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An inevitable feature of ultrasound-based diagnoses is that the quality of the ultrasound images produced depends directly on the skill of the physician operating the probe. This is because physicians have to constantly adjust the probe position to obtain a cross section of the target organ, which is constantly shifting due to patient respiratory motions. Therefore, we developed an ultrasound diagnostic robot that works in cooperation with a visual servo system based on deep learning that will help alleviate the burdens imposed on physicians.Our newly developed robotic ultrasound diagnostic system consists of three robots: an organ tracking robot (OTR), a robotic bed, and a robotic supporting arm. Additionally, we used different image processing methods (YOLOv5s and BiSeNet V2) to detect the target kidney location, as well as to evaluate the appropriateness of the obtained ultrasound images (ResNet 50). Ultimately, the image processing results are transmitted to the OTR for use as motion commands.In our experiments, the highest effective tracking rate (0.749) was obtained by YOLOv5s with Kalman filtering, while the effective tracking rate was improved by about 37% in comparison with cases without such filtering. Additionally, the appropriateness probability of the ultrasound images obtained during the tracking process was also the highest and most stable. The second highest tracking efficiency value (0.694) was obtained by BiSeNet V2 with Kalman filtering and was a 75% improvement over the case without such filtering.While the most efficient tracking achieved is based on the combination of YOLOv5s and Kalman filtering, the combination of BiSeNet V2 and Kalman filtering was capable of detecting the kidney center of gravity closer to the kidney's actual motion state. Furthermore, this model could also measure the cross-sectional area, maximum diameter, and other detailed information of the target kidney, which meant it is more practical for use in actual diagnoses.

Activation of androgen receptor (AR) stimulates the growth of not only androgen-dependent but also of androgen-refractory prostate cancer. However, neither the role of AR in invasion/metastasis nor the relationship between invasiveness and androgen-refractory status has been established. In this study, we used the androgen-dependent prostate cancer cell line MDA PCa 2b, derived from a human bone metastasis, to generate an invasive subline (MDA-I) using a Matrigel chamber. MDA-I cells expressed higher levels of AR and prostate-specific antigen than their less invasive parental cells. Blocking AR function or removal of androgen suppressed the invasion of MDA-I cells, whereas stimulating AR increased invasion. In addition, forced AR overexpression increased the invasiveness of MDA PCa 2b cells. Next, we showed that an androgen-refractory subline (MDA-hr) of MDA PCa 2b cells also expressed higher levels of AR and were more invasive than their parental androgen-dependent cells. Blocking AR function suppressed the invasiveness of MDA-hr cells. Gelatin zymography indicated that matrix metalloproteinase 2 (MMP-2) and MMP-9 activities were regulated by AR signaling and closely correlated with the invasiveness of the androgen-dependent and androgen-refractory prostate cancer cells. These data suggest that AR promotes the invasiveness of both androgen-dependent and androgen-refractory prostate cancer and that a more invasive phenotype might develop through AR activation during cancer progression. These findings potentially support the use of adjuvant hormonal therapy and the future development of more potent androgen blockade therapy. [Cancer Res 2008;68(4):1128–35]

Supplementary Figures 1-2 from Androgen Receptor and Invasion in Prostate Cancer

Purpose Renal function is frequently impaired in the patients with upper tract urothelial carcinoma. We aimed to evaluate the impact of renal function and its change after surgery on survival rates in patients with upper tract urothelial carcinoma after nephroureterectomy. Methods The study cohort comprised 755 patients with upper tract urothelial carcinoma who underwent nephroureterectomy between 1995 and 2016 at nine hospitals in Japan. Estimated glomerular filtration rate was calculated using the three-variable Japanese equation for glomerular filtration rate estimation from serum creatinine level and age. Outcomes were recurrence-free, cancer-specific and overall survivals. Univariate and multivariate Cox proportional hazards regression analyses were used. Results Median patients’ age was 72 years old. Pre- and post-surgical median estimated glomerular filtration rate were 55.5 and 42.9 ml/min/1.73 m2, respectively. Median estimated glomerular filtration rate decline after surgery, which represents function of the affected side kidney, was 13.1 ml/min/1.73 m2. The 5-year recurrence-free, cancer-specific and overall survivals were 68.3, 79.4 and 74.0%, respectively. Multivariate analysis indicated that lower preoperative estimated glomerular filtration rate and estimated glomerular filtration rate decline were associated with poorer recurrence-free, cancer-specific and overall survivals, but post-operative estimated glomerular filtration rate was not. Estimated glomerular filtration rate decline was more significant poor-prognosticator than preoperative estimated glomerular filtration rate. Proportions of the patients with estimated glomerular filtration rate Conclusions Lower preoperative renal function, especially of the affected side kidney, was significantly associated with poor prognosis after nephroureterectomy for upper tract urothelial carcinoma. Many patients with locally advanced disease have reduced renal function at diagnosis and even more after surgery.

Introduction The combination of ipilimumab plus nivolumab has been used as first-line therapy for metastatic renal cell carcinoma. While it is well known that hemodialysis patients have a higher rate of renal cell carcinoma compared to the general population, no reports have described the safety of ipilimumab-nivolumab in metastatic renal cell carcinoma patients on hemodialysis. Case presentation A 73-year-old man with a 21-year history of dialysis was referred to our department in 2019 for bilateral renal tumors and multiple lung nodules. He had already been diagnosed with bilateral renal tumors in 2015, without undergoing surgery due to comorbidities. In May 2019, contrast-enhanced computed tomography revealed multiple lung metastases in addition to the existing renal tumors; consequently, he was treated with four doses of nivolumab-ipilimumab with no adverse events. Conclusion The combination of ipilimumab plus nivolumab was safely used in a hemodialysis patient with metastatic renal cell carcinoma.

