Hinotori Surgical Robot System, a novel robot-assisted surgical platform: Preclinical and clinical evaluation.

OBJECTIVES: To evaluate the safety and efficacy of the hinotori™ Surgical Robot System in preclinical and clinical studies. METHODS: Preclinical studies on 10 living female porcine and four fresh male cadavers were conducted. Different types of urologic surgical procedures were performed by experienced urological surgeons using the hinotori system: partial nephrectomy, vesicourethral anastomosis, and pelvic lymph node dissection in porcine, and partial nephrectomy, radical prostatectomy, and pelvic lymph node dissection in cadavers. In a multi-institutional single-arm clinical study, radical prostatectomy was performed in 30 patients with localized prostate cancer to evaluate safety outcomes. The primary endpoint was safety profiles, including device errors and perioperative complications, and the secondary endpoints were console time, blood loss, and positive surgical margin rate. RESULTS: The preclinical results were similar to those reported for the daVinci surgical system. The performance of the hinotori was equivalent to that of the daVinci surgical system, based on a global assessment by the surgeons. Safety was confirmed in a first-in-human clinical study of robot-assisted radical prostatectomy using hinotori in 30 patients. The procedures were completed as planned in all cases, and three (10%) perioperative adverse events were observed. CONCLUSIONS: The safety of the newly developed hinotori surgical system was shown in the present preclinical and clinical studies. Further studies are required to confirm its clinical efficacy.

Separation Effect and Development of Implantation Technique of Hydrogel Spacer for Prostate Cancers.

PURPOSE: The purpose of this study is to improve the placement of a hydrogel spacer in patients with prostate cancer receiving radiation therapy. METHODS AND MATERIALS: A total of 160 patients with prostate cancer were classified into 3 groups: No spacer (group 1; n = 30), spacer placed using conventional technique (group 2; n = 100), and spacer placed using new technique (group 3; n = 30). When placing the spacer, the tip of the needle is placed at the middle of the prostate gland (group 2), or at a level corresponding to a cranial:caudal ratio of 6:4 and as close to the prostate gland as possible (group 3). The separation effect was examined and compared among the groups. RESULTS: The separation in group 2 was larger than that in group 1 from the base to the apex level of the prostate (4 mm), but the separation in group 3 was larger than that in group 2 from the middle to the apex level of the prostate (4 mm). The separation values for the middle to the apex, the spacer thickness from the apex level to the apex (10 mm), the rectal exclusion from the middle to the apex, and the laterality were correlated with the 50 and 60 Gy relative biologic effectiveness (Gy[RBE]) rectal dose (P = 4.1 × 10-9 - .046). The separation vales were strongly correlated with the spacer thickness at the apex (10 mm) and the apex (4 mm; P = 1.1 × 10-18 - 1.8 × 10-17). The rectal volumes at 10 to 60 Gy(RBE) differed among the groups (P = 5.1 × 10-19 - 5.4 × 10-3). The rectal volumes in group 2 were smaller than those in group 1 at all dose levels, but those in group 3 were smaller than those in group 2 at dose levels of 30 to 50 Gy(RBE). CONCLUSIONS: The separation, spacer thickness, and rectal exclusion from the middle to the apex of the prostate and the laterality of the hydrogel spacer affected the reduction in the rectal dose. The rectal dose can be further reduced by implanting a spacer on the caudal and prostate side.

The Use of Urine Mycobacterium tuberculosis Complex Polymerase Chain Reaction as a Predictive Factor for Recurrence and Progression After Intravesical Bacillus Calmette-Guérin Therapy in Patients with Non-muscle­invasive Bladder Cancer.

