Published papers

© 2018 Elsevier Inc. Purpose: Monitoring the serum level of prostate specific antigen (PSA) is indispensable for surveillance after radical therapy, and the aim of this study was to establish the optimal follow-up schedule. Materials and methods: We retrospectively reviewed the clinicopathological data of 1,010 consecutive patients who underwent radical prostatectomy. After excluding patients who received neoadjuvant or adjuvant therapy and those without a nadir PSA level<0.2 ng/ml, the remaining 779 patients were enrolled. Biochemical recurrence (BCR) was defined as elevation of PSA to >0.2 ng/ml. We investigated the PSA doubling time (PSA-DT) following BCR at various times after surgery. Results: During a mean follow-up of 8.8 years, BCR occurred in 180/779 patients. The annual BCR rate was 6% in the first year after surgery, 6% between 1 and 2 years, 3% between 2 and 3 years, 3% between 3 and 5 years, and 2% at >5 years postoperatively. During these periods, the minimum PSA-DT after BCR was 1.6, 2.4, 3.1, 6.1, and 6.4 months, respectively. These minimum PSA-DTs were used to determine the optimal follow-up interval during each period after surgery. If the baseline level is 0.1 ng/ml, PSA should be measured at approximately 3-month intervals for the first year, at 4-month intervals between 1 and 2 years, at 6-month intervals between 2 and 3 years, and annually thereafter to definitely detect BCR before the serum PSA level exceeds 0.4 ng/ml. Conclusion: The PSA-DT following BCR varies according to the time after surgery. Our data on minimum PSA-DT values after BCR are useful for setting the optimal follow-up schedule.

© Kobayashi et al. Background: We previously reported high expression of vasohibin-1 (VASH1), which is specifically expressed in activated vascular endothelial cells, was a prognostic indicator of disease progression in prostate cancer. The aim of this study was to assess whether VASH1 expression at the area of normal prostatic tissue as well as that of intratumoral tissue could reflect the grade of malignancy of prostate cancer. Results: Pathological upgrade of Gleason Score ≥7 by radical prostatectomy was observed in 48 patients (upgraded group). The median VASH1 densities of the intratumoral and normal areas were 9.7 ± 9.5 and 13.3 ± 11.8, respectively, and the median MVDs were 58.6 ± 20.3 and 64.1 ± 23.5, respectively. We detected a strong positive correlation with each other for both VASH1 density (ρ = 0.589, p < 0.001) and MVD (ρ = 0.342, p < 0.001). VASH1 density was significantly higher in the upgreaded group than in the non-upgraded group regardless of prostatic location (intratumoral area: p < 0.001, normal area: p < 0.001). Conclusions: Even if the tumor volume was low in biopsy samples, VASH1 density reflected the grade of malignancy throughout the prostate. These results suggested that VASH1 expression could be a novel microenvironmental biomarker for patient risk reclassification in low-risk prostate cancer. Materials and Methods: Among the 1177 patients who underwent radical prostatectomy, 104 patients diagnosed with Gleason Score ≤6 and positive cores ≤3 were included. We immunohistochemically examined the microvessels positive for anti-CD34 as microvessel density (MVD), and those with activated endothelial cells as VASH1 density using prostatic biopsy samples, and evaluated the association between their expressions and clinicopathological findings.

© 2018, Society of Surgical Oncology. Background: The programmed cell death-1 (PD-1) pathway has been suggested to play an important role in tumor immune escape. We evaluated changes in PD-1 expression before and after Bacillus Calmette–Guérin (BCG) therapy and its prognostic significance in non-muscle-invasive bladder cancer (NMIBC) patients. Methods: We examined 78 paired tissue samples of NMIBC in tumors just before BCG therapy and BCG-relapsing tumors, defined as recurrence after achieving disease-free status by initial BCG instillations for 6 months. We counted PD-1-positive cells, and PD-1 expression was defined as high when the number of PD-1-positive cells was more than 18 under ×200 magnification. Results: The median number of PD-1-positive cells in tumors just before BCG therapy was 3.5, significantly lower than that in BCG-relapsing tumors (17.0, p < 0.001). High PD-1 expression was observed in 20 tumors just before BCG therapy (25.6%) and 36 BCG-relapsing tumors (46.2%). Fifty-two cases (66.6%) showed an increase in the number of PD-1-positive cells in BCG-relapsing tumors. High PD-1 expression in BCG-relapsing tumors was independently associated with subsequent tumor recurrence (p = 0.011) and stage progression (p = 0.033). The 5-year recurrence-free and progression-free survival rates were 40.7 and 74.1% in patients with high PD-1 expression in BCG-relapsing tumors, significantly lower than those in their counterparts (72.9 and 94.1%, respectively). Conclusions: PD-1 was induced by BCG therapy, and its expression in BCG-relapsing tumors may be an important indicator for predicting worse clinical outcomes in NMIBC patients treated with BCG therapy.