A 39-year-old man was referred to us for further examination of a right inguinal mass. He had noticed the mass several months prior and had undergone positron emission tomography/computed tomography, which revealed a mass with an SUVmax of 1.48 at the right inguinal subcutis. Magnetic resonance imaging (MRI) showed a well-circumscribed, heterogeneously enhanced adipose tumor 7cm in length, adjacent to the right spermatic cord and corpora cavernosa with clear boundaries. The tumor was a suspected atypical lipomatous tumor (well-differentiated liposarcoma), and he underwent tumor extirpation surgery. At surgery, the right inguinal canal was not opened, and the right spermatic cord and corpora cavernosa were safely spared. The excised specimen was composed of lipomatous tissue macroscopically. Histopathological diagnosis was of a spindle cell lipoma. Spindle cell lipomas are relatively rare, benign tumors, comprising only 1.5% of all lipomatous tumors. They arise most commonly in the shoulder and posterior region of the neck, and rarely develop in the groin. Differential diagnosis includes atypical lipomatous tumors, but radiological diagnosis is often difficult because of similar findings on MRI. Spindle cell lipomas typically present as a subcutaneous tumor, while atypical lipomatous tumors arise in the deep layers of connective tissue. This difference in the site of the tumor may contribute to their differential diagnosis before surgery.

Aims To determine whether ultrasound-assisted prompted voiding (USAPV) care is more efficacious than conventional prompted voiding (CPV) care for managing urinary incontinence in nursing homes. Methods Thirteen participating nursing homes in Japan were randomized to CPV (n = 7) or USAPV care group (n = 6). Residents of the allocated nursing homes received CPV (n = 35) or USAPV (n = 45) care for 8 weeks. In the CPV group, caregivers asked the elderly every 2-3 h whether they had a desire to void and prompted them to void when the response was yes. In the USAPV group, caregivers regularly monitored bladder urine volume by an ultrasound device and prompted them to void when the volume reached close to the individually optimized bladder capacity. Frequency-volume chart was recorded at the baseline and after the 8-week intervention to measure the daytime urine loss. Results The change in daytime urine loss was statistically greater in the USAPV (median, -80.0 g) than in the CPV (median, -9.0 g; P = .018) group. The proportion of elderly individuals whose daytime urine loss decreased by >25% was 51% and 26% in the USAPV and CPV group, respectively (P = .020). Quality-of-life measures of elderly participants showed no significant changes in both groups. The care burden scale score of caregivers was unchanged in the USAPV group (P = .59) but significantly worsened in the CPV group (P = .010) after the intervention. Conclusions USAPV is efficacious and feasible for managing urinary incontinence in nursing homes.

Objectives To investigate predictors of continence outcomes after robot-assisted radical prostatectomy. Methods Clinical records of 272 patients who underwent robot-assisted radical prostatectomy were investigated. Preoperative Overactive Bladder Symptom Score, International Prostate Symptom Score and clinicopathological factors were investigated, and relationships between factors and recovery of continence after robot-assisted radical prostatectomy were assessed. The presence of overactive bladder was defined as having urgency for more than once a week and having ≥3 points according to the Overactive Bladder Symptom Score. Results Age (≤66 years) was significantly associated with continence within 6 months after robot-assisted radical prostatectomy (P = 0.033). The absence of overactive bladder and lower Overactive Bladder Symptom Score (

[abstFig src='/00290002/15.jpg' width='300' text='Proposed method for tracking and following respiratory organ motion' ] High intensity focused ultrasound (HIFU) is potentially useful for treating stones and/or tumors. With respect to HIFU therapy, it is difficult to focus HIFU on the focal lesion due to respiratory organ motion, and this increases the risk of damaging the surrounding healthy tissues around the target focal lesion. Thus, this study proposes a method to cope with the fore-mentioned problem involving tracking and following the respiratory organ motion via a visual feedback and a prediction model for respiratory organ motion to realize highly accurate servoing performance for focal lesions. The prediction model is continuously updated based on the latest organ motion data. The results indicate that respiratory kidney motion of two healthy subjects is successfully tracked and followed with an accuracy of 0.88 mm by the proposed method and the constructed system.

