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Objectives: To validate the diagnostic accuracy of a stepwise algorithm to differentiate fat‐poor angiomyolipoma (fp‐AML) from renal cancer in small renal masses (SRMs). Methods: We prospectively enrolled 223 patients with solid renal masses <4 cm and no visible fat on unenhanced computed tomography (CT). Patients were assessed using an algorithm that utilized the dynamic CT and MRI findings in a stepwise manner. The diagnostic accuracy of the algorithm was evaluated in patients whose histology was confirmed through surgery or biopsy. The clinical course of the patients was further analyzed. Results: The algorithm classified 151 (68%)/42 (19%)/30 (13%) patients into low/intermediate/high AML probability groups, respectively. Pathological diagnosis was made for 183 patients, including 10 (5.5%) with fp‐AML. Of these, 135 (74%)/36 (20%)/12 (6.6%) were classified into the low/intermediate/high AML probability groups, and each group included 1 (0.7%)/3 (8.3%)/6 (50%) fp‐AMLs, respectively, leading to the area under the curve for predicting AML of 0.889. Surgery was commonly opted in the low and intermediate AML probability groups (84% and 64%, respectively) for initial management, while surveillance was selected in the high AML probability group (63%). During the 56‐month follow‐up, 36 (82%) of 44 patients initially surveyed, including 13 of 18 (72%), 6 of 7 (86%), and 17 of 19 (89%) in the low/intermediate/high AML probability groups, respectively, continued surveillance without any progression. Conclusions: This study confirmed the high diagnostic accuracy for differentiating fp‐AMLs. These findings may help in the management of patients with SRMs. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the incidence and risk factors of a 20% decrease from new baseline (NB)‐estimated glomerular filtration rate (eGFR) within 2 years after radical nephrectomy (RN) and partial nephrectomy (PN) and to examine the difference in the incidence of end‐stage renal disease (ESRD) with or without the 20% decrease. Methods: This retrospective study included 238 patients undergoing RN and 369 undergoing PN for cT1a‐cT3a renal cancer. The incidence of a 20% decrease from NB‐eGFR within 2 years after RN/PN was examined and its potential risk factors including surgery type were assessed by multivariate logistic regression analysis. The development of ESRD was analyzed as an endpoint and its incidence was compared according to the presence or absence of the 20% decrease from NB‐eGFR within 2 years. Results: Overall, the 20% decrease from NB‐eGFR within 2 years was observed in 37 patients (6.1%), including 10 (4.2%) and 27 (7.3%) after RN and PN, respectively (p = 0.117). Diabetes mellitus, proteinuria, and perioperative complications were shown to be independent risk factors for the 20% decrease from NB‐eGFR, while surgery type was not. During the median follow‐up of 65 months, the ESRD‐free survival rate at 6 years was 75.5% and 99.6% in patients with and without the 20% decrease from NB‐eGFR, respectively (p < 0.001), while no significant difference was observed between patients undergoing RN and PN (98.1% and 98.7%, p = 0.561). Conclusions: Because the incidence of ESRD after the 20% decrease from NB‐eGFR within 2 years was as high as 24.5% at 6 years, these patients should be followed with utmost care. [ABSTRACT FROM AUTHOR]

Partial nephrectomy (PN) is the standard treatment for T1 renal cell carcinoma. PN is affected more by surgical variations and requires greater surgical experience than radical nephrectomy. Patient‐specific simulations and navigation systems may help to reduce the surgical experience required for PN. Recent advances in three‐dimensional (3D) virtual reality (VR) imaging and 3D printing technology have allowed accurate patient‐specific simulations and navigation systems. We reviewed previous studies about patient‐specific simulations and navigation systems for PN. Recently, image reconstruction technology has developed, and commercial software that converts two‐dimensional images into 3D images has become available. Many urologists are now able to view 3DVR images when preparing for PN. Surgical simulations based on 3DVR images can change surgical plans and improve surgical outcomes, and are useful during patient consultations. Patient‐specific simulators that are capable of simulating surgical procedures, the gold‐standard form of patient‐specific simulations, have also been reported. Besides VR, 3D printing is also useful for understanding patient‐specific information. Some studies have reported simulation and navigation systems for PN based on solid 3D models. Patient‐specific simulations are a form of preoperative preparation, whereas patient‐specific navigation is used intraoperatively. Navigation‐assisted PN procedures using 3DVR images have become increasingly common, especially in robotic surgery. Some studies found that these systems produced improvements in surgical outcomes. Once its accuracy has been confirmed, it is hoped that this technology will spread further and become more generalized. [ABSTRACT FROM AUTHOR]

At present, surgery is still the gold standard for the local treatment of renal cancer. Nonetheless, in several clinical scenarios, stereotactic body radiation therapy (SBRT) also known as stereotactic ablative body radiotherapy (SABR) is emerging as a highly effective ablative technique in fragile patients and those with significant comorbidities, as well as in cases where percutaneous therapy (cryoablation or radiofrequency) is not viable. However, considering the intrinsic radioresistance of renal tumors, the optimal treatment schemes have not been established. In oligometastatic patients, it has been reported that the control of the oligometastases can be a potentially curable approach. Being a technique than can be administered exclusively or in combination with systemic therapy, treatment individualization based on patient characteristics is key. Another scenario under investigation is oligoprogression, where SBRT offers the possibility of delaying further lines of systemic therapy by eliminating subclones of resistant tumor with ablative doses, with the additional opportunity of stimulating the immune system (immunomodulatory role). In this review, we have conducted an analysis of recently published studies that test the role of this technique in different clinical scenarios of this disease. We have found promising results that make SBRT a potent therapeutic approach with low toxicity. We also comment on ongoing studies that will generate the necessary evidence needed for the implementation of this technique in our daily clinical practice. [ABSTRACT FROM AUTHOR]

Background: IMA901 is the first therapeutic vaccine for renal cell cancer (RCC). It contains multiple tumor‐associated peptides (TUMAPs) that are naturally present in human cancers. Methods: In a phase I/II study, we treated a total of 10 Japanese patients with advanced RCC who were human leukocyte antigen A (HLA‐A)*02 +. Vaccination involved i.d. injection of GM‐CSF (75 μg), followed within 15–30 min by i.d. injection of IMA901 (containing 413 μg of each peptide). No treatment with either anticancer agents or immunosuppressants was allowed within 4 weeks before entering the trial. Patients were scheduled to receive 7 vaccinations during the first 5 weeks of treatment (induction period), followed by 10 further vaccinations at 3‐week intervals for up to 30 weeks (maintenance period). The primary endpoints were safety and tolerability, while the secondary endpoints were PFS, OS, and immunogenicity. Results: There were no treatment‐related serious adverse events or deaths during the study period. When the response was assessed after 4 months, 10% of patients showed a partial response, 80% had stable disease, and 10% had progressive disease. Among patients in whom the T‐cell response was analyzed, five patients showed a vaccine‐induced T‐cell response against at least one HLA class I‐restricted TUMAP and two patients had T‐cell responses to multiple TUMAPs. PFS was 5.5 months and OS was 18 months. Conclusions: This study demonstrated the safety and tolerability of IMA901 vaccine in Japanese RCC patients, and also showed that vaccination elicited an immune response. [ABSTRACT FROM AUTHOR]

