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Interaural time differences (ITDs) are the primary cue animals, including humans, use to localize low-frequency sounds. In vertebrate auditory systems, dedicated ITD processing neural circuitry performs an exacting task, the discrimination of microsecond differences in stimulus arrival time at the two ears by coincidence-detecting neurons. These neurons modulate responses over their entire dynamic range to sounds differing in ITD by mere hundreds of microseconds. The well-understood function of this circuitry in birds has provided a fruitful system to investigate how inhibition contributes to neural computation at the synaptic, cellular, and systems level. Our recent studies in the chicken have made significant progress in bringing together many of these findings to provide a cohesive picture of inhibitory function. [ABSTRACT FROM AUTHOR]

GABAergic modulation of activity in avian cochlear nucleus neurons has been studied extensively in vitro. However, how this modulation actually influences processing in vivo is not known. We investigated responses of chicken nucleus magnocellularis (NM) neurons to sound while pharmacologically manipulating the inhibitory input from the superior olivary nucleus (SON). SON receives excitatory inputs from nucleus angularis (NA) and nucleus laminaris (NL), and provides GABAergic inputs to NM, NA, NL, and putatively to the contralateral SON. Results from single-unit extracellular recordings from 2 to 4 weeks posthatch chickens show that firing rates of auditory nerve fibers increased monotonically with sound intensity, while that of NM neurons saturated or even decreased at moderate or loud sound levels. Blocking GABAergic input with local application of TTX into the SON induced an increase in firing rate of ipsilateral NM, while that of the contralateral NM decreased at high sound levels. Moreover, local application of bicuculline to NM also increased the firing rate of NM neurons at high sound levels, reduced phase locking, and broadened the frequency-tuning properties of NM neurons. Following application of DNQX, clear evidence of inhibition was observed. Furthermore, the inhibition was tuned to a broader frequency range than the excitatory response areas. We conclude that GABAergic inhibition from SON has at least three physiological influences on the activity of NM neurons: it regulates the firing activity of NM units in a sound-level-dependent manner; it improves phase selectivity; and it sharpens frequency tuning of NM neuronal responses. [ABSTRACT FROM AUTHOR]

Abstract: We investigated the chicken auditory system to understand how an interaural level difference (ILD) is processed. Sound intensity is extracted in the nucleus angularis (NA) and an ILD is processed in the dorsal lateral lemniscal nucleus (LLD). We found that the neural activity in these nuclei is affected by the interaural phase difference (IPD). Activity in the NA was suppressed by strong contralateral sound when binaural stimuli were presented in-phase, but the activity was enhanced by out-of-phase stimuli. These IPD dependent suppression or enhancement probably occurs through acoustic interference across the interaural canal connecting the middle ears of the two sides. The LLD neurons were excited by contralateral sound and inhibited by ipsilateral sound, reflecting excitation by the contralateral NA and inhibition from the ipsilateral NA, probably through the contralateral LLD as in the barn owl. The LLD unit activity encoded an ILD and was strongly modulated by the IPD. We propose a simple model to explain the interaural coupling effects and IPD modulation of LLD activity, and conclude that the modulation of neuronal activity by IPD may improve ILD processing and the direction sensitivity of LLD neurons to the contralateral ear, compensating for the small ILD cues. [Copyright &y& Elsevier]

Nucleus magnocellularis (NM) is a division of the avian cochlear nucleus that extracts the timing of auditory signals. We compared me membrane excitability and synaptic transmission along the tonotopic axis of NM. Neurons expressed a Kv1.1 potassium channel mRNA and protein predominantly in the high characteristic frequency (CF) region of NM. In contrast, the expression of Kv1.2 mRNA did not change tonotopically. Neurons also showed tonotopic gradients in resting potential, spike threshold, amplitude, and membrane rectification. All neurons were sensitive to 100 nM dendrotoxin, but the effects were most significant in the high CF neurons. The EPSC recorded by minimal stimulation of auditory nerve fibers (ANFs) was 13 times larger in high CF neurons than in low CF neurons. Moreover, EPSCs were generated in an all-or-none manner in the high CF neurons when stimulus intensity was increased, whereas EPSCs were graded in the low CF neurons, indicating multiple axonal inputs. ANF synaptic terminals were visualized by DiI. ANF formed enfolding end-bulbs of Held around the cell body in the high and middle CF region but not in the low CF region. These observations indicate coordinated gradients of neuronal properties both presynaptically and postsynaptically along the tonotopic axis. Such specializations may be suitable for extracting and preserving the timing information of auditory signals over a wide range of acoustic frequencies. [ABSTRACT FROM AUTHOR]

Objective: To clarify the diagnostic performance of the three-dimensional reconstructed virtual image (3D-RVI) in evaluating RENAL nephrometry score (RENAL-NS).Methods: This study included 130 patients who underwent preoperative contrast-enhanced computed tomography followed by partial nephrectomy for renal tumors suggestive of renal cell carcinoma. RENAL-NS was calculated prior to the surgery, and tumor resection was performed referring to the score. We retrospectively reviewed preoperative contrast-enhanced computed tomography images. We calculated the inter-observer variability of RENAL-NS using 3D-RVI vs two-dimensional (2D) imaging and compared the ability of RENAL-NS using 3D-RVI vs 2D imaging to predict the risk of opening of the urinary collecting system. We also compared the two modalities for the time required to evaluate RENAL-NS.Results: RENAL-NS evaluated using 3D-RVI showed a higher inter-observer agreement compared to 2D-imaging (rs = 0.85 vs rs = 0.65). The "nearness to sinus" score was more strongly associated with the opening of the urinary collecting system when evaluated using 3D-RVI than 2D-imaging (AUC = 0.71 vs AUC = 0.57, P = .016). RENAL-NS using 2D-imaging required a significantly longer time compared to 3D-RVI (P = .036).Conclusion: Using 3D-RVI improves the accuracy, reliability and efficiency of RENAL-NS evaluation in preoperative assessment and can play an important role in preoperative assessment and intraoperative navigation. [ABSTRACT FROM AUTHOR]

The interaural time difference (ITD) is a cue for localizing a sound source along the horizontal plane and is first determined in the nucleus laminaris (NL) in birds. Neurons in NL are tonotopically organized, such that ITDs are processed separately at each characteristic frequency (CF). Here, we investigated the excitability and coincidence detection of neurons along the tonotopic axis in NL, using a chick brainstem slice preparation. Systematic changes with CF were observed in morphological and electrophysiological properties of NL neurons. These properties included the length of dendrites, the input capacitance, the conductance of hyperpolarization-activated current, and the EPSC time course. In contrast to these gradients, the conductance of low-threshold K+ current and the expression of Kv1.2 channel protein were maximal in the central (middle-CF) region of NL. As a result, the middle-CF neuron had the smallest input resistance and membrane time constant, and consequently the fastest EPSP, and exhibited the most accurate coincidence detection. The specialization of middle-CF neurons as coincidence detectors may account for the high resolution of sound-source localization in the middle-frequency range observed in avians. [ABSTRACT FROM AUTHOR]

