Predictive Value of the Prostate-specific Antigen Doubling Time for the Effectiveness of Metastasis-directed Radiotherapy in Patients With Oligometastases After Radical Treatment for Non-metastatic Prostate Cancer.

Background/Aim: Data on metastasis-directed radiotherapy (MDRT) are limited, particularly regarding its association with the prostate-specific antigen (PSA) doubling time (PSADT). The present study evaluated the oncological outcomes of MDRT on the basis of the PSADT in oligo-recurrent prostate cancer patients. Patients and Methods: We retrospectively reviewed clinical data of 35 MDRTs for 29 patients at the Kitasato University Hospital, targeting oligometastatic prostate cancer developed after radical treatment for non-metastatic prostate cancer. Thirty-five MDRTs were classified into the PSADT >3 months (n=25) or PSADT ≤3 months group (n=10). Statistical analyses were performed to compare associations between the two PSADT groups and oncological outcomes such as progression-free survival (PFS) and PSA response after MDRT. Results: There were no significant differences between the two groups in terms of the clinicopathological features. Kaplan-Meier analysis showed that PFS was significantly better in the PSADT >3 months group than in the PSADT ≤3 months group [median: 13.3 versus (vs.) 2.6 months, p=0.046]. Regarding castration sensitivity, the predictive role of PSADT >3 months was maintained in 21 patients who received MDRT without prior salvage hormone therapy (median PFS: 12.7 vs. 2.6 months, p=0.024). In the castration-resistant setting (n=14), the frequency of a decrease in serum PSA levels after MDRT by 90% was 54.5% (median PFS: 23.1 months). Conclusion: MDRT can provide benefit especially for patients with PSADT ≥3 months who had oligo-recurrence after the radical treatment for non-metastatic prostate cancer.

Enhancement of mineral density and mechanical properties in root caries treated with silver diammine fluoride and glass ionomer cement, with emphasis on silver ion distribution.

OBJECTIVES: This study aimed to measure the distribution of silver ion (Ag+), mineral recovery, and nanohardness in carious lesions and comprehensively evaluate the degree of dentin restoration. METHODS: Sixty human teeth with root caries were randomly assigned to the control, silver diammine fluoride (SDF) [Safo], and SDF+Glass ionomer cement (GIC) treatment [Safo+Fuji] groups. Micro-computed tomography (micro-CT) was performed at five time points for each sample before/after treatment to evaluate mineral density within and around carious lesions. Three months following treatment, 12 samples were selected for synchrotron radiation X-ray fluorescence analysis to evaluate Ag+ distribution, while 15 samples were selected for nanoindentation. Data were analyzed using Dunnett's T3 test for micro-CT and Wilcoxon rank sum test with Bonferroni correction (p = 0.017) for nanoindentation. The correlation between hardness and mineral change was analyzed using the Spearman rank correlation coefficient. RESULTS: The Safo and Safo+Fuji groups showed significantly higher mineral recovery rates than did the control group (p < 0.001). In the Safo group, Ag+ accumulated in the deeper layers rather than the superficial layer of caries. In the Safo+Fuji group, Ag+ was found evenly distributed throughout caries, with only a few Ag+ detected in the GIC layer. Hardness in the Safo+Fuji group was significantly higher compared with the Safo group at depths in the range of 10-50 µm. CONCLUSION: In the presence of GICs, SDF exhibited high remineralization capacity when diffusing throughout carious lesions over time. Combined treatment with SDF and GIC could strengthen root dentin even in the presence of caries. CLINICAL SIGNIFICANCE: We found that combination treatment with SDF and GIC could increase mineral density in caries and improve the hardness of the tooth structure compared with fluoride-based agents alone. These findings might pave the way for future clinical trials to determine the therapeutic potential of nanotechnology-based restorative materials.

Real-world data on the comprehensive genetic profiling test for Japanese patients with metastatic castration-resistant prostate cancer.

