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

BACKGROUND: The aim of this study was to investigate the prognostic significance of multiple preoperative laboratory abnormalities in upper urinary tract urothelial carcinoma (UUTUC) patients. METHODS: This study included a total of 135 consecutive patients with clinically localized UUTUC who underwent radical nephroureterectomy (RNU). The impact of several preoperative blood-based markers in addition to conventional clinical factors on extravesical recurrence-free survival (eRFS) in these patients was retrospectively evaluated. RESULTS: Despite the lack of a significant correlation between conventional clinical factors and any of the postoperative pathologic parameters, preoperative laboratory abnormalities were shown to have a significant impact on some pathological factors reflecting an aggressive phenotype as follows-C-reactive protein (CRP) level on pathological stage, De Ritis (aspartate transaminase/alanine transaminase) ratio on nodal involvement, and neutrophil-lymphocyte ratio (NLR) on pathological stage. During the observation period of this study (median 36.1 months), extravesical disease recurrence was detected in 44 (32.6%) of the 135 patients with a 5-year eRFS rate of 62.1%. Of several factors examined, the CRP level, De Ritis ratio, and NRL were significantly correlated with eRFS on univariate analysis. Of these significant factors, the De Ritis ratio and NRL were identified as independent predictors of eRFS on multivariate analysis. Moreover, there were significant