Background: We aimed to establish an external validation of the Briganti 2019 nomogram in a Japanese cohort to preoperatively evaluate the probability of lymph node invasion in patients with high-risk, clinically localized prostate cancer. Methods: The cohort consisted of 278 patients with prostate cancer diagnosed using magnetic resonance imaging-targeted biopsy who underwent radical prostatectomy and extended pelvic lymph node dissection from 2012 to 2020. Patients were rated using the Briganti 2019 nomogram, which evaluates the probability of lymph node invasion. We used the area under curve of the receiver operating characteristic analysis to quantify the accuracy of the nomogram. Results: Nineteen (6.8%) patients had lymph node invasion. The median number of lymph nodes removed was 18. The area under the curve for the Briganti 2019 was 0.71. When the cutoff was set at 7%, 84 (30.2%) patients with extended pelvic lymph node dissection could be omitted, and only 1 (1.2%) patient with lymph node invasion would be missed. Sensitivity, specificity, and negative predictive values at the 7% cutoff were 94.7, 32.0, and 98.8%, respectively. Conclusion: This external validation showed that the Briganti 2019 nomogram was accurate, although there may still be scope for individual adjustments. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the efficacy and safety profiles of first‐line etoposide, ifosfamide and cisplatin and primary prophylaxis with pegfilgrastim as first‐line chemotherapy for disseminated germ cell cancer. Methods: This study reviewed 154 consecutive patients with previously untreated disseminated germ cell cancer who received first‐line etoposide, ifosfamide and cisplatin between 1995 and 2020. Of these, 54 patients were managed with primary prophylaxis using pegfilgrastim (primary prophylaxis group), and 100 were managed with the therapeutic use of short‐acting granulocyte colony‐stimulating factor (non‐primary prophylaxis group). Results: The International Germ Cell Cancer Collaborative Group classification identified 90 (58%)/40 (26%)/24 (16%) patients with good/intermediate/poor prognosis, respectively. Overall, 139 patients (90%) were disease free after etoposide, ifosfamide and cisplatin with/without post‐chemotherapy surgery. The median relative dose intensity of etoposide, ifosfamide and cisplatin was 96%, and there was a significant difference between the primary prophylaxis and non‐primary prophylaxis groups (100% vs 90%, P < 0.01). The 5‐year salvage treatment‐free and overall survival rates were 83% and 94%, respectively. In total, 138 patients (90%) developed grade 4 hematological toxicities, and there were no treatment‐related deaths due to myelosuppression. Grade 4 neutropenia was less commonly observed in the primary prophylaxis group compared with the non‐primary prophylaxis group (80% vs 95%, P < 0.01). Conclusions: This is the largest study of first‐line etoposide, ifosfamide and cisplatin, and its sufficient efficacy and safety profiles are confirmed in current clinical practice. Primary prophylaxis using pegfilgrastim might further improve the feasibility of etoposide, ifosfamide and cisplatin. [ABSTRACT FROM AUTHOR]

Background: We evaluated patient‐reported outcomes (PRO) during neoadjuvant androgen deprivation therapy (ADT) plus external beam radiation therapy (EBRT) followed by either adjuvant continuous ADT (CADT) or intermittent ADT (IADT) for patients with locally advanced prostate cancer (Pca). Methods: A multicenter, randomized phase III trial enrolled 303 patients with locally advanced Pca. The patients were treated with 6 months (M) of ADT followed by 72 Gy of EBRT, and were randomly assigned to CADT or IADT after 14 M. The PROs were evaluated at sic points: baseline, 6 M, 8 M, 14 M, 20 M, and 38 M using FACT‐P questionnaires and EPIC urinary, bowel, and sexual bother subscales. Results: The FACT‐P total scores were significantly better (p < 0.05) in IADT versus CADT at 20 M (121.6 vs.115.4) and at 38 M (119.9 vs. 115.2). The physical well‐being scores (PWB) were significantly better (p < 0.05) in IADT versus CADT at 38 M (25.4 vs. 24.0). The functional scores were significantly better in IADT than those in CADT at 14 M (20.2 vs18.7, p < 0.05) and at 20 M (21.0 vs.18.9, p < 0.05). Conclusion: The PRO was significantly favorable in IADT on FACT‐P total score at 20 M and 38 M, PWB and functional scores at 38 M. [ABSTRACT FROM AUTHOR]

Introduction: In spite of the high incidence of infectious complications (ICs), appropriate duration of antimicrobial prophylaxis (AMP) for radical cystectomy (RC) with intestinal urinary diversion (IUD) has not been established. We compared the incidence of ICs after RC with IUD in patients using only intraoperative AMP or extended duration AMP. Risk factors for ICs were also investigated. Patients and Methods: One hundred twenty-three consecutive patients who underwent RC with IUD were divided into 2 groups based on the AMP duration (intraoperative only vs. extended duration for a median of 3 days). Between the groups, the incidence of ICs was compared. Risk factors for ICs were investigated in multivariate analysis. Results: The IC rate was 44%. No significant difference was found in the rate of ICs between the groups. The IC rate was significantly higher in patients with lower estimated glomerular filtration rate (eGFR). Rates of ICs were 60 and 38% in patients with eGFR of less than 60 and equal or more than 60 mL/min/1.73 m2, respectively. Conclusions: Our result indicates that AMP that is administered more than intraoperatively may be excessive in RC with IUD. Patients with a lower eGFR should be particularly cared for postoperative ICs. [ABSTRACT FROM AUTHOR]

Background: To date, research has not determined the optimal procedure for adjuvant androgen deprivation therapy (ADT) in patients with locally advanced prostate cancer (PCa) treated for 6 months with neoadjuvant ADT and external-beam radiation therapy (EBRT).Methods: A multicenter, randomized, phase 3 trial enrolled 303 patients with locally advanced PCa between 2001 and 2006. Participants were treated with neoadjuvant ADT for 6 months. Then, 280 patients whose prostate-specific antigen levels were less than pretreatment levels and less than 10 ng/mL were randomized. All 280 participants were treated with 72 Gy of EBRT in combination with adjuvant ADT for 8 months. Thereafter, participants were assigned to long-term ADT (5 years in all; arm 1) or intermittent ADT (arm 2). The primary endpoint was modified biochemical relapse-free survival (bRFS) with respect to nonmetastatic castration-resistant prostate cancer (nmCRPC) progression, clinical relapse, or any cause of death.Results: The median follow-up time after randomization was 8.2 years. Among the 136 and 144 men assigned to trial arms 1 and 2, respectively, 24 and 30 progressed to nmCRPC or clinical relapse, and 5 and 6 died of PCa. The 5-year modified bRFS rates were 84.8% and 82.8% in trial arms 1 and 2, respectively (hazard ratio, 1.132; 95% confidence interval, 0.744-1.722).Conclusions: Although modified bRFS data did not demonstrate noninferiority for arm 2, intermittent adjuvant ADT after EBRT with 14 months of neoadjuvant and short-term adjuvant ADT is a promising treatment strategy, especially in a population of responders after 6 months of ADT for locally advanced PCa. [ABSTRACT FROM AUTHOR]

Objectives: To analyze the incidence and predictors of deep vein thrombosis (DVT) in patients with elevated D-dimer prior to surgery for urologic malignancy. Methods: Between January 2015 and September 2017, 987 consecutive patients underwent surgery for urologic malignancy under general anesthesia in our institution. Of these, 191 patients underwent preoperative venous ultrasonography of the lower extremities for DVT due to elevated D-dimer. We analyzed the incidence and predictors of DVT in these patients. Results: The median age was 69 years. DVT was detected in 18% of patients (35/191). Multivariate analysis showed that the primary site of urologic malignancy (p < 0.01) and older age (p < 0.01) were independent predictors of DVT. Patients with bladder cancer had the highest incidence of DVT. When bladder cancer and age of 70 or older were defined as predictors for DVT, the incidence of DVT in zero, 1, and 2 predictors was 3.4% (3/89), 29% (22/77), and 44% (11/25), respectively. Conclusions: DVT was found in 18% of patients with elevated D-dimer prior to surgery for urologic malignancy. Bladder cancer patients and older patients in whom D-dimer has been elevated should undergo careful early examination for DVT. [ABSTRACT FROM AUTHOR]

Background: In order to help in selecting the optimum bone-modifying agent (BMA; zoledronic acid or denosumab), we investigated the impact of the BMA on the renal function of patients with bone metastases. Materials and methods: The present study consisted of 118 patients who were treated with denosumab for bone metastases secondary to prostate cancer, renal cell cancer, and urothelial cancer at our hospital between 2012 and 2015. The clinical course of the renal function of these patients, treated with zoledronic acid or denosumab, was retrospectively evaluated. Results: Of the 118 patients who were treated with denosumab during the study period, 57 (48 %) had previously been administered zoledronic acid and 61 (52 %) had received denosumab as the first-line BMA. The reasons for changing from zoledronic acid to denosumab were increased creatinine serum level (26 patients, 46 %), patient preference (16 patients, 28 %), difficulty with venous infusion (10 patients, 17 %), and other reasons (5 patients, 9 %). The median level of creatinine clearance in the patients who changed from zoledronic acid to denosumab due to increased serum creatinine level was 59.9 ml/min before administration of zoledronic acid, 40.9 ml/min at the beginning of denosumab treatment, 47.5 ml/min at 3 months after administration of denosumab, and 52.0 ml/min at the last follow-up. There were significant differences. Conclusions: For the first time, we demonstrated that the renal function of some patients, which had deteriorated following zoledronic acid administration, successfully improved after changing to denosumab. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article "Successful 2-year-long remission following repeated salvage surgery in a patient with chemotherapy-resistant metastatic non seminomatous germ cell tumor: an additional report to Int J Clin Oncol 2007," by H. Takeshita in the 2010 issue.

