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Nivolumab plus ipilimumab (NIVO+IPI) has a long-term response rate of 30% for patients with metastatic renal cell carcinoma (mRCC). However, 20% of patients develop primary resistant disease (PRD) to NIVO+IPI and show poor survival outcomes. In this study, we aimed to evaluate the effect of PRD as a second-line treatment in patients with mRCC. The data used in this multi-institutional, retrospective cohort were collected between August 2015 and January 2023. In total, 189 patients with mRCC were treated with NIVO+IPI and then with a vascular endothelial growth factor receptor-tyrosine kinase inhibitor. Associations between PRD and progression-free survival of second-line treatment (PFS), progression-free survival 2 (PFS2), and overall survival (OS) were analyzed. The median age at NIVO+IPI initiation was 67 years in the male-dominant population (n = 140, 74.1%), and most patients had clear cell histology (n = 140, 74.1%). PRD was recorded in 42 (22.2%) of 189 patients during NIVO+IPI therapy. Patients who experienced PRD showed poor PFS (hazard ratio [HR], 1.788; 95% confidence interval [CI], 1.176-2.718; p = 0.007), PFS2 (HR, 4.127; 95% CI, 2.649-6.431; p < 0.001), and OS (HR, 3.330; 95% CI, 2.040-5.437; p < 0.001). Before starting second-line therapy, patients with PRD tended to have a poor performance status compared with non-PRD patients and a higher IMDC risk. Second-line drug therapy was not associated with treatment outcomes in patients with PRD. PRD in patients with mRCC receiving NIVO+IPI as first-line treatment was associated with poor clinical course, even with second-line therapy., (© 2024 The Author(s). Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

Objectives: This study aimed to assess the prognostic outcomes in mRCC patients receiving second-line TKI following first-line IO combination therapy., Methods: This study retrospectively included 243 mRCC patients receiving second-line TKI after first-line IO combination therapy: nivolumab plus ipilimumab (n = 189, IO-IO group) and either pembrolizumab plus axitinib or avelumab plus axitinib (n = 54, IO-TKI group). Oncological outcomes between the two groups were compared, and prognostication systems were developed for these patients., Results: In the IO-IO and IO-TKI groups, the objective response rates to second-line TKI were 34.4% and 25.9% (p = 0.26), the median PFS periods were 9.7 and 7.1 months (p = 0.79), and the median OS periods after the introduction of second-line TKI were 23.1 and 33.5 months (p = 0.93), respectively. Among the several factors examined, non-CCRCC, high CRP, and low albumin levels were identified as independent predictors of both poor PFS and OS by multivariate analyses. It was possible to precisely classify the patients into 3 risk groups regarding both PFS and OS according to the positive numbers of the independent prognostic factors. Furthermore, the c-indices of this study were superior to those of previous systems as follows: 0.75, 0.64, and 0.61 for PFS prediction and 0.76, 0.70, and 0.65 for OS prediction by the present, IMDC, and MSKCC systems, respectively., Conclusions: There were no significant differences in the prognostic outcomes after introducing second-line TKI between the IO-IO and IO-TKI groups, and the histopathology, CRP and albumin levels had independent impacts on the prognosis in mRCC patients receiving second-line TKI, irrespective of first-line IO combination therapies., (© 2024 The Japanese Urological Association.)

Immuno-oncology (IO) combination therapy is utilized as a first-line systemic treatment for advanced renal cell carcinoma. However, evidence supporting the use of cabozantinib after IO combination therapy is lacking. We retrospectively analyzed patients who received second-line cabozantinib after IO combination therapy using the Japanese Urological Oncology Group (JUOG) database. In total, 254 patients were enrolled in the JUOG global study, and 118 patients who received second-line cabozantinib comprised the study cohort. The objective response rate, disease control rate, second-line cabozantinib progression-free survival (PFS), and overall survival from second-line for overall were 32%, 75%, 10.5 months, and not reached, respectively, for first-line IO-IO therapy were 37%, 77%, 11.1 months, and not reached, respectively, versus 24%, 71%, 8.3 months, and not reached, respectively, for first-line IO-tyrosine kinase inhibitor therapy. In univariate and multivariate analyses, discontinuation of first-line treatment because of progressive disease and liver metastasis were independent risk factors for PFS. All-grade adverse events occurred in 72% of patients, and grade 3 or higher adverse events occurred in 28% of patients. Second line-cabozantinib after first-line IO combination therapy for advanced renal cell carcinoma was expected to be effective after either IO-IO or IO-TKI treatment and feasible in real-world practice., (© 2023. The Author(s).)

Background: The aim of this study was to investigate the prognostic significance of multiple preoperative laboratory abnormalities in upper urinary tract urothelial carcinoma (UUTUC) patients., Methods: This study included a total of 135 consecutive patients with clinically localized UUTUC who underwent radical nephroureterectomy (RNU). The impact of several preoperative blood-based markers in addition to conventional clinical factors on extravesical recurrence-free survival (eRFS) in these patients was retrospectively evaluated., Results: Despite the lack of a significant correlation between conventional clinical factors and any of the postoperative pathologic parameters, preoperative laboratory abnormalities were shown to have a significant impact on some pathological factors reflecting an aggressive phenotype as follows-C-reactive protein (CRP) level on pathological stage, De Ritis (aspartate transaminase/alanine transaminase) ratio on nodal involvement, and neutrophil-lymphocyte ratio (NLR) on pathological stage. During the observation period of this study (median 36.1 months), extravesical disease recurrence was detected in 44 (32.6%) of the 135 patients with a 5-year eRFS rate of 62.1%. Of several factors examined, the CRP level, De Ritis ratio, and NRL were significantly correlated with eRFS on univariate analysis. Of these significant factors, the De Ritis ratio and NRL were identified as independent predictors of eRFS on multivariate analysis. Moreover, there were significant differences in eRFS according to the positive numbers of these two independent risk factors., Conclusions: These findings suggest that it is important to consider laboratory abnormalities, particularly the De Ritis ratio and NLR, to predict disease recurrence following RNU in patients with clinically localized UUTUC.

Objectives: To evaluate the impact of metabolic syndrome on the early recovery of urinary continence after robot-assisted radical prostatectomy., Methods: The present study included a total of 302 consecutive Japanese patients with clinically localized prostate cancer who underwent robot-assisted radical prostatectomy. In this study, postoperative urinary continence was defined as no leak or the use of a security pad. The continence status was assessed by interviews before and 1 and 3 months after robot-assisted radical prostatectomy. Metabolic syndrome was defined as follows: body mass index ≥25 kg/m 2 and two or more of the following: hypertension, diabetes mellitus and dyslipidemia. The effect of the presence of metabolic syndrome on the continence status of these patients was retrospectively examined., Results: A total of 116 (38.4%) and 203 (67.2%) of the 302 patients were continent at 1 and 3 months after robot-assisted radical prostatectomy, respectively. A total of 31 (10.3%) patients were judged to have metabolic syndrome. Despite the operative time being longer in patients with metabolic syndrome, no significant differences were observed in the remaining preoperative, intraoperative or postoperative variables between patients with or without metabolic syndrome. On multivariate logistic regression analysis, metabolic syndrome and the duration of hospitalization were significantly correlated with the 1-month continence status. Similarly, metabolic syndrome and estimated blood loss during surgery were independent predictors of continence rates at 3 months after robot-assisted radical prostatectomy., Conclusions: These findings suggest that the presence of metabolic syndrome could have a significant impact on the early recovery of urinary continence after robot-assisted radical prostatectomy., (© 2017 The Japanese Urological Association.)

Objective: To develop a Web-based audiovisual telementoring system for robot-assisted radical prostatectomy (RARP) and to assess the utility of this system., Methods: A telementoring system for RARP, consisting of a 3-dimensional high-definition view of the operating field, overview of the operating room, annotation function, and 2-channel audio feed with bidirectional connectivity between 2 institutions, was developed. The outcome of RARP performed for the initial 30 patients by 2 surgeons with telementoring was compared with that for 2 surgeons who received direct mentoring., Results: This system was shown to function properly with an acceptable latency. There were no significant differences in several parameters reflecting surgical outcomes, including the operating time, complication rate, early continence status, and positive margin rate between the telementoring and direct mentoring groups., Conclusion: These findings suggest the usefulness of the telementoring system for promoting the spread of precise surgical techniques associated with RARP. To our knowledge, this is the first report concerning telementoring for robot-assisted surgery., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Malignant mesothelioma of the tunica vaginalis is rare, and is usually not diagnosed until surgery is undertaken. We report here a case in a 62-year-old man with malignant mesothelioma tunica vaginalis testis. He was referred to our hospital with a painless swelling of the left scrotal contents. There is a thickening of mesothelia of the tunica vaginalis with left sided hydrocele by ultrasonography and computed tomography scan. The tumor was resected under the diagnosis of testicular malignant tumor. However, the pathologist reported malignant mesothelioma and positive margin. He received external beam radiation therapy at a total dose of 44 Gy. Disease progression was not apparent 2 years after treatment. To our knowledge, 26 cases of malignant mesothelioma in the perineum or intrascrotum have been reported in Japan and this case is thought to be the 27th case in Japan.