BACKGROUND: Intravesical bacillus Calmette-Guérin (BCG) instillation is a standard treatment for non-muscle-invasive bladder cancer (NMIBC); however, not all patients benefit from BCG therapy. Currently, no surrogate marker exists to predict BCG efficacy, and thereby, identify patients who will benefit from this treatment. OBJECTIVE: To evaluate the utility of urine Mycobacterium tuberculosis complex polymerase chain reaction (MTC-PCR) assay as a predictive marker for recurrence and progression following BCG therapy. DESIGN SETTING AND PARTICIPANTS: A prospective analysis was carried out for of intermediate- or high-risk NMIBC patients who received BCG instillation for the first time. Urine samples, for MTC-PCR assay, were collected at baseline and annually for up to 10 yr after the last BCG instillation, including induction and maintenance therapy. The first postoperative sample for MTC-PCR was taken at 1 yr from the last instillation. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: A survival analysis was performed using the Kaplan-Meier method, and risk factors for recurrence and progression after BCG treatment were assessed using Cox regression analysis. RESULTS AND LIMITATIONS: During follow-up (median: 57 mo), 468/521 samples (89.8%) were MTC-PCR positive, and 108/123 patients (87.8%) exhibited MTC-PCR positivity at least once. Five-year recurrence- and progression-free survival in patients who were not MTC-PCR positive was significantly lower than in patients who were MTC-PCR positive at least once (p < 0.001). Using multivariable Cox regression analysis, MTC-PCR positivity at least once was a significant prognostic factor for recurrence (hazard ratio [HR]: 36.782, p < 0.001) and progression (HR: 47.209, p < 0.001). CONCLUSIONS: Patients who were not MTC-PCR positive, even once after BCG therapy, were extremely likely to exhibit recurrence and progression. Urine MTC-PCR may be an extremely useful, noninvasive surrogate marker to predict recurrence and progression following BCG therapy. PATIENT SUMMARY: Urine Mycobacterium tuberculosis complex polymerase chain reaction may be a novel biomarker capable of identifying patients at risk of recurrence and progression after bacillus Calmette-Guérin (BCG) immunotherapy.

Significance of the timing of ureteral ligation on prognosis during radical nephroureterectomy for upper urinary tract urothelial cancer.

OBJECTIVES: To investigate the impact on intravesical recurrence and prognosis according to the ureteral ligation timing during radical nephroureterectomy for upper urinary tract urothelial carcinoma. METHODS: We carried out a retrospective chart review of 664 patients with non-metastatic upper urinary tract urothelial carcinoma who underwent radical nephroureterectomy with ureteral ligation (supplementary analysis of JCOG1110A). We excluded patients with previous and/or synchronous bladder cancer, clinically node-positive disease, no ureteral ligation data, those without ureteral ligation and those with any missing data. We investigated the cumulative incidence of intravesical recurrence and cancer-specific mortality, and overall survival between patients with ureteral ligation before renovascular ligation (early ureteral ligation), or ureteral ligation after renovascular ligation (late ureteral ligation). RESULTS: Early and late ureteral ligation was carried out in 243 patients (36.6%) and 421 patients (63.4%), respectively. Intravesical recurrence occurred in 218 patients (32.8%) during follow up (median 3.9 years). No significant difference in the intravesical recurrence was found between early and late ureteral ligation groups. Meanwhile, survival in the early ureteral ligation group was significantly worse compared with the late ureteral ligation group. Multivariable analysis showed that early ureteral ligation was an independent prognostic factor for overall survival (hazard ratio 1.88, 95% confidence interval 1.24-2.85, P = 0.003) and cancer-specific mortality (hazard ratio 1.93, 95% confidence interval 1.14-3.25, P = 0.014). CONCLUSIONS: Our findings suggest that the incidence of intravesical recurrence is not affected by the timing of ureteral ligation during radical nephroureterectomy. However, early ureteral ligation might have a negative impact on survival outcomes.

A preliminary oncologic outcome and postoperative complications in patients undergoing robot-assisted radical cystectomy: Initial experience.