A letter to the editor is presented in response to the article on profound bicalutamide withdrawal syndrome in a hormone-refractory prostate cancer permitting both salvage radiotherapy and cessation of hormonal therapy that was published in the previous issue.

Background: The outcome of treatment of Japanese patients with urachal cancer is not well known. The purpose of this study is to clarify the characteristics and outcomes of Japanese patients with urachal cancer. Materials and methods: The medical records of patients with urachal cancer who were treated in our hospital between 1994 and 2014 were retrospectively reviewed and statistically analyzed. Results: We found 28 patients who had been diagnosed with urachal cancer and treated in our hospital during the study period. The median age of these patients was 52.3 years [interquartile range (IQR), 46.0-56.8 years]. Seventeen patients underwent surgery in our department. The median observation period of these patients was 42.6 months (IQR, 21.1-49.7 months). Among patients who had undergone surgery, cancer recurred in 7 (41 %). The estimated median time from surgery to recurrence and overall survival (OS) period were 35.8 months [95 % confidence interval (CI), 7.7 months-not determined] and not reached, respectively. Seventeen patients received chemotherapy for metastatic disease. The estimated median OS time from initial metastasis was 23.5 months (95 % CI, 11.8-33.3 months). Conclusions: Urachal cancer is usually locally advanced at presentation and it has a high risk of distant metastases. However, long-term survival following surgical treatment occurs in a significant fraction of patients. This study indicates the current treatment results for patients with urachal cancer in Japanese clinical practice. To establish a standard operation method and chemotherapy, a multicenter, prospective study is needed in a larger population in the future. [ABSTRACT FROM AUTHOR]

Objective: To determine the diagnostic accuracy of 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) for detecting metastasis and its impact on patient management with upper tract urothelial carcinoma (UTUC). Patients and Methods: Consecutive patients with UTUC underwent 18F-FDG PET/CT after CT for initial staging (n = 47) and for restaging at recurrence (n = 9). Diagnostic accuracy for detecting metastases with PET/CT and CT was compared statistically. The impact of PET/CT on patient management was assessed by comparing questionnaires that were completed by the attending physicians before and after PET/CT. Results: In the lesion-based analysis, 142 lesions were diagnosed as metastases. The sensitivity of PET/CT was significantly better than that of CT (85 vs. 50%, p = 0.0001). In the patient-based analysis, 22 patients were diagnosed as having metastases. The sensitivity/specificity/accuracy of PET/CT tended to be superior to those of CT, but these values were not significantly different (95, 91, and 93% vs. 82, 85, and 84%; p = 0.25, 0.50, and 0.063, respectively). The clinicians changed their assessments of disease extent and management plans in 18 (32%) and 11 (20%) patients, respectively, based on the PET/CT results. Conclusions: The diagnostic accuracy of PET/CT for detecting metastasis was superior to that of CT. PET/CT provided additional information to the CT-based staging, which had an impact on patient management. © 2015 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: The outcome of surveillance for Japanese patients with clinical stage I testicular germ cell cancer (GCC) was investigated in the multi-detector computed tomography (MDCT) era. Methods: The medical records of 92 Japanese patients with stage I GCC, who received treatment in our institution between March 1999 and February 2013, were reviewed. As six patients requested and received prophylactic chemotherapy and two patients seriously deviated from surveillance schedule, these patients were excluded from the study. Data from a total 84 patients were analyzed, Results: The median follow-up period following diagnosis was 5.1 years (inter-quartile range: IQR, 2.3-7.7 years). Of the 84 patients, eight (9.5 %) had a recurrence of their cancer in this observation period. Regarding histologic subtypes, the recurrence rates were five (9.3 %) of the 54 patients with seminoma and three (10 %) of the 30 patients with nonseminomatous germ cell tumor (NSGCT). All eight patients who experienced a recurrence did so within 2 years; they all underwent induction chemotherapy and remain alive at the time of writing, with no evidence of disease. Among 31 seminoma patients with a tumor more than 4 cm in size and rete testis invasion, cancer recurred in three (9.7 %) during the surveillance period. On the other hand, among the 13 patients with NSGCT and vascular invasion, three (23 %) experienced a recurrence, whereas the figure was zero for the 11 (0 %) patients without vascular invasion. Conclusion: Fewer than 10 % of Japanese patients with stage I testicular GCC suffered a recurrence in the 5-year observation period of this study. The risk of occult disease, which will result in relapse, might be decreased in the MDCT era. All patients must be fully informed of the anticipated recurrence rate and the potential risks of exposure to chemotherapy agents. [ABSTRACT FROM AUTHOR]

Background: To determine the indications for post-chemotherapy consolidative surgery in patients with clinical lymph node (LN) metastatic (cN+) urothelial carcinoma (UC). Methods: Sixty UC patients with measurable cN+ but without detectable systemic visceral/bone dissemination received induction platinum-based chemotherapy. Consolidative surgery was offered to all patients except for those with progressive disease. We retrospectively analyzed the clinicopathological response to induction chemotherapy and identified prognostic factors for overall survival (OS). Results: The primary cancer site was the urinary bladder in 31 patients (52 %) and upper urinary tract in 29 (48 %). The median number of chemotherapy courses was 4. Forty-five patients (75 %) showed a clinically objective response to the induction chemotherapy. Fifty-one patients (85 %) underwent subsequent consolidative surgery. Histopathological analysis indicated pT0 status in 10 (20 %) and pN0 in 17 (33 %). When all 60 patients were considered, clinical tumor response was found to be significantly correlated with achievement of pathological complete response. At the median follow-up of 22 months, the median progression-free survival and OS periods were excellent: 18.6 and 31.6 months, respectively. In the multivariate analysis, clinical tumor response was found to be an independent pre-surgical prognostic factor for OS, and pathologically negative lymph node, negative resection margin, more LNs removed, and negative lymphovascular invasion were found to be independent post-surgical prognostic parameters for OS. Conclusions: The median OS in induction chemotherapy followed by consolidative surgery was very encouraging. Our results suggest that achieving a good clinical response to pre-surgical induction chemotherapy is a good indication for subsequent consolidative surgery in UC patients with cN+ to improve OS through a good pathological response. [ABSTRACT FROM AUTHOR]

Objective To investigate the diagnostic performance and safety of a three-dimensional 14-core biopsy ( 3D14PBx) method, which is a combination of the transrectal six-core and transperineal eight-core biopsy methods. Patients and Methods Between December 2005 and August 2010, 1103 men underwent 3D14PBx at our institutions and were analysed prospectively. Biopsy criteria included a PSA level of 2.5-20 ng/mL or abnormal digital rectal examination ( DRE) findings, or both. The primary endpoint of the study was diagnostic performance and the secondary endpoint was safety. We applied recursive partitioning to the entire study cohort to delineate the unique contribution of each sampling site to overall and clinically significant cancer detection. Results Prostate cancer was detected in 503 of the 1103 patients (45.6%). Age, family history of prostate cancer, DRE, PSA, percentage of free PSA and prostate volume were associated with the positive biopsy results significantly and independently. Of the 503 cancers detected, 39 (7.8%) were clinically locally advanced (≥ cT3a), 348 (69%) had a biopsy Gleason score ( GS) of ≥7, and 463 (92%) met the definition of biopsy-based significant cancer. Recursive partitioning analysis showed that each sampling site contributed uniquely to both the overall and the biopsy-based significant cancer detection rate of the 3D14PBx method. The overall cancer-positive rate of each sampling site ranged from 14.5% in the transrectal far lateral base to 22.8% in the transrectal far lateral apex. As of August 2010, 210 patients (42%) had undergone radical prostatectomy, of whom 55 (26%) were found to have pathologically non-organ-confined disease, 174 (83%) had prostatectomy GS ≥7 and 185 (88%) met the definition of prostatectomy-based significant cancer. Conclusions This is the first prospective analysis of the diagnostic performance of an extended biopsy method, which is a simplified version of the somewhat redundant super-extended three-dimensional 26-core biopsy. As expected, each sampling site uniquely contributed not only to overall cancer detection, but also to significant cancer detection. 3D14PBx is a feasible systematic biopsy method in men with PSA <20 ng/mL. [ABSTRACT FROM AUTHOR]