To evaluate the efficacy of adjuvant systemic chemotherapy for locally advanced (pT3-4pN0/xM0) upper tract urothelial carcinoma (UTUC). We retrospectively reviewed the medical records of 109 patients with pT3-4pN0/xM0 UTUC who had undergone radical nephroureterectomy between 1996 and 2013 at our four institutions. The patients were divided into two groups: those who received adjuvant chemotherapy (AC group) and those who did not (surgery-alone: SA group). All chemotherapy regimens were cisplatin-based. Cox proportional hazards regression models addressed the associations between clinicopathological factors and recurrence-free survival (RFS) and cancer-specific survival (CSS). Forty-three (39.5%) out of the 109 patients underwent one to four cycles of adjuvant chemotherapy after nephroureterectomy. Median follow-up was 46.5 months. There were no significant differences in the background characteristics of the two groups, except for age. Recurrence developed in 11 (25.6%) and 29 (43.9%) patients in the AC and SA groups, respectively. Ultimately, six (14.0%) and 18 (27.3%) patients in the AC and SA groups, respectively, died of disease progression. On univariate analysis, hydronephrosis, nuclear grade, lymphovascular invasion, and adjuvant chemotherapy were significantly associated with both RFS and CSS. Charlson comorbidity index was associated only with CSS. On multivariate analysis, adjuvant chemotherapy was the only independent factor associated with improved RFS (p = 0.0178, HR = 0.41). Moreover, adjuvant chemotherapy (p = 0.0375, HR = 0.33), lower nuclear grade (p = 0.0070), and the absence of hydronephrosis (p = 0.0493) were independently associated with better CSS. Locally advanced (pT3-4pN0/xM0) UTUC patients who underwent cisplatin-based adjuvant chemotherapy demonstrated better RFS and CSS than those without adjuvant chemotherapy.

Objectives To assess the efficacy and feasibility of ultrasound-assisted prompted voiding for the management of urinary incontinence in nursing homes. Methods Nursing home residents who had received prompted voiding care for urinary incontinence were enrolled. The voided urinary volume and residual urinary volume were initially measured for a few days. The sum of the mean values of these volumes was considered as the optimal intravesical urinary volume for voiding. Thereafter, the participants underwent regular monitoring of intravesical urinary volume using an ultrasound device, and were prompted to void in a toilet when the monitored volume almost reached the optimal volume. The primary outcome for efficacy was the change in the absorbent cost before and after ultrasound-assisted prompted voiding care over 12 weeks. The feasibility was assessed by the change in activity of daily living of residents and quality of life measures of the care workers. Results A total of 77 residents completed the 12-week ultrasound-assisted prompted voiding intervention. The absorbent cost decreased in 40 participants (51.9%), and the overall cost decreased by 11.8% from the baseline value (P = 0.006). The activity of daily living did not significantly change. The quality of life of the care workers significantly improved for subscales of role emotional (P = 0.020) and mental health (P = 0.007). Conclusions The management of urinary incontinence for nursing homes residents through ultrasound-assisted prompted voiding seems to reduce the absorbent cost and to partially improve care workers' quality of life.

The patient is a 43-year-old male, presented with numbness of the left lower extremities. Imaging studies showed a pelvic tumor 20 cm in diameter, involving the left ureter, left common iliac vessels, left internal and external iliac vessels, and inferior mesenteric artery, which was deemed unresectable. Tumor biopsy confirmed liposarcoma. As chemotherapy was not effective, he was referred to us. Following femoral-femoral artery bypass in advance, the tumor was resected with the sigmoid colon, left kidney, ureter, left iliac vessels, and interior mesenteric artery. Removal of the tumor caused massive venous hemorrhage from the pre-sacral plexus, which was scarcely managed by gauze packing. Open abdominal management was selected to avoid abdominal compartment syndrome by severe intestinal edema. The packed gauze was retrieved on the fourth post-operative day, with laparotomy closed. The postoperative course was uneventful.

This study was conducted with the aim to investigate the feasibility of intermittent treatment with docetaxel chemotherapy for castration-resistant prostate cancer (CRPC). A total of 51 men with CRPC received docetaxel at 75 mg/m2 every 3 weeks combined with oral dexamethasone 1.0-2.0 mg/day between 2008 and 2013. The prostate-specific antigen (PSA) level was monitored every 3 weeks. Chemotherapy was suspended when the serum PSA level decreased to < 4 ng/ml, with a reduction rate of >50% from the baseline. Treatment was resumed when serum PSA increased to > 2 ng/ml, with an increase rate of >50% from the nadir. Of the 51 cases, 27 (52.9%) qualified for intermittent treatment; 17 patients received two courses of docetaxel chemotherapy and 10 received three courses. The median off-treatment interval was 266 days for the first drug holiday, 129.5 days for the second and 146.5 days for the third. The multivariate analysis indicated low baseline PSA (

Objective The aim of this study was to evaluate the efficacy and toxicity of the combination of docetaxel, ifosfamide and cisplatin as salvage chemotherapy after failure of standard cisplatin-based regimens for metastatic urothelial carcinoma. Methods We prospectively administered docetaxel, ifosfamide and cisplatin chemotherapy to patients with metastatic urothelial carcinoma refractory to standard cisplatin-based regimens from 2003 to 2013. Patients who had received only adjuvant and/or neoadjuvant chemotherapy were excluded. Eligible patients received every 28 days docetaxel 60 mg/m(2) on Day 1, ifosfamide 1.0 g/m(2) on Days 2-6 and cisplatin 20 mg/m(2) on Days 2-6. The primary endpoints were progression-free survival and overall survival, calculated from the start of docetaxel, ifosfamide and cisplatin chemotherapy. Secondary endpoints included objective response and related toxicity. Results Twenty-six cases received a median of 3.0 cycles of docetaxel, ifosfamide and cisplatin chemotherapy (interquartile range: 2-5), resulting in a median progression-free survival of 3 months (interquartile range: 2-9.5 months) and median overall survival of 8.5 months (interquartile range: 6.5-18.75 months), respectively. Of 26 patients, seven (27%) achieved major treatment responses, with one complete response (4%) and six partial responses (23%). Most of Grade 3/4 toxicities were hematologic events, including leukopenia (77%), anemia (54%) and thrombocytopenia (46%). No death from toxicity was observed. Conclusions Our results indicate that docetaxel, ifosfamide and cisplatin chemotherapy is a tolerable and moderately active regimen for metastatic urothelial carcinoma after failure of standard cisplatin-based regimens.