Objectives: To compare the accuracy to diagnose micrometastases to pelvic lymph nodes (LNs) in patients undergoing radical prostatectomy (RP) by real-time reverse transcriptase-polymerase chain reaction (RT-PCR) targeting several genes specifically expressed in the prostate., Materials and Methods: Expression of prostate-specific antigen (PSA), prostate-specific membrane antigen (PSMA), human kallikrein 2 (hK2), prostate stem cell antigen (PSCA), and differential display code 3 (DD3) in 2215 LNs isolated from 120 patients with localized prostate cancer were assessed by fully quantitative real-time RT-PCR., Results: In addition to pathologically diagnosed LN metastases in 11 patients, real-time RT-PCR targeting PSA, PSMA, hK2, PSCA, and DD3 further identified micrometastases in 23, 29, 31, 15, and 11, respectively. In this series, biochemical recurrence (BR) occurred in 32 patients, of whom 25, 22, 28, 10, and 9 were diagnosed as having micrometastases by real-time RT-PCR targeting PSA, PSMA, hK2, PSCA, and DD3, respectively. Univariate analysis identified pathologic stage, pathologic LN metastases, Gleason score, surgical margin status, and micrometastases detected by real-time RT-PCR targeting PSA, PSMA, hK2, and their combinations as significant predictors for BR-free survival (BRFS), of which only surgical margin status and micrometastases detected by real-time RT-PCR targeting PSA and hK2 appeared to be independently associated with BRFS on multivariate analysis., Conclusions: Of PSA, PSMA, hK2, PSCA, DD3, and their combinations, combined analysis of PSA and/or hK2 expression in pelvic LNs by real-time RT-PCR could provide findings most precisely predicting BRFS following RP., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Intravascular large B-cell lymphoma (IVLBCL) is a rare subtype of malignant lymphoma. Although the involvement of adrenal glands in IVLBCL is often observed, primary adrenal IVLBCL is rare. Most reported cases of adrenal IVLBCL showed bilateral lesions resulting in rapidly progressive adrenal failure and poor prognosis. Here, we report a case of slowly progressive primary adrenal IVLBCL manifesting initially with unilateral adrenal incidentaloma. This case is a silent IVLBCL and shows that the enlargement of both adrenal glands can be followed.

Before the advent of molecular-targeted agents, immunotherapy using cytokines, such as interferon-α (IFN-α) and interleukin-2 (IL-2), had been the mainstay of treatment for patients with metastatic renal cell carcinoma (mRCC), and this therapy may still be occasionally recommended for such patients. In this report, we present two cases of mRCC who were treated with very-low-dose IL-2 therapy and subsequently achieved complete response (CR). Both cases received adjuvant IFN-α therapy following radical nephrectomy; however, multiple lung metastases developed 4 and 12 months after surgery, and low-dose IL-2 (0.7 million U/day) was then administered twice per week for 14 and 35 months, respectively. In both cases, metastatic lesions completely regressed 3 and 20 months after the start of IL-2 therapy, and these responses have persisted for 81 and 67 months, respectively, to date. These findings suggest that immunotherapy with IL-2, even at a very-low-dose setting, may achieve the induction of CR in mRCC; accordingly, IL-2-based immunotherapy should be considered as the initial treatment for appropriately selected patients with mRCC.

A 60-year-old man presented with drug-resistant hypertension with hypokalemia, a high plasma aldosterone concentration (PAC) and suppressed plasma rennin activity (PRA). Imaging examinations showed multiple macronodules in the left adrenal gland. Endocrinological findings demonstrated autonomous aldosterone secretion and (131)I-adosterol scintigraphy demonstrated a left sided uptake. Laparoscopic left adrenalectomy normalized serum potassium levels and PAC, and substantially improved hypertension. Pathological and immunohistochemical analysis demonstrated that these nodules were positive for 3β-hydroxysteroid dehydrogenase (HSD3B) but not for CYP17. In addition, zona glomerulosa demonstrated "paradoxical hyperplasia", in which these cells were negative for HSD3B. All of these data indicated that the nodules in the left adrenal gland were mainly responsible for the autonomous aldosterone secretion. We conclude that the primary aldosteronism in this case was caused by multiple macronodules. This is a very rare case of primary aldosteronism caused by multiple adrenocortical macronodules.

Objective: To characterize the impact of sorafenib treatment on health-related quality of life (HRQL) in Japanese patients with mRCC., Patients and Methods: We performed a prospective observational study including 85 consecutive patients undergoing radical nephrectomy who were diagnosed as having mRCC refractory to cytokine therapy and subsequently treated with sorafenib for at least 3 months. HRQL in these patients was assessed using the Medical Outcomes Study 36-Item Short Form (SF-36)., Results: Before treatment all eight scores in the 85 patients were significantly inferior to those in the age-matched control population in Japan. Three months after sorafenib treatment, one score (mental health) in the 85 patients was significantly higher than what it was before treatment. Three scores (body pain, role limitations because of emotional problems, mental health) in patients who had some degree of tumour shrinkage were significantly better than those in the remaining patients, while there were no significant differences in all but one score (social function) between patients with and without severe AEs. Furthermore, there were no significant differences in any scores 3, 6 and 12 months after sorafenib treatment in 26 patients who could be followed for at least 12 months., Conclusions: Despite non-randomized study including a comparatively small number of patients, the findings of the present study suggest that sorafenib treatment may not impair HRQL in patients with mRCC, and HRQL in patients receiving sorafenib is likely to be affected by the efficacy rather than AEs during treatment., (© 2010 THE AUTHORS. JOURNAL COMPILATION © 2010 BJU INTERNATIONAL.)

The objective of this study was to characterize features of thyroid dysfunction in Japanese patients with metastatic renal cell carcinoma (RCC) who were treated with sorafenib. We performed a prospective observational study including 69 Japanese patients who were diagnosed as having metastatic RCC refractory to cytokine therapy and subsequently treated with sorafenib for at least 12 weeks. Thyroid function was assessed before and every 4 weeks after the initiation of sorafenib treatment. Of the 69 patients, 23 (33.3%) did not show any biochemical thyroid abnormality, while the remaining 46 (67.7%) developed hypothyroidism. However, 11 (23.9%) of these 46 hypothyroid patients initially had a suppressed thyroid-stimulating hormone (TSH) value accompanying the increase in free triiodothyronine (T3) and/or free thyroxine (T4) before developing hypothyroidism, suggesting sorafenib-induced thyroiditis. During the observation period of this study, 4 patients (5.8%) demonstrated severe clinical symptoms caused by hypothyroidism and received thyroid hormone replacement. Among several factors examined, only age was significantly associated with the risk for hypothyroidism. These findings suggest that although the incidence of clinically significant hypothyroidism requiring thyroid hormone replacement therapy was not very high, biochemical thyroid abnormality was frequently observed in Japanese RCC patients treated with sorafenib. Accordingly, regular surveillance of thyroid function by the measurement of TSH, free T3, and T4 is warranted during sorafenib treatment in Japanese RCC patients., (Copyright (c) 2010 Elsevier Inc. All rights reserved.)

Objectives: To characterize the anatomical extension pattern of prostate cancer arising in the peripheral zone (PZ) in radical prostatectomy (RP) specimens and to evaluate its prognostic significance., Patients and Methods: Of 174 consecutive patients undergoing RP, 128 diagnosed as having PZ cancer (PZC) were enrolled. The maximum tumour area (MTA) and maximum tumour volume (MTV) in RP specimens were measured using digital planimetry. A circle with an area equal to the MTA, in which the central point was the intersection of the longest line of the MTA and the line perpendicularly bisecting the first line, was defined as a hypothetical extension area, regardless of anatomical structure. The area within this circle that did not overlap the MTA was defined as DeltaTA., Results: There was a significant correlation between the MTV and DeltaTA/MTA, introduced as a variable representing the degree of PZC extension along the anatomical shape of the PZ. The DeltaTA/MTA in patients with a MTV of >5 mL was significantly greater than that in those with a MTV of < or = 5 mL. Furthermore, DeltaTA/MTA was significantly associated with several prognostic indicators, including extracapsular extension, surgical margin status and perineural invasion. Multivariate analysis identified DeltaTA/MTA in addition to preoperative serum prostate-specific antigen level, extracapsular extension and surgical margin status as independent predictors of biochemical recurrence after RP., Conclusions: PZC tends to extend along the anatomical shape of the PZ during progression, resulting in higher DeltaTA/MTA value in advanced PZC than that in early PZC.