Objective To assess the change in disease-specific health-related quality of life and to evaluate patient-perceived satisfaction after radical prostatectomy (RP) or intensity-modulated radiotherapy (IMRT) with androgen deprivation therapy (ADT) for patients with high-risk prostate cancer (PCA) that has been defined by the European Association of Urology guideline. Methods Between 2006 and 2010, 150 patients with high-risk PCA who underwent either RP (n = 97) or IMRT with ADT (n = 53) were enrolled in this prospective health-related quality of life study. Disease-specific health-related quality of life at baseline, 3, 6, 12, and 24 months and patient-perceived satisfaction at 12 and 24 months after these treatments were estimated using the Expanded Prostate Cancer Index Composite. Results Urinary bother and irritation and obstruction scores did not change significantly between both treatment groups throughout the 2-year follow-up. ADT greatly influenced sexual and hormonal functions and bothers in patients who received IMRT with ADT. The patient-perceived satisfaction at 12 months after the treatments was approximately 80% in both treatment groups, and there was no significant difference between the 2 groups. At 12 months after the treatments, urinary function ( P = .001) was identified as the most significant predictor of patient-perceived satisfaction, although it was not associated with the treatment type. Conclusion The majority of patients with high-risk PCA who received RP or IMRT with ADT reported high patient-perceived satisfaction after the treatments. This study showed that improvement in urinary function might contribute to patient-perceived satisfaction after the treatments. [ABSTRACT FROM AUTHOR]

Background: This study was designed to compare the long-term oncological outcome of patients with clinical T3 (cT3) prostate cancer (PCA) treated with either radical prostatectomy (RP) or external-beam radiation therapy (EBRT) and to identify predictors of oncological outcomes. Methods: A total of 231 patients with cT3 PCA underwent either RP ( n = 112) or EBRT ( n = 119). Local progression-free (LPFS), distant metastasis-free (DMFS), cancer-specific (CSS), and overall survival curves were generated with the Kaplan-Meier method, and the differences in survival rates between the two groups were assessed with a log-rank test. Cox proportional stepwise multivariate analysis was used to assess the association of variables to the oncological outcomes. Results: The median follow-up of the RP and EBRT groups was 93 and 85 months, respectively ( p = 0.004).The 10-year LPFS, DMFS, and CSS rates were not statistically different between the two groups (90.2, 73.9, and 93.7 % in the RP group and 82.7, 88.2, and 85.1 % in the EBRT group; p = 0.25, 0.10, and 0.10, respectively). The Cox proportional multivariate analysis revealed that clinical T3b (cT3b) ( p = 0.001) and a biopsy Gleason score of 7-10 ( p = 0.043) were significant predictors of cancer-specific mortality and that cT3b was also a significant predictor of local progression and all-cause mortality. Conclusion: In cT3 PCA, both RP and EBRT provide an excellent long-term oncological outcome. cT3b was the strongest predictor of oncological outcome for the patients with locally advanced PCA who underwent the definitive therapy. [ABSTRACT FROM AUTHOR]

Background: This study re-evaluated the efficacy and tolerability of cisplatin, etoposide, and ifosfamide (VIP) combination chemotherapy as an alternative first-line regimen for patients with disseminated germ cell cancer (GCC) in this granulocyte colony-stimulating factor (G-CSF) era. Methods: The medical records of 91 consecutive patients with previously untreated disseminated GCC who received first-line VIP between 1995 and 2011 were retrospectively reviewed. Results: The 5-year overall survival rates for patients with good (n = 49), intermediate (n = 22) and poor (n = 20) prognoses according to the International Germ Cell Cancer Collaborative Group classification were 100, 79 and 83%, respectively. G-CSF was given to all patients, and no treatment-related deaths due to myelosuppression occurred. Conclusion: The present study is the first to examine the therapeutic outcomes and safety profile of first-line VIP after routine G-CSF use. VIP might be an alternative first-line regimen for patients with disseminated GCC in this G-CSF era. © 2014 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Purpose: The purpose of the study is to assess longitudinal changes in general and disease-specific health-related quality-of-life (HRQOL) indices after intensity-modulated radiotherapy (IMRT) monotherapy for patients with localized prostate cancer (PCA). Methods: Between 2006 and 2010, 91 patients with localized PCA underwent IMRT monotherapy and were enrolled into this prospective study. At baseline, and at 3, 6, 12, and 24 months after IMRT, the general and prostate-specific HRQOL were estimated using physical (PCS) and mental component summaries (MCS) calculated using the Medical Outcomes Study 8-Item Short Form Health Survey and Expanded Prostate Cancer Index Composite (EPIC). Results: For 2 years, there were no significant changes in EPIC scores in all subscales of urinary domain, hormonal function, and bother. Bowel and sexual function scores decreased after IMRT and did not return to those at baseline ( p = 0.006 and < 0.001, respectively). PCS began to decrease at 3 months after IMRT and then returned to the baseline score at 24 months. In contrast, the MCS score began to significantly increase after IMRT, and thereafter the score remained constant until 24 months ( p < 0.001). On multivariate logistic regression analysis, urinary ( p = 0.003) and sexual functions ( p = 0.0005) at baseline were identified as significant predictors of EPIC urinary irritative/obstructive score and sexual function at 24 months after IMRT. Conclusion: Urinary function, including irritative/obstruction symptoms and hormonal function, was not affected by IMRT. However, bowel and sexual function decreased after IMRT. These findings will provide important information for PCA patients considering IMRT. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the long-term effect of the processus vaginalis transection method, which we previously developed to prevent postradical prostatectomy inguinal hernia. Methods: Our hernia prevention procedure is designed to prevent postoperative indirect hernias. The procedure is performed in the following order: (1) the spermatic cord is isolated and mobilized in the pelvis, (2) the vas deferens is isolated from the spermatic cord and ligated, and (3) the processus vaginalis is dissected free of the other spermatic cord elements, mainly spermatic vessels, ligated near the peritoneum, and transected. Between February 2006 and August 2008, 435 consecutive patients underwent the inguinal hernia prevention procedure concurrently with open radical retropubic prostatectomy. The control group comprised 433 patients who had undergone radical retropubic prostatectomy without hernia prevention immediately before the introduction of this hernia prevention procedure was introduced (between January 2001 and January 2006). Results: No significant complications associated with the hernia prevention procedure were observed, except for a few minor peritoneal injuries that were easily repaired during surgery. An inguinal hernia developed postoperatively in 109 of the 433 control patients (25.2%) during the median follow-up of 68 months. In contrast, 4 of the 435 patients (0.9%) who underwent the hernia prevention procedure developed an inguinal hernia during the median follow-up of 42 months. Conclusion: The processus vaginalis transection method is safe and effective in the long-term prevention of postradical prostatectomy inguinal hernia. [ABSTRACT FROM AUTHOR]