Carbon‐ions are charged particles with a high linear energy transfer, and therefore, they make a better dose distribution with greater biological effects on the tumors compared with photons and protons. Since prostate cancer, renal cell carcinoma, and retroperitoneal sarcomas such as liposarcoma and leiomyosarcoma are known to be radioresistant tumors, carbon‐ion radiotherapy, which provides the advantageous radiobiological properties such as an increasing relative biological effectiveness toward the Bragg peak, a reduced oxygen enhancement ratio, and a reduced dependence on fractionation and cell‐cycle stage, has been tested for these urological tumors at the National Institute for Radiological Sciences since 1994. To promote carbon‐ion radiotherapy as a standard cancer therapy, the Japan Carbon‐ion Radiation Oncology Study Group was established in 2015 to create a registry of all treated patients and conduct multi‐institutional prospective studies in cooperation with all the Japanese institutes. Based on accumulating evidence of the efficacy and feasibility of carbon‐ion therapy for prostate cancer and retroperitoneal sarcoma, it is now covered by the Japanese health insurance system. On the other hand, carbon‐ion radiotherapy for renal cell cancer is not still covered by the insurance system, although the two previous studies showed the efficacy. In this review, we introduce the characteristics, clinical outcomes, and perspectives of carbon‐ion radiotherapy and our efforts to disseminate the use of this new technology worldwide. [ABSTRACT FROM AUTHOR]

Antibody‐drug conjugates represent a promising new treatment option that uses the targeting ability of an antibody to deliver cytotoxic drugs directly to tumors. Antibody‐drug conjugates provide the opportunity to deliver drugs to antigen‐expressing cancer cells while minimizing toxicity to normal tissue, achieving wider therapeutic windows. To date, three antibody‐drug conjugates have been approved by the US Food and Drug Administration, and many antibody‐drug conjugates are under clinical development for urological malignancies. In this paper, we review the mechanism, history, and development of antibody‐drug conjugates, and review the current landscape of antibody‐drug conjugates in urological malignancies including 12 targets and 18 antibody‐drug conjugates in prostate cancer, renal cancer, and urothelial cancer. Furthermore, we review the rational combination of antibody‐drug conjugates with immune checkpoint inhibitors and consider future prospects to enhance the therapeutic activity of antibody‐drug conjugates in urological malignancies. [ABSTRACT FROM AUTHOR]

Objectives: We sought to assess if adding a biopsy proven histologic subtype to a model that predicts overall survival that includes variables representing competing risks in observed, biopsy proven, T1a renal cell carcinomas, enhances the model's performance. Methods: The National Cancer Database was assessed (years 2004–2015) for patients with observed T1a renal cell carcinoma who had undergone renal mass biopsy. Kaplan–Meier curves were utilized to estimate overall survival stratified by histologic subtype. We utilized C‐index from a Cox proportional hazards model to evaluate the impact of adding histologic subtypes to a model to predict overall survival for each stage. Results: Of 132 958 T1a renal masses identified, 1614 had biopsy proven histology and were managed non‐operatively. Of those, 61% were clear cell, 33% papillary, and 6% chromophobe. Adjusted Kaplan–Meier curves demonstrated a difference in overall survival between histologic subtypes (P = 0.010) with greater median overall survival for patients with chromophobe (85.1 months, hazard rate 0.45, P = 0.005) compared to clear cell (64.8 months, reference group). Adding histology to a model with competing risks alone did not substantially improve model performance (C‐index 0.65 vs 0.64 respectively). Conclusions: Incorporation of histologic subtype into a risk stratification model to determine prognostic overall survival did not improve modeling of overall survival compared with variables representing competing risks in patients with T1a renal cell carcinoma managed with observation. These results suggest that performing renal mass biopsy in order to obtain tumor histology may have limited utility. Future studies should further investigate the overall utility of renal mass biopsy for observed T1a kidney cancers. [ABSTRACT FROM AUTHOR]

Objective: Local tumor ablation to treat small renal mass is increasing. The aim of the present study was to compare oncologic outcomes among patients with T1 renal mass treated with partial nephrectomy and local tumor ablation. Methods: To reduce the inherent differences between patients undergoing laparoscopic or robot‐assisted partial nephrectomy (n = 405) and local tumor ablation (n = 137), we used a 1:1 propensity score‐matched analysis. Local tumor ablation consisted of radiofrequency ablation and cryoablation. Disease‐free survival, overall survival and other causes mortality‐free survival rates were estimated using the Kaplan–Meier method. Multivariable logistic regression and competing‐risk regression models were used to identify predictors of complications, recurrence and other causes mortality, respectively. Results: Partial nephrectomy had higher disease‐free survival estimates, as compared with local tumor ablation (92.8% vs 80.4% at 5 years, P = 0.02), with no significant difference between radiofrequency ablation and cryoablation (P = 0.9). Ablation showed comparable overall survival estimates to partial nephrectomy (91% vs 95.8% at 5 years, P = 0.6). The 5‐year recurrence rates were 7.9% versus 23.8% for patients aged ≤70 years, and 2.5% versus 11.9% for patients aged >70 years treated with partial nephrectomy and ablation, respectively; the 5‐year other causes mortality rates were 0% and 2.2% for patients treated with partial nephrectomy and ablation aged ≤70 years, and 3% versus 10.9% for patients aged >70 years treated with partial nephrectomy and ablation, respectively. At multivariable analysis, ablation was associated with fewer complications (odds ratio 0.41; P = 0.01). At competing risks analysis, age (hazard ratio 0.96) and ablation (hazard ratio 4.56) were independent predictors of disease recurrence (all P ≤ 0.008). Conclusions: Local tumor ablation showed a higher risk of recurrence and lower risk of complications compared with partial nephrectomy, with comparable overall survival rates. [ABSTRACT FROM AUTHOR]

Urological cancers are common malignancies worldwide. Several conventional models, for example, two‐dimensional cell culture and animal models have been used for decades to study tumor genetics. Nonetheless, these methods have limitations in reflecting the real tumor microenvironment in vivo, thereby hindering the development of anti‐cancer therapeutic agents. Recently, three‐dimensional culture models have gained attention because they can overcome the drawbacks of traditional methods. Above all, three‐dimensional organoid models are able to mimic the tumor microenvironment in human bodies more closely as they are able to demonstrate the interactions between cells and extracellular matrix. This type of model has therefore extended our understanding of urological cancers. Tumor cells in organoid models can also be co‐cultured with other cellular components, such as peripheral blood lymphocytes, and allow further understanding of the effect of tumor microenvironments on tumor growth. Furthermore, organoid models allow a prolonged culturing period, therefore, tumor evolution, progression and maintenance can also be assessed. Organoid models can be derived from each specific patient, and this facilitates investigation of individual cancer‐specific mutations and their subtypes. As a result, the development of personalized medication targeting the signaling pathways or biomolecules of interest will be possible. In the present review, we summarize the development and applications of three‐dimensional organoid cultures in urological cancers, mainly focusing on prostate, urinary bladder and kidney cancers, and assess the future prospects of this model. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the trends and safety of robot‐assisted partial nephrectomy during the initial 2‐year period after government approval for this type of procedure in April 2016. Methods: This nationwide retrospective study included 3722 received robot‐assisted partial nephrectomy cases carried out from April 2016 to March 2018 in 124 participating institutions. The institutions were divided into lower‐ and higher‐volume institutions according to the median of 19 robot‐assisted partial nephrectomy cases during the study period. Surgical outcomes between 616 cases from lower‐volume institutions and 3106 cases from higher‐volume institutions were compared using propensity score matching. Results: During the study period, both the number of robot‐assisted partial nephrectomy surgeries and the number of institutions in which the surgery was carried out steadily increased. Overall, the median anesthesia time was 217 min, the median postoperative length of stay was 9 days, and the proportion of blood transfusions, complications and readmissions were 0.8%, 5.1% and 1.0%, respectively. There were no significant differences in anesthesia time, incidence of blood transfusions, and complication rates between the lower‐volume and higher‐volume institutions. However, a slightly, but significantly, longer postoperative length of stay and a lower incidence of readmission were observed in lower‐volume institutions both before and after propensity score matching. Conclusions: Robot‐assisted partial nephrectomy has become widespread during the initial 2‐year period after government approval with an acceptable safety profile, regardless of the institutional caseloads. This technique has become a standard of care for stage 1 renal cancer patients in Japan. [ABSTRACT FROM AUTHOR]