Objectives: The objective of this study was to investigate and characterize the clinicopathological features of incidentally detected prostate cancer in radical cystoprostatectomy specimens from Japanese men with bladder cancer., Materials and Methods: We reviewed the pathological reports of 251 male patients who underwent radical cystoprostatectomy for bladder cancer at our institution and identified men with incidentally detected prostate cancer in these specimens. Clinicopathological data of patients with incidental prostate cancer in cystoprostatectomy specimens (group A) were compared with those of 193 patients with clinically detected prostate cancer who underwent radical prostatectomy (group B). Immunohistochemical staining was also performed to measure the expression levels of Ki-67, p53 and androgen receptor (AR) proteins in specimens from both groups A and B., Results: In this series, a total of 31 patients (12.3%; group A) were incidentally diagnosed as having prostate cancer in radical cystoprostatectomy specimens. Clinically significant cancer, defined as any tumor greater than 0.5 cc according to the report by Stamy et al. (Cancer 71:933-938, 1993) was detected in 9 (29.0%) in group A and 170 (88.1%) in group B. Mean age in group A was significantly older than that in group B, while despite the lack of significant difference in the incidence of seminal vesicle invasion between these two groups, other parameters in group A were significantly more favorable than those in group B, including serum prostate-specific antigen, pathological stage, Gleason score, perineural invasion and capsular penetration. None of the patients in group A had biochemical recurrence (median observation period, 82 months); however, biochemical recurrence occurred in 41 (21.2%) in group B (median observation period, 46 months). Furthermore, immunohistochemical study demonstrated the significantly greater expression of Ki-67, p53 and AR proteins in group B than in group A., Conclusions: Clinicopathological features of incidentally detected prostate cancer are markedly more favorable than those of clinically detected prostate cancer, which may reflect less aggressive biological phenotypes of incidental prostate cancer arising in Japanese men.

The objective of this study was to evaluate the expression levels of multiple potential molecular markers in prostate cancer to clarify the significance of these markers as prognostic indicators in patients undergoing radical prostatectomy (RP). This study included a total of 193 patients with clinically organ-confined prostate cancer who underwent RP without any neoadjuvant therapies. Expression levels of 12 proteins, including Ki-67, p53, androgen receptor (AR), matrix metalloproteinase (MMP)-2, MMP-9, vascular endothelial growth factor, Aurora-A, Bcl-2, clusterin, heat shock protein 27 (HSP27), HSP70, and HSP90, in RP specimens obtained from these 193 patients were measured by immunohistochemical staining. Of the 12 molecules, Ki-67, p53, AR, MMP-2, MMP-9, and HSP27 expression were significantly associated with several conventional prognostic factors. Univariate analysis identified these 6 markers as significant predictors for biochemical recurrence as well, while prostate-specific antigen, Gleason score, seminal vesicle invasion (SVI), surgical margin status (SMS), lymph node metastasis, and tumor volume were also significant. Of these significant factors, Ki-67 expression, SVI, and SMS appeared to be independently related to biochemical recurrence by multivariate analysis. Furthermore, there were significant differences in biochemical recurrence-free survival according to positive numbers of these three independent risk factors. These findings suggest that consideration of expression levels of potential molecular markers in RP specimens, in addition to conventional prognostic parameters, would contribute to accurate prediction of biochemical recurrence following RP in patients with clinically localized prostate cancer, and that combined evaluation of Ki-67 expression, SVI, and SMS would be particularly useful for further refinement of the system in predicting biochemical outcome., (Copyright 2010 Elsevier Inc. All rights reserved.)

Objectives: To assess whether the serum level of clusterin and its density could be used as novel biomarkers of prostate cancer., Methods: Sera were obtained from 380 patients with prostate cancer and 120 with benign prostatic hyperplasia. Serum clusterin level was measured by a sandwich enzyme immunoassay, and clusterin density, which was determined by dividing the serum clusterin level by the prostate volume, was also calculated. These findings were analyzed with respect to several clinicopathologic factors., Results: The mean serum level of clusterin in prostate cancer patients was significantly higher than that in the benign prostatic hyperplasia group. Both the serum clusterin level and clusterin density in prostate cancer patients were significantly associated with major prognostic factors other than biopsy Gleason score. Of the 380 prostate cancer patients, 162 underwent radical prostatectomy and pelvic lymphadenectomy, and 104 and 58 were diagnosed as having organ-confined and extraprostatic diseases, respectively. The clusterin density in patients with organ-confined disease was significantly higher than that in patients with extraprostatic disease; however, there was no significant difference in the serum clusterin level between these 2 groups. Furthermore, biochemical recurrence-free survival in patients with elevated clusterin density was significantly lower than that in patients with normal density., Conclusions: These findings suggest that serum clusterin level and its density could serve as a useful practical adjuncts to conventional parameters for estimating the extension of prostate cancer., (2010 Elsevier Inc. All rights reserved.)

The objective of this study was to retrospectively investigate clinical outcomes of combined immunotherapy with interferon-alpha (IFN-alpha) and low-dose interleukin-2 (IL-2) in Japanese patients with metastatic renal cell carcinoma (RCC). This study included a total of 52 patients with metastatic RCC who were treated by combined immunotherapy with IFN-alpha and low-dose IL-2 following radical nephrectomy. These patients received a subcutaneous injection of IFN-alpha (5 to 6 million U/d) three times per week and intravenous injection of IL-2 (1.4 million U/d) twice per week. Tumor response was evaluated every 16 weeks, and as a rule, this weekly regimen was repeated 50 times in patients with evidence of objective response or stable disease. In this series, complete response and partial response were achieved in 1 and 11 patients, respectively; however, the remaining 20 and 20 patients were diagnosed as showing stable disease and progressive disease, respectively. Of several parameters examined, presence of metastases at diagnosis and C-reactive protein (CRP) level were significantly associated with response to this combined therapy. The 1-, 3-, and 5-year cancer-specific survival rates of these 52 patients were 80.4%, 51.7%, and 38.8%, respectively. Furthermore, cancer-specific survival was significantly associated with performance status, presence of metastases at diagnosis, metastatic organ and CRP level on univariate analysis; however, only performance status and presence of metastases at diagnosis appeared to be independent predictors of cancer-specific death by multivariate analysis. Toxicities related to this therapy were generally mild and tolerable, limited to World Health Organization (WHO) grade 1 or 2 in the majority of patients. Collectively, these findings suggest that combined immunotherapy with IFN-alpha and low-dose IL-2 could achieve comparatively acceptable oncological outcomes in patients with metastatic RCC; however, other therapeutic options should be considered in patients with unfavorable performance status and/or those positive for metastatic diseases at diagnosis.

Objectives: To evaluate the expression levels of multiple molecular markers in radical nephrectomy specimens from patients with metastatic renal cell carcinoma (RCC) who received combined immunotherapy with interferon-alpha (IFN-alpha) and low-dose interleukin-2 (IL-2) and to identify factors predicting susceptibility to this therapy., Methods: This study included 40 patients with metastatic clear cell RCC undergoing combined immunotherapy with IFN-alpha and low-dose IL-2 following radical nephrectomy. Expression levels of 10 markers, including Aurora-A, Bcl-2, clusterin, heat shock protein 27, heat shock protein 90, Ki-67, matrix metalloproteinase-2, matrix metalloproteinase-9, p53 and vascular endothelial growth factor, in RCC specimens were measured using immunohistochemical staining., Results: In this series, one, 10, 15 and 16 patients were diagnosed as showing complete response, partial response, stable disease and progressive disease, respectively. Expression levels of Bcl-2 and Ki-67 had significant impacts on the response to this therapy. Furthermore, cancer-specific survival was significantly associated with the expression levels of Ki-67 and Bcl-2 in addition to performance status, presence of metastases at diagnosis, metastatic organ and C-reactive protein on univariate analysis. Only the presence of metastases at diagnosis and Ki-67 expression level appeared to be independent predictors of cancer-specific survival on multivariate analysis., Conclusions: It would be useful to consider the expression levels of potential molecular markers, particularly Ki-67, in addition to clinical parameters, such as the presence of metastases at diagnosis, to select metastatic RCC patients likely to benefit from combined immunotherapy.