Objective To investigate the association between lower urinary tract symptoms status and prostate cancer risk at initial extended biopsy. Methods Between 2005 and 2011, the International Prostate Symptom Score was completed on 1467 consecutive men with prostate-specific antigen <10 ng/mL and non-suspicious digital rectal examination. After excluding 308 men treated with alpha-blockers, the remaining 1159 men were enrolled in the present study. Lower urinary tract symptoms status was divided into absent or mild ( International Prostate Symptom Score scores of 0-7) and moderate or severe lower urinary tract symptoms ( International Prostate Symptom Score scores of 8-35). The risks of prostate cancer diagnosis and high-grade ( Gleason score ≥4 + 3) prostate cancer diagnosis in relation to lower urinary tract symptoms status was evaluated using logistic regression. A stratified analysis based on prostate volume (<30 cc, 30-50 cc and >50 cc) was also carried out. Results Of 1159 patients, 421 (36.3%) had a positive biopsy and 590 (51.0%) had moderate or severe lower urinary tract symptoms. On multivariate analysis, absent or mild lower urinary tract symptoms had a significant and positive impact on the risk of prostate cancer and high-grade disease (odds ratio 1.64 and 1.70, P = 0.0007 and 0.0121, respectively). Furthermore, the aforementioned findings for prostate cancer detection did not change throughout every prostate volume subgroup. In contrast, in men with prostate volume ≤50 cc, but not in those with prostate volume >50 cc, prostate-specific antigen or %free prostate-specific antigen remained as a significant predictor of prostate cancer. Conclusion In men with elevated prostate-specific antigen, absent or mild lower urinary tract symptoms are positively associated with prostate cancer and high-grade disease regardless of the prostate volume. This finding is especially useful in men with enlarged prostates. [ABSTRACT FROM AUTHOR]

Background: C-reactive protein (CRP) was an independent prognostic factor for metastatic renal cell carcinoma in the cytokine era. However, the impact of CRP on the survival of metastatic renal cell carcinoma patients treated with tyrosine kinase inhibitors has not yet been investigated. Therefore, we further evaluated the prognostic impact of CRP for patients with metastatic renal cell carcinoma treated with molecular-targeted agents of tyrosine kinase inhibitors. Methods: Fifty-two patients were treated with tyrosine kinase inhibitors for metastatic renal cell carcinoma at our institution. Overall, 31 and 21 patients were administered sunitinib and sorafenib, respectively. The prognostic value of all variables, including CRP, for overall survival was assessed using the Cox proportional hazards model. Results: The median baseline CRP level was 4.9 mg/l. In multivariate analysis, CRP was an independent predictor for overall survival as both continuous and categorical variable. The median overall survival times of patients with non-elevated CRP concentration (<8 mg/l) were not reached, compared with those of patients with elevated CRP concentration (8 mg/l or greater) of 15.9 months. There was a significant difference in overall survival rates between the two groups, with 1- and 3-year overall survival rates of 92.8 and 69.3 % versus 50.2 and 22.9 % for the non-elevated CRP group and the elevated CRP group ( p = 0.003), respectively. Conclusions: CRP has a significant impact on overall survival of patients with metastatic renal cell carcinoma carcinoma treated with tyrosine kinase inhibitors. [ABSTRACT FROM AUTHOR]

Background: Bisphosphonates play an indisputable role in preventing skeletal-related events (SREs) secondary to bone metastases, and also have a direct effect on tumor cells. However, it remains unclear whether bisphosphonates improve overall survival (OS) for renal cell carcinoma (RCC) patients with bone metastases. Methods: Between 1978 and 2010, a total of 45 patients who had RCC metastatic to bone and were classified as intermediate risk according to Memorial Sloan-Kettering Cancer Center criteria were included in this retrospective study. In this cohort, 23 patients received zoledronic acid (ZOL) treatment (ZOL-treated group) whereas the other 22 did not (non-ZOL-treated group). The primary endpoint was OS and the secondary endpoint was the SRE rate defined as the total number of SREs divided by the total years under study. Results: For the cohort of 45 patients, the median OS from diagnosis of bone metastases was 27.2 months. Multivariate analysis showed that lower serum calcium ( p = 0.0083) and ZOL treatment ( p = 0.0013) were independent factors predicting longer survival. The ZOL-treated group had significantly longer OS than the non-ZOL-treated group ( p = 0.0034). Patients in the ZOL-treated group experienced a lower SRE rate than patients in the non-ZOL-treated group ( p = 0.0453). In particular, none of the patients in the ZOL-treated group developed spinal compression whereas 6 (28 %) in the non-ZOL-treated group did ( p = 0.0479). Conclusions: The current study indicates that ZOL not only reduces SREs but possibly improves OS in these patients. [ABSTRACT FROM AUTHOR]

Objectives To determine the relationship between body mass index and prostate cancer risk at biopsy in Japanese men, and to compared the risk with that of Caucasian men. Methods We retrospectively evaluated 3966 men with prostate-specific antigen levels from 2.5 to 19.9 ng/ mL who underwent an initial extended prostate biopsy. Using logistic regression, odds ratios of each body mass index category for risk of prostate cancer and high-grade disease ( Gleason score ≥4 + 3) were estimated after controlling for age, prostate-specific antigen, %free prostate-specific antigen, prostate volume, digital rectal examination findings, family history of prostate cancer and the number of biopsy cores. Patients were divided into six categories according to their body mass index (kg/m2) as follows: <21.0, 21.0-22.9, 23.0-24.9, 25.0-26.9, 27.0-29.9 and ≥30.0. Results A significant positive association was observed between body mass index and prostate cancer risk at biopsy, with an increased risk observed in men whose body mass index was ≥27.0 compared with the reference group. A significantly increased risk starting at body mass index ≥25.0 was found in high-grade disease. In contrast to our results, there has been no reported increase in the risk of prostate cancer at biopsy in Caucasians within the overweight range (body mass index of 25.0-29.9 based on World Health Organization classification). Conclusions Japanese men within the overweight body mass index range who have an elevated prostate-specific antigen level also have a significant risk of harboring prostate cancer, especially high-grade disease. Overweight Japanese might be at greater prostate cancer risk at biopsy than overweight Caucasians. [ABSTRACT FROM AUTHOR]

Objective: The RENAL nephrometry scoring system charac-terizes tumors according to their size, growth pattern, loca-tion and nearness to the renal sinus or collecting system. The current study alms to evaluate the RENAL nephrometry scor-ing system in adopting nephron-sparing surgery (NSS) for cTI renal cancer. Methods: Clinicopathological data of 200 con-secutive patients who had undergone radical nephrectomy (RN) or NSS for clinical stage T1 renal cell cancer at our single institution during 2005-2009 were investigated retrospec-tively. Results: Of 200 patients, 103 were scheduled for RN, whereas 97 were planned to undergo NSS, 9 of whom actu-ally underwent RN. Those who were planned to undergo NSS were youngerand had smaller tumors (p<0.001).The median RENAL score was significantly lower among those who were originally assigned to NSS (5, range 4-10) versus RN (8, range 4-11) (p < 0.001). Three months after surgery, the renal func-tion of patients who had been scheduled for NSS was signifi-cantly better than in those treated by RN (p < 0.001). Conclu-sions: This study suggests that the RENAL nephrometry scor-ing system is a useful tool in adopting NSS for cTI renal cancer and that objective decision-making for NSS was possible. [ABSTRACT FROM AUTHOR]

Study Type - Prognosis (inception cohort) Level of Evidence 2 What's known on the subject? and What does the study add? The criteria used for selecting patients with prostate cancer for active surveillance (AS) are still not satisfactory due to the difficulty in predicting the significance of the prostate cancer. Urologists could predict insignificant prostate cancer by incorporating cumulative cancer length and biopsy Gleason score, derived from extended biopsy. The present study has added new criteria for predicting insignificant prostate cancer, which would lead to a better selection of candidates for AS. OBJECTIVE To develop extended biopsy based criteria for predicting insignificant cancer (IC) using extended biopsy findings., PATIENTS AND METHODS From 2000 to 2009, 1575 patients with prostate cancer were primarily treated by radical prostatectomy in two referral hospitals., Of these, the study cohort comprised 499 patients with extended biopsy confirmed, clinically organ-confined (cT1-2N0M0) prostate cancer with PSA levels of <20 ng/mL., Cancer information obtained through extended biopsy included cumulative cancer length (CCL) divided by the number of biopsy cores (CCL/core)., RESULTS Pathological examination revealed 39 ICs (7.8%). All these ICs fell in a category of prostate cancer with clinical stage ≤T2a and 2005 International Society of Urological Pathology Consensus Conference (ISUP) modified biopsy Gleason score ≤7., Accordingly, we analysed predictors of IC in a subset cohort of 370 patients in this category. A multivariate logistic regression analysis revealed that 2005 ISUP modified biopsy Gleason score and CCL/core were independently significant predictors of IC., We determined a threshold value of CCL/core of 0.20 mm for predicting IC using receiver operating characteristic analysis., Based on these findings, we developed simple extended biopsy based criteria for predicting IC as follows: (i) PSA level of <20 ng/mL; (ii) Clinical stage ≤T2a; (iii) 2005 ISUP modified biopsy Gleason score ≤6; (iv) CCL/core of <0.20 mm., The specificity of the criteria was 91%, which was significantly higher than the value from a subset of criteria without item iv ( P < 0.001)., CONCLUSION We have developed extended biopsy based criteria for predicting IC incorporating the 2005 ISUP modified biopsy Gleason score and CCL/core. [ABSTRACT FROM AUTHOR]