PURPOSE: Robot-assisted radical cystectomy (RARC) was originally intended to replace open radical cystectomy (ORC) as a minimally invasive surgery for patients with invasive bladder cancer. The purpose of this study was to evaluate the advantages of robotic surgery, comparing perioperative and oncologic outcomes between RARC and ORC. MATERIALS AND METHODS: Between June 2012 and August 2016, 49 bladder cancer patients were given a radical cystectomy, 21 robotically and 28 by open procedure. We compared the clinical variables between the RARC and ORC groups. RESULTS: In the RARC group, the median estimated blood loss (EBL) during cystectomy, total EBL, operative time during cystectomy, and total operative time were 0 mL, 457.5 mL, 199 minutes, and 561 minutes, respectively. EBL during cystectomy (p<0.001), total EBL (p<0.001), and operative time during cystectomy (p=0.003) in the RARC group were significantly lower compared with the ORC group. Time to resumption of a regular diet (p<0.001) and length of stay (p=0.017) were also significantly shorter compared with the ORC group. However, total operative time in the RARC group (median, 561 minutes) was significantly longer compared with the ORC group (median, 492.5 minutes; p=0.015). CONCLUSIONS: This Japanese study presented evidence that RARC yields benefits in terms of BL and time to regular diet, while consuming greater total operative time. RARC may be a minimally invasive surgical alternative to ORC with less EBL and shorter length of stay.

Automated renal cortical volume measurement for assessment of renal function in patients undergoing radical nephrectomy.

BACKGROUND: Renal volume change greatly affects renal function after nephrectomy. Although various measuring techniques were reported, no standard measuring method is available. In this study, we examined the computational automated volumetric method, and evaluated the volumetric change to assess the functional outcome in patients undergoing radical nephrectomy. We developed the predictive equation for postoperative renal function from volume alternation and validated the performance. METHODS: Thirty-two patients undergoing radical nephrectomy participated in this study. Renal volume was calculated using three different methods [ellipsoid method, conventional manual voxel count method for renal parenchyma (manual RPV), and automated voxel count method for renal cortex (automated RCV)] through newly developed imaging software. Statistical analysis was performed to evaluate the correlation between renal functional alternation 7 days after the nephrectomy and renal volumetric change. A simple predictive equation for the postoperative renal function by renal volume loss was developed and externally validated through another 12 cases. RESULTS: The automated RCV method had the strongest correlation between renal function alternation and RCV change (R = 0.82), than manual RPV (R = 0.69) and ellipsoid method (R = 0.50). Subsequently, a simple equation for postoperative renal function by renal volume alternation was developed: predicted postoperative estimated glomerular filtration rate (eGFR) from renal volume change = preoperative eGFR × (postoperative renal volume / preoperative renal volume). In the external validation cohort, automated RCV demonstrated the predictive performance of the constructed equations for renal function (R = 0.77). CONCLUSIONS: The computational automated RCV measurements is a simple estimation of renal functional outcome for patients undergoing radical nephrectomy.

Effectiveness of platinum-based adjuvant chemotherapy for muscle-invasive bladder cancer: A weighted propensity score analysis.