Objective: To compare the voiding status in elderly patients (aged >or=80 years) with that in younger patients undergoing orthotopic neobladder substitution during long-term survival., Patients and Methods: The voiding status was assessed in 111 patients (ileal neobladder in 62, ascending colonic neobladder in 14, sigmoid colonic neobladder in 21 and ileocolonic neobladder in 14) who lived for >5 years after radical cystectomy with an orthotopic neobladder, using a self-completed questionnaire and uroflowmetry. According to the age at the time of these assessments, patients were divided into two groups (group 1, <80 years, 94; group 2, >or=80 years, 17). The voiding status was compared between the groups., Results: In all, 78 patients (92%) in group 1 and 16 (94%) in group 2 were capable of spontaneous voiding. In group 1 and 2, respectively, daytime continence was achieved by 67 (74%) and 12 (75%) patients, but night-time continence was achieved by 54 (60%) and six (38%), although the difference was not statistically significant. In groups 1 and 2, respectively, the median maximum flow rate was 13.3 and 11.7 mL/s and the median postvoid residual urine volume was 19 and 18 mL. The only statistically significant difference was for voiding posture, assessed in men., Conclusions: There was no significant difference in voiding status of patients with orthotopic neobladders except for voiding posture between patients aged <80 or carefully selected elderly patients aged >or=80 years during long-term survival. However, night-time continence might be clinically worse in the elderly than in the younger group.

Objective: To compare the usefulness between real-time reverse transcriptase polymerase chain reaction (RT-PCR) with that of conventional RT-PCR for detecting micrometastases in pelvic lymph nodes (PLN) dissected during radical prostatectomy (RP) for prostate cancer., Patients and Methods: In all, 120 patients with clinically localized prostate cancer who underwent RP and pelvic lymphadenectomy were included. Expression of prostate-specific antigen (PSA) and prostate-specific membrane antigen (PSMA) in 2215 PLNs obtained from these 120 patients were assessed by fully quantitative real-time RT-PCR and as well as conventional RT-PCR. Specimens, in which either PSA or PSMA mRNA was positive, were regarded as showing the 'presence of micrometastasis'., Results: Pathological examinations detected tumour cells in 29 PLNs from 11 patients, while real-time RT-PCR and conventional RT-PCR further identified micrometastasis in 143 and 81 PLNs from 32 and 19 patients, respectively, with no pathological evidence of nodal involvement; that is, the sensitivity of real-time RT-PCR for detecting micrometastases was significantly higher than that of conventional RT-PCR. In this series, biochemical recurrence occurred in 32 patients, and in both assays, there were significant differences in biochemical recurrence-free survival between patients with and with no micrometastases. However, despite the significant association of micrometastases detected by both assays with biochemical recurrence on univariate analysis, the presence of micrometastases detected by real-time RT-PCR but not that detected by conventional RT-PCR appeared to be useful as an independent predictor on multivariate analysis., Conclusion: Although micrometastatic tumour foci in PLNs that were missed by routine pathological examination could be diagnosed by both real-time RT-PCR and conventional RT-PCR assays, it would be strongly recommended to use real-time RT-PCR to detect micrometastases considering its high sensitivity and the close association between the outcome of this assay and the probability of biochemical recurrence.

Objectives: The objective of this study was to evaluate the significance of capsular incision (CI) at radical prostatectomy (RP) for men with prostate cancer., Materials and Methods: This study included 267 men who underwent RP without neoadjuvant therapy and were pathologically diagnosed as having organ-confined disease. CI was defined as exposing benign or malignant glands at the inked margin without documented extraprostatic extension., Results: Pathological examinations identified CI in 53 RP specimens (19.9%), while CI was not detected in the remaining 214 specimens (80.1%). The locations of CIs in RP specimens from these 53 patients were as follows: 39 (73.6%) at the apex, 11 (20.0%) at the anterior site, 4 (7.5%) at the posterior site and 12 (22.6%) at the bladder neck. The incidence of CI was significantly affected by surgical procedure, preoperative serum PSA and microvenous invasion in RP specimen. During the observation period of this study, biochemical recurrence occurred in 10 (18.9%) of the 53 with CI and 20 (9.3%) of the 214 without CI, and the biochemical recurrence-free survival in patients with CI was significantly poorer than those without CI. Furthermore, of several factors examined, biochemical recurrence was significantly associated with preoperative serum PSA, Gleason score, perineural invasion and capsular incision, among which only preoperative serum PSA appeared to be an independent predictor of biochemical recurrence., Conclusions: Despite the lack of independent significance, the presence of CI has an adverse impact on biochemical outcome in patients undergoing RP for clinically localized prostate cancer.

The aim of this study was to evaluate preoperative erectile function and attempted nerve-sparing procedure as predictors for early recovery of urinary continence after retropubic and laparoscopic radical prostatectomy. Patients were divided into two groups according to surgical approach (retropubic or laparoscopic) and learning curve for laparoscopic approach: group 1--retropubic approach (37 patients operated on from April 2000 to June 2006), group 2--laparoscopic approach (109 patients operated on from April 2003 to June 2006). We assessed state of urinary continence at 1, 3, 6, and 12 months after removal of the urinary catheter. Overall rates of urinary continence were 18%, 49%, 68%, and 80% at 1, 3, 6, and 12 months, respectively. Between groups 1 and 2, no statistically significant differences in recovery of urinary continence were evident, being 27% versus 15% at 1 month, 54% versus 47% at 3 months, 77% versus 65% at 6 months, and 91% versus 77% at 12 months in groups 1 and 2, respectively. An attempted nerve-sparing procedure (one or both neurovascular bundles) was statistically associated with urinary continence at 3 month, and International Index of Erectile Function-5 (IIEF-5) score (>or=14) was identified as a significant factor predicting urinary continence at 6 months after laparoscopic radical prostatectomy. Younger age tended to result in early recovery of urinary continence after retropubic radical prostatectomy.

Objectives: The objectives of this study were to retrospectively examine the outcomes of adjuvant cisplatin-based combination chemotherapy following radical cystectomy in patients with invasive bladder cancer in order to identify parameters predicting the prognosis of these patients., Methods: This study included a total of 51 patients with muscle invasive bladder cancer who underwent radical cystectomy between January 1995 and December 2004, and subsequently received at least two cycles of either MVAC (methotrexate, vinblastine, doxorubicin and cisplatin) or MVP-CAB (methotrexate, doxorubicin, vincristine, cyclophosphamide, bleomycin and cisplatin) chemotherapy in an adjuvant setting because of the presence of diseases corresponding to pT3/4 and/or pN1/2 without clinical evidence of metastasis. The significance of several clinicopathological factors as predictors of disease recurrence and cancer-specific death was evaluated using univariate and multivariate analyses., Results: During the observation period of this study (median, 26.5 months), disease-recurrence and cancer-specific death were observed in 21 and 16 patients, respectively. The 5-year recurrence-free and cancer-specific survival rates were 48.6% and 54.1%, respectively. Among several factors examined in this series, lymph node metastasis and concomitant carcinoma in situ (CIS) were identified as significant predictors of both disease-recurrence and cancer-specific death, and these were also independently associated with disease-recurrence and cancer-specific death., Conclusions: Adjuvant cisplatin-based combination chemotherapy for patients with extravesically extended bladder cancer following radical cystectomy resulted in comparatively unsatisfactory outcome concerning cancer-control; accordingly, it would be necessary to develop a more efficacious therapeutic strategy for such patients, particularly for those with lymph node metastasis and/or concomitant CIS.