Bone metastases often create serious clinical problems: they lead to poor performance status due to pathologic fractures, spinal cord compression and intractable pain, commonly referred to as skeletal-related events. The receptor activator of nuclear factor-κB (RANK), the RANK ligand (RANKL), and osteoprotegerin, a decoy receptor for RANK, regulate osteoclastogenesis and may play a key role in bone metastasis. Denosumab (XGEVA; Amgen, Thousand Oaks, CA), a fully human monoclonal antibody that binds to and neutralizes RANKL, inhibits osteoclast function, prevents generalized bone resorption and local bone destruction, and has become a therapeutic option for preventing or delaying first on-study skeletal-related events in various malignancies. In the context of urological cancer, three main Phase III clinical studies have been published in prostate cancer. This article provides a brief overview of the characteristics of bone metastasis in urological cancers, reviews the mechanisms of bone metastasis, including the RANK/RANKL/osteoprotegerin axis, the current standard of care, zoledronic acid, and describes the efficacy of the novel bone-targeted agent denosumab in bone metastasis. Denosumab is emerging as a key therapeutic option in the treatment of bone metastases from urological cancers. [ABSTRACT FROM AUTHOR]

Study Type - Prognosis (cohort) Level of Evidence 2a What's known on the subject? and What does the study add? C-reactive protein (CRP) level has been shown to be a significant prognostic factor for various malignancies, including urothelial carcinoma treated surgically. Apart from CRP level, several prognostic factors have been identified for advanced urothelial carcinoma patients receiving a second-line chemotherapy. CRP could also be a significant prognostic factor for advanced urothelial carcinoma patients receiving a second-line chemotherapy. CRP kinetics, the dynamic change of CRP concentration, has a strong impact on survival. Adding to the baseline CRP status at the start of treatment, the normalization of CRP during treatment is significantly associated with prognosis. The period with normalized CRP level was strongly correlated with survival period. Therefore, CRP could be a potential biomarker for advanced urothelial carcinoma patients. OBJECTIVE To assess the impact of C-reactive protein (CRP) kinetics, the effect of dynamic changes of CRP concentration on the survival of patients with locally advanced or metastatic urothelial carcinoma (UC) treated by single chemotherapeutic regimen including cisplatin was examined., PATIENTS AND METHODS Eighty patients with advanced UC, who failed treatment of advanced UC with the first-line chemotherapy or who received perioperative treatment of neoadjuvant or adjuvant settings, were treated with gemcitabine, etoposide and cisplatin (GEP) as second-line chemotherapy., Patients were divided into three groups according to CRP kinetics based on baseline and nadir CRP concentrations. Patients whose baseline CRP levels were <5 mg/L, patients whose baseline CRP levels were ≥5 mg/L and normalized (<5 mg/L), and patients whose baseline CRP levels were ≥5 mg/L and never normalized were assigned to non-elevated, normalized and non-normalized CRP groups, respectively., The prognostic impact of CRP kinetics and the correlation between normalized CRP period and overall survival period were determined., RESULTS In 46 (57%) of the 80 patients, CRP levels were elevated at the diagnosis of advanced UC. During treatment, after a median follow-up period of 12 months CRP levels were normalized in 24 (71%) of 34 patients, whereas CRP levels remained elevated in the remaining 10 patients., Overall survival rates were significantly different between the non-elevated, normalized, and non-normalized CRP groups ( P < 0.001), with 1-year survival rates of 72, 51 and 14%, respectively. On multivariate analysis including Eastern Cooperative Oncology Group performance status, visceral metastasis, number of metastatic sites, previous definitive surgery, anaemia, baseline and nadir CRP levels (mg/L), and CRP kinetics status, CRP kinetics was an independent and significant factor for overall survival., The normalized CRP period was significantly correlated with the overall survival period in 52 patients who died., CONCLUSIONS CRP kinetics is significantly associated with the prognosis and survival period of patients with advanced UC treated by chemotherapy., Although larger confirmatory studies are warranted to validate our results, CRP can potentially be a useful biomarker for patients with advanced UC. [ABSTRACT FROM AUTHOR]

Objectives: Obese men with benign prostate hyperplasia might have lower serum prostate-specific antigen because of hemodilution, resulting in underestimation of total prostate volume by serum prostate-specific antigen. The aim of this study was to compare the performance of prostate-specific antigen mass as the absolute amount of prostate-specific antigen protein secreted into circulation with that of serum prostate-specific antigen in the prediction of total prostate volume. Methods: A total of 1517 men with serum prostate-specific antigen up to 10 ng/mL, including 1425 with biopsy-proven benign prostate hyperplasia, were enrolled in this study. Height and weight were used to estimate body mass index, body surface area and plasma volume. Prostate-specific antigen mass was calculated as serum prostate-specific antigen multiplied by plasma volume. The association between serum prostate-specific antigen or prostate-specific antigen mass and transrectal ultrasound-measured total prostate volume were evaluated by Pearson's correlation coefficient (Υ), linear regression analyses and receiver operating characteristic curves. Results: Serum prostate-specific antigen had an inverse relationship with plasma volume, decreasing as plasma volume increased, after adjustment of total prostate volume. Larger total prostate volume per serum prostate-specific antigen was found in men with higher body mass index or plasma volume. Among all participants, the correlation (Υ = 0.456) between prostate-specific antigen mass and total prostate volume was apparently stronger than that (Υ = 0.442) between serum prostate-specific antigen and total prostate volume. Prostate-specific antigen mass outperformed serum prostate-specific antigen at estimating total prostate volume cut-off values of 30 and 40 mL. These findings were more significant in men aged ≥60 years. Conclusions: Prostate-specific antigen mass performs better than serum prostate-specific antigen in estimating TPV, especially in men aged ≥60 years. [ABSTRACT FROM AUTHOR]

A correction to the article "Successful long-term remission following repeated salvage surgery in a patient with chemotherapy-resistant metastatic non-seminomatous germ cell tumor: an additional report to Int J Clin Oncol 2007" which was published in a previous issue of 2010 is presented.

Objective: To investigate the association of diabetes mellitus (DM) with prostate cancer (PCa) risk and grade among Japanese patients undergoing extended biopsy and to investigate how obesity modifies these relationships. Methods: We retrospectively evaluated the data from 2038 patients with a prostate-specific antigen (PSA) level <10 ng/mL undergoing initial extended biopsy at our institutions. The DM history was determined by self-report and medication use. Multivariate analyses of DM for PCa risk and grade were done using logistic regression. Moreover, we examined whether these associations were modified by the body mass index using subgroup analyses (nonobese <25 kg/m2 or obese ≥25 kg/m2) and interaction tests. Cancer grade was classified according to the Gleason score (GS): low-grade (GS ≤6), intermediate-grade (GS 7), and high-grade (GS 8-10). Results: Of 2038 patients, obesity and DM was observed in 606 (30%) and 213 (11%), respectively. Also, 836 patients (41%) had positive biopsy findings. On multivariate analysis, we found no significant association of DM with the risk of overall PCa (P = .106) or the risk of low-grade (P = .735), intermediate-grade (P = .119), or high-grade (P = .110) disease. When stratified by obesity, the relative risk (RR) of PCa detection for diabetic men apparently increased with higher cancer grade (low grade, RR = 1.19, P = .71; intermediate grade, RR = 2.01, P = .099; high-grade, RR = 4.03, P = .025). However, in the nonobese men, no association was noted between DM and PCa risk, irrespective of grade. Obesity modified the effect of DM on high-grade disease risk with a trend (P for interaction = .087). Conclusion: DM was associated with more aggressive PCa detection among Japanese obese patients with gray-zone PSA levels undergoing extended biopsy. [ABSTRACT FROM AUTHOR]

