67 expression with oncologic outcomes in muscle-invasive bladder cancer (MIBC) patients treated with chemoradiotherapy (CRT)-based bladder-sparing protocol. Materials and Methods Between 1998 and 2011, 190 consecutive MIBC patients were treated with CRT-based bladder-sparing protocol. After transurethral resection of the bladder tumor, the patients underwent induction CRT (40 Gy with concurrent cisplatin) followed by partial cystectomy for bladder preservation or radical cystectomy (RC). Included in this study were 94 patients who were histologically diagnosed with urothelial carcinoma and whose tumor tissues before CRT were available for immunohistochemical evaluation of Ki-67 expression status. Results After induction CRT, 16 (17%) and 53 (56%) patients underwent partial cystectomy and RC, respectively, while the remaining 25 (27%) did not undergo cystectomy. Successful bladder preservation was achieved in 34 patients (36%). Higher Ki-67 labeling index (LI) independently predicted CRT response clinically and pathologically. Among the clinicopathologic variables available before CRT and cystectomy, high Ki-67 LI (≥ 20%) was independently associated with better cancer-specific survival (CSS) (5-year CSS rate, 78% vs. 46% for low Ki-67 LI; P = .019). The difference in CSS according to Ki-67 expression status was more remarkable in patients with cT3 disease (5-year CSS rate, 72% vs. 29%; P = .0098). Conclusion High Ki-67 expression predicts favorable CSS in MIBC patients treated with CRT-based bladder-sparing protocol. MIBC patients with high Ki-67 expression status might benefit from CRT-based multimodal approaches in terms of prognosis and quality of life as a result of bladder preservation.

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 (

Increasing age is a potential risk factor for periodontal tissue breakdown, which may be affected by commensal flora. The aim of this study evaluated age-related changes in CD4GF and SPF mice at 8 (n = 6/group) and 22 weeks old (n = 6/group) were used. Immunohistochemical analyses were performed to determine the effects of aging on protein expression in periodontal tissues. Age-related changes in alveolar bone were quantified using micro-CT analysis.SPF mice, but not GF mice, showed an age-related increase in alveolar bone loss (P 0.01). SPF mice at 22 weeks of age increased expression of CD4SPF mice induced an age-related increase in CD4

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.

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.

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.

Background Positive results from voided urine cytology (VUC) indicate the fragility of the intercellular adhesion of bladder cancer cells, a critical biological process for invasion and metastasis, along with the presence of atypical cells. Few studies have focused on the prognostic role of VUC in non–muscle-invasive bladder cancer (NMIBC). Methods Between 2000 and 2010, 326 patients diagnosed pathologically with Ta or T1 bladder urothelial carcinoma underwent 597 transurethral resections of bladder tumor (TURBTs). Clinicopathological data were prospectively collected at each TURBT. Reports of cells of class IIIb or greater were considered positive VUC results. Muscle-invasive or metastatic recurrences were considered progression. Risk factors for progression and cancer-specific mortality (CSM) were determined using time-fixed and time-dependent Cox models. Variables at the study entry and at each TURBT were used for time-fixed and time-dependent models, respectively. Results The 5-year cumulative progression and CSM rates were, respectively, 7% and 5% (median follow-up, 46 months). The 5-year cumulative progression and CSM rates for patients with positive VUC were 20% and 15%, respectively, compared with 2% ( P P = .0002), respectively, for patients with negative VUC results. A positive VUC result was a significant and independent risk factor for progression and CSM in the time-fixed and time-dependent models. In time-dependent models, 7 predictors for progression or CSM were identified (positive VUC results, T1 disease, lack of intravesical instillation, higher prior recurrence rate, higher histological grade, male gender, and advanced age), whereas 3 predictors were identified in time-fixed models (positive VUC, T1 disease, and higher prior recurrence rate). VUC results consistently outperformed histological grade as a prognostic predictor. Conclusion Positive VUC results predict the progression and CSM of NMIBC, independent of and outperforming histological grade.