In recent years, HIFU (High Intensity Focused Ultrasound) therapy, which is one of the non-invasive therapies utilizing focused ultrasound, have attracted a great attention as a novel treatment method for a focal lesion, such as a tumor and a stone. However, the focal lesion moves in accordance with respiration, which may cause the damage for the surrounding normal tissues. To cope with this problem, we have developed a non-invasive ultrasound theragnostic system (NIUTS). In this report, we propose a novel tracking method, which is implemented in NIUTS, based on “Partial Active Shape Model” to enhance the servo performance for the focal lesion. Experimental results shows the effectiveness of the proposed servo method concerning the precision and robustness for a kidney phantom.

Resection of metastatic lesions (metastasectomy) is performed for highly selected patients with metastatic urothelial carcinoma (mUC). This study aimed to identify the clinicopathologic factors associated with oncologic outcome for patients who underwent metastasectomy for mUC. This analysis included 37 UC patients who underwent metastasectomy with curative intent at nine Japanese hospitals. The primary end point was cancer-specific survival. The Kaplan–Meier method with the log-rank test and the multivariable Cox proportional hazards model addressed the relationship between clinical characteristics and survival. Metastasectomy was performed for pulmonary (n = 23), nodal (n = 7), and other (n = 7) metastases. The median survival time was 35.4 months (interquartile range [IQR] 15.5, not reached) from the detection of metastasis and 34.3 months (IQR 13.1, not reached) from metastasectomy. The 5-year cancer-specific survival rate after detection of metastasis was 39.7%. In the multivariate analysis, the time from primary surgery to detection of metastasis (time-to-recurrence [TTR]) of 15 months or longer (hazard ratio [HR] 0.23; p = 0.0063), no symptoms of recurrence (HR 0.23; p = 0.0126), and serum C-reactive protein (CRP) levels lower than than 0.5 mg/dl (HR 0.24; p = 0.0052) were significantly associated with better survival. Long-term survival could be achieved for some patients with mUC who underwent metastasectomy. Lung and lymph nodes were predominant sites for metastasectomy. Symptoms, TTR, and CRP value were identified as associated with survival and should be taken into account when metastasectomy is considered.

We report early experiences of contact laser vaporization of the prostate for symptomatic benign prostatic hyperplasia (BPH).A total of 80 patients recruited at four institutions in Japan from April 2013 through September 2014 underwent contact laser vaporization of the prostate using 980 nm high power diode laser with an end-firing fiber in the contact mode. Patients were followed prospectively at 1 day, 2, 4, 8, 12, and 24 weeks, postoperatively per protocol, and at 1 and 2 years post-protocol.Of 76 eligible patients, 64 (84.2%) achieved more than 50% decrease in International Prostate Symptom Score at 24 weeks (95% confidence interval: 74.0-91.6%), clearing the pre-fixed non-inferiority efficacy level to transurethral resection of the prostate (65%). Symptom scores, maximum flow rate, post-void residual urine, and prostate volume showed significant improvements at 12 and 24 weeks after the surgery. Perioperative complications included transient urinary retention (n = 20), retrograde ejaculation (5), bladder neck contracture (4), urethral stricture (3), stone in prostatic bed (3), bladder stone (2), bladder perforation (1), bladder deformity (1), and transient urgency incontinence (1). Urinary retention and bladder neck contracture occurred almost exclusively at one institution. Improved symptom scores, maximum flow rate, and post-void residual urine observed at 24 weeks remained virtually unchanged at 1 and 2 years.Early experience of contact laser vaporization in Japan showed efficacy comparable to transurethral resection of the prostate as a surgical procedure for BPH at 24 weeks. Long-term efficacy of the procedure remains uncertain.

PURPOSE To evaluate the effectiveness of computed tomography (CT) for detection of exit-site and tunnel infections with a Tenckhoff catheter. MATERIALS AND METHODS The study enrolled patients with exit-site or tunnel infections who underwent ultrasonography (US), CT scans, and subsequent catheter removal or partial catheter reimplantation from 2010 to 2014. Control cases on peritoneal dialysis who underwent abdominal CT scans for other reasons were randomly selected. Attenuation of the soft tissue around the Tenckhoff catheter was measured in Hounsfield units (HU). RESULTS 9 infected cases and 15 control cases were identified. CT showed increased attenuation around the catheter in all cases, while ultrasonography detected a hypoechoic area only in one case with abscess formation. Maximal attenuation of the inflamed soft tissue was high (median, 36 HU) compared with normal fatty tissue (median, -75 HU). In all cases, one or two sites with increased fat density were observed focally along the catheter, and these areas did not always extend directly from the exit site. CONCLUSIONS In this retrospective study comprising a small number of cases, increased attenuation of fatty tissue around the Tenckhoff catheter correlated with exit-site or tunnel infections. CT might be an auxiliary tool for diagnosis, although CT costs much more than US and is not always available in general practice. Further prospective studies are needed. .