Objectives: The objective of this study was to analyze the health-related quality of life (HRQoL) in patients undergoing lithotripsy for urinary stones., Materials and Methods: This study comprised 76 patients with urinary stones who were treated by lithotripsy, which included shock wave lithotripsy (SWL), ureteroscopic lithotripsy, percutaneous nephrolithotripsy and ureterolithotomy in 66 patients, 25 patients, six patients and three patients, respectively. During the observation period of this series, 37 patients received additional lithotripsy for recurrent urinary stones. HRQoL was evaluated using the Short Form-36 (SF-36) survey assessing eight aspects associated with general health status., Results: There were no significant differences in any scale scores between the 76 patients with urinary stones and age- and gender-matched Japanese norms. Bodily pain (BP) in 37 patients undergoing lithotripsy twice or more appeared to be significantly lower than that in 39 undergoing lithotripsy only once; however, there were no significant differences in the remaining seven scores according to the number of courses of lithotripsy. Furthermore, 47 patients treated by SWL alone had a significantly higher score for general health perception (GH) than 29 who underwent lithotripsy by methods other than SWL, while there were no significant differences in the remaining seven scores between these two groups., Conclusions: In general, patients undergoing lithotripsy for urinary stones may have a comparatively favorable HRQoL; however, BP and GH were impaired in patients undergoing lithotripsy twice or more and those treated by invasive modalities, respectively. Considering these findings, it would be important to prevent recurrent stone formation and to develop less invasive procedures to further improve HRQoL in patients undergoing lithotripsy for urinary stones.

The aim is to evaluate the efficacy and toxicity of weekly docetaxel and estramustine for Japanese men with hormone refractory prostate cancer who were treated at a single institution. Twenty eligible patients had histologically proven adenocarcinoma of the prostate with metastases that were progressing despite complete androgen blockade and antiandrogen withdrawal. All of the patients received docetaxel 30 mg/m(2) weekly (days 1, 8, 15, 22, 29, and 36). After a two week break, the treatment schedule was repeated. Patients were scheduled to receive daily oral estramustine 560 mg/day throughout the protocol. In the serum prostate specific antigen (PSA) response, three (15%) patients achieved a complete response, and 8 (40%) acheived a partial response. Overall survival and time to progression were 13.4 months and 6.4 months, respectively, however sixty-seven percent of the patients had to discontinue treatment because of toxicity. The high toxicity of this protocol suggests that the regimen and/or the timing should be altered for Japanese patients.

Objectives: The objectives of this study were to evaluate the usefulness of serum prostate-specific antigen (PSA) screening in detecting prostate cancer in Japanese men on hemodialysis, and to analyze features of prostate cancer detected in these patients., Materials and Methods: This study included 115 male hemodialysis patients aged > 55 years who agreed to the measurement of serum PSA value (group A) and 7529 men aged > 55 years participating in a PSA mass screening test in Kobe City (group B) between April 2005 and March 2006. Prostate biopsy was recommended in men with serum PSA > 4.0 ng/ml in both groups. Seventy-eight patients with normal renal function aged > 55 years diagnosed as having prostate cancer during the same time period as groups A and B were also included as a comparison group (group C)., Results: There was no significant difference in the distribution of serum PSA values between groups A and B. Prostate biopsy was performed in 8 and 205 men in groups A and B, respectively, and prostate cancer was detected in 5 and 68 in groups A and B, respectively; that is, there was no significant difference in the rate of positive prostate biopsy between these two groups (group A, 62.5%; group B, 33.2%), while the cancer detection rate in group A (4.3%) was significantly greater than that in group B (0.90%). In addition, there was no evident metastasis in five patients on hemodialysis who were diagnosed as having prostate cancer, and their serum PSA, clinical T stage and biopsy Gleason score were similar to those in group C. However, the percent of positive biopsy cores in these five was significantly greater than that in group C. All five were treated by maximal androgen blockade therapy, and all are currently alive without emergence of hormone-refractory diseases., Conclusions: These findings indicate that hemodialysis patients may have an increased risk of prostate cancer, and that prostate cancer detected in such patients tends to be relatively advanced. Therefore, it would be recommended for hemodialysis patients to undergo PSA testing to screen for prostate cancer.

The objective of this study was to retrospectively analyze the clinical outcomes of ureteroscopic lithotripsy (USL) performed in patients with ureteral stones, and to investigate the factors associated with therapeutic outcomes. This study included a total of 2,129 patients with ureteral stones who underwent USL between December 1985 and March 2006 in a single institution in Japan. In this series, ultrasonic lithotripsy was primarily performed, and forceps and/or baskets were occasionally used for the removal of stones. Complete removal was defined as total clearance 1 day after the initial USL. The initial stone-free rate following a single treatment with USL was 73.3%. Of 569 patients diagnosed as having fragmentation of residual stones, additional therapy was not performed for 115 with stones likely to pass spontaneously, while the remaining 454 subsequently underwent extracorporeal shock wave lithotripsy. Thereafter, ureterolithotomy or percutaneous nephrolithotripsy was further added in 14. Ureteral perforation occurred in 14 patients, of whom 2 underwent nephrectomy; however, there were no other serious complications that could not be managed by conservative treatment. Whether ureteral stones were completely removed by an initial USL was significantly associated with the history of ureteral stone, severity of clinical symptoms, number of stones, localization of stones and maximal diameter of stones. Furthermore, multivariate analysis identified the severity of clinical symptoms, number of stones, localization of stones and maximal diameter of stones as independent predictors for complete removal of ureteral stones by the initial USL application. These findings suggest that USL could be a safe and effective treatment option for ureteral stones; however, other therapeutic strategies should also be considered in patients with currently identified risk factors associated with treatment failure following a single USL procedure.

The objective of this study was to evaluate Aurora-A expression in human renal cell carcinomas (RCCs) to clarify the clinical significance of Aurora-A expression in this disease. Expression levels of Aurora-A messenger ribonucleic acids and proteins in both normal kidney and RCC specimens obtained from 131 patients undergoing radical nephrectomy were determined by real-time reverse transcriptase polymerase chain reaction and immunohistochemical staining, respectively. Various levels of Aurora-A protein expression were noted in 127 of the 131 RCC specimens (96.9%), while only 101 of the 131 normal kidney tissues (77.1%) showed Aurora-A staining. In addition, the expression levels of Aurora-A protein in both normal and RCC specimens were in proportion to those of Aurora-A messenger ribonucleic acids. Aurora-A protein expression in RCC tissues was significantly related to tumor grade, but not with age, gender, tumor size, pathologic stage, or histologic cell type. Cell proliferative activity in RCC specimens was significantly associated with Aurora-A expression, while there was no significant correlation between the apoptotic index and Aurora-A protein expression. Furthermore, there was no significant difference in recurrence-free survival between patients with strong Aurora-A expression and those with weak expression. In conclusion, despite the detection in the majority of RCC tissues, Aurora-A expression failed to show the significant association with major pathologic factors and prognosis in patients with RCC.

Purpose: Routine pathologic examination can miss micrometastatic tumor foci in the lymph nodes of patients with prostate cancer, resulting in confusion during tumor staging and clinical decision-making. The objective of this study was to clarify the significance of micrometastases in pelvic lymph nodes in patients who underwent radical prostatectomy for prostate cancer., Experimental Design: The expression of prostate-specific antigen (PSA) and prostate-specific membrane antigen (PSMA) in 2,215 lymph nodes isolated from 120 patients with clinically localized prostate cancer was assessed by a fully quantitative real-time reverse transcriptase-PCR. We regarded specimens in which either PSA or PSMA mRNAs were positive as proof of the "presence of micrometastasis." Immunohistochemical staining of lymph node specimens with an antibody against PSA was also done., Results: Pathologic examinations detected tumor cells in 29 lymph nodes from 11 patients, and real-time reverse transcriptase-PCR further identified micrometastasis in 143 lymph nodes from 32 patients with no pathologic evidence of lymph node involvement. The presence of micrometastatic cancer cells was confirmed by immunohistochemical staining in 61 lymph nodes from 17 patients with pathologically negative lymph nodes. The presence of micrometastases was significantly associated with other conventional prognostic variables, including serum PSA value, pathologic stage, Gleason score, and tumor volume. Biochemical recurrence was detected in 32 patients, 17 of whom were negative for lymph node metastasis by pathologic examination (including 4 patients with pathologically organ-confined disease), but were diagnosed as having micrometastasis. Biochemical recurrence-free survival rate in patients without micrometastasis was significantly higher than in those with micrometastasis irrespective of the presence of pathologically positive nodes. Furthermore, only the presence of micrometastasis was independently associated with biochemical recurrence regardless of other factors examined., Conclusions: These findings suggest that approximately 30% of clinically localized prostate cancers shed cancer cells to the pelvic lymph nodes, and that biochemical recurrence after radical prostatectomy could be explained, at least in part, by micrometastases in pelvic lymph nodes.