Highlights • BMP-induced bone formation was evaluated in mice fed a Soy, Can, or H2-Soy diet. • Ectopic bone formation was greater in the Can and H2-Soy groups. • Altered levels of VK2 and VK-dependent protein(s) might affect the bone formation., Canola oil (Can) and hydrogenated soybean oil (H2-Soy) are commonly used edible oils. However, in contrast to soybean oil (Soy), they shorten the survival of stroke-prone spontaneously hypertensive (SHRSP) rats. It has been proposed that the adverse effects of these oils on the kidney and testis are caused at least in part by dihydro-vitamin K (VK) 1 in H2-Soy and unidentified component(s) in Can. Increased intake of dihydro-VK1 is associated with decreased tissue VK2 levels and bone mineral density in rats and humans, respectively. The aim of the present study was to determine the effects of these oils on bone morphogenetic protein (BMP)-induced ectopic bone formation, which is promoted by VK2 deficiency, in relation to the role of VK in the γ-carboxylation of osteocalcin and matrix Gla protein. A crude extract of BMPs was implanted into a gap in the fascia of the femoral muscle in 5-week-old mice maintained on a Soy, Can, or H2-Soy diet. Newly formed bone volume, assessed by three-dimensional X-ray micro-computed tomography and three-dimensional reconstruction imaging for bone, was 4-fold greater in the Can and H2-Soy groups than in the Soy group. The plasma carboxylated osteocalcin (Gla-OC) and total OC (Gla-OC plus undercarboxylated osteocalcin [Glu-OC]) levels were significantly lower in the Can group than in the Soy group (p < 0.05). However, these levels did not significantly differ between the H2-Soy and Soy groups. The plasma Gla-OC/Glu-OC ratio in the Can and H2-Soy groups was significantly lower (in Can; p = 0.044) or was almost significantly lower (in H2-Soy; p = 0.053) than that in the Soy group. In conclusion, Can and H2-Soy accelerated BMP-induced bone formation in mice to a greater extent than Soy. Further research is required to evaluate whether the difference in accelerated ectopic bone formation is associated with altered levels of VK2 and VK-dependent protein(s) among the three dietary groups.

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/mm2 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

To investigate the role of apparent diffusion coefficient (ADC) as a biomarker reflecting the aggressiveness of upper urinary tract urothelial cell carcinoma (UUT-UCC).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).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).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.• 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.

INTRODUCTION AND OBJECTIVES: Several studies have shown the impact of systemic inflammation on the prognosis in patients with various types of cancers, including urothelial carcinoma (UC). The aim of this study was to evaluate the prognostic significance of pretreatment inflammatory markers in patients with metastatic UC who underwent first-line gemcitabine plus cisplatin (GC) chemotherapy. METHODS: We reviewed the medical records of 214 metastatic UC patients who received first-line GC at 14 institutions between 2005 and 2014. The associations of pretreatment clinical factors, including the neutrophil-to-lymphocyte ratio (NLR), derived NLR, platelet-tolymphocyte ratio, Onodera’s prognostic nutritional index and C-reactive protein (CRP), with progression-free survival (PFS) and overall survival (OS) were assessed. The Cox proportional hazards model was used for multivariate analysis. RESULTS: After excluding 27 patients with missing data, 187 patients were finally enrolled. The median PFS and OS were 7.5 months (IQR 3.6-11.9) and 11.7 months (IQR 7.3-19.9), respectively. Multivariate analysis showed that pretreatment CRP 1.0 mg/dL and liver or bone metastasis were independent poor prognostic factors for PFS and OS (Table). A prognostic model predicting OS was constructed based on the number of these three variables present (0, 1 and 2). The classified patients showed significantly different OS (p < 0.0001, log-rank test, Figure) and Harrell’s concordance index was 0.66 (95%CI 0.58 0.74). CONCLUSIONS: Pretreatment CRP elevation is an independent poor prognostic factor for mUC in patients undergoing first-line GC chemotherapy. Our newly developed prognostic model using the pretreatment CRP is a good discriminator of OS in metastatic UC patients. Source of Funding: none

Purpose In chemoradiation (CRT)-based bladder-sparing approaches for muscle invasive bladder cancer (MIBC), patients who respond favorably to induction CRT enjoy the benefits of bladder preservation, whereas nonresponders do not. Thus, accurate prediction of CRT sensitivity would optimize patient selection for bladder-sparing protocols. Diffusion-weighted MRI (DW-MRI) is a functional imaging technique that quantifies the diffusion of water molecules in a noninvasive manner. We investigated whether DW-MRI predicts CRT sensitivity of MIBC. Methods and Materials The study cohort consisted of 23 MIBC patients (cT2/T3 = 7/16) who underwent induction CRT consisting of radiotherapy to the small pelvis (40 Gy) with two cycles of cisplatin (20 mg/day for 5 days), followed by partial or radical cystectomy. All patients underwent DW-MRI before the initiation of treatment. Associations of apparent diffusion coefficient (ADC) values with CRT sensitivity were analyzed. The proliferative potential of MIBC was also assessed by analyzing the Ki-67 labeling index (LI) in pretherapeutic biopsy specimens. Results Thirteen patients (57%) achieved pathologic complete response (pCR) to CRT. These CRT-sensitive MIBCs showed significantly lower ADC values (median, 0.63 × 10−3 mm2/s; range, 0.43–0.77) than CRT-resistant (no pCR) MIBCs (median, 0.84 × 10−3 mm2/s; range, 0.69–1.09; p = 0.0003). Multivariate analysis identified ADC value as the only significant and independent predictor of CRT sensitivity (p < 0.0001; odds ratio per 0.001 ×10−3 mm2/s increase, 1.03; 95% confidence interval, 1.01–1.08). With a cutoff ADC value at 0.74 × 10−3 mm2/s, sensitivity/specificity/accuracy in predicting CRT sensitivity was 92/90/91%. Ki-67 LI was significantly higher in CRT-sensitive MIBCs (p = 0.0005) and significantly and inversely correlated with ADC values (ρ = −0.67, p = 0.0007). Conclusions DW-MRI is a potential biomarker for predicting CRT sensitivity in MIBC. DW-MRI may be useful to optimize patient selection for CRT-based bladder-sparing approaches.