© 2018 Elsevier Inc. Purpose: It is still unknown whether switching the bacillus Calmette-Guérin (BCG) strain at the second induction course of BCG therapy has a therapeutic benefit in patients with tumor recurrence after the initial BCG therapy (BCG-relapsing tumor). Materials and methods: We retrospectively reviewed the clinicopathological features of 97 patients treated with a second induction course of BCG therapy between 1986 and 2014. Among the patients initially treated with BCG Tokyo-172, the second course was either BCG Tokyo-172 in 56 (57.8%) or BCG Connaught in 15 (15.5%). Among those who were initially treated with BCG Connaught, the corresponding numbers were 13 (13.4%) or 13 (13.4%), respectively. Twenty-eight (28.9%) patients were given a different BCG strain at the 2 BCG therapies (switching group), and 69 (71.1%) patients were given the same BCG strain (non-switching group). Result: The 5-year recurrence-free survival rate of the switching group was 64.7 ± 9.6%, which was not significantly different from that of the non-switching group (54.8 ± 6.9%, P = 0.427). Switching or not switching the BCG strain was not significantly associated with tumor recurrence after the second BCG therapy. The 5-year progression-free survival rate of the switching group was 95.4 ± 2.6%, which was also not significantly different from that of the non-switching group (96.0 ± 3.9%, P = 0.674). Patients treated with BCG Tokyo-172 to Tokyo-172 had significantly higher incidences of side effects during the second BCG therapy. Conclusions: The results of this study indicate that in patients with a BCG-relapsing tumor after the initial BCG therapy, the same BCG strain as that administered at the initial BCG therapy could be utilized effectively for the second BCG therapy. Patients treated with BCG Tokyo-172 for an initial tumor had a higher incidence of side effects during the second BCG therapy using the same strain.

© 2018 Dustri-Verlag Dr. K. Feistle. Introduction: To evaluate nephrostomy catheter displacement, we assessed the cumulative nephrostomy catheter displacement rate in patients with percutaneous nephrostomy and compared the nephrostomy displacement rates between pigtail and balloon catheters. Materials and methods: Between 2003 and 2011, 87 patients who underwent percutaneous nephrostomy catheter placement and more than one subsequent catheter replacement were retrospectively identified. We evaluated their inadvertent nephrostomy catheter displacement. Results: 20 patients (23.0%) experienced incidental nephrostomy catheter displacement during the follow-up period. Kaplan-Meier analysis revealed that the 1-year nephrostomy catheter displacement-free survival rate was 62 ± 9%. No significant independent risk factors for predicting nephrostomy catheter displacement were identified, including the type of catheter. The median time from initial placement to displacement of pigtail catheters was shorter than that of balloon catheters. Conclusion: There were no significant differences in the nephrostomy catheter displacement-free survival rates between the two types of catheters. Regardless of the type of catheter, our results indicated that careful handling and guiding during catheter placement are important for all patients because of the high risk of inadvertent events.

© 2018 Elsevier Inc. Because accumulating evidence underlines the association of systemic inflammation with metastatic renal-cell carcinoma (mRCC) progression, we evaluated baseline C-reactive protein (CRP) levels as a prognostic marker in 107 intermediate-risk mRCC patients treated with first-line targeted therapy. Baseline CRP could be a biomarker correlated with overall survival in the intermediate-risk group. Its cost efficacy and availability make CRP a helpful tool for reclassifying the intermediate-risk group. Background: Almost half of patients with metastatic renal-cell carcinoma (mRCC) are classified as intermediate risk by the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) model. The aim of this study was to evaluate whether baseline C-reactive protein (CRP) levels predict overall survival (OS) in intermediate-risk group mRCC patients. Patients and Methods: Data from 107 intermediate-risk group mRCC patients receiving first-line targeted therapy were retrospectively reviewed. We evaluated the correlation between baseline CRP levels as well as other indices and OS. Results: Of the 107 patients with intermediate-risk disease, 46 patients (43%) were classified as having elevated CRP levels. The elevation of pretreatment serum CRP levels was the independent prognostic factor of OS in patients with intermediate risk (hazard ratio, 4.609; P =.001). The 1- and 3-year survival rates of patients with intermediate–nonelevated CRP were 90.0% and 64.7% compared to the favorable-risk group, at 92.1% and 68.5%, respectively. In contrast, the 1- and 3-year survival rates of patients with intermediate–elevated CRP were 80.5% and 37.4% compared to the poor-risk group, at 65.2% and 24.2%, respectively. Conclusion: Baseline CRP levels could divide mRCC patients in the intermediate-risk group into 2 prognostic subgroups.