Study Type - Therapy (case series) Level of Evidence 4 What's known on the subject? and What does the study add? A randomized prospective phase III clinical trial for systemic treatment-naïve metastatic renal cell cancer (RCC) patients demonstrated the superiority of sunitinib over interferon with an acceptable safety profile. However, a commonly asked question is whether patients with RCC in clinical trials are representative of those with this disease being seen in ordinary clinical practice. To our knowledge, this is the first report of sunitinib for the Japanese patients with metastatic RCC in ordinary clinical practice. The estimated median PFS and OS in this study were 9.3 and 32.2 months, respectively. The application of the MSKCC model distinctly separated OS curves ( P < 0.001), suggesting that MSKCC prognostic factors might be still valid to predict survival in metastatic RCC in the era of molecular targeted therapy. OBJECTIVES To report the treatment efficacy and safety profile of sunitinib for patients with metastatic renal cell carcinoma (RCC) in ordinary clinical practice. [ABSTRACT FROM AUTHOR]

Study Type - Diagnostic (exploratory cohort) Level of Evidence 3a What's known on the subject? and What does the study add? Initial transrectal 12-core biopsy has a small but definite risk of missing anterior significant prostate cancers irrespective of age, PSA, prostate volume and DRE findings. Our study yields valuable information for diagnosis and treatment decision of prostate cancer based on transrectal 12-core biopsy. OBJECTIVE [ABSTRACT FROM AUTHOR]

Objective: To verify the prognostic impact of C-reactive protein (CRP) for patients with castration-resistant prostate cancer (CRPC) treated with docetaxel in a single institution. Methods: A group of 80 consecutive patients with CRPC were treated with docetaxel in our institution from January 2005 to May 2010. The patients received 75 mg/m2 of docetaxel intravenously every 3 weeks. The prognostic value of all covariables, including CRP, was assessed using the Cox proportional hazard model. Risk stratification for overall survival was described from the results of the multivariable analysis. Results: The median survival period for all patients was 14.5 months. The multivariable analysis showed that CRP and hemoglobin levels were independent prognostic factors for overall survival. Based on the presence of an elevated CRP concentration and/or a low hemoglobin level, all patients were stratified into 3 risk groups: those with no risk factors (low-risk group), those with 1 risk factor (intermediate-risk group), and those with 2 risk factors (high-risk group). The overall survival curves were clearly tiered according to the risk groups, with the 1-year overall survival rates being 86.3%, 60.5%, and 23.0% for the low-, intermediate-, and high-risk groups, respectively (P <.001). Conclusion: CRP is an independent prognostic factor for overall survival of patients with CRPC treated with docetaxel. Risk stratification based on CRP and hemoglobin could be helpful for estimating the overall survival. [ABSTRACT FROM AUTHOR]

Objective: It was the aim of this study to assess the outcome of prostate cancer patients with preoperative prostate-specific antigen (PSA) levels ≥100 ng/ml who were treated with antegrade radical prostatectomy with intended wide resection (aRP). Patients and Methods: Eighteen patients who underwent aRP had an initial PSA level ≥100 ng/ml. Overall survival, disease-specific survival and biochemical progression-free survival (bPFS) rates were determined, and predictors of treatment outcome were examined. Results: The median serum PSA level was 159.5 ng/ml. All patients but one had received neoadjuvant androgen deprivation therapy (ADT), while only 2 patients received adjuvant ADT. Five patients were classified as stage pT2, 6 as pT3a, 6 as pT3b and 1 as pT4. Four patients had locoregional lymph node metastases. Twelve patients developed PSA failure. Eight of them received salvage ADT. The estimated 10-year bPFS rate was 25.0% and the overall survival and disease-specific survival rates were 92.9 and 100%, respectively, at a median follow-up of 6 years. Multivariate analysis revealed only the clinical stage to be predictive of bPFS based on preoperative variables. On the other hand, surgical margin status, extracapsular extension and organ-confined disease were identified as being significant postoperative predictors. Conclusions: This study showed a comparatively satisfactory outcome for clinically non-metastatic prostate cancer with PSA levels ≥100 ng/ml treated by aRP. Copyright © 2011 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the prognostic effect of age in patients with localized renal cell carcinoma (RCC) and investigate the incidence of Xp11 translocation RCC in young patients who developed recurrence. Methods: From 1990 to 2007, 2403 Japanese patients underwent nephrectomy for presumed RCC at 9 institutions. Of those, 1143 patients had localized RCC (Stage pT1-2N0M0). Their clinical data were retrospectively reviewed. In the present study, 131 patients (11%) were considered young (≤45 years at diagnosis). In the young patients with recurrence, the nephrectomy specimens were immunostained with TFE3 to determine the incidence of Xp11 translocation RCC. Results: During the median follow-up of 47 months, 3 cancer deaths (2.2%) occurred among young patients and 51 (5.0%) among older patients. The 5-year cancer-specific survival (CSS) rate was significantly better for the younger patients than for the older patients (P = .049). Multivariate analysis showed that age was significantly associated with CSS, as were the pathologic T stage, tumor grade, and symptoms at diagnosis. The hazard ratio of young age was 0.31 (95% confidence interval 0.077-0.87). The recurrence-free survival curves revealed no difference between these 2 groups. Of the 74 patients with recurrence, the CSS after recurrence was significantly better in the younger patients than in the older patients (P = .0010). Of the 8 young patients with recurrence, 4 had Xp11 translocation RCC, and 3 survived for >5 years after recurrence. Conclusions: Compared with the older patients, the young patients with RCC had similar recurrence-free survival rates but better CSS rates. This might have been because significant numbers of the young patients had Xp11 translocation RCC. [ABSTRACT FROM AUTHOR]

Objectives: To develop a nomogram based on a cohort examined with 3-dimensional (3D) protocol for diagnosis of prostate cancer on repeat biopsy. Methods: Of 4074 consecutive men undergoing prostate biopsy at our institutions between 2000 and 2009, 775 men with at least 1 previous negative biopsy underwent repeat biopsy with a 3D protocol. Men with previous atypical glands or atypical small acinar proliferation and/or without available prostate-specific antigen (PSA) kinetics information were excluded. The remaining 515 men constituted the study cohort. We developed a logistic regression–based nomogram with 70% of the cohort selected randomly; we validated it with the remaining 30%. Predictive accuracy and performance characteristics were assessed using the area under the receiver operating characteristic curve (AUC) and calibration plots, respectively. The threshold probability was evaluated with decision curve analysis. Results: We developed a novel repeat biopsy nomogram incorporating age, free to total PSA ratio, prostate volume, history of previous extended biopsy, and PSA doubling time. Validation confirmed predictive accuracy with an AUC value of 0.791. Calibration plots showed good agreement. The decision curve of the nomogram was superior to the decision curve of biopsying all men in a range of threshold probability over 0.15. At the threshold of 0.2, the number of unnecessary biopsies could be reduced by 10 per 100, without missing prostate cancer. Conclusions: We developed a novel repeat biopsy nomogram based on a cohort examined with 3D protocol. This repeat biopsy nomogram is clinically beneficial, preventing a substantial number of unnecessary biopsies. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the correlations between the initial tumor size and size reduction rate in patients treated with targeted agents. To select the patients who can benefit the most from treatment with targeted agents, it will be necessary to find a tumor characteristic that predicts their effectiveness. Methods: The data from 139 metastatic and 16 primary lesions treated with the targeted agents were retrospectively analyzed. They consisted of 86 sunitinib-treated and 69 sorafenib-treated lesions in 54 patients with metastatic renal cell carcinoma who had undergone treatment from April 2008 to July 2010. The relationship between the longest tumor diameter at baseline and the rate of reduction in tumor size was assessed using the Spearmancorrelation test. Results: A linear, moderate to strong association between the initial tumor size and tumor size reduction rate was shown (correlation coefficient −0.441, P < .001). When these tumors were divided into 2 groups at the threshold value (23.95 mm), which was decided by the receiver operating characteristic curve analysis, the smaller tumors demonstrated a significantly greater size reduction than the larger tumors according to the Mann-Whitney U test (P < .001). Both univariate and multivariate linear regression analyses revealed that only the initial tumor size was associated with the rate of reduction in individual tumors (P < .001). Conclusions: The initial tumor size was a good predictor of the tumor size reduction. This simple observation could be useful for physicians who treat patients with metastatic renal cell carcinoma. In addition, in assessing clinical trials of targeted agents for metastatic renal cell carcinoma using the ResponseEvaluation Criteria in Solid Tumors, perhaps this association should be considered. [ABSTRACT FROM AUTHOR]