Purpose: We evaluated concanavalin A (Con A)-induced acute hepatic 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: We allocated 18 rats into 3 groups of six each and intravenously injected them with either 10 mg/kg body weight (BW) of Con A (Con A [10] group), 20 mg/kg BW of Con A (Con A [20] group), or a single dose of of saline (4 mL/kg BW, normal control group). We performed the DCE-MRI studies using Gd-EOB-DTPA (0.025 mmol Gd/kg; 0.1 mL/kg BW) as the contrast agent 24 hours after injection of Con A or saline. We then sampled blood, measured serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT), and calculated the rate of contrast uptake (α), rate of contrast washout (β), area under the curve (AUC), time to maximum relative enhancement (RE) (Tmax), and elimination half-life of RE (T1/2) from the time-signal intensity curves using the EMM. Results: β values were significantly smaller in the Con A (10) and Con A (20) groups than the control group, but α did not differ significantly among the 3 groups. The AUC value was significantly greater in the Con A (10) group than controls, and the Tmax and T1/2 values were significantly greater in the Con A (20) group than controls. The β, Tmax, and T1/2 values correlated significantly with AST and ALT. Conclusion: In conclusion, the EMM is useful for evaluating Con A-induced acute hepatic injury using DCE-MRI with Gd-EOB-DTPA.

We undertook this study to investigate the usefulness of a dual-input single-compartment model for evaluating thioacetamide (TAA)-induced acute liver injury in rats by use of dynamic contrast-enhanced computed tomography (DCE-CT). The rats in the TAA-treated group were injected intravenously with 140 mg/kg (n = 10) or 280 mg/kg (n = 10) of TAA, whereas those in the control group (n = 10) were injected with saline. The rate constants for the transfer of the contrast agent from the hepatic artery to the liver (K(1a)), from the portal vein to the liver (K(1p)), and from the liver to the blood (k₂), as well as liver perfusion (LP), the arterial fraction of LP (AFLP), distribution volume (DV), and mean transmit time (MTT) were estimated with use of the dual-input single-compartment model. Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were also measured. K(1p), k₂, and LP decreased significantly in the TAA-treated group compared to those in the control group, whereas K(1a), AFLP, DV, and MTT increased significantly. The above parameters except for K (1a) were significantly correlated with both AST and ALT. We concluded that DCE-CT using the dual-input single-compartment model is useful for quantitative evaluation of TAA-induced acute liver injury.

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. 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. 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

Aim: Androgen-deprivation therapy for prostate cancer decreases bone mineral density and increases the risk of fracture. The effect of risedronate, a potent third-generation oral bisphosphonate, on bone loss during androgen deprivation therapy was investigated. Methods: Sixty-one prostate cancer patients with a mean age (±SD) of 79 ± 6 years who had received androgen deprivation therapy for 42 ± 29 months were enrolled, and were treated with 2.5 mg of risedronate daily for six months. Bone mineral density was measured at the femoral neck, lumbar spine, and ultradistal radius by dual energy X-ray absorptiometry. The percent change of bone mineral density after treatment with risedronate was calculated as the primary efficacy variable. Urinary N-telopeptide of type I collagen was measured as a bone resorption marker. Results: Bone mineral density remained stable in the femoral neck and radius during risedronate therapy. In contrast, the bone mineral density of the lumbar spine showed a significant increase from 1069 ± 488 mg/cm2−1112 ± 497 mg/cm2 (P

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 hemoglobin 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.

Few studies have examined epithelial attachment to zirconia and the proliferative ability of epithelial cells on zirconia surfaces.To evaluate the adhesion properties of zirconia materials for epithelial cell attachment and compare this with titanium and alumina.Human oral epithelial cells were cultured on smooth-surfaced specimens of commercially pure titanium (cpTi), ceria-stabilized zirconia/alumina nano-composite (P-NANOZR), yttria-stabilized zirconia (Cercon), and alumina oxide (inCoris AL). The cell morphology, the cell viability and mRNA of integrin βMorphology of cells attached to specimens was similar among all groups. The viable cell numbers on Cercon and inCoris AL after 24 hours culture were significantly higher than for cpTi. Integrin βZirconia may support binding of epithelial cells through hemidesmosomes comparable with titanium. Furthermore, P-NANOZR may impart resistance to exogenous stimuli through strong intercellular contacts with peri-implant mucosal cells when used as an abutment and implant superstructure.