OBJECTIVE: comprehensive genomic profiling test has been covered by Japanese health insurance since June 2019. However, no real-world data on the test have been reported with a focus on Japanese patients with prostate cancer. METHODS: we retrospectively reviewed the data of 45 consecutive patients with metastatic castration-resistant prostate cancer, who underwent the comprehensive genomic profiling tests at Kitasato University Hospital between August 2019 and December 2022. Patients' characteristics, prevalence of gene alterations and therapeutic impact of genotype-matched therapy were assessed. RESULTS: genomic data were obtained using a tissue-based test (n = 32) and liquid-based test (n = 13). Actionable genomic alternations were identified in 51.1% of patients, and 22.2% were treated with genotype-matched therapy. The main reason for not receiving genotype-matched therapy was disease progression, accounting for 46.2% (6/13). Kaplan-Meier analysis showed significantly longer overall survival after the comprehensive genomic profiling tests in patients with genotype-matched therapy under public insurance (17.8%, n = 8) than those without it (median: not reached vs. 18.1 months; P = 0.003). Five (62.5%) out of the eight patients with genotype-matched therapy under public insurance had BRCA1 or 2 deleterious alteration. Multivariate analyses showed that BRCA deleterious alteration (17.8%, n = 8) was an independent risk factor for shorter time to castration-resistant prostate cancer (hazard ratio: 2.46, 95% confidence interval: 1.04-5.87; P = 0.041), and no patients with the alteration had ≤5 bone metastases. CONCLUSIONS: the results of this study showed the promising survival outcomes in patients with genotype-matched therapy under public insurance, even in the castration-resistant prostate cancer setting. Further detection of promising therapeutic target gene is expected to increase the number of patients who reach genotype-matched therapies.

Membranous Expression of Heart Development Protein with EGF-like Domain 1 Is Associated with a Good Prognosis in Patients with Bladder Cancer.

OBJECTIVE: To investigate the correlation between total protein expression of heart development protein with EGF-like domain 1 (HEG1) and clinicopathological characteristics in patients with bladder cancer (BC) after radical cystectomy (RC). PATIENTS AND METHODS: We retrospectively analyzed data from 110 patients who underwent RC at Kitasato University Hospital. And we prepared an anti-HEG1 monoclonal antibody W10B9, which can detect total HEG1 protein. HEG1 protein expression in tumor cells was evaluated separately for membrane and cytoplasmic staining using immunohistochemistry. RESULTS: Membranous HEG1 expression was associated with absent lymphovascular invasion (p < 0.01) and low pT stage (p < 0.01). Kaplan-Meier analysis revealed that the membranous HEG1-positive group had significantly long recurrence-free survival (RFS) (p < 0.01) and cancer-specific survival (p = 0.01). Expression of membranous HEG1 was identified as an independent prognostic factor for RFS (p = 0.04). There were no significant differences between cytoplasmic HEG1 expression and clinicopathologic factors including prognosis. CONCLUSION: The expression of membranous HEG1 could serve as a favorable prognostic indicator in patients with BC treated with RC.

Expression of S100A16 Is Associated with Biological Aggressiveness and Poor Prognosis in Patients with Bladder Cancer Who Underwent Radical Cystectomy.

S100 calcium binding protein A16 (S100A16) is expressed in various cancers; however, there are few reports on S100A16 in bladder cancer (BC). We retrospectively investigated clinical data including clinicopathological features in 121 patients with BC who underwent radical cystectomy (RC). Immunohistochemical staining was performed to evaluate S100A16 expression in archived specimens. Cases with >5% expression and more than moderate staining intensity on cancer cells were considered positive. S100A16 expression was observed in 54 patients (44.6%). Univariate analysis showed that S100A16 expression was significantly associated with age, pT stage, recurrence, and cancer-specific death. Kaplan-Meier analyses showed that patients with S100A16 expression had shorter overall survival (OS), cancer-specific survival (CSS), and recurrence-free survival (RFS) than those without S100A16 expression. In multivariate analysis, pT stage was an independent prognostic factor for OS and lymph node metastasis for CSS and RFS. S100A16 expression may be a biomarker of a biologically aggressive phenotype and poor prognosis in patients with BC who underwent RC. The PI3k/Akt signaling pathway is probably associated with S100A16 and may be a therapeutic target.

Efficacy of Intravesical Instillation Therapy with Low-Dose Tokyo-172 Bacillus Calmette-Guérin to Prevent Recurrence of Non-Muscle-Invasive Bladder Cancer and Treat Carcinoma in situ: A Multi-Institutional Retrospective Study.