Purpose We aimed to identify prognostic clinicopathological factors and to create a nomogram able to predict overall survival (OS) in recurrent urothelial carcinoma of the bladder (UCB) after radical cystectomy (RC). Materials and methods Among 1,087 patients with UCB who had undergone RC at our 11 institutions between 1990 and 2010, 306 patients who subsequently developed distant metastasis or local recurrence or both were identified. Clinical data were collected with medical record review. Univariate and multivariate Cox regression models addressed OS after recurrence. A nomogram predicting postrecurrence OS was constructed based on Cox proportional hazards model, without using postrecurrence factors (systemic chemotherapy and resection of metastasis). The performance of the nomogram was internally validated by assessing concordance index and calibration plots. Results Of the 306 patients, 268 died during follow-up with a median survival of 7 months (95% CI: 5.8–8.5). Postrecurrence chemotherapy was administered in 119 patients (38.9%). Multivariable analysis identified 9 independent predictors for OS; period of time from RC to recurrence (time-to-recurrence), symptomatic recurrence, liver metastasis, hemoglobin level, serum alkaline phosphatase level, serum lactate dehydrogenase level, serum C-reactive protein level, postrecurrence chemotherapy, and resection of metastasis. A nomogram was formed with the following 5 variables to predict OS: time-to-recurrence, symptomatic recurrence, liver metastasis, albumin level, and alkaline phosphatase level. Concordance index rate was 0.75 (95% CI: 0.72–0.78) by internal validation using Bootstraps with 1,000 resamples. Calibration plots showed that the nomogram fitted well. Conclusions We identified 9 clinicopathological factors as independent OS predictors in postcystectomy recurrence of UCB. We also created a validated nomogram with 5 variables that efficiently stratified those patients regardless of eligibility for chemotherapy. The nomogram would be useful for acquiring relevant prognostic information and for stratifying patients for clinical trials.

Adjuvant androgen deprivation therapy is a common treatment option for prostate cancer after radical prostatectomy, especially in Asia. However, no study has investigated the oncological outcome after cessation of long-term adjuvant androgen deprivation therapy with favorable prostate-specific antigen control.Among 855 patients undergoing radical prostatectomy at our institution between 2000 and 2012, we identified 56 men with pT2-4N0-1M0 prostate cancer who had received long-term (2 years) adjuvant androgen deprivation therapy after radical prostatectomy and subsequently stopped it under a condition of continued prostate-specific antigen values0.1 ng/mL. The oncological outcome was evaluated using biochemical recurrence, defined as two consecutive prostate-specific antigen values ≥0.2 ng/mL, as the primary endpoint. Cox proportional hazards model was used for multivariate analysis. Age at androgen deprivation therapy cessation was dichotomized as68 years and ≥68 years, based on the most discriminatory cutoff.Median duration of adjuvant androgen deprivation therapy was 70 months. Overall, 13 of 56 (23%) patients developed biochemical recurrence with a median follow-up period of 41 months after androgen deprivation therapy cessation. Multivariate analysis identified age at androgen deprivation therapy cessation68 years and pN1 as independent predictors of biochemical recurrence. Predisposition of younger age to poorer survival may be related to more frequent testosterone recovery in younger men (73 vs 33%, P = 0.0299). One patient had evidence of clinical metastasis and no one died of prostate cancer.Androgen deprivation therapy cessation would be feasible in most men who received long-term adjuvant androgen deprivation therapy after radical prostatectomy with favorable prostate-specific antigen control. Risk factors of biochemical recurrence after androgen deprivation therapy cessation included younger age at androgen deprivation therapy cessation and pN1.

Background The optimal timing of salvage radiotherapy for biochemical recurrence after radical prostatectomy is controversial. In particular, the prognostic significance of salvage radiotherapy delivered before a current definition of biochemical recurrence, i.e. ultra-early salvage radiotherapy, is unclear. Methods We reviewed 76 patients with pT2-3N0M0 prostate cancer who underwent salvage radiotherapy for post-prostatectomy biochemical recurrence at the following three timings: ultra-early salvage radiotherapy (n = 20) delivered before meeting a current definition of biochemical recurrence (two consecutive prostate-specific antigen [PSA] values ≥0.2 ng/mL); early salvage radiotherapy (n = 40) delivered after meeting the definition but before PSA reached 0.5 ng/mL; and delayed salvage radiotherapy (n = 16) delivered after PSA reached 0.5 ng/mL. The primary endpoint was failure of salvage radiotherapy, defined as a PSA value ≥0.2 ng/mL. The log-rank test and Cox proportional hazards model were used for univariate and multivariate analyses, respectively. Results During the follow-up period (median: 70 months), four of 20 (20 %), nine of 40 (23 %) and seven of 16 (44 %) patients failed biochemically in the ultra-early, early and delayed salvage radiotherapy groups, respectively. On univariate analyses, the outcome of delayed salvage radiotherapy was worse than the others, while there was no significant difference between ultra-early and early groups. Multivariate analysis demonstrated the presence of Gleason pattern 5, perineural invasion and delayed salvage radiotherapy as independent predictors of poorer survival. Conclusions No survival benefit of ultra-early salvage radiotherapy was demonstrated, whereas delayed salvage radiotherapy was associated with worse outcome as reported in previous studies. Our results may support the current recommendations that salvage radiotherapy should be undertaken after two consecutive PSA values ≥0.2 ng/mL and before reaching 0.5 ng/mL.