Objective: To examine the association between hospital volume and postoperative 5‐year survival for patients with prostate, kidney, and bladder cancer. Method: Using Osaka Cancer Registry data, we identified 9285 patients who were diagnosed as having prostate, kidney, or bladder cancer and who underwent surgery between 2007 and 2011 in Osaka, Japan. The surgical hospital volume of each hospital was calculated and then divided into quartiles (high, medium, low, very low). We estimated the hazard ratios of hospital volume (quartiles) for 5‐year survival using Cox proportional hazard models. Results: For all three cancer sites, the mortality hazard of hospitals with the lowest hospital volume was significantly higher than that of hospitals with the highest volume. The difference in adjusted 5‐year survival rates between hospitals with the highest and lowest hospital volume was 3.6% for prostate cancer, 6.6% for kidney cancer, and 13.3% for bladder cancer. Conclusion: Hospital surgical volume seems to affect 5‐year survival for patients with urological cancers, especially kidney and bladder cancer. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the clinicopathological features and outcomes of targeted therapy in patients with recurrence of renal cell carcinoma in <5 years or ≥5 years after the surgical treatment for renal cell carcinoma. Methods: Patients with metastatic renal cell carcinoma treated with targeted therapy in a multicenter database were retrospectively characterized according to time from surgery to recurrence. Early recurrence was defined as recurrence within 5 years after surgery, and late recurrence was defined as occurring ≥5 years after surgery. The propensity scores for recurrence status were calculated, and patients with late recurrence were matched to patients with early recurrence at a 1:3 ratio. The oncological outcomes of targeted therapy in both groups were compared. Results: Among 716 patients, 512 (71.5%) experienced early recurrence and 204 (28.5%) experienced late recurrence. The patients with late recurrence presented with younger age at surgery, lower tumor stages and Fuhrman grade, and fewer sarcomatoid features and lymphovascular invasion (all P < 0.005). All differences in clinicopathological characteristics before targeted therapy disappeared after matching. Patients with late recurrence had significantly longer median overall survival (56 months vs 36 months; P < 0.0001) and median first‐line progression‐free survival (12 months vs 8 months; P = 0.031). The early recurrence status was a significantly worse predictor for overall survival and first‐line progression‐free survival (hazard ratio 1.30, P = 0.007; and hazard ratio 1.76, P < 0.001, respectively). Conclusions: Late recurrence might have prognostic value in terms of oncological outcomes in metastatic renal cell carcinoma treated with targeted therapy. [ABSTRACT FROM AUTHOR]

This article discusses the impact of tumor location on the survival of patients with upper tract urothelial carcinoma (UTUC). It notes that ureteral cancer generally has a worse prognosis than renal pelvic cancer due to factors such as the presence of blood vessels and lymphatic channels in the extra-ureteric fat. The article suggests that subclassifying UTUC based on the infiltration of surrounding adipose tissue can help predict patient outcomes and guide the selection of adjuvant therapy. However, it also acknowledges that other factors, such as the extension of parenchymal invasion and tumor location in the ureter, may need to be considered. The author concludes by suggesting the need for novel classification models that incorporate additional pathological factors or biomarkers. [Extracted from the article]

Renal cryoablation has become accepted as treatment for small renal tumors as an alternative to surgery. However, parallel with the increase in the use of this therapy, there also has been increases in the number of reports of complications related to renal cryoablation. One potential complication is injury to important non‐renal structures adjacent to the ablated renal tumor, such as the colon, duodenum, ureter, psoas muscle and so on. To prevent injury of adjacent organs, separating organs from the tumor is desirable. Over the past 15 years, several techniques have been developed to protect against injury of organs adjacent to renal tumors that are targets of cryoablation. The most commonly used technique for this purpose has been hydrodissection. Others include dissection with gas, balloon dissection and probe traction. To avoid injury of a ureter running near the renal tumor, pyeloperfusion is known to be useful. The rate of cases necessitating avoidance of organ injury by using these techniques is relatively high. In some cases, more than two techniques are combined. In the present review, we provided an overview of techniques currently available to protect against organ injuries, and discussed the advantages and disadvantages of each technique. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the change in the operated parenchymal volume during robot‐assisted partial nephrectomy limited to the enucleation technique, and to analyze the predictors of decrease in operated parenchymal volume, including the tumor contact surface area. Methods: The study included 135 patients who underwent robot‐assisted partial nephrectomy for T1 renal tumors using the enucleation technique. Measurements of the parenchymal volume, tumor volume and contact surface area were obtained in the venous phase on enhanced computed tomography. All measurements, including volumetric and renal function analysis, were carried out <2 months before and 6 months after surgery. Results: The mean age of included participants was 56 years, and the mean tumor size was 33 mm. The mean tumor volume was 26 cc, and the mean contact surface area was 22 cm2. In the complete cohort, the mean preoperative and postoperative normal parenchymal volumes of the operated kidney were 158 and 141 cc, respectively. The mean change in parenchymal volume of the operated kidney was −10%. In contrast, the mean change in global estimated glomerular filtration was just −4.0%. Univariate analysis showed that the RENAL nephrometry score, contact surface area, tumor volume and warm ischemia time were associated with the change in the operated kidney parenchymal volume. However, in the multivariate analysis, a large contact surface area was the only independent predictor of decreased operated parenchymal volume <10 cm3. Conclusion: Contact surface area is a strong predictor of the decrease in the parenchymal volume in the operated kidney during robot‐assisted partial nephrectomy carried out using the enucleation technique for T1 renal tumors. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the trends in the presentation and surgical management of renal tumors at Singapore General Hospital, Singapore. Methods: We accessed our uro‐oncological registry to extract the clinicopathological data of patients with renal tumors who underwent nephrectomy from 2000 to 2015. Binary logistic regression was used to identify predictors of nephron‐sparing surgery utilization, Clavien–Dindo grade ≥III complications and progression to stage ≥3 chronic kidney disease. Cox regression models were created to evaluate the proportional hazards of the risk factors for overall survival and cancer‐specific survival. Results: A total of 1208 cases of nephrectomy were carried out between 2000 and 2015. The proportion of cT1a tumors increased from 2000–2004 to 2010–2015, which was accompanied by the doubling of utilization rates of nephron‐sparing surgery and minimally invasive surgery. Charlson Comorbidity Index score <2, asymptomatic presentation, clinical T1a tumors and having an estimated glomerular filtration rate ≥30 mL/min/1.73 m2 were all independent predictors of nephron‐sparing surgery utilization. Age, symptomatic presentation and nephron‐sparing surgery utilization were all significantly associated with greater odds of having Clavien–Dindo grade ≥III complications, whereas minimally invasive surgery was associated with decreased risk. The utilization of partial nephrectomy and minimally invasive surgery was significantly associated with a decreased risk of developing postoperative stage ≥3 chronic kidney disease. Both overall survival and cancer‐specific survival were not significantly affected by whether nephron‐sparing surgery was utilized. Conclusions: There has been an increasing proportion of small renal masses diagnosed incidentally with a shift towards nephron‐sparing surgery for clinically localized tumors. With the adoption of nephron‐sparing surgery, progression to stage 3 chronic kidney disease has decreased, without any compromise in oncological and survival outcomes. [ABSTRACT FROM AUTHOR]