INTRODUCTION: There are various doses, durations, and strains of bacillus Calmette-Guérin (BCG) intravesical instillation therapy, but optimal treatment has not yet been established. We retrospectively investigated the efficacy and safety of low-dose BCG therapy for non-muscle-invasive bladder cancer (NMIBC) and carcinoma in situ (CIS) in a multicenter study. METHODS: From 1991 to 2019, 323 patients who received BCG therapy to prevent recurrence of NMIBC were analyzed as group A. Similarly, 147 patients who received BCG therapy for the treatment of CIS were analyzed as group B. Patients received low- or full-dose Tokyo-172 strain or full-dose Connaught strain, and the three strains were compared. Survival curves were estimated by the Kaplan-Meier method, and independent risk factors for intravesical recurrence were examined by multivariate logistic regression. RESULTS: Recurrence-free survival (RFS) in group A was significantly better for the Connaught strain than the low-dose Tokyo-172 strain (p = 0.026), but not between the low- and full-dose Tokyo-172 strains (p = 0.443). RFS of group B, cancer-specific survival, and progression-free survival in both groups did not show statistically significant differences. Logistic analysis of group A showed that for intravesical recurrence, only pT1 was a significant risk factor, and there were no differences between the BCG strain and dose and no significant factors in group B. There were also no differences in the completion rate in both groups, but adverse events such as urinary frequency and feeling of residual urine were significantly lower with the low-dose Tokyo-172 strain. CONCLUSION: There was no difference in efficacy between the low- and full-dose Tokyo-172 strains, but to minimize adverse events, the low-dose Tokyo-172 strain may be worth considering.

Patients with Non-Muscle-Invasive Bladder Cancer Previously Treated with Nephroureterectomy Have a High Risk of Recurrence after Bacillus Calmette-Guérin Intravesical Instillation Therapy.

BACKGROUND: There is a high incidence of intravesical recurrence after transurethral resection of bladder tumor for non-muscle-invasive bladder cancer (NMIBC). Intravesical instillation of bacillus Calmette-Guérin (BCG) is widely used to prevent recurrence and progression. There are two types of NMIBC: primary NMIBC and subsequent NMIBC after radical nephroureterectomy (RNU). We compared the clinical outcomes of BCG intravesical instillation therapy between the two types of NMIBC. PATIENTS AND METHODS: This study included a total of 357 patients, who received BCG intravesical instillation therapy to prevent recurrence of NMIBC (pTa/pT1) between 1991 and 2019. Among them, 34 patients had subsequent NMIBC after RNU, and the remaining 323 patients had primary NMIBC. This retrospective study analyzed 68 patients extracted by propensity score matching. Survival curves were estimated using the Kaplan-Meier method, and independent prognostic factors for survival were examined by the Cox proportional hazards model. RESULTS: The 3-year recurrence-free survival (RFS) rates in patients with primary NMIBC and subsequent NMIBC after RNU were 70.7% and 54.8%, respectively (p = 0.036). However, there were no significant differences between the two groups in progression-free survival and cancer-specific survival. Multivariate analysis of RFS showed that only a previous history of upper tract urothelial carcinoma was an independent prognostic and predictive factor. CONCLUSION: Patients with subsequent NMIBC after RNU treated with BCG intravesical instillation therapy have a higher risk of recurrence than those with primary NMIBC. Thus, stringent follow-up is necessary for patients with subsequent NMIBC after RNU.

A multi-institutional retrospective study of open versus laparoscopic nephroureterectomy focused on the intravesical recurrence.