Objectives: To investigate intraoperative and early postoperative complications of antegrade radical prostatectomy with intended wide resection (aRP) for clinically locally advanced prostate cancer (cLAD) and to compare with those of aRP for clinically localized prostate cancer (cLD). Methods: Between March 1994 and June 2007, 800 consecutive Japanese patients including 625 with cLD and 175 with cLAD underwent aRP and bilateral limited lymphadenectomy. Clinicopathological data including intraoperative and early postoperative complications (within 30 days after operation) were compared between cLD and cLAD groups. Results: No deaths occurred. Operative time and blood loss did not differ significantly between the groups. Intraoperative and early postoperative complications were observed in 11 (1.4%) and 123 (15.4%) of the entire cohort, respectively. Prevalent early postoperative complications were pelvic hematoma, wound infection, urinary retention and lymphocele or prolonged lymph drainage. There were no significant differences in the entire intraoperative and early postoperative complications between the groups. The majority of the early postoperative complications were minor. Conclusions: aRP for cLAD is technically feasible and a safe surgical procedure. If radical prostatectomy could be established as a standard treatment for cLAD in the future, aRP might be valuable as the first step of multimodal treatments. [ABSTRACT FROM AUTHOR]

Objectives: To examine Japanese patients who had received androgen-deprivation therapy (ADT) for longer periods, as it is known that ADT of patients with prostate cancer reduces their bone mineral density (BMD). However, our previous cross-sectional study revealed that short-term ADT (average, 23.5 months) does not significantly increase the prevalence of osteoporosis in Japanese patients. Methods: The subjects consisted of 201 native Japanese patients with prostate cancer. They comprised 113 ADT-treated and 88 hormone-naive patients. Lumbar spine, total hip, and femoral neck BMDs were measured by dual-energy x-ray absorptiometry and expressed in standard deviation units relative to the scores of young adult men (T-score) or age-matched men (Z-score). Serum levels of bone metabolism markers were also measured. Results: The ADT-treated patients had significantly lower BMD values, T-scores, and even Z-scores than the hormone-naive patients (P <.001). For patients who were hormone-naive, ADT-treated for less than 2 years, and ADT-treated for more than 2 years, the osteoporosis prevalence was 4.5% (4/88), 12.1% (4/33), and 10.8% (4/37), respectively. The ADT-treated patients had significantly higher serum amino-terminal telopeptide levels than the hormone-naive patients (P = .014), but significantly lower serum carboxy-terminal telopeptide of type-I collagen levels than the ADT-treated patients with bone metastasis (P <.001). Conclusions: Our cross-sectional study confirmed that both ADT-treated and hormone-naive Japanese patients with prostate cancer have low rates of osteoporosis. These findings are different from those of studies in western countries. Genetic and hormonal or other environmental factors may result in population differences in the characteristics of prostate cancer and BMD. [Copyright &y& Elsevier]

Objectives: To present a novel technique to prevent inguinal hernias after radical retropubic prostatectomy (RRP). The incidence of inguinal hernia after RRP has been reported to occur in the range 12%-21%. Indirect hernias are more common than direct hernias after RRP. Methods: A total of 569 Japanese patients with prostate cancer underwent antegrade RRP between January 2001 and February 2007. Since February 2006, 138 patients underwent procedures for concurrent inguinal hernia prevention at the time of RRP. For hernia prevention, the processus vaginalis was ligated close to the peritoneal cavity and transected. The remaining 431 patients who underwent the same RRP procedures without hernia prevention were considered control group. The incidence rates of postoperative inguinal hernia in the 2 groups were statistically compared. Results: An inguinal hernia developed postoperatively in 105 (24%) of the 431 control patients during follow-up of median 42 months. Hernia-free survival rates were 87%, 81%, and 77%, for 1-, 2-, and 3-year, respectively. By contrast, 2 of the 138 patients (1.4%) who underwent hernia prevention developed an inguinal hernia during follow-up of median 24 months. Hernia-free survival rates were both 99% for 1- and 2-year (P <.0001). The hernia prevention procedure added approximately 10 minutes to the surgery time. There were no significant complications associated with the hernia prevention procedure. Conclusions: Our results suggest that this prophylactic measure is safe and effective to prevent post-RRP inguinal hernias. However, a longer follow-up period is needed to confirm the results. [Copyright &y& Elsevier]

OBJECTIVE To investigate the rate of objective response and the skeletal-related event (SRE)-free survival after combined therapy with radiotherapy (RT) and zoledronate in patients with bone metastases from renal cell carcinoma (RCC). PATIENTS AND METHODS In all, 23 patients with RCC metastatic to bone were included in this retrospective study, of whom 13 had RT to bone metastases with no bisphosphonate therapy between 2000 and 2006, while the remaining 10 had combined therapy with RT and zoledronate (RT + Z) in 2006 and 2007. Significant calcifications of osteolytic metastases and/or shrinkage of bone lesions, as measured by computed tomography, were defined as a partial response. SREs were defined as any of pathological fracture, spinal cord compression, bone surgery, or additional RT to the bone. RESULTS In the RT + Z group, six patients had a partial response, showing evidence of calcification of their osteolytic bone metastases, while in the RT group, only one patient did ( P = 0.019). One patient in the RT + Z group had an SRE, while 10 in the RT group had SREs ( P = 0.003). The median SRE-free survival time was not reached in the RT + Z group, but in the RT group it was 18.7 months ( P = 0.046). CONCLUSION Combined therapy as RT + Z achieved a higher objective response rate (six of 10) and prolonged SRE-free survival than RT alone in patients with bone metastases from RCC. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the prognostic effect of the prostate cancer (PCa) volume involving the seminal vesicles (CVSVs) in the radical prostatectomy specimen from patients with Stage pT3bpN0 PCa. Methods: We retrospectively reviewed the clinical records of 27 patients with Stage pT3bpN0 PCa who had undergone radical prostatectomy alone. We measured the CVSVs using a grid method on the glass slide under microscopic inspection and investigated the association of the CVSVs with clinicopathologic variables. Results: Prostate-specific antigen (PSA) failure was confirmed in 11 of the 27 patients (41%) during a median follow-up of 34 months. The 3-year PSA failure-free survival rate was 48%. The median CVSVs was 1.14 cm3. On univariate analysis, a CVSVs of >1.63 cm3 was associated with positive surgical margins (P = .018), bilateral seminal vesicle involvement (P = .03), a long maximal tumor dimension (P = .031), and a greater preoperative PSA level (P = .0007). The 3-year PSA failure-free survival rate for those with a CVSVs of ≤1.63 cm3 vs >1.63 cm3 was 80% and 0%, respectively (P = .0009). On multivariate analysis, only the PSA level and CVSVs were identified as significant and independent predictors of PSA failure. Stratifying patients into 3 risk groups by these predictors, the PSA failure-free survival rate for patients with a PSA level ≥10 ng/mL and a CVSVs of >1.63 cm3 was significantly worse than for any other group. Conclusions: The CVSVs is useful and invaluable as an independent predictor of PSA failure in patients with Stage pT3bpN0 PCa. The measurement of the CVSVs is simple and helped to determine the indication for adjuvant treatment after radical prostatectomy. [Copyright &y& Elsevier]