We evaluated short- and long-term renal function in patients after radical cystectomy with urinary diversion and identified risk factors for the deterioration of renal function. This retrospective study comprised 91 patients who underwent radical cystectomy and urinary diversion for bladder cancer and survived ≥3 years after surgery. The estimated glomerular filtration rate (eGFR) was calculated, and longitudinal changes of eGFR were assessed. Deterioration in renal function in early and late postoperative years was defined as a ≥25 % decrease in the eGFR from preoperative to postoperative year one, and a reduction in the eGFR of >1 mL/min/1.73 m2 annually in subsequent years, respectively. Univariate and multivariate logistic regression analyses were used to evaluate its association with clinicopathologic features. The median follow-up period after surgery was 7 years (range 3–26). The mean eGFR decreased from preoperative 65.1 to 58.9 mL/min/1.73 m2 1 year after the surgery, followed by a continuous decline of ~1.0 mL/min/1.73 m2 per year thereafter. Multivariate analyses identified ureteroenteric stricture as the sole risk factor associated with early renal function deterioration [odds ratio (OR) 4.22, p = 0.037]. Diabetes mellitus (OR 8.24, p = 0.015) and episodes of pyelonephritis (OR 4.89, p = 0.038) were independently associated with the gradual decline in the late postoperative period. In cystectomy patients with urinary diversion, the rapid deterioration of renal function observed during the first year after surgery and the gradual but continuous decline in function thereafter were found to be associated with different risk factors.

Gleason pattern 5 (GP5), including tertiary GP5, at radical prostatectomy has reportedly been associated with poorer clinical outcome. However, it is undetermined how tertiary GP5 is handled in the new Gleason grade grouping starting in 2016, and its prognostic value in patients undergoing salvage treatment for postoperative biochemical recurrence (BCR) remains unclear.We retrospectively reviewed 116 patients with pT2-3N0M0 prostate cancer (PC) who received salvage treatment for BCR after radical prostatectomy between 2003 and 2014. The primary endpoint was failure of salvage treatment, defined as a single prostate-specific antigen (PSA) value ≥0.2 ng/ml after PSA nadir following salvage treatment. Associations of various clinicopathological factors, including GP5, with failure-free survival were assessed. Cox proportional hazards model was used for multivariate analysis.Patients received salvage treatment with either radiotherapy (n = 48), androgen-deprivation therapy (n = 61), or both (n = 7) for BCR. Twenty-three patients (19.8 %) experienced failure of salvage treatment, with a median follow-up period of 79 months. Univariate analysis associated GP5, Gleason score-based parameters, lymphovascular invasion, and PSA doubling time 6 months with poorer failure-free survival. Receiver operating characteristic curve analyses identified the area under the curve for GP5 (0.654) as the largest among those parameters (P = 0.0060). Multivariate analysis demonstrated that GP5 was the only independent predictor of poor outcome.The presence of GP5 is an independent predictor of poor prognosis in patients with pT2-3N0M0 PC undergoing salvage treatment for BCR after radical prostatectomy. GP5 may thus be a more useful marker than conventional Gleason score in this setting.

Study Type – Harm (case series) Level of Evidence 4 What's known on the subject? and What does the study add? The common clinical practice for advanced prostatic adenocarcinoma is combination therapy of zoledronic acid (ZA) and docetaxel (TAX). Little is known about the consequences of this combination therapy with regard to osteonecrosis of the jaw (ONJ). This study shows that the combination therapy of ZA and TAX increases the risk of ONJ and that tooth extraction and leukopenia induced by TAX are the risk factors. OBJECTIVE • To determine whether docetaxel (TAX) can increase the risk of osteonecrosis of the jaw (ONJ) in patients with prostatic adenocarcinoma (PC) receiving zoledronic acid (ZA), a bisphosphonate (BP) used in the treatment of patients with cancer. MATERIALS AND METHODS • The medical records of 111 patients with PC who received ZA between September 2006 and March 2011 at our institutions were reviewed to assess the incidence and risk factors for ONJ. RESULTS • Nine patients (8.1%) developed ONJ during a median follow-up of 14.5 months. • Using univariate analysis we found that TAX chemotherapy (P = 0.037, hazard ratio [HR] 6.611), tooth extraction during ZA therapy (P

The prognostic factors of retroperitoneal liposarcoma have yet to be clearly determined due to its rarity, whereas the prognostic value of symptoms at diagnosis has never been evaluated to date. In this context, we reviewed 24 consecutive patients with primary retroperitoneal liposarcoma who underwent surgical resection with curative intent at our institution. The Kaplan-Meier analysis and the log-rank test were used to estimate progression-free survival (PFS; primary endpoint) and sarcoma-specific survival (SSS; secondary endpoint). The effect of various clinicopathological factors, including symptoms at diagnosis, on these two endpoints was assessed with a Cox proportional hazards model. During the study period, 11 patients (45.8%) developed recurrence after the initial surgery and 8 (33.3%) succumbed to retroperitoneal liposarcoma, with a median follow-up of 64 months. A total of 16 patients (66.7%) had symptoms at diagnosis, while the remaining 8 (33.3%) were diagnosed incidentally. The symptoms were palpability of the tumor (n=8); abdominal pain/fullness (n=3); flank pain/fullness (n=2); lower extremity pain (n=1); testicular pain due to varicocele (n=1); and discomfort on urination (n=1). Patients with symptoms at diagnosis were significantly more likely to develop recurrence (log-rank test, P=0.0196) and were also more likely to succumb to sarcoma (P=0.0778) compared with asymptomatic patients. On the multivariate analysis, symptoms at diagnosis and dedifferentiated components were independent predictors of poor PFS, while positive surgical margins were predictors of poor SSS. Given that symptoms at diagnosis are easily accessible for physicians, they may prove to be useful additional prognostic factors for primary retroperitoneal liposarcoma.