Purpose: We evaluated expression levels of major heat shock proteins in radical prostatectomy specimens to clarify the significance of heat shock protein expression in prostate cancer., Materials and Methods: Expression levels of heat shock proteins 27, 70 and 90 in radical prostatectomy specimens from 172 patients with clinically organ confined prostate cancer who had not received neoadjuvant hormonal therapy were measured by immunohistochemical staining. Cell proliferative activities and apoptotic features in these specimens were investigated using Ki-67 immunostaining and TUNEL assay, respectively. These findings were analyzed with respect to several clinicopathological factors., Results: Various levels of heat shock protein 27 expression were noted in all prostate cancer specimens. Expression levels of heat shock protein 27 in prostate cancer tissues was significantly associated with pathological stage, Gleason score, surgical margin status, lymph node metastasis and tumor volume but not with other parameters, including patient age, serum prostate specific antigen and perineural invasion. Similarly most prostate cancer tissues showed heat shock protein 70 and 90 expression. However, there was no significant correlation between expression levels of these 2 heat shock proteins and several clinicopathological factors examined. Cell proliferative activity in prostate cancer specimens was significantly associated with heat shock protein 27 expression but not with that of heat shock proteins 70 and 90, while there was no significant correlation between the apoptotic index and the expression of these 3 heat shock proteins. Furthermore, despite the lack of prognostic significance in heat shock proteins 70 and 90 expression, biochemical recurrence-free survival in patients with strong heat shock protein 27 expression in radical prostatectomy specimens was significantly lower than that in those with weak heat shock protein 27 expression. However, multivariate analysis showed that strong heat shock protein 27 expression could not be an independent predictor of biochemical recurrence after radical prostatectomy., Conclusions: These findings suggest that, despite the limited significance of heat shock proteins 70 and 90 expression, heat shock protein 27 may be involved in the progression of prostate cancer. The expression level of heat shock protein 27 in prostate cancer tissue could be used as a useful predictor of biochemical recurrence in patients undergoing radical prostatectomy.

Objective: To clarify the significance of micrometastases in pelvic lymph nodes in patients treated by radical prostatectomy (RP) for prostate cancer after neoadjuvant hormonal therapy (NHT)., Patients and Methods: The study included 52 patients with clinically localized prostate cancer who received NHT followed by RP. The expression of prostate-specific antigen (PSA) and prostate-specific membrane antigen (PSMA) in 989 lymph nodes isolated from the 52 patients were assessed by a fully quantitative real-time reverse-transcriptase polymerase chain reaction (RT-PCR). We regarded specimens in which either PSA or PSMA mRNA were positive as showing the 'presence of micrometastasis'. Lymph node specimens were also stained immunohistochemically with an antibody against PSA., Results: Pathological examinations detected tumour cells in 11 lymph nodes from four patients, and real-time RT-PCR further identified micrometastasis in 40 lymph nodes from 19 patients with no pathological evidence of nodal involvement. The presence of micrometastatic cancer cells was confirmed by immunohistochemical staining in 19 lymph nodes from 11 patients with pathologically negative nodes. The presence of micrometastases was significantly associated with other conventional prognostic variables, including the pretreatment serum PSA level, biopsy Gleason score and surgical margin status. The biochemical recurrence-free survival rate in patients with no micrometastasis was significantly higher than that in those with micrometastasis. Furthermore, multivariate analysis identified the presence of micrometastasis as an independent factor predicting biochemical recurrence., Conclusions: Although residual foci of atrophic prostate cancer cells in resected lymph nodes after NHT can be difficult to diagnose by routine pathological examination, the present results show the usefulness of quantitative real-time RT-PCR targeting PSA and PSMA genes for detecting micrometastatic tumour foci in pelvic lymph nodes from patients with localized prostate cancer treated by NHT followed by RP. Furthermore, the present findings suggest that micrometastases in pelvic lymph nodes might be, at least partly, important in the development of biochemical recurrence in some patients undergoing RP after NHT.

Objectives: The objective of this study was to investigate the clinical features of non-gonococcal urethritis in men who attended a urological outpatient clinic in Japan., Materials and Methods: This study included a total of 194 patients diagnosed as having non-gonococcal urethritis and subsequently judged as cured following antibiotic therapy between January 2001 and June 2005. Clinical data were analyzed after dividing these patients into two groups as follows: 96 patients with chlamydial urethritis (CU) and 98 with non-chlamydial urethritis (NCU)., Results: The incubation period in the CU group was significantly longer than that in the NCU group (P = 0.0020). The incidence of severity of symptoms in the NCU group was significantly greater than that in the CU group (P = 0.022), and the interval between the appearance of the initial symptom and consulting the clinic was significantly shorter in the NCU group than in the CU group (P = 0.0015). The proportion of commercial sex workers (CSWs) as the causative partner in the NCU group was significantly greater that in the CU group (P < 0.001), and the incidence of oral sex as the causative mode of sexual interaction was significantly more frequent in the NCU group than that in the CU group (P = 0.021). The duration of antibiotic therapy until cured was significantly longer in the CU group than in the NCU group (P = 0.0051). Furthermore, multivariate analysis showed that whether the infection involved CU or NCU was independently associated with the treatment interval irrespective of other factors examined (P = 0.041)., Conclusions: These findings suggest that the clinical characteristics of CU and NCU clearly differ and that CU tends to require a longer time to cure than NCU; therefore, among patients with non-gonococcal urethritis, it would be particularly important to effectively control the spread of CU.

Introduction: The objective of this study was to determine whether an increased number of transrectal biopsy cores improves the accuracy of the biopsy Gleason score., Materials and Methods: This study included a total of 225 patients who were diagnosed as having prostate cancer by transrectal needle biopsy and subsequently underwent radical prostatectomy (RP) without neoadjuvant therapy. The rate of grading concordance between biopsy and RP specimens was analyzed by dividing these patients into 2 groups as follows: group A, 107 patients who underwent transrectal biopsy sampling of 9 cores or less (median 8 cores), and group B, 118 patients who underwent biopsy sampling of 10 cores or more (median 12 cores)., Results: Concordance between the biopsy and RP Gleason scores in group A (53.3%) was significantly lower than that in group B (69.5%). Upgrading of the biopsy Gleason score in group A (38.3%) was significantly more frequent than that in group B (21.2%). Furthermore, these findings tended to be more prominent as the biopsy Gleason score was lower. Multivariate analysis identified the number of biopsy cores and percent of positive biopsy cores as independent predictors of accurate Gleason grading regardless of other parameters examined in this study., Conclusion: These findings suggest that obtaining a greater number of biopsy cores contributes to improving the accuracy of the biopsy Gleason score for predicting the RP Gleason score; therefore, extended sampling of biopsy cores could provide optimal guidance to determine the therapeutic options in patients with prostate cancer., ((c) 2007 S. Karger AG, Basel.)

Objectives: To determine whether the expression level of clusterin in prostate cancer could be used as a prognostic predictor in patients who have undergone radical prostatectomy (RP)., Methods: This study included 172 consecutive patients undergoing RP for clinically organ-confined prostate cancer without neoadjuvant hormonal therapy. Immunohistochemical staining was performed in RP specimens obtained from these patients to evaluate the expression level of clusterin protein. The cell proliferative activities and apoptotic features in these specimens were investigated using Ki-67 immunostaining and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assay, respectively., Results: Varying levels of clusterin expression were noted in 169 of 172 prostate cancer specimens; 32 of the 172 normal prostatic tissue specimens did not exhibit any clusterin staining. Clusterin expression in prostate cancer tissue was significantly related to the Gleason score, but not to the other parameters, including age, serum prostate-specific antigen level, pathologic stage, perineural invasion, tumor volume, and lymph node metastasis. In addition, cell proliferative activity in the prostate cancer specimens was significantly associated with clusterin expression; however, no correlation was found between the apoptotic index and clusterin expression. In this series, 34 (19.8%) of 172 patients developed biochemical recurrence. No significant difference was found in biochemical/recurrence-free survival between patients with strong clusterin expression and those with weak expression., Conclusions: Despite its detection in most prostate cancer tissue, clusterin expression failed to show a significant association with prognosis in patients undergoing RP without neoadjuvant hormonal therapy. This suggests a limited role for clusterin in the progression of clinically organ-confined prostate cancer in the absence of proapoptotic stimuli.