OBJECTIVES: To evaluate the clinical benefit of adjuvant platinum-based chemotherapy after radical cystectomy for muscle-invasive bladder cancer in routine clinical practice. METHODS: The present observational study was carried out to compare the effectiveness of adjuvant chemotherapy versus observation post-radical cystectomy in patients with clinically muscle-invasive bladder cancer. Cancer-specific survival and overall survival between the adjuvant chemotherapy group and radical cystectomy alone group were compared using Kaplan-Meier method and log-rank test. After adjusting for background factors using propensity score weighting, differences in cancer-specific survival and overall survival between these two groups were compared. Subgroup analyses by the pathological characteristics were carried out. RESULTS: In total, 322 patients were included in the present study. Of these, 23% received adjuvant chemotherapy post-radical cystectomy. Clinicopathological characteristics showed that patients in the adjuvant chemotherapy group were pathologically more advanced and were at higher risk than the radical cystectomy alone group. In the unadjusted population, although it is not significant, the adjuvant chemotherapy group had lower overall survival (3-year overall survival; 61.5% vs 73.6%, HR 1.33, P = 0.243, log-rank test, adjuvant chemotherapy vs radical cystectomy alone). In the weighted propensity score analysis, although it is not significant, the adjuvant chemotherapy group were superior to radical cystectomy alone groups (overall survival: HR 0.65, 95% CI 0.39-1.09, P = 0.099, log-rank test, adjuvant chemotherapy vs radical cystectomy alone). Subgroup analyses showed that adjuvant chemotherapy significantly reduced the hazard ratio of overall survival and cancer-specific survival in the ≥pT3, pN+, ly+ and v+ subgroups. CONCLUSIONS: Platinum-based adjuvant chemotherapy might be associated with increased cancer-specific survival and overall survival in patients with high-risk invasive bladder cancer.

Aryl hydrocarbon receptor signaling involved in the invasiveness of LNCaP cells.

There is now mounting evidence that the aryl hydrocarbon receptor (AhR) plays an important role in physiologic responses such as development, cell cycle regulation, immune function and also malignant transformation in various tissues. The strong nuclear AhR expression is observed in the invasive phenotype, and an elevated nuclear AhR expression is associated with a poor prognosis of human prostate cancer. On the other hand, there are conflicting results that the AhR deficiency results in increased susceptibility to prostate tumors in mouse model. In the present study, we investigated AhR expression and its role in the growth and invasiveness of human prostate cancer cells. The AhR protein expression was detected in prostate cancer cell lines and human prostate cancer tissues. A small interfering RNA targeting AhR, constitutive active AhR expression vector, and AhR agonist and antagonist were used to moderate its expression and signaling. The induction of AhR signaling attenuated invasiveness of prostate cancer cells without affecting the cellular growth rate. These results suggest that AhR signaling in prostate cancer cells facilitates invasion of these cells, and modulation with this signaling can be a potential therapeutic target of invasive tumors.

Development and Validation of a Novel Recurrence Risk Stratification for Initial Non-muscle Invasive Bladder Cancer in Asia.

BACKGROUND: Some risk classifications to determine prognosis of patients with non-muscle invasive bladder cancer (NMIBC) have disadvantages in the clinical setting. We investigated whether the EORTC (European Organization for Research and Treatment of Cancer) risk stratification is useful to predict recurrence and progression in Japanese patients with NMIBC. In addition, we developed and validated a novel, and simple risk classification of recurrence. METHODS: The analysis was based on 1085 patients with NMIBC at six hospitals. Excluding recurrent cases, we included 856 patients with initial NMIBC for the analysis. The Kaplan-Meier method with the log-rank test were used to calculate recurrence-free survival (RFS) rate and progression-free survival (PFS) rate according to the EORTC risk classifications. We developed a novel risk classification system for recurrence in NMIBC patients using the independent recurrence prognostic factors based on Cox proportional hazards regression analysis. External validation was done on an external data set of 641 patients from Kyorin University Hospital. FINDINGS: There were no significant differences in RFS and PFS rates between the groups according to EORTC risk classification. We constructed a novel risk model predicting recurrence that classified patients into three groups using four independent prognostic factors to predict tumour recurrence based on Cox proportional hazards regression analysis. According to the novel recurrence risk classification, there was a significant difference in 5-year RFS rate between the low (68.4%), intermediate (45.8%) and high (33.7%) risk groups (P<0.001). INTERPRETATION: As the EORTC risk group stratification may not be applicable to Asian patients with NMIBC, our novel classification model can be a simple and useful prognostic tool to stratify recurrence risk in patients with NMIBC. FUNDING: None.

Both cancerous miR-21 and stromal miR-21 in urothelial carcinoma are related to tumour progression.