Objective: To investigate peritumoral pseudocapsule status in patients with renal cell carcinoma who underwent robot‐assisted laparoscopic partial nephrectomy, and to examine predictive factors associated with the absence of peritumoral pseudocapsule. Methods: A total of 367 patients with clinical T1 renal cell carcinoma who underwent robot‐assisted laparoscopic partial nephrectomy were divided into two groups according to peritumoral pseudocapsule status. The groups were compared in terms of patient and tumor characteristics. Multivariate logistic regression analysis was carried out to identify predictive factors for the absence of peritumoral pseudocapsule. Results: Of the 367 tumors, 323 (88%) were surrounded by a peritumoral pseudocapsule. The mean tumor size was 30 mm, and 70% of the patients were male. Tumors with a peritumoral pseudocapsule had a larger diameter than those without (31 vs 26 mm; P = 0.0008). A peritumoral pseudocapsule was observed in 92% of the clear cell, in 89% of the papillary and in 86% of the clear cell papillary renal cell carcinoma cases compared with just 50% in the chromophobe renal cell carcinoma cases (P < 0.0001). Sex, age, Fuhrman grade and tumor complexity did not differ among patients. A multivariate analysis showed that smaller tumor size (≥34 vs <34 mm, odds ratio 3.31; P = 0.0023) and chromophobe renal cell carcinoma (vs other subtypes, odds ratio 12.5; P < 0.0001) predicted an absence of peritumoral pseudocapsule. Conclusions: Small tumor size and chromophobe renal cell carcinoma were significant predictors of a lack of peritumoral pseudocapsule, suggesting that a positive surgical margin must be avoided for these tumors when an enucleation technique is used for robot‐assisted laparoscopic partial nephrectomy. [ABSTRACT FROM AUTHOR]

The present review provides an update about the major achievements and recent advances of immunotherapy in renal cell carcinoma, urothelial carcinoma, and prostate cancer. Although the treatment strategy for renal cell carcinoma and urothelial carcinoma includes traditional cancer immunotherapies, such as interleukin‐2 and interferon‐alfa, the clinical outcomes of these therapies are unsatisfactory. In recent years, the development of immune checkpoint inhibitors has drastically changed the treatment strategy for various cancers, including genitourinary cancer. The present review summarizes the approved cancer immunotherapies for renal cell carcinoma, urothelial carcinoma and prostate cancer. Furthermore, we review the response evaluation and biomarkers for immune checkpoint inhibitors with a distinctive mode of action that is different from cytotoxic agents. Finally, future perspectives for cancer immunotherapy are discussed. [ABSTRACT FROM AUTHOR]

Objective: To report the outcomes of laparoscopic radical nephrectomy with inferior vena cava thrombectomy for right renal cell carcinoma at Kobe City Medical Center General Hospital, Kobe, Hyogo, Japan. Method: A retrospective review of the clinical records of five patients who underwent laparoscopic radical nephrectomy with inferior vena cava thrombectomy for right renal cell carcinoma between 2013 and 2017 was carried out. The surgical procedure included ligation and cutting of the right renal artery, followed by kidney mobilization. The left renal vein, and the caudal and cephalad sides of the inferior vena cava thrombus were clamped using laparoscopic vascular clamps, and the inferior vena cava was incised. The free kidney and tumor thrombus were placed en bloc in a retrieval bag. Subsequently, the inferior vena cava was laparoscopically closed using a continuous suture. Results: The median operative time, pneumoperitoneum time, blood loss and postoperative hospital stay were 316 min, 266 min, 400 mL and 7 days, respectively. The median clamp time was 28 min (range 13–105 min). One patient (20%) required a perioperative blood transfusion. The surgical margin was negative in all patients. Only one patient experienced a major complication (Clavien–Dindo grade ≥3), namely a postoperative hemorrhage requiring transarterial embolism. Conclusion: En bloc laparoscopic radical nephrectomy with inferior vena cava thrombectomy is a challenging yet feasible procedure for experienced surgeons in carefully selected patients. Further studies of this surgical procedure are required for standardization and safe application. [ABSTRACT FROM AUTHOR]

Objectives: To clarify treatment patterns and outcomes for patients with unresectable or metastatic renal cell carcinoma in the molecular target therapy era in Japan. Methods: A multicenter, retrospective medical chart review study was carried out. Patients diagnosed with unresectable or metastatic renal cell carcinoma between January 2012 and August 2015 were enrolled. Data extracted from medical records included treatment duration, grade ≥3 adverse events, reason for discontinuation for each targeted therapy and survival data until August 2016. Results: Of 277 eligible patients, 266, 170 and 77 received first‐, second‐ and third‐line systemic treatment, respectively. Tyrosine kinase inhibitors were the most common first‐line therapy (72.2%), followed by mammalian target of rapamycin inhibitors (14.3%) and cytokines (13.5%). Among 170 patients who received second‐line treatment, tyrosine kinase inhibitor–tyrosine kinase inhibitor was the most common sequence (58.8%), followed by tyrosine kinase inhibitor–mammalian target of rapamycin inhibitor (14.1%) and cytokine–tyrosine kinase inhibitor (14.1%). With a median follow‐up period of 19.8 months, median overall survival was not reached at 48 months. Patients who discontinued first‐line tyrosine kinase inhibitors in <6 months showed poorer overall survival compared with patients who received first‐line tyrosine kinase inhibitors for ≥6 months. Conclusions: The present analysis illustrates the contemporary treatment patterns and prognosis for patients with unresectable or metastatic renal cancer in a real‐world setting in Japan. Tyrosine kinase inhibitor–tyrosine kinase inhibitor represents the most commonly used sequence. Shorter treatment duration of first‐line tyrosine kinase inhibitors is associated with poorer prognosis, suggesting the need for better treatment options. [ABSTRACT FROM AUTHOR]

The article presents information on the 16th Urological Association of Asia Congress 2018. Topics discussed include immunotherapy in kidney cancer, immunotherapy for urothelial cancer in Asia 2018, and the role of oxidative stress in castration-resistant prostate cancer, and its diagnostic and therapeutic implications.

Abstract: Extracellular vesicles are nanometer‐sized lipid membranous vesicles that are released from almost all types of cells into the extracellular space. Extracellular vesicles have gained considerable attention in the past decade, and emerging evidence suggests that they play novel roles in mediating cancer biology. Extracellular vesicles contain pathogenic components, such as proteins, DNA fragments, messenger ribonucleic acids, non‐coding ribonucleic acids and lipids, all of which mediate paracrine signaling in the tumor microenvironment. Extracellular vesicles impact the multistep process of cancer progression through modulation of the immune system, angiogenesis and pre‐metastatic niche formation through transfer of their contents. Therefore, a better understanding of their roles in urological cancers will provide opportunities for novel therapeutic strategies. In addition, the contents of extracellular vesicles hold promise for the discovery of liquid‐based biomarkers for prostate, kidney and bladder cancers. Here, we summarize the current research regarding extracellular vesicles in urological cancer and discuss potential clinical applications for extracellular vesicles in urological cancer. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the outcomes of robotic partial nephrectomy compared with those of laparoscopic partial nephrectomy for T1 renal tumors in Japanese centers. Methods: Patients with a T1 renal tumor who underwent robotic partial nephrectomy were eligible for inclusion in the present study. The primary end‐point consisted of three components: a negative surgical margin, no conversion to open or laparoscopic surgery and a warm ischemia time ≤25 min. We compared data from these patients with the data from a retrospective study of laparoscopic partial nephrectomy carried out in Japan. Results: A total of 108 patients were registered in the present study; 105 underwent robotic partial nephrectomy. The proportion of patients who met the primary end‐point was 91.3% (95% confidence interval 84.1–95.9%), which was significantly higher than 23.3% in the historical data. Major complications were seen in 19 patients (18.1%). The mean change in the estimated glomerular filtration rate in the operated kidney, 180 days postoperatively, was −10.8 mL/min/1.73 m2 (95% confidence interval −12.3–9.4%). Conclusions: Robotic partial nephrectomy for patients with a T1 renal tumor is a safe, feasible and more effective operative method compared with laparoscopic partial nephrectomy. It can be anticipated that robotic partial nephrectomy will become more widely used in Japan in the future. [ABSTRACT FROM AUTHOR]