AIM: Intravesical recurrence (IVR) after nephroureterectomy for upper tract urothelial carcinoma (UTUC) is relatively frequent, occurring in about 30-50% of patients. The aim of this study was to investigate the differences of the prognosis and IVR between open and laparoscopic surgery and to elucidate the risk factor of IVR. PATIENTS AND METHODS: We retrospectively analyzed data from 403 patients with UTUC treated with laparoscopic or open nephroureterectomy at six affiliated hospitals between 1990 and 2015. The clinicopathological factors of each group were examined using Kaplan-Meier plots, and univariate and multivariate analyses. RESULTS: There was no difference in recurrence and cancer-specific mortality between open and laparoscopic surgery in univariate and multivariate analyses. There was no significant difference in IVR rate between the laparoscopic and open groups (p = .22). Among the patients with IVR, 84% of patients relapsed within 2 years. Univariate analysis of IVR showed a significant increase in patients with low-grade (p = .03, HR = 1.64) or low-stage urothelial carcinoma (pT1 or lower, p = .006, HR = 1.77) with no lymph node involvement (p = .002, HR = 10.3) or lymphovascular invasion (p = .009, HR = 1.79). Surgical modality was not an independent factor. In multivariate analysis, there was no independent predictive factor for IVR. CONCLUSIONS: There was no difference in recurrence, cancer-specific mortality, and IVR between open and laparoscopic surgery. On the other hand, our results suggested that the low malignant potential tumor may be a risk factor for IVR. This finding provides insight into IVR, which may help with the development of personalized prevention and treatment strategies.

Analysis of swallowing function after anterior/posterior surgery for cervical degenerative disorders and factors related to the occurrence of postoperative dysphagia.

BACKGROUND CONTEXT: Dysphagia is one of the postoperative complications of cervical degenerative disorders. However, few studies have evaluated the pre- and postoperative swallowing function in detail. PURPOSE: To analyze pre- and postoperative swallowing dynamics kinetically and investigate factors associated with postoperative dysphagia in patients with cervical degenerative disorders. STUDY DESIGN: Retrospective review of prospectively collected data. PATIENT SAMPLE: A total of 41 consecutive patients who underwent an anterior approach (anterior cervical discectomy/corpectomy and fusion (ACDF, ACCF), hybrid surgery (ACDF+ACCF) and total disc replacement) and 44 consecutive patients who underwent a posterior approach (laminoplasty and laminoplasty/laminectomy with fusion). OUTCOME MEASURES: We compared the pre- and postoperative functional oral intake scale (FOIS), dysphagia severity scale (DSS), esophageal dysphagia, anterior/superior hyoid movement, upper esophageal sphincter (UES) opening, pharyngeal transit time, bolus residue scale (BRS), and the number of swallows. METHODS: Videofluoroscopy was performed on the day before surgery and within two weeks after surgery. Data related to age, gender, disease, surgical procedure, surgical site, operative time, and blood loss were collected from the medical records. Pre- and postoperative data were compared for each item in the anterior and posterior approaches. The odds ratio of dysphagia after an anterior approach was also calculated. RESULTS: In the anterior approach, DSS, FOIS, the anterior and superior hyoid movements, maximum UES opening, BRS, and number of swallows worsened postoperatively (p<.05, respectively). In the posterior approach, DSS, FOIS, the anterior hyoid movement, and BRS worsened postoperatively (p<.05, respectively). The factors associated with dysphagia were a proximal surgical site above C3 (OR: 14.40, CI: 2.84-73.02), blood loss >100 mL (OR: 9.60, CI: 2.06-44.74), an operative time >200 minutes (OR: 8.18, CI: 1.51-44.49), and an extensive surgical field of more than three intervertebral levels (OR: 6.72, CI: 1.50-30.07). The decline in swallowing function after the posterior approach was related to aging (p=.045). CONCLUSIONS: Each approach may decrease swallowing function, especially because of the limitation on the anterior hyoid movement. Dysphagia after anterior approaches was associated with the operative site, operative time, and blood loss.

Noninferior oncological outcomes in adults aged 80 years or older compared with younger patients who underwent radical nephroureterectomy for upper tract urothelial carcinoma.

AIM: Radical nephroureterectomy (RNU) is the gold standard treatment for upper tract urothelial carcinoma (UTUC), but the usefulness of this surgery for older patients is rarely discussed. The prognosis following RNU for patients ≥80 years old remains controversial. We retrospectively investigated the prognosis of UTUC in patients ≥80 years old who underwent RNU. METHODS: Between January 1990 and December 2015, 451 patients with UTUC underwent RNU at six hospitals affiliated with Kitasato University (Kanagawa, Japan), eight patients who underwent neoadjuvant chemotherapy and two patients with metastases before surgery were excluded. Patients were divided into three groups according to their age at the time of RNU: ≤64 years (n = 135), 65-79 years (n = 254), and ≥80 years (n = 52). Recurrence-free survival (RFS), cancer-specific survival (CSS), and overall survival (OS) curves were estimated using Kaplan-Meier analysis for all patients and each pT stage. Independent prognostic factors for survival were examined via multivariate analysis. RESULTS: RFS and CSS did not significantly differ between the three groups, but OS was significantly poorer in patients ≥80 years old. Stratification by pT stage (≤pT1, ≥pT2, and ≥pT3) yielded the same results. In the multivariate analysis for OS, an age of ≥80 years was a significant independent risk factor (hazard ratio: 3.01, p = .01), but RFS and CSS did not significantly differ. CONCLUSION: Oncological outcomes showed the same anticancer effects in patients ≥80 years old who underwent RNU for UTUC compared with those of younger patients. Our study suggests that surgical treatment is a beneficial option for older patients who can tolerate radical surgery.