Background: The objective of this study was to retrospectively characterize differences in the clinicopathological features of prostate cancer according to the zonal origin., Methods: Among 185 consecutive patients who underwent radical prostatectomy without any neoadjuvant hormonal therapies, this study included 134 patients who were diagnosed as having either transition zone (TZ) or peripheral zone (PZ) cancer according to the following criteria: TZ or PZ cancers were considered when more than 70% of the cancer area was located in the TZ or PZ, respectively. The various clinicopathological features were then compared according to this classification., Results: In this series, 27 patients were diagnosed as having TZ cancer, while the remaining 107 were diagnosed as having PZ cancer. The percent of positive biopsy cores in TZ cancers was significantly lower than that in PZ cancers; however, there were no significant differences in the anatomical location of positive cores between these two groups except for the middle of prostate where TZ cancer showed a significantly lower rate of positive biopsies than PZ cancer. The preoperative serum prostate-specific antigen (PSA) value in patients with TZ cancer was significantly higher than that in those with PZ cancer. Furthermore, tumor volume in TZ cancers was significantly greater than that in PZ cancers. However, there was no significant difference in biochemical recurrence-free survival between patients with TZ and PZ cancers., Conclusions: Despite the significantly high PSA value as well as great tumor volume compared with those of PZ cancers, TZ cancers had similar biochemical cure rates following radical prostatectomy, suggesting a less aggressive phenotype of TZ cancers than that of PZ cancers.

Background: The objectives of this study were to characterize changes in the expression of heat shock protein 27 (HSP27) in prostate cancer before and after androgen withdrawal therapy and to assess the prognostic significance of HSP27 expression in patients undergoing radical prostatectomy (RP) following neoadjuvant hormonal therapy (NHT)., Materials and Methods: This study included 97 patients with clinically localized prostate cancer who received NHT followed by RP. Paired needle biopsy and corresponding RP specimens obtained from these patients were analyzed for expression of the HSP27 protein by immunohistochemical staining. These findings were evaluated with respect to several clinicopathological factors., Results: HSP27 expression in the RP specimens following NHT was significantly up-regulated compared with that in the corresponding needle biopsy specimens. The expression level of HSP27 in the biopsy specimens was significantly associated with the biopsy Gleason score, but not with other factors available before RP. HSP27 expression in the RP specimens was significantly correlated with the pre-operative value of serum prostate-specific antigen and pathological stage, but not with other pathological factors. Biochemical recurrence-free survival in patients with strong HSP27 expression in the RP specimens was significantly lower than that in those with weak HSP27 expression; however, the expression level of HSP27 was not an independent predictor of biochemical recurrence., Conclusion: Despite the lack of independent significance, the expression level of HSP27 in prostate cancer tissue after NHT, which may inversely reflect the therapeutic effect of NHT, could be a useful parameter predicting biochemical recurrence in patients undergoing RP.

Introduction: The objective of this study was to characterize clinicopathological features of patients with biochemical recurrence after radical prostatectomy who did not exhibit a progressive rise in serum prostate-specific antigen (PSA) during the follow-up period., Materials and Methods: We analyzed data from 162 consecutive patients who underwent radical prostatectomy for clinically organ-confined prostate cancer without neoadjuvant hormonal therapy and were followed postoperatively for at least 1 year. The serum PSA value was measured using an ultrasensitive PSA assay system (Roche Diagnostics, Mannheim, Germany), and biochemical recurrence was defined as a serum PSA of >or=0.1 ng/ml., Results: A total of 32 patients (19.8%) were diagnosed as having biochemical recurrence. Among these patients, we identified 10 (31.3%) with a serum PSA>0.1 ng/ml who had not shown PSA or clinical progression during a median follow-up of 34 months after radical prostatectomy. In these 10 patients, the median time to biochemical recurrence was 17 months, the median PSA velocity after biochemical recurrence was 0.034 ng/ml/year, and there was no patient whose serum PSA value became >0.4 ng/ml. There were no clinicopathological parameters except for PSA velocity that were significantly associated with the features of these 10 patients., Conclusion: Because of the presence of a subset of patients with biochemical recurrence after radical prostatectomy who will not show a progressive increase in serum PSA value, the indication for adjuvant therapy for such patients should be cautiously determined considering several factors, such as PSA kinetics., (Copyright (c) 2006 S. Karger AG, Basel.)

Introduction: The objective of this study was to determine whether the nadir value of serum prostate-specific antigen (PSA) measured by an ultrasensitive assay could be a useful predictor of biochemical recurrence after radical prostatectomy for clinically localized prostate cancer., Materials and Methods: This study included 127 patients who underwent radical prostatectomy for clinically localized prostate cancer without neoadjuvant hormonal therapy and were pathologically diagnosed as negative for lymph node metastasis. The serum PSA value was measured using an ultrasensitive PSA assay system (Roche Diagnostics, Mannheim, Germany), and the findings were analyzed with respect to several clinicopathological factors. In this series, biochemical recurrence was defined as PSA persistently >0.2 ng/ml., Results: Based on the nadir PSA value, we divided 127 patients into three groups as follows: group A (n=99):or=0.05 ng/ml. The nadir PSA value was significantly associated with preoperative PSA value, but not other conventional clinicopathological prognostic parameters. During the observation period (median 31 months, range 6-75 months), biochemical recurrence occurred in 16 patients, that is, 1 in group A (6.3%), 4 in group B (25.0%), and 11 in group C (91.7%). Multivariate analysis using the Cox proportional hazards regression model indicated that the nadir PSA value was an independent predictor for biochemical recurrence after radical prostatectomy., Conclusion: These findings suggest that the nadir serum PSA value measured by an ultrasensitive assay could be a useful predictor of biochemical recurrence after radical prostatectomy for clinically localized prostate cancer, and that careful follow-up should be considered in cases demonstrating a nadir PSA value>0.01 ng/ml because of the significantly higher probability of biochemical recurrence in such cases., (Copyright (c) 2006 S. Karger AG, Basel.)

Introduction: The objective of this study was to review our experience with urinary reconstruction in patients undergoing surgical management for locally advanced pelvic cancer, and to evaluate the role of urologists in these procedures., Materials and Methods: This study included a total of 37 patients undergoing some type of urinary reconstruction due to invasion of the urological organs by locally advanced pelvic cancers, including 17 rectal cancers, 9 cervical cancers, 4 sigmoid cancers, 4 retroperitoneal sarcomas, 2 ovarian cancers and 1 appendiceal cancer. Among these 37, 18 were recurrent cancers following initial surgery for primary tumors. The clinical outcomes of these approaches were retrospectively analyzed., Results: Of the 37 patients, 9 underwent cystectomy (group A) with the following urinary diversions: ileal neobladder in 3, ileal conduit in 5 and colon conduit in 1, and 12 underwent partial cystectomy (group B), among whom 11 received additional urinary reconstruction as follows: bladder flap repair in 5, psoas hitch in 2, ileal ureter in 2, bladder augmentation in 1 and ureteroureterostomy in 1, while the remaining 16 (group C), in whom complete bladder preservation was possible, underwent the following types of urinary reconstruction: bladder flap repair in 6, psoas hitch in 3, en bloc removal of the rectum with prostate in 3, ileal ureter in 2, and ureteroureterostomy in 2. There were 10 early urological complications, including leakage of urine in 7 and acute pyelonephritis in 3. As a late urological complication, hydronephrosis was observed in 8 patients, but ureteral stent was not required in any of these 8. There were no significant differences in the incidence of postoperative complications, the status of surgical margin and the survival among groups A-C., Conclusion: Our experience with extended surgical management of non-urological pelvic cancer with reconstruction of the urinary tract suggests that the urological portion of this procedure can be performed with acceptable morbidity, and that the role of the urological surgeon during this procedure is potentially important., (Copyright (c) 2006 S. Karger AG, Basel.)

Background: The objective of this study was to investigate the clinicopathological features of recurrent transitional cell carcinoma (TCC) of the bladder in patients who had previously undergone radical cystectomy., Materials and Methods: This study included 124 patients who underwent radical cystectomy for transitional cell carcinoma (TCC) of the bladder in our institution. Several clinicopathological factors were analyzed to characterize differences between patients with and without disease recurrence, and determined predictive factors for disease recurrence using multivariate analysis. We further analyzed prognostic parameters that affect survival after disease recurrence was diagnosed., Results: Of the 124 patients, 24 (19.5%) developed recurrence, and the median time to recurrence was 9.5 months (range, 1-44 months). The 5-year recurrence-free survival in these 124 patients was 75.6%. The incidence of disease recurrence was significantly associated with gender, pathological stage, lymph node metastasis, lymphatic invasion and blood vessel invasion. Multivariate analysis identified gender, pathological stage and lymph node metastasis as independent predictors of disease recurrence following radical cystectomy. After disease recurrence, the 1-year cancer-specific survival of the 24 patients was 16.7%; that is, 23 of the 24 patients had died of progressive recurrent diseases, while the remaining 1 who survived had developed recurrence in the upper urinary tract., Conclusions: These findings suggest that careful follow-up should be performed after radical cystectomy for TCC of the bladder considering gender, pathological stage and nodal involvement; however, once recurrent disease develops, the prognosis of such patients is extremely poor. Therefore, it would be potentially important to establish a multimodal therapeutic approach targeting recurrent TCC of the bladder.