Objectives: To determine the complexity of renal masses by using an objective novel imaging parameter (intraparenchymal tumor volume) based on computed tomography scans, to correlate this parameter to perioperative outcomes and to the RENAL nephrometry score. Methods: After institutional review board approval, 87 patients who underwent partial nephrectomy between 2012 and 2016 at Singapore General Hospital, Singapore, were retrospectively analyzed. Preoperative computed tomography intravenous pyelogram scans were reviewed by a single senior radiologist who calculated the intraparenchymal tumor volume. Once the intraparenchymal tumor volume scores were obtained, they were compared with perioperative renal and surgical outcomes, and nephrometry scores. Furthermore, intraparenchymal tumor volume was subdivided into two categories, low and high intraparenchymal tumor volume, both using the 89th percentile. Results: The mean patient age was 60 years, and the mean tumor size was 2.9 cm. The mean nephrometry score was 7.8, and the mean intraparenchymal tumor volume score was 12.7 cm³. The cut‐off for high intraparenchymal tumor volume was >27.26 cm³. As a continuous variable, intraparenchymal tumor volume showed a significant relationship with the percentage of creatinine change (P = 0.009) and nephrometry scores (P < 0.001). As a categorical variable, high intraparenchymal tumor volume showed significance when compared with absolute creatinine change (P = 0.018), percentage of creatinine change (P = 0.004) and nephrometry score (P < 0.001). Conclusions: Intraparenchymal tumor volume represents a novel objective tool based on computed tomography imaging to determine the complexity of a renal mass. This tool correlates with renal functional outcomes of partial nephrectomy, and it also shows good correlation with RENAL nephrometry score. [ABSTRACT FROM AUTHOR]

Editorial Comment to Does histologic subtype impact overall survival in observed T1a kidney cancers compared with competing risks? These findings suggest that the utility of renal mass biopsy to obtain tumor histology for management decisions in patients with observed T1a kidney cancer has been under discussion. Does histologic subtype impact overall survival in observed T1a kidney cancers compared with competing risks?. [Extracted from the article]

Objectives To study the behavior of specific coagulation factors in different types of non-metastatic urological cancers, and to identify their possible role as diagnostic and prognostic markers. Methods This was a prospective controlled study, which included three cancer patient groups and a control group of healthy individuals. The cancer subgroups consisted of renal ( n = 44), prostate ( n = 56) and bladder cancer ( n = 47). We excluded patients receiving anticoagulant therapy, or with significant comorbidity. In all patients, certain coagulation parameters were measured (prothrombin time, international normalized ratio, partial thromboplastin time, D-dimers, fibrinogen, F1 + 2, thrombin-antithrombin complex). Statistical analysis was carried out to explore the association of hemostasis markers with tumor-nodes-metastasis stage, Gleason score, transitional cell carcinoma grade, Fuhrman grade and prostate-specific antigen. Results Our final sample consisted in 58 control patients and 147 patients with urological cancer. We found specific patterns of increased coagulation factors in the different cancers that were statistically significant. Renal cancer showed increased levels of D-dimers, partial thromboplastin time and fibrinogen. D-dimers and fibrinogen were increased in prostate cancer; whereas in bladder cancer, only fibrinogen was elevated. Correlations were found between certain factors and tumor stage and grading, with D-dimers being independently associated with higher tumor grade. Thrombin-antithrombin complex was associated with Gleason score. Furthermore, D-dimers, fibrinogen and F1 + 2 were associated with higher tumor stages (II-IV). Conclusions The coagulation pathway seems to be activated in urological malignancies. Specific panels of coagulation factors might play a role as screening or prognostic tools in earlier stages of renal, prostate and bladder cancer. Further research should also focus on their role in the association of cancer with thromboembolic events. [ABSTRACT FROM AUTHOR]

Among patients in whom the T-cell response was analyzed, five patients showed a vaccine-induced T-cell response against at least one HLA class I-restricted TUMAP and two patients had T-cell responses to multiple TUMAPs. Although a phase III trial using IMA901 vaccine plus sunitinib compared to sunitinib monotherapy as first line treatment in patients with metastatic RCC has not shown survival benefit,[4] IMA901-specific CD8-positive T cell responses were recognized in some patients. Editorial Comment to Phase I/II study of multipeptide cancer vaccine IMA901 after single-dose cyclophosphamide in Japanese patients with advanced renal cell cancer with long-term follow up. [Extracted from the article]

Birt-Hogg-Dubé syndrome is an autosomal dominantly inherited disease that predisposes patients to develop fibrofolliculoma, lung cysts and bilateral multifocal renal tumors, histologically hybrid oncocytic/chromophobe tumors, chromophobe renal cell carcinoma, oncocytoma, papillary renal cell carcinoma and clear cell renal cell carcinoma. The predominant forms of Birt-Hogg-Dubé syndrome-associated renal tumors, hybrid oncocytic/chromophobe tumors and chromophobe renal cell carcinoma are typically less aggressive, and a therapeutic principle for these tumors is a surgical removal with nephron-sparing. The timing of surgery is the most critical element for postoperative renal function, which is one of the important prognostic factors for Birt-Hogg-Dubé syndrome patients. The folliculin gene ( FLCN) that is responsible for Birt-Hogg-Dubé syndrome was isolated as a novel tumor suppressor for kidney cancer. Recent studies using murine models for FLCN, a protein encoded by the FLCN gene, and its two binding partners, folliculin-interacting protein 1 (FNIP1) and folliculin-interacting protein 2 (FNIP2), have uncovered important roles for FLCN, FNIP1 and FNIP2 in cell metabolism, which include AMP-activated protein kinase-mediated energy sensing, Ppargc1a-driven mitochondrial oxidative phosphorylation and mTORC1-dependent cell proliferation. Birt-Hogg-Dubé syndrome is a hereditary hamartoma syndrome, which is triggered by metabolic alterations under a functional loss of FLCN/FNIP1/FNIP2 complex, a critical regulator of kidney cell proliferation rate; a mechanistic insight into the FLCN/FNIP1/FNIP2 pathway could provide us a basis for developing new therapeutics for kidney cancer. [ABSTRACT FROM AUTHOR]

The standard treatment for advanced renal cell carcinoma has changed dramatically in the past decade, from cytokine therapy to targeted therapy. Since sorafenib was approved in April 2008, four tyrosine kinase inhibitors and two mammalian target of rapamycin inhibitors have become available in Japan. Most Japanese renal cell carcinoma patients are treated by urologists who are involved in not only kidney surgeries, but also targeted therapy using tyrosine kinase inhibitors, as well as mammalian target of rapamycin inhibitors. Optimal treatment methods are selected from theoretically-based global recommendations, such as the National Comprehensive Cancer Network and European Society for Medical Oncology guidelines; however, real-world clinical practice might be different from that in non-Asian countries. This might be because of different practical conditions; for example, different adverse events and efficacy profiles, different healthcare system, and so on. In the present review, we examine current pharmacotherapy for renal cell carcinoma from evidence-based global data, and compare the reality of Japanese clinical practice to explore the importance of individualized patient therapy. [ABSTRACT FROM AUTHOR]

Objectives To incorporate C-reactive protein into nomograms estimating survival in patients with renal cell carcinoma. Methods Patients undergoing surgery for renal cell carcinoma from 2005-2012 were studied retrospectively. Multivariable Cox proportional hazards regression and competing risks regression models including stage, grade, C-reactive protein levels and presence of metastatic disease were constructed. Outcomes analyzed include overall mortality overall mortality and renal cell carcinoma-specific mortality. Results The cohort included 516 patients with a mean follow up of 1.7 years ( SD 1.4 years). One- and 3-year renal cell carcinoma-specific mortality was 8.8% and 13.5%, respectively. Four nomograms were generated using overall mortality and renal cell carcinoma-specific mortality as end-points, two each for pre- and postoperative counseling. The factor with the largest effect on all nomograms was preoperative C-reactive protein. Based on the internal validation with bootstrapping, the concordance indices for renal cell carcinoma-specific mortality in the preoperative nomogram, postoperative nomogram, and the Mayo Clinic stage, size, grade and necrosis score were 0.889, 0.893, and 0.832, respectively ( P = 0.005 and 0.002 comparing with stage, size, grade and necrosis scores for preoperative or postoperative nomograms). For overall mortality, the preoperative nomogram, postoperative nomogram, and stage, size, grade and necrosis score showed concordance indices of 0.866, 0.897, and 0.828, respectively ( P = 0.123 and 0.008 compared with stage, size, grade and necrosis score for preoperative or postoperative nomograms). Conclusions We have generated nomograms incorporating serum C-reactive protein levels that effectively predict overall mortality and renal cell carcinoma specific mortality. Our findings warrant external validation. [ABSTRACT FROM AUTHOR]