Gemcitabine-Paclitaxel Chemotherapy for Patients with Advanced Urothelial Cancer Refractory to Cisplatin-Based Chemotherapy: Predictive Role of PGK1 for Treatment Response to Cytotoxic Chemotherapy.

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.

Diagnostic Potential of Circulating Tumor Cells, Urinary MicroRNA, and Urinary Cell-Free DNA for Bladder Cancer: A Review.

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.

Perforated Hydrogels Consisting of Cholesterol-Bearing Pullulan (CHP) Nanogels: A Newly Designed Scaffold for Bone Regeneration Induced by RANKL-Binding Peptides and BMP-2.

The receptor activator of NF-κB ligand (RANKL)-binding peptide, OP3-4, is known to stimulate bone morphogenetic protein (BMP)-2-induced bone formation, but peptides tend to aggregate and lose their bioactivity. Cholesterol-bearing pullulan (CHP) nanogel scaffold has been shown to prevent aggregation of peptides and to allow their sustained release and activity; however, the appropriate design of CHP nanogels to conduct local bone formation needs to be developed. In the present study, we investigated the osteoconductive capacity of a newly synthesized CHP nanogel, CHPA using OP3-4 and BMP-2. We also clarified the difference between perforated and nonperforated CHPA impregnated with the two signaling molecules. Thirty-six, five-week-old male BALB/c mice were used for the calvarial defect model. The mice were euthanized at 6 weeks postoperatively. A higher cortical bone mineral content and bone formation rate were observed in the perforated scaffold in comparison to the nonperforated scaffold, especially in the OP3-4/BMP-2 combination group. The degradation rate of scaffold material in the perforated OP3-4/BMP-2 combination group was lower than that in the nonperforated group. These data suggest that perforated CHPA nanogel could lead to local bone formation induced by OP3-4 and BMP-2 and clarified the appropriate degradation rate for inducing local bone formation when CHPA nanogels are designed to be perforated.

Impact of salvage cytotoxic chemotherapy on prognosis in patients with recurrence after radical cystectomy: a multi-institutional retrospective study.

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.

DJ-1 Expression Might Serve as a Biologic Marker in Patients with Bladder Cancer.

The overexpression of DJ-1 protein and its secretion into the bloodstream has been reported in various neoplasms. However, serum levels and the subcellular localization of DJ-1 have not been analyzed in detail in bladder cancer (BC). Our comprehensive analysis of these variables started with the measurement of DJ-1 in serum from 172 patients with BC, 20 patients with urolithiasis and 100 healthy participants. Next, an immunohistochemical study of DJ-1 expression and localization was conducted in 92 patients with BC, and associations with clinicopathologic factors and patient outcomes were evaluated. Serum DJ-1 was significantly higher in patients with BC than in those with urolithiasis or in healthy participants. Immunohistochemically, a cytoplasm-positive (Cy+) and nucleus-negative (N-) DJ-1 pattern was associated with age and pathologic stage. Log-rank tests indicated that the Cy+, N- pattern was significantly associated with overall survival (OS), recurrence-free survival (RFS), and cancer specific survival (CSS). In addition, the Cy+, N- pattern was an independent prognostic factor in the multivariate analysis adjusted for the effects of the clinicopathologic outcomes. The investigation of DJ-1 expression might help physicians to make decisions regarding further follow-up and additional treatments.

Expression of Membranous CD155 Is Associated with Aggressive Phenotypes and a Poor Prognosis in Patients with Bladder Cancer.