Background: The objective of this study was to evaluate the clinical significance of additional routine transition zone (TZ) biopsies in Japanese men undergoing transrectal ultrasound (TRUS)-guided systematic 8-core peripheral zone (PZ) biopsies., Methods: Between October 2002 and December 2004, a total of 788 consecutive patients underwent TRUS-guided systematic biopsy of the prostate for the fi rst time. As a rule, 10 cores were taken from each patient; that is, 8 cores from the PZ, including the standard sextant cores and 2 cores from the anterior lateral horns, and 2 additional cores from the bilateral TZ. The cancer detection rate was calculated according to several parameters. We also assessed the disease extent on radical prostatectomy specimens according to the cancer location within the biopsy specimens., Results: Prostate cancer was detected by 10-core biopsies in 209 (26.5%) of the 788 patients, and 11 of these patients had positive cores only in the TZ; that is, the increase in cancer detection rate by sampling two additional cores from the TZ was 5.3%. Among 209 patients diagnosed as having prostate cancer, radical prostatectomy without any neoadjuvant therapy was performed in 59 patients with positive biopsy cores in the PZ, 7 in the TZ and 32 in both the PZ and TZ. Patients with positive cores in both zones showed significantly less favorable characteristics, indicating more advanced disease than that in those with positive cores in either zone., Conclusions: Routine TZ biopsy did not significantly increase the detection rate of prostate cancer; however, the anatomical location of positive biopsy cores could provide additional information concerning disease extension in patients undergoing radical prostatectomy.

The objective of this study was to characterize changes in clusterin expression in prostate cancer before and after neoadjuvant hormonal therapy (NHT), and to assess the prognostic significance of clusterin expression following NHT in patients undergoing radical prostatectomy. Paired needle biopsy and corresponding radical prostatectomy (RP) specimens obtained from 76 patients were analyzed for expression of clusterin protein by immunohistochemical staining with an antibody recognizing all of the clusterin isoforms. RP specimens following NHT demonstrated stronger expression of clusterin than the corresponding needle biopsy specimens. Clusterin protein was present in the cytoplasm of both biopsy and RP specimens; however, there was no nuclear staining identified in any specimens. The expression level of clusterin in biopsy specimens was significantly associated with the biopsy Gleason score, but not with other parameters available before RP. Furthermore, clusterin expression in RP specimens was significantly associated with the preoperative prostate specific antigen value and pathological stage, but not with other pathological factors. Biochemical recurrence-free survival in patients with strong clusterin expression in RP specimens was significantly lower than that in those with weak clusterin expression; however, the level of clusterin expression could not be used as an independent predictor of biochemical recurrence. These findings suggest that despite the lack of independent significance, the expression level of the secreted form of clusterin in prostate cancer tissue after NHT, which may inversely reflect the therapeutic effect of NHT, could be a useful parameter predicting biochemical recurrence in patients undergoing RP.

Objectives: To evaluate the significance of clusterin expression in surgically resected renal cell carcinoma (RCC) specimens., Patients and Methods: Normal kidney and RCC specimens were obtained from 131 patients who had radical surgery. The expression of clusterin protein was analysed by immunohistochemical staining with an antibody recognizing all isoforms of clusterin. Cell proliferative activities and apoptotic features in these specimens were investigated using Ki-67 immunostaining and the terminal deoxynucleotidyl transferase mediated dUTP nick-end labelling assay, respectively. Findings were evaluated in relation to several clinicopathological factors., Results: There were various levels of clusterin expression in 128 of the 131 RCC specimens, while 37 of 131 normal kidney tissues (28.2%) had no clusterin staining. Clusterin protein was present in the cytoplasm of both normal and cancer cells, but there was no nuclear staining identified in either type of cell. The expression level of clusterin protein in RCC tissues was significantly related to tumour stage and grade, but not to age, gender or histological cell type. Cell proliferative activity in RCC specimens was significantly associated with clusterin expression, while the apoptotic index was inversely related to clusterin expression. Furthermore, recurrence-free survival in patients with strong clusterin expression was significantly lower than that in those with weak expression., Conclusions: These findings suggest that the secreted form of clusterin may be involved in the progression of RCC, and that overexpression of clusterin could be a useful prognostic variable after radical surgery in patients with RCC.

Background: The objectives of this study were to investigate the association between urinary levels of vascular endothelial growth factor (VEGF) and the progression of prostate cancer, and to evaluate changes in urinary VEGF levels before and after initial treatment., Materials and Methods: A total of 97 patients with prostate cancer were included in this study. Of these 97, 52 underwent radical prostatectomy and the remaining 45 received hormonal therapy as initial treatment. Urinary VEGF levels were measured using a sandwich enzyme immunoassay, and the results were analyzed with respect to several clinicopathological factors., Results: The mean urinary level of VEGF in patients with prostate cancer was significantly higher than that in healthy controls. The urinary level of VEGF in prostate cancer patients with metastasis was significantly elevated compared with that in those without metastasis. Among 52 patients who underwent radical prostatectomy, the urinary levels of VEGF in patients with pathologically organ-confined disease were significantly lower than that in those with extraprostatic disease. Furthermore, the urinary VEGF level in 52 patients after radical prostatectomy was significantly lower than that before radical prostatectomy, while there was no significant difference in urinary VEGF level in 45 patients before and after hormonal therapy., Conclusion: These findings suggest that the elevation of urinary VEGF could be a useful predictor of disease progression in prostate cancer, and that the urinary levels of VEGF reflect the therapeutic effect of radical prostatectomy, but not that of hormonal therapy.

Purpose: The objective of this study was to clarify the significance of micrometastases in pelvic lymph nodes in patients who underwent radical cystectomy for bladder cancer., Experimental Design: We included 40 patients with locally invasive bladder cancer who underwent radical cystectomy and pelvic lymphadenectomy. Expression of cytokeratin 19 (CK19), uroplakin II (UP II), and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) in 760 lymph nodes were assessed by a fully quantitative real-time reverse transcription-PCR (RT-PCR) assay. The quantification value of CK19 or UP II mRNA was described as each value relative to GAPDH mRNA. In this study, we regarded specimen in which either CK19 or UP II mRNA was positive as "presence of micrometastasis.", Results: Routine pathologic examinations detected tumor cells in 29 lymph nodes from six patients. Real-time RT-PCR identified positive expression of CK19 and UP II mRNAs in 49 lymph nodes from 10 patients and 98 lymph nodes from 16 patients, respectively. Of 633 lymph nodes from 34 patients with no pathologic evidence of nodal involvement, 13 nodes from five patients and 58 nodes from 10 patients were diagnosed as positive for CK19 and UP II mRNAs expression, respectively, by real-time RT-PCR. Presence of micrometastases was significantly associated with other conventional prognostic variables, including pathologic stage and microvascular invasion. Disease recurrence was occurred in eight patients, among whom four patients were negative for lymph node metastasis by routine pathologic examination and diagnosed as having micrometastasis by real-time RT-PCR assay. Furthermore, cause-specific survival rate in patients without micrometastasis was significantly higher than that in those with micrometastasis, irrespective of the presence of pathologic-positive nodes., Conclusions: Approximately 30% of locally invasive bladder cancer shed cancer cells to pelvic lymph nodes, and disease recurrence after radical cystectomy could be explained, at least in part, by micrometastases in pelvic lymph nodes.

A 51-year-old woman had been administered 5 mg/day of prednisolone due to systemic lupus erythematosus (SLE). She developed hypertension, hypokalemia and a pathologic pubic fracture during two years before admission. Although iatrogenic Cushing's syndrome was initially suspected, we diagnosed her as concomitant Cushing's syndrome due to a left adrenal tumor. The elevated endogeneous glucocorticoids were evaluated from urinary excretions of 17-hydroxycorticosteroids, which was 2-fold higher than normal and equivalent to 10 mg of prednisolone. After laparoscopic left adrenalectomy, SLE was favorably controlled with 15 mg of prednisolone, the dosage of which was equivalent to the estimated amount of preoperative glucocorticoids.