Objectives To evaluate the efficacy of targeted therapy after complete resection of metastatic lesions in patients with metastatic renal cell carcinoma. Methods We retrospectively reviewed the medical records of 53 patients with metastatic renal cell carcinoma who underwent complete surgical resection of metastatic lesions between January 2006 and December 2012. Immediate postoperative targeted therapy was given to a subgroup of patients. Progression-free survival and cancer-specific survival were assessed. Results All patients underwent curative surgery for a primary tumor. A total of 13 patients (24.5%) had metastatic disease at initial diagnosis, and 49 (92.5%) had single-organ involvement at the time of first metastasis. None of the patients met the poor-risk criteria. Of the 19 patients who received immediate postoperative targeted therapy, five (26.3%) experienced relapse. Of the 34 patients who did not receive immediate postoperative targeted therapy, 27 (79.4%) experienced disease recurrence. Targeted therapy was restarted in 30 patients (93.8%) after relapse with excellent disease control rates (complete response: 3.3%, partial response: 36.7%, stable disease: 46.7%). Immediate postoperative targeted therapy was associated with better median progression-free survival (not reached vs 20.0 months; P = 0.017), but not better cancer-specific survival. Conclusions Postoperative targeted therapy after complete metastasectomy seems to be associated with better progression-free survival in patients with metastatic renal cell carcinoma, but not with cancer-specific survival. [ABSTRACT FROM AUTHOR]

Objective The objectives of the present study were analyze specific comorbidities associated with survival and actual causes of death for patients with small renal masses, and to suggest a simplified measure associated with decreased overall survival specific to this population. Methods The Surveillance, Epidemiology and End Results-Medicare database (1995-2007) was queried to identify patients with localized T1a kidney cancer undergoing partial nephrectomy, radical nephrectomy or deferring therapy. We explored independent associations of specific comorbidities with causes of death, and developed a simplified cardiovascular index. Cox proportional hazards, and Fine and Gray competing risks regression were used. Results Of 7177 Medicare beneficiaries in the study population, 754 (10.5%) deferred therapy, 1849 (25.8%) underwent partial nephrectomy and 4574 (63.7%) underwent radical nephrectomy with none of the selected comorbidities identified in 3682 (51.3%) patients. Congestive heart failure, chronic kidney disease, peripheral vascular disease, chronic obstructive pulmonary disease, diabetes and cerebrovascular disease were associated with decreased overall survival. The cardiovascular index provided good survival risk stratification, and reclassified 1427 (41%) patients with a score ≥1 on the Charlson Comorbidity Index to a 0 on the cardiovascular index with minimal concession of 5-year survival. Conclusions Congestive heart failure, chronic kidney disease, peripheral vascular disease, chronic obstructive pulmonary disease, diabetes and cerebrovascular disease were associated with decreased overall survival among Medicare beneficiaries with small renal masses. The cardiovascular index could serve as a clinically useful prognostic aid when advising older patients that are borderline candidates for surgery or active surveillance. [ABSTRACT FROM AUTHOR]

Over the last number of years, the treatment of metastatic renal cell cancer has evolved tremendously with the advent of targeted therapy. Previously, immunotherapies, such as interferon alpha and interleukin-2, were the only treatment options available for this chemoresistant malignancy. Currently, seven additional agents, including sunitinib, sorafenib, axitinib, pazopanib, bevacizumab, everolimus and temsirolimus, have been approved for use in metastatic renal cell cancer, with several more in development. The efficacy of these agents depends primarily on inhibition of the vascular endothelial growth factor and mammalian target of rapamycin pathways, and have drastically improved the outcomes of patients diagnosed with metastatic renal cell cancer. This article reviews the major treatment advances that have occurred for metastatic renal cell cancer with the advent of targeted treatments, summarizes the evidence to support their use and addresses clinical issues that have arisen with them. To help guide clinicians in their decision-making with these emerging therapeutic choices, the evidence for sequencing and combining these agents, and the need for biomarkers will be addressed. The role of surgical management options, such as cytoreductive nephrectomy and metastectomy, in the era of targeted treatment is also reviewed. Several novel treatments are also on the horizon, which might serve as future avenues for treatment advancement in metastatic renal cell cancer. [ABSTRACT FROM AUTHOR]

Objective To evaluate the association between the RENAL nephrometry score and annual growth rates of renal masses presumed to be renal cell carcinoma. Methods The current study included 47 renal tumors followed up for at least 12 months, of which 26 tumors were found to be pathologically proven renal cell carcinomas. Annual tumor growth rates were calculated from changes in the maximal diameter on computed tomography, and RENAL nephrometry scores were recorded on initial imaging by two senior urologists. The associations between clinical characteristics including the RENAL nephrometry score and annual growth rates were analyzed using a linear regression model. Results The median tumor size at diagnosis was 1.7 cm (range 0.6-5.8). The median nephrometry score at diagnosis was 7 (range 4-10). Overall, the median tumor growth rate was 0.34 cm per year (range −0.19-2.0). Linear regression analysis showed that the annual tumor growth rate was associated with the RENAL nephrometry score ( P < 0.0001), but it was independent of the age at diagnosis, sex and initial tumor size. In addition, the correlation between the RENAL nephrometry score and annual growth rate remained significant in the 26 pathologically proven renal cell carcinomas. Conclusions The RENAL nephrometry score is associated with the annual growth rate of renal masses. Our findings further support the association between the RENAL nephrometry score and tumor biology. [ABSTRACT FROM AUTHOR]

Objective A wide variety of parameters have been investigated in the prognostic significance of non-conventional clear cell renal cell carcinoma. Aim of the present study was to compare its clinical outcome and to determine the independent prognostic factors according to the histology. Methods This retrospective study enrolled localized non-conventional clear cell renal cell carcinomas ( T1a- T4N0M0), including Xp11.2 translocation ( Xp11.2t), all surgically treated in a single institution between 1988 and 2011. The study statistically analyzed the clinicopathological parameters to compare the prognostic outcomes among the different histological subtypes of non-conventional clear cell renal cell carcinoma and to define any independent prognostic factors. Results A total of 374 cases were examined, including 126 papillary (33.7%), 164 chromophobe (43.9%), eight collecting duct (2.1%), 40 unclassified (10.7%), 16 Xp11.2t (4.3%), seven mucinous tubular and spindle cell (1.8%) renal cell carcinomas and 13 oncocytomas (3.5%). The mean follow up was 56.4 months, with s mean tumor size of 4.9 ± 3.4 cm. The 4-year recurrence-free survival, overall survival and cancer-specific survival were inversely related to the increase of pathological T stages ( P < 0.001). For histological type other than 13 oncocytomas and seven mucinous tubular and spindle cell renal cell carcinomas, the chromophobe showed the best prognosis of survival, followed by papillary, Xp11.2t, unclassified and collecting duct renal cell carcinomas, in this order. All survival rates were significantly different, as according to the histology ( P = 0.009). The significant prognostic factors were preoperative body mass index (hazard ratio 0.76), serum albumin (hazard ratio 0.64), T stage (hazard ratio 2.28), the sarcomatoid differentiation (hazard ratio 33.45) and lymphovascular invasion (hazard ratio 12.40) in pathology ( P < 0.05). Conclusions Different non-conventional clear cell renal cell carcinoma subtypes have significantly different clinical characteristics of prognosis with many suggestive predictive factors of survival. [ABSTRACT FROM AUTHOR]