Introduction: Lower extremity neuropathy (LEN) is a well-recognized complication that arises during robotic surgeries in lithotomy-Trendelenburg position (L-T position). It is caused by persistent compression to the nerves. Our aim was to investigate the levels of compression to the nerves by measuring the contact pressure of the lower extremities in men undergoing robot-assisted radical prostatectomy (RARP). Materials and Methods: A total of 138 patients undergoing RARP were enrolled prospectively. The contact pressure of the lower extremities was measured using a portable contact pressure measurement device (Cello®, Cape Co., Kanagawa, Japan) in lithotomy position (L position) and L-T position preoperatively, and in L position postoperatively. Patient positioning was readjusted when the preoperative contact pressure was over 32 mm Hg. The contact pressure was compared between pre- and postoperative values. Results: A total of 33 patients (23.9%) needed readjustment of positioning due to high contact pressure. No one developed LEN. The contact pressure in the L position significantly increased postoperatively (right: 21.4 mm Hg, p < 0.0001; left: 18.6 mm Hg, p = 0.0011). A high body mass index (BMI) was associated with a postoperative increment of pressure in the L position. Conclusions: The contact pressure of the lower extremities increased after RARP and the increase was correlated with BMI.

Background Although radical prostatectomy (RP) and external beam radiotherapy (EBRT) have been considered as comparable treatments for localized prostate cancer (PC), it is controversial which treatment is better. The present study aimed to compare outcomes, including mortality, of RP and EBRT for localized PC. Methods We retrospectively analyzed 891 patients with cT1-4N0M0 PC who underwent either RP (n = 569) or EBRT (n = 322) with curative intent at our single institution between 2005 and 2012. Of the EBRT patients, 302 (93.8%) underwent intensity-modulated radiotherapy. Primary endpoints were overall survival (OS) and cancer-specific survival (CSS). Related to these, other-cause mortality (OCM) was also calculated. Biochemical recurrence-free survival was assessed as a secondary endpoint. Cox proportional hazards model was used for multivariate analysis. Results Median follow-up durations were 53 and 45 months, and median ages were 66 and 70 years (P

Study Type – Therapy (symptom prevalence) Level of Evidence 2a What's known on the subject? and What does the study add? The International Prostate Symptom Score (IPSS) has been most commonly used for the symptom assessment of men with lower urinary tract symptoms (LUTS). However, LUTS in men are so variable that they may not be fully captured by the IPSS questionnaire alone. This study has demonstrated that the Core Lower Urinary Tract Symptom Score (CLSS) questionnaire, which addresses 10 important symptoms, is an appropriate initial assessment tool for LUTS in men with various diseases/conditions. OBJECTIVE • International Prostate Symptom Score (IPSS) has been commonly used to assess lower urinary tract symptoms (LUTS). We have recently developed Core Lower Urinary Tract Symptom Score (CLSS). The aim of this study is to compare IPSS and CLSS for assessing LUTS in men. PATIENTS AND METHODS • Consecutive 515 men fulfilled IPSS and CLSS questionnaires. • IPSS QOL Index was used as the QOL surrogate. • The clinical diagnoses were BPH (n = 116), BPH with OAB wet (n = 80), prostate cancer (n = 128), prostatitis (n = 68), underactive bladder (n = 8), others (n = 72), and controls (e.g., occult blood) (n = 42). • Simple statistics and predictability of poor QOL (QOL Index 4 or greater) were examined. RESULTS • All symptom scores were significantly increased in symptomatic men compared with controls. Scores of corresponding symptoms of two questionnaires were significantly correlated (r = 0.58–0.85, all P

The main problem on HIFU (High Intensity Focused Ultrasound) therapy is the difficulty to locate HIFU focus precisely onto the focal lesion, which is located in the moving organ such as livers/kidneys, due to the deformation and rotation, which is caused by respiration. Furthermore, rib bones frequently block the acoustic path to the lesion. The acoustic shadow, which is generated by the rib bone, is observed in the ultrasound images and the lesion is hidden in the shadow. To cope with this problem, we have developed a novel method to track, follow, and monitor the lesion by utilizing the contour information of the organ, which incorporate the lesion under those difficult conditions. As for the tracking method, the contour of the organ, which is deformed and rotated in accordance with respiration, is extracted automatically in 2-D ultrasound images. The missing contour information in the acoustic shadow area is estimated and compensated by the surrounding contours, which are successfully extracted. To con...

The transition from androgen-dependent to castration-resistant prostate cancer (CRPC) is a lethal event of uncertain molecular etiology. Comparing gene expression in isogenic androgen-dependent and CRPC xenografts, we found a reproducible increase in N-cadherin expression, which was also elevated in primary and metastatic tumors of individuals with CRPC. Ectopic expression of N-cadherin in nonmetastatic, androgen-dependent prostate cancer models caused castration resistance, invasion and metastasis. Monoclonal antibodies against the ectodomain of N-cadherin reduced proliferation, adhesion and invasion of prostate cancer cells in vitro. In vivo, these antibodies slowed the growth of multiple established CRPC xenografts, blocked local invasion and metastasis and, at higher doses, led to complete regression. N-cadherin–specific antibodies markedly delayed the time to emergence of castration resistance, markedly affected tumor histology and angiogenesis, and reduced both AKT serine-threonine kinase activity and serum interleukin-8 (IL-8) secretion. These data indicate that N-cadherin is a major cause of both prostate cancer metastasis and castration resistance. Therapeutic targeting of this factor with monoclonal antibodies may have considerable clinical benefit.