AIMS: Urothelial carcinoma (UC) is a globally common cancer. miR-21 appears to be important in the tumorigenesis of almost all types of human cancer. However, its precise localization and significance in UC have yet to be clarified. The aim of this study was to examine miR-21 expression in UC and reveal its clinicopathological importance. METHODS AND RESULTS: Tissue arrays of 232 UCs were examined for miR-21 by the use of in-situ hybridization. One hundred and forty-eight transurethral resection specimens and 84 surgically resected specimens were used. After miR-21 positivity had been evaluated separately in tumour cells and the tumour stroma, it was compared with clinicopathological factors and overall survival. miR-21 was strongly expressed in tumour cells in 9% of cases and in the tumour stroma in 6% of cases. Stromal miR-21 positivity was lower than that of cancerous miR-21. Both miR-21s were correlated with each other and related to tumour stage, locus, and histological grade. In addition, strong positivity of miR-21 in cancer and the stroma was significantly related to poorer prognosis among surgically resected cases. In a Cox proportional hazard model, cancerous miR-21 was the only independent prognostic factor except for tumour stage. CONCLUSIONS: miR-21 in both cancer and stromal cells is closely related to tumour progression in UC. miR-21 may be a prognostic marker for cancer progression.

Impact of aging and comorbidity on the efficacy of low-intensity shock wave therapy for erectile dysfunction.

OBJECTIVES: To evaluate the efficacy of low-intensity shock wave therapy and to identify the predictive factors of its efficacy in Japanese patients with erectile dysfunction. METHODS: The present study included 57 patients with erectile dysfunction who satisfied all the following conditions: more than 6-months history of erectile dysfunction, sexual health inventory for men score of ≤ 12 without phosphodiesterase type-5 inhibitor, erection hardness score grade 1 or 2, mean penile circumferential change by erectometer assessing sleep related erection of < 25 mm and non-neurological pathology. Patients were treated by a low-energy shock waves generator (ED1000; Medispec, Gaithersburg, MD, USA). A total of 12 shock wave treatments were applied. Sexual health inventory for men score, erection hardness score with or without phosphodiesterase type-5 inhibitor, and mean penile circumferential change were assessed at baseline, 1, 3 and 6 months after the termination of low-intensity shock wave therapy. RESULTS: Of 57 patients who were assigned for the low-intensity shock wave therapy trial, 56 patients were analyzed. Patients had a median age of 64 years. The sexual health inventory for men and erection hardness score (with and without phosphodiesterase type-5 inhibitor) were significantly increased (P < 0.001) at each time-point. The mean penile circumferential change was also increased from 13.1 to 20.2 mm after low-intensity shock wave therapy (P < 0.001). In the multivariate analysis, age and the number of concomitant comorbidities were statistically significant predictors for the efficacy. CONCLUSIONS: Low-intensity shock wave therapy seems to be an effective physical therapy for erectile dysfunction. Age and comorbidities are negative predictive factors of therapeutic response.

Autoimmune hemolytic anemia associated with renal urothelial cancer: A case report and literature review.

BACKGROUND: Autoimmune hemolytic anemia (AIHA) is hemolytic anemia characterized by autoantibodies directed against red blood cells. AIHA can be induced by hematological neoplasms such as malignant lymphoma, but is rarely observed in the urological field. We report a case of renal urothelial cancer inducing Coombs-positive warm AIHA and severe thrombocytopenia that was responsive to nephroureterectomy. CASE PRESENTATION: A 52-year-old man presented with a 1-month history of general weakness and dizziness. Hemoglobin level was 4.2 g/dL, and direct and indirect Coombs tests both yielded positive results. Abdominal computed tomography revealed huge left hydronephrosis due to a renal pelvic tumor measuring 4.0 x 4.0 x 3.0 cm, and renal regional lymph-node involvement was also observed and suspected as metastasis. Corticosteroid therapy was administered, and nephroureterectomy was performed. After surgical resection, the hemoglobin level gradually normalized, and direct and indirect Coombs tests yielded negative results. We thus diagnosed warm AIHA associated with renal urothelial cancer. CONCLUSION: To the best of our knowledge, this represents the first report of AIHA associated with renal urothelial cancer and severe thrombocytopenia responsive to nephroureterectomy. Renal urothelial cancer needs to be included in the differential diagnoses for warm AIHA, and nephroureterectomy represents a treatment option for AIHA.