Mannitol has been administered during partial nephrectomy as a renal protective agent for ischemic damage. However, we do not have any high-level clinical evidence of its effectiveness. The aim of the present study was to evaluate the effect of mannitol during open partial nephrectomy by comparing the postoperative renal function of patients who received it and those who did not. We retrospectively reviewed the records of 55 patients who underwent open partial nephrectomy for renal cancer in a solitary kidney from January 1990 to December 2012, and who were followed up postoperatively for at least 6 months. Of the 55 patients, mannitol was given to 20 patients (group M+) and not to the other 35 patients (group M−). We compared not only the postoperative estimated glomerular filtration rate, but also its decrease rate and the incidence of acute kidney injury requiring dialysis in the two groups. There were no significant differences in perioperative patient characteristics between the two groups. Mannitol made no significant difference in both the postoperative estimated glomerular filtration rate and its decrease rate at any point within 6 months of the postoperative period. The incidence of acute kidney injury requiring dialysis was one (5.0%) in group M+ and two (5.7%) in group M−. These findings suggest that there might be no advantage from the administration of mannitol during open partial nephrectomy. [ABSTRACT FROM AUTHOR]

Objective To identify complex changes in cell biology occurring during metastatic progression of renal cell carcinoma using a novel gene expression analysis algorithm. Methods Whole genome expression profiling was carried out on 32 snap-frozen samples of clear-cell renal cell carcinoma metastases, 29 primary tumors (14 low grade, 15 high grade) and 14 samples of normal kidney tissue using oligonucleotide microarrays. These data were analyzed with the gene set enrichment analysis method, which is able to detect even small, but significant, expression changes in functionally connected genes that cannot be shown by gene-by-gene comparisons. Results There were 95 gene sets (pathways) with significant upregulation in metastases compared with normal kidney tissue ( P < 0.01), and 77 gene sets with significant downregulation, respectively. Low-grade and high-grade tumors showed deregulation of various pathways that have previously not been described in renal cell carcinoma. There were significant changes of genes involved in cell cycle control, apoptosis, cell motility, metabolism, cell adhesion and cytoskeleton. Some promising new potential therapy targets were identified in renal cell carcinoma metastases; for example, aurora-kinase A and flap structure-specific endonuclease 1. Conclusion Expression profiling of metastatic renal cell carcinoma using the gene set enrichment analysis pathway analysis method provides new and detailed insights in alterations occurring in renal cell carcinoma during malignant transformation and progression. These data can help to develop new and specifically targeted renal cell carcinoma therapies. [ABSTRACT FROM AUTHOR]

The article presents abstracts on urology including "How do you teach your residents on open renal cancer surgery?," "High-risk prostate cancer: What is the best approach?," and "Antimicrobial prophylaxis for urological surgeries."

Objectives To investigate mortality rates and to comprehensively analyze prognostic indicators after radical nephrectomy for renal cell carcinoma. Methods Data were collected from 147 patients who underwent potentially curative radical nephrectomy for renal cell carcinoma. The following data were analyzed: tumor pathology, patient demographics and clinical parameters, such as pre- and postoperative estimated glomerular filtration rate, as well as the cause of death. Cause-specific survival rates were calculated including deaths caused by renal cell carcinoma and cardiovascular disease. A Cox proportional hazard model was used for statistical analysis. Results A univariate analysis showed that age at surgery (≥70 years), postoperative estimated glomerular filtration rate (<45 mL/min/1.73 m2), pathological high T stage, grade and venous invasion were significant poor prognostic indicators. The multivariate analysis provided evidence that pathological venous invasion was a significant poor prognostic indicator, whereas age at surgery (≥70 years), pre- (<65 mL/min/1.73 m2) or postoperative (<45 mL/min/1.73 m2) estimated glomerular filtration rate and pathological high grade were significant poor prognostic indicators in T1 tumor cases. Conclusions Post-radical nephrectomy renal function insufficiency can lead to a poor prognostic outcome, especially in patients with T1 renal cell carcinoma. Physicians should consider a comprehensive follow up focusing on possible causes of death, including those related to both renal cell carcinoma and cardiovascular disease events after radical nephrectomy. [ABSTRACT FROM AUTHOR]

The article presents abstracts of papers presented at the 8th American Urological Association (AUA) and the Japanese Urological Association International Affiliate Society Meeting including the trends in minimally-invasive surgery for kidney cancer, the developed of gasless laparoendoscopic single-port surgery (GasLESS) for urological tumors and the management of stone disease in the 21st century.

Objectives: Accurate tumor identification during partial nephrectomy is essential for successful tumor control. Intraoperative laparoscopic ultrasonography is useful for tumor localization, but the ultrasound probe is controlled by the assistant rather than the surgeon. We evaluated our initial experience using a robotic ultrasound probe that is controlled by the console surgeon. Methods: Partial nephrectomy was carried out in 22 consecutive patients between November 2010 and March 2011. A robotic ultrasound probe under console surgeon control was used in all the cases. All patients had at least 1 year follow up. Results: Mean patient age was 59 years and mean tumor size was 2.7 cm. There were six hilar tumors (27%) and 21 (95%) endophytic tumors. Mean R.E.N.A.L. nephrometry score was 6.9 (range 6-9). Mean operative time was 205.7 min and mean warm ischemia time was 17.9 min (range 6-28 min). All patients had negative tumor margins and were free of disease recurrence at a mean follow up of 13 months. Conclusion: The use of a robotic ultrasound probe during partial nephrectomy allows the surgeon to optimize tumor identification with maximal autonomy, and to benefit from the precision and articulation of the robotic instrument during this key step of the partial nephrectomy procedure. [ABSTRACT FROM AUTHOR]

Metanephric adenoma is an uncommon benign renal tumor that occurs predominantly in adult females and rarely in children. On histomorphology it shows a resemblance to Wilms' tumor, nephrogenic rests and papillary renal cell carcinoma. Multifocality along with multicentricity has not been documented in English literature till date. From a diagnostic and therapeutic viewpoint, recognition of this entity is of the utmost importance, because it shows a favorable clinical outcome. We describe a rare case of bilateral, multicentric metanephric adenoma associated with triphasic Wilms' tumor (stage II) of the left kidney in a male child. [ABSTRACT FROM AUTHOR]

Objective: To examine the actual impact of renal dysfunction on cardiovascular events in Japanese patients undergoing radical nephrectomy for renal cancer. Methods: This retrospective study included 178 Japanese patients who underwent radical nephrectomy between 1980 and 2010. Kaplan-Meier survival curves with a log-rank test and the Cox proportional hazards model were used to investigate the impact of the estimated glomerular filtration rate at 1 month after the radical nephrectomy on cardiovascular-event-free, cancer-specific and overall survivals. Results: During a median follow up of 68 months, 23 patients experienced cardiovascular events and 32 died. Postoperative renal dysfunction (estimated glomerular filtration rate <45 mL/min/1.73 m2 1 month after radical nephrectomy) was a significant risk factor for postoperative cardiovascular events in addition to age and history of cardiovascular disease. After adjustment for preoperative characteristics, postoperative renal dysfunction increased the risk of cardiovascular events by 3.48-fold (95% confidence interval 1.28-8.66). For overall and cancer-specific survivals, postoperative renal dysfunction did not represent an independent risk factor. Conclusion: Renal dysfunction has a significant impact on cardiovascular events in patients undergoing radical nephrectomy for renal cancer. [ABSTRACT FROM AUTHOR]