The authors have investigated a construction methodology for a non-invasive ultrasound theragnostic system, called NIUTS, to track and follow moving body targets, such as tumors / stones located in moving organs (kidneys, livers, etc.), robustly and precisely, so as to compensate for nearly 90 percent of target motions in ultrasound images, while irradiating therapeutic ultrasound to focal lesions. In the present report, we propose a novel servo recovery algorithm for NIUTS. We confirm the effectiveness of the implemented servo recovery algorithm for a real human kidney, which, as far as we know, is the first successful report of semi-autonomous servo recovery systems for lost body targets. This robust servo recovery method could provide an indispensable tool for precise, safe, and efficient treatments of tumors and stones.

Objective To elucidate whether the lower ureteral lesion can predict subsequent intravesical recurrence (IVR) in patients with upper tract urothelial carcinoma (UTUC) who underwent radical nephroureterectomy (RNU). Patients and methods We retrospectively reviewed 186 consecutive patients with UTUC who underwent RNU at our institution between 1996 and 2013. Associations of various clinicopathological factors with subsequent IVR were assessed. Lower ureteral lesion was defined as the pathologically confirmed lowest carcinoma component within 5 cm from the lower end of the ureter. The log-rank test and Cox proportional hazards model were used for univariable and multivariable analysis, respectively. Results Overall, 86 patients (46%) developed IVR during the follow-up, with a median follow-up period of 43 months (interquartile range: 17–79 mo). In all, 53 patients (28%) had lower ureteral lesions, and 34 (64%) of them developed IVR. Univariable analysis demonstrated that lower ureteral lesion was significantly associated with IVR, as well as tumor multifocality, lymphatic invasion, and history of bladder cancer. Multivariable analysis identified the lower ureteral lesion as a sole independent predictor of IVR ( P = 0.0304, hazard ratio = 1.74). Conclusions Lower ureteral lesion was an independent predictor of IVR in patients with UTUC treated with RNU. Such patients may deserve prophylactic treatment and intensive follow-up.

The purpose of the study was to evaluate the prognostic value of sarcopenia (muscle loss) in patients with metastatic urothelial carcinoma (UC), in a comparison of several methods of computed tomography (CT)-based evaluation of sarcopenia.We retrospectively reviewed 100 patients with metastatic UC who underwent first-line systemic chemotherapy between 2003 and 2014. Sarcopenia was assessed by the following CT-based methods: skeletal muscle index (SMI), total psoas area (TPA), axial and/or transversal psoas thickness at the level of the third lumbar vertebrae, and axial and/or transversal psoas thickness at the umbilicus level (U-TPT). All parameters were standardized by either height or height squared. Cutoff points were SMI: 55 cm(2)/m(2) (men), 39 cm(2)/m(2) (women); others: lowest sex-specific quartiles. Predictive values for cancer-specific survival (CSS) were assessed using the Cox proportional hazards regression model.Sixty-four patients met the eligibility criterion for analysis: those who underwent CT scans within 30 days before chemotherapy. Of them, 52 (81%) died of UC during the follow-up, with a median survival time of 13 months. Univariate analysis associated decreased SMI, TPA, and U-TPT with poor CSS. Multivariate analysis together with other pretreatment clinicopathologic parameters showed decreased SMI to be an independent predictor of poor CSS.Evaluation using SMI showed sarcopenia was an independent predictor of poor prognosis for patients with metastatic UC who underwent first-line systemic chemotherapy. Our results might improve stratification of patients and help optimize evaluation of sarcopenia.

Background Adjuvant androgen deprivation therapy (ADT) is a treatment option for prostate cancer (PC) patients after radical prostatectomy (RP). Although it can achieve a good progression-free survival rate, some patients still develop clinical metastasis. We here investigated risk factors of clinical metastasis in post- prostatectomy patients who received immediate adjuvant ADT. Materials and methods We identified 197 patients with non-metastatic PC who underwent RP at our institution between 2000 and 2012, followed by adjuvant ADT. The associations of various clinicopathologic factors with clinical metastasis (primary endpoint) and cancer-specific survival (secondary endpoint) were assessed. Multivariate analysis was conducted using a Cox proportional hazards model. Median follow-up was 87 months after RP. Results Nine (4.6%) patients developed clinical metastasis and six (3.0%) died from PC. Eight of nine metastatic patients had a pathologic Gleason score (GS) 9 and developed bone metastasis, while the remaining one had pathologic GS 7 and developed metastasis only to para-aortic lymph nodes. On multivariate analyses, pathologic GS ≥9 and regional lymph node metastasis (pN1) were independent predictors of clinical metastasis and pathologic GS ≥9 was an independent predictor of cancer-specific death. Conclusions Pathologic GS ≥9 and pN1 were independent predictors of clinical metastasis in post-prostatectomy patients who received immediate adjuvant ADT. Furthermore, pathologic GS ≥9 was an indispensable condition for bone metastasis, which may imply that patients with GS ≤8 on adjuvant ADT are unlikely to develop bone metastasis.