The Impact of Increased Bladder Blood Flow on Storage Symptoms after Holmium Laser Enucleation of the Prostate.

In order to investigate how holmium laser enucleation of the prostate (HoLEP) improves urinary storage symptoms, we assessed blood flow in the urinary bladder mucosa of patients with benign prostatic hyperplasia (BPH) before and after laser surgery. Seventy-four consecutive patients with BPH (median age 69 years, range; 53-88) underwent HoLEP at our institution and are included in this study. We prospectively assessed the International Prostate Symptom Score (IPSS), IPSS-QOL Score, the Overactive Bladder Symptom Score (OABSS), uroflowmetry, and blood flow in the urinary bladder, before and after surgery. Blood flow in the bladder mucosa was measured using the OMEGA FLOW (OMEGAWAVE, Tokyo, Japan) laser Doppler flowmeter. The median volume of the enucleated adenomas was 45.0 g (range: 25.0 to 83.2). The median IPSS improved significantly from 20 (range: 6-35) to 3 (0-22) (p < 0.001; Wilcoxon signed-rank test), as did the storage symptoms score, which decreased from 13 (2-20) to 3 (1-8) (p < 0.001). Median bladder blood flow increased at the trigone from 9.57 ± 0.83 ml/sec to 17.60 ± 1.08 ml/sec. Multiple regression analysis for the improved storage symptom score eliminated all explanatory variables except increased bladder perfusion. The data suggest that HoLEP improves blood flow in the bladder mucosa, which independently leads to the improvement of storage symptoms.

Circulating pigment epithelium-derived factor (PEDF) is associated with pathological grade of prostate cancer.

BACKGROUND/AIM: Pigment epithelium-derived factor (PEDF) plays a protective role against oxidative stress. Levels of circulating PEDF have not been examined in patients with prostate cancer. We examined whether PEDF can be used to predict the clinical features of prostate cancer prior to therapy. MATERIALS AND METHODS: Two hundred patients with an abnormal serum level of prostate-specific antigen (PSA) who underwent biopsy between 2008 and 2011 were identified for retrospective analysis. We determined the relationship of the PEDF level to clinical parameters of prostate cancer. We measured levels of PEDF and 8-hydroxy-2'-deoxyguanosine (8-OHdG) in all 200 patients, 100 of whom had histologically-confirmed prostate cancer at the outset. We also investigated the PEDF expression in prostate cancer tissues by immunohistochemistry. RESULTS: The PEDF level was significantly higher in patients with prostate cancer than in those without. Statistical analysis confirmed that PEDF was significant, positively associated with pathological grading (Gleason score). However, PEDF expression was only detected in few prostate cancer cells by immunohistochemistry. Levels of the oxidative marker, 8-OHdG, in patients with prostate cancer are higher than in those without cancer. CONCLUSION: Preoperative PEDF measurement in patients with prostate cancer may provide clinically relevant information regarding the pathological grade of tumor.

Feasibility and accuracy of computational robot-assisted partial nephrectomy planning by virtual partial nephrectomy analysis.