So far, metastatic renal cell carcinoma has been one of the most treatment-resistant cancers. The extensive use of cytokines, such as interferon-α and interleukin-2, were carried out for metastatic renal cell carcinoma. However, significant advances in understanding the molecular mechanisms underlying renal cell carcinoma have led to the development of molecular target-based drugs, which were desperately awaited for a long time, and now two types of molecular target-based drugs are available. Two vascular endothelial growth factor receptor tyrosine kinase inhibitors and two mammalian target of rapamycin inhibitors have been approved and available in Japan. The molecular target-based drugs have unique and characteristic adverse events, whose profile are not well understood in Japanese patients, because most of the clinical trials were carried out in Europe and America. In contrast, immunotherapy is being reconsidered in the selection of more appropriate patients or as a combined treatment form with other drugs, because of few complete responses obtained and unexpected adverse events by molecular targeted treatments. We have several molecular targeted-drugs available at present and will have more, and we will actually use these drugs in various clinical settings, such as the presurgical setting, the adjuvant setting, sequential administration and combined administration, in addition to cytokines. Therefore, we need more elaborate studies to obtain the optimal treatment methods to maximize the effect of such agents to extend overall survival while maintaining quality of life of metastatic renal cell carcinoma patients. In this article, we reviewed the issues related to the current status of pharmacotherapy available for metastatic renal cell carcinoma. [ABSTRACT FROM AUTHOR]

Renal mass sampling (RMS) can be carried out by core biopsy or fine needle aspiration with each presenting potential advantages and limitations. The literature about RMS is confounded by a lack of standardized techniques, ambiguous terminology, imprecise definitions of accuracy, substantial rates of non-informative biopsies, and recurrent diagnostic challenges with respect to eosinophilic neoplasms. Despite these concerns, RMS has an expanding role in the evaluation and treatment of renal masses, in order to stratify biological aggressiveness and guide management that can range from surgery to active surveillance. Non-informative biopsies can be managed with surgical excision or repeat biopsy, with the latter showing encouraging results in recent studies. We propose a new classification in which all biopsies are categorized as non-informative versus informative, with the latter being subclassified as confirmed accurate, presumed accurate or confirmed inaccurate. This terminology will facilitate the comparison of results from various studies and stimulate progress. Incorporation of novel biomarkers and molecular fingerprinting into RMS protocols will likely allow for more rational management of patients with renal masses in the near future. [ABSTRACT FROM AUTHOR]

To gain information about overexpressed antigens in renal cell carcinoma (RCC) by using a chemical proteomics approach. RCC cell line 769P was cultured and proteome analysis was subsequently carried out in the culture supernatants. By using sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and tandem mass spectrometry (LC-MS/MS), proteins in the culture supernatants were searched. A MEDLINE search to define the functions of the identified proteins was carried out. Four differentially regulated proteins (profilin 1, amyloid beta A4 protein [APP], proprotein convertase subtilisin/kexin type 1 inhibitor [ProSAAS], galectin-3-binding protein [LGALS3BP]) were selected. These were not overexpressed in normal kidney tissue or reported in RCC. Their levels were measured through western blotting of normal kidney and RCC tissues. No differences were observed in the expression levels of APP, ProSAAS or LGALS3BP between RCC and normal kidney tissues. Profilin 1 was overexpressed in RCC tissue. On the basis of this observation, an immunohistochemical analysis of profilin 1 in normal kidney and RCC tissues was carried out. In normal tissues, tubules that were sources of RCC stained positive for profilin 1. In RCC tissue, in contrast, the stromal cells in the tumors stained positive. Profilin 1 can be a key element in the pathological processes of RCC, such as tumorigenesis and/or tumor growth. Thus, it has the potential to serve as a diagnostic or progression biomarker and therapeutic target in RCC. [ABSTRACT FROM AUTHOR]

To analyze the characteristics and the prognostic significance of chromophobe renal cell carcinomas (chRCC). Data about 2981 patients with non-metastatic renal cell carcinomas (RCC) at the time of surgery were retrospectively collected from 26 institutions between 1998 and 2008. All patients had undergone partial or radical nephrectomies. Of the 2981 patients, 2602 patients with conventional RCC (cRCC) and 148 with chRCC were studied. Clinical and pathological parameters were determined in all patients. Recurrence-free survival (RFS) and cancer-specific survival (CSS) were assessed. Patients with chRCC differed significantly from those with cRCC on the following parameters: younger age ( P = 0.026), greater female ratio ( P < 0.001), and larger tumor diameter ( P < 0.001). Both groups were alike with respect to body mass index ( P = 0.943), Eastern Cooperative Oncology Group performance status ( P = 0.163), T stage ( P = 0.375), and Fuhrman's grade ( P = 0.134). The 5-year RFS rates in patients with chRCC and cRCC were 82.7% and 83.3%, respectively ( P = 0.762). The 5-year CSS rates in patients with chRCC and cRCC were 88.8% and 92.2%, respectively ( P = 0.980). Both groups showed equivalent oncological outcomes in terms of RFS and CSS for cases stratified by T stage and Fuhrman's grade. In multivariate analysis, the histological subtype was not retained as an independent prognostic variable (RFS: P = 0.893; CSS: P = 0.729). Despite being significantly different from cRCC in terms of several clinical and pathological parameters, chRCC shows equivalent oncological outcomes. [ABSTRACT FROM AUTHOR]

The objective of the present study was to document the treatment efficacy and safety of sorafenib in Japanese patients with advanced renal cell carcinoma (RCC). A retrospective analysis of 50 consecutive patients with metastatic RCC between January 2005 and December 2009 was carried out. Patients received sorafenib after failed cytokine therapy or first-line sorafenib treatment. All received 400 mg of sorafenib orally twice daily. Five of 14 patients with bone metastases were also given bisphosphonates. Tumor response was evaluated every 1–2 months according to the Response Evaluation Criteria in Solid Tumors. Adverse events (AE) were evaluated at each visit during and after treatment, and were recorded according to the National Cancer Institute's Common Terminology Criteria for Adverse Events version 3.0. Dose modification of sorafenib was permitted if grade 3 or 4 AE occurred. Treatment continued until disease progression or treatment intolerance occurred. Partial response, and stable disease as best objective responses were observed in 11 (22%) and 23 (46%) patients, respectively. Median progression-free survival was 7.3 months and median overall survival was 11.9 months. All patients experienced AE and one or more grade 3/4 AE occurred in 43 of 50 (86%) patients. Although it requires close monitoring, sorafenib treatment seemed to be effective in the present study population. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to determine trends in the incidence of benign lesions in patients undergoing surgery for suspicious renal masses on preoperative computed tomography scan. Methods: The records of 1065 patients who underwent open consecutive partial nephrectomy (PN) or radical nephrectomy (RN) between January 2001 and December 2008 were reviewed. Patients who underwent PN during the periods 2001–2002, 2003–2004, 2005–2006, and 2007–2008 were assigned to groups 1, 2, 3 and 4, respectively. The frequencies of benign and malignant lesions in these groups were assessed according to size and histology subtypes. Results: The ratio of PN to RN was 12.4%, 18.3%, 24.3% and 37.2% in groups 1, 2, 3 and 4, respectively ( P < 0.05). The mean size of resected lesions was 2.6 cm (range 0.8–6.2 cm). Of the 290 cases, histopathology revealed benign findings in 52 (17.9%). Benign pathology was found in three of 18 cases (16.7%) in group 1, seven of 36 cases (19.4%) in group 2, 12 of 63 cases (19.0%) in group 3 and 30 of 173 cases (17.3%) in group 4. There was no significant difference in the frequency of benign histology among groups. Conclusion: PN, as opposed to RN, has shown a rising tendency over time. The frequency of benign pathology findings after PN for suspicious renal masses on preoperative computed tomography imaging has not decreased. Proper management should favor nephron-sparing surgery for renal lesions if such lesions can be removed satisfactorily with PN. [ABSTRACT FROM AUTHOR]