© 2018 Elsevier Inc. In an investigation of the relationship between albumin-to-globulin ratio (AGR) and oncologic outcomes in 364 non–muscle-invasive bladder cancer (NMIBC) patients, those with AGR < 1.6 had significantly poorer recurrence-free and progression-free survival than those with AGR ≥ 1.6. Multivariate analysis revealed that AGR < 1.6 is significantly associated with tumor recurrence. Low AGR is an independent risk factor for recurrence in NMIBC patients. Purpose: To investigate the relationship between albumin-to-globulin ratio (AGR) and oncologic outcomes in patients with non–muscle-invasive bladder cancer (NMIBC). Patients and Methods: We identified 364 patients with primary NMIBC who underwent transurethral surgery between 2000 and 2015. The association between pretreatment AGR and clinicopathologic variables, including oncologic outcomes, was statistically evaluated. Results: One hundred twenty patients (33.0%) experienced at least one tumor recurrence, and 23 (6.3%) developed muscle-invasive disease. The median (interquartile range) pretreatment AGR was 1.73 (1.53-1.89). The Kaplan-Meier curve revealed that tumor recurrence was strongly predicted in patients with pretreatment AGR < 1.6, and similar results were observed for disease progression (P <.01 and P <.01, respectively). On multivariate analysis, we found that pretreatment AGR < 1.6 is an independent risk factor for tumor recurrence (hazard ratio, 0.53; P <.01). On univariate analysis, pretreatment AGR < 1.6 was also associated with disease progression (hazard ratio, 0.24; P <.01). Conclusion: Low pretreatment AGR is an independent risk factor for tumor recurrence and is one risk factor for disease progression in NMIBC patients. This inexpensive and easily accessible biomarker may become useful in selecting patients with NMIBC with higher risk of recurrence and progression.

© 2018 American Urological Association Education and Research, Inc. Purpose: We investigated the clinical impact of the purified protein derivative skin test prior to bacillus Calmette-Guérin therapy in patients with nonmuscle invasive bladder cancer treated with adjuvant bacillus Calmette-Guérin therapy. Materials and Methods: A total of 498 patients with nonmuscle invasive bladder cancer treated with adjuvant bacillus Calmette-Guérin were included in study, of whom 320 underwent the purified protein derivative skin test 1 to 2 weeks prior to therapy. Oncologic outcomes and the rate of bacillus Calmette-Guérin related side effects were statistically evaluated. Results: The mean ± SD 5-year recurrence-free survival rate in patients who did vs did not undergo the purified protein derivative skin test was 66.6% ± 2.8% and 59.1% ± 4.1%, respectively, which was significantly different (p = 0.048). No significant difference was observed in the progression-free survival rate between patients who did vs did not undergo the test. Multivariate Cox regression analysis revealed that a history of recurrence (HR 1.59, p = 0.02), multiple tumors (HR 1.95, p <0.01), the bacillus Calmette-Guérin Connaught strain (HR 0.71, p = 0.04), 7 or more bacillus Calmette-Guérin instillations (HR 0.70, p = 0.04) and undergoing the purified protein derivative skin test (HR 0.72, p = 0.04) were independently associated with tumor recurrence. Major bacillus Calmette-Guérin related side effects were noted in 77 of the 320 patients (24.1%) who did vs 27 of the 178 (15.2%) who did not undergo the test, which was significantly different (p = 0.02). Conclusions: The purified protein derivative skin test prior to bacillus Calmette-Guérin treatment enhances the therapeutic effects of this treatment and potentially results in a higher incidence of major bacillus Calmette-Guérin related side effects. Combination therapy with bacillus Calmette-Guérin using the purified protein derivative skin test may improve the oncologic outcomes of that therapy.