Objective: To investigate the relationship between clinicopathological findings and membranous CD155 (mCD155) or cytoplasmic CD155 (cCD155) expression in bladder cancer (BC). Methods: We retrospectively analyzed 103 patients with BC who underwent radical cystectomy between 1990 to 2015 at Kitasato University Hospital. Immunohistochemical staining was performed to evaluate CD155 expression in tumor cells. Cases with > 10% expression on the membrane or cytoplasm of tumor cells were positive. The Fisher's exact test was used for categorical variables and the Kaplan−Meier method was used for survival outcomes. Univariate and multivariate Cox regression hazard models were used to evaluate the survival risk factors. Results: Cases that were mCD155-positive were associated with high-grade tumors (p = 0.02), nodal status (p < 0.01), and pT stage (p = 0.04). No association with any clinicopathological factor was observed in the cCD155 cases. Kaplan−Meier analysis showed that mCD155-positive cases had shorter periods of recurrence-free survival (p = 0.015) and cancer-specific survival (p = 0.005). Only nodal status was an independent predictor for both cancer-specific survival and recurrence-free survival in multivariate analysis (p = 0.02 and p < 0.01, respectively). Conclusion: mCD155 expression may be a marker of an aggressive phenotype and a poor prognosis in patients with BC.

Serum Epiplakin Might Be a Potential Serodiagnostic Biomarker for Bladder Cancer.

Tumor markers that can be detected at an early stage are needed. Here, we evaluated the epiplakin expression levels in sera from patients with bladder cancer (BC). Using a micro-dot blot array, we evaluated epiplakin expression levels in 60 patients with BC, 20 patients with stone disease, and 28 healthy volunteers. The area under the curve (AUC) and best cut-off point were calculated using receiver-operating characteristic (ROC) analysis. Serum epiplakin levels were significantly higher in patients with BC than in those with stone disease (p = 0.0013) and in healthy volunteers (p < 0.0001). The AUC-ROC level for BC was 0.78 (95% confidence interval (CI) = 0.69-0.87). Using a cut-off point of 873, epiplakin expression levels exhibited 68.3% sensitivity and 79.2% specificity for BC. However, the serum epiplakin levels did not significantly differ by sex, age, pathological stage and grade, or urine cytology. We performed immunohistochemical staining using the same antibody on another cohort of 127 patients who underwent radical cystectomy. Univariate and multivariate analysis results showed no significant differences between epiplakin expression, clinicopathological findings, and patient prognoses. Our results showed that serum epiplakin might be a potential serodiagnostic biomarker in patients with BC.

[Clinicopathological Characteristics of Adolescent and Young-Adult Patients with Bladder Cancer].

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.

Prognostic Impact of AHNAK2 Expression in Patients Treated with Radical Cystectomy.

Data regarding expression levels of AHNAK2 in bladder cancer (BCa) have been very scarce. We retrospectively reviewed clinical data including clinicopathological features in 120 patients who underwent radical cystectomy (RC) for BCa. The expression levels of AHNAK2 in the specimens obtained by RC were classified as low expression (LE) or high expression (HE) by immunohistochemical staining. Statistical analyses were performed to compare associations between the two AHNAK2 expression patterns and the prognoses in terms of recurrence-free survival (RFS) and cancer-specific survival (CSS). A Kaplan-Meier analysis showed that patients with HE had a significantly worse RFS and CSS than those with LE (hazard ratio [HR]: 1.78, 95% confidence interval [CI]: 1.02-2.98, p = 0.027 and HR: 1.91, 95% CI: 1.08-3.38, p = 0.023, respectively). In a multivariate analysis, independent risk factors for worse RFS and CSS were shown as HE (HR: 1.96, 95% CI: 1.08-3.53, p = 0.026 and HR: 2.22, 95% CI: 1.14-4.31, p = 0.019, respectively) and lymph node metastasis (HR: 2.04, 95% CI: 1.09-3.84, p = 0.026 and HR: 1.19, 95% CI: 1.25-4.97, p = 0.009, respectively). The present study showed that AHNAK2 acts as a novel prognostic biomarker in patients with RC for BCa.

PD-L1 expression in tumor-infiltrating lymphocytes (TILs) as an independent predictor of prognosis in patients with pN0 bladder cancer undergoing radical cystectomy.

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.