Prognostic outcomes in patients with metastatic renal cell carcinoma receiving second-line treatment with tyrosine kinase inhibitor following first-line immune-oncology combination therapy.

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.

Significance of multiple preoperative laboratory abnormalities as prognostic indicators in patients with urothelial carcinoma of the upper urinary tract following radical nephroureterectomy.

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.

Impact of metabolic syndrome on early recovery of continence after robot-assisted radical prostatectomy.

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/m2 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.

[Malignant mesotheliomas of the tunica vaginalis testis].

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.

Efficacy and safety of second-line cabozantinib after immuno-oncology combination therapy for advanced renal cell carcinoma: Japanese multicenter retrospective study.

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.

Long-term complete response to very-low-dose interleukin-2 therapy in patients with metastatic renal cell carcinoma: report of two cases.

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.

Characterization of the anatomical extension pattern of localized prostate cancer arising in the peripheral zone.

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.

Impact of sorafenib on health-related quality of life in Japanese patients with metastatic renal cell carcinoma: a prospective evaluation.

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.

Improved sensitivity for detecting micrometastases in pelvic lymph nodes by real-time reverse transcriptase polymerase chain reaction (RT-PCR) compared with conventional RT-PCR in patients with clinically localized prostate cancer undergoing radical prostatectomy.

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.

Assessment of voiding function of orthotopic neobladders in elderly patients with long-term survival.

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.

Prediction of response to combined immunotherapy with interferon-alpha and low-dose interleukin-2 in metastatic renal cell carcinoma: expression patterns of potential molecular markers in radical nephrectomy specimens.

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.

Quantitative detection of micrometastases in pelvic lymph nodes in patients with clinically localized prostate cancer by real-time reverse transcriptase-PCR.

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.

Prognostic significance of adjuvant cisplatin-based combination chemotherapy following radical cystectomy in patients with invasive bladder cancer.

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.

Combination chemotherapy with weekly docetaxel and estramustine for hormone refractory prostate cancer in Japanese patients.

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.

Health-related quality of life in patients undergoing lithotripsy for urinary stones.

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.

Screening for prostate cancer using prostate-specific antigen testing in Japanese men on hemodialysis.

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.

Significance of Aurora-A expression in renal cell carcinoma.

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.

Improved accuracy for predicting the Gleason score of prostate cancer by increasing the number of transrectal biopsy cores.

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.

A comparison of clinical features between chlamydial and non-chlamydial urethritis in men negative for gonococcal infection who attended a urological outpatient clinic in Japan.

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.

Enhanced expression of heat shock protein 27 following neoadjuvant hormonal therapy is associated with poor clinical outcome in patients undergoing radical prostatectomy for prostate cancer.

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.