OBJECTIVES: To evaluate the feasibility and accuracy of virtual partial nephrectomy analysis, including a color-coded three-dimensional virtual surgical planning and a quantitative functional analysis, in predicting the surgical outcomes of robot-assisted partial nephrectomy. METHODS: Between 2012 and 2014, 20 patients underwent virtual partial nephrectomy analysis before undergoing robot-assisted partial nephrectomy. Virtual partial nephrectomy analysis was carried out with the following steps: (i) evaluation of the arterial branch for selective clamping by showing the vascular-supplied area; (ii) simulation of the optimal surgical margin in precise segmented three-dimensional model for prediction of collecting system opening; and (iii) detailed volumetric analyses and estimates of postoperative renal function based on volumetric change. At operation, the surgeon identified the targeted artery and determined the surgical margin according to the virtual partial nephrectomy analysis. The surgical outcomes between the virtual partial nephrectomy analysis and the actual robot-assisted partial nephrectomy were compared. RESULTS: All 20 patients had negative cancer surgical margins and no urological complications. The tumor-specific renal arterial supply areas were shown in color-coded three-dimensional model visualization in all cases. The prediction value of collecting system opening was 85.7% for sensitivity and 100% for specificity. The predicted renal resection volume was significantly correlated with actual resected specimen volume (r(2) = 0.745, P < 0.001). The predicted estimated glomerular filtration rate was significantly correlated with actual postoperative estimated glomerular filtration rate (r(2) = 0.736, P < 0.001). CONCLUSIONS: Virtual partial nephrectomy analysis is able to provide the identification of tumor-specific renal arterial supply, prediction of collecting system opening and prediction of postoperative renal function. This technique might allow urologists to compare various arterial clamping methods and resection margins with surgical outcomes in a non-invasive manner.

Maintenance monotherapy with gemcitabine after standard platinum-based chemotherapy in patients with advanced urothelial cancer.

OBJECTIVES: To investigate the outcomes of gemcitabine maintenance monotherapy treatment for metastatic urothelial cancer. METHODS: Gemcitabine maintenance monotherapy was used for metastatic urothelial cancer patients after standard platinum-based chemotherapy. A standard dose of 1000 mg/m(2)/month was given. If patients suffered adverse events or a noticeably compromised quality of life, treatment intervals were extended and doses lowered. Patients with metastatic urothelial cancer receiving only best supportive care after standard chemotherapy served as the retrospective control group. RESULTS: A total of 33 patients were included in the study group as well as in the control group. Maintenance therapy was administered a median of nine times (range 2-49 times) with a median dose of 984.2 mg (range 500-1400 mg) per time. An adverse event of the Common Terminology Criteria of Adverse Events grade 3 or greater was observed in 10 (30.3%) patients, while nine patients (27.3%) experienced hematotoxicity. After standard chemotherapy pretreatment, disease-specific survival in the maintenance therapy group was an average of 15.0 months, significantly more favorable (P < 0.001) than that of the control group (4.0 months). On multivariate analysis, efficacy of prior chemotherapy (P = 0.018), visceral metastasis (P = 0.007) and gemcitabine maintenance therapy (P < 0.001) were statistically significant prognostic parameters of disease-specific survival. CONCLUSION: The present study findings suggest that gemcitabine maintenance monotherapy in metastatic urothelial cancer might not only be useful as a palliative treatment, but it could also have a certain level of therapeutic effectiveness.

Novel prediction model of renal function after nephrectomy from automated renal volumetry with preoperative multidetector computed tomography (MDCT).

BACKGROUND AND PURPOSE: The predictive model of postoperative renal function may impact on planning nephrectomy. To develop the novel predictive model using combination of clinical indices with computer volumetry to measure the preserved renal cortex volume (RCV) using multidetector computed tomography (MDCT), and to prospectively validate performance of the model. PATIENTS AND METHODS: Total 60 patients undergoing radical nephrectomy from 2011 to 2013 participated, including a development cohort of 39 patients and an external validation cohort of 21 patients. RCV was calculated by voxel count using software (Vincent, FUJIFILM). Renal function before and after radical nephrectomy was assessed via the estimated glomerular filtration rate (eGFR). Factors affecting postoperative eGFR were examined by regression analysis to develop the novel model for predicting postoperative eGFR with a backward elimination method. The predictive model was externally validated and the performance of the model was compared with that of the previously reported models. RESULTS: The postoperative eGFR value was associated with age, preoperative eGFR, preserved renal parenchymal volume (RPV), preserved RCV, % of RPV alteration, and % of RCV alteration (p < 0.01). The significant correlated variables for %eGFR alteration were %RCV preservation (r = 0.58, p < 0.01) and %RPV preservation (r = 0.54, p < 0.01). We developed our regression model as follows: postoperative eGFR = 57.87 - 0.55(age) - 15.01(body surface area) + 0.30(preoperative eGFR) + 52.92(%RCV preservation). Strong correlation was seen between postoperative eGFR and the calculated estimation model (r = 0.83; p < 0.001). The external validation cohort (n = 21) showed our model outperformed previously reported models. CONCLUSIONS: Combining MDCT renal volumetry and clinical indices might yield an important tool for predicting postoperative renal function.

Clinical efficacy and prognostic factors of tumor progression in Japanese patients with advanced renal cell carcinoma treated with sorafenib.

OBJECTIVE: Result of clinical trial for registration purpose is often difficult to generalize because of its limited population in number and inclusion criteria. METHODS: To understand the efficacy of sorafenib under daily medical practice, we retrospectively investigated therapeutic outcomes of 175 Japanese patients with advanced renal cell carcinoma treated with sorafenib at 15 centers. RESULTS: The objective response rate and disease control rate were 15.4 and 77.1%, respectively, being similar to those in the Phase II study in Japanese patients (19.4 and 73.6 months). Any tumor shrinkage was observed with 53% of patients, while tumor control without growth was in 61%. Lung lesions were more sensitive to sorafenib than other lesions, in terms of any tumor shrinkage (54%) and the extent of maximal shrinkage, while tumor control was better in lymph node metastases (77%) than in lung (69%). Liver was worse in any tumor shrinkage (35%), tumor control (55%) and the extent of tumor growth. Slightly, shorter median overall survival of 21.1 months compared with Phase II clinical trial (25.3 months) is likely to be attributable to different patient population, because median overall survival was improved to 26.4 months when the population was matched to that in Phase II trial. Univariate and multivariate analyses identified prognostic factors for worse overall survival, including intermediate and poor Memorial Sloan-Kettering Cancer Center risk, Eastern Cooperative Oncology Group performance status ≥1, the presence of non-clear cell component and the presence of liver metastasis. CONCLUSIONS: In conclusion, the present study confirmed the efficacy of sorafenib in the real-world setting on advanced renal cell carcinoma.

Circulating tumor cell count during zoledronic acid treatment in men with metastatic prostate cancer: a pilot study.

PURPOSE: Recent clinical trials have demonstrated that zoledronic acid (ZOL) significantly prolongs survival in prostate cancer patients undergoing androgen deprivation therapy. This pilot study investigated the influence of ZOL on circulating tumor cell (CTC) counts in prostate cancer patients in association with prostate-specific antigen (PSA) used as a serum biomarker. METHODS: Patients with metastatic castration-resistant prostate cancer (CRPC) who were CTC-positive (n=4) were enrolled in treatment with ZOL between April 2012 and December 2013. CTCs were detected using the Cell Search System. The study evaluated CTC fluctuations at 1, 2, and 3 months versus baseline, as well as patient outcomes and adverse events. RESULTS: Two patients showed evidence of temporally decreased CTCs after ZOL treatment. Instead of decreasing the number of CTCs, the PSA level did not go down during the ZOL treatment. One patient could not undergo ZOL treatment due to rapid disease progression. CONCLUSIONS: Although CTC count arguably provides useful information about patients undergoing ZOL treatment, the positive influence of ZOL may be limited to temporary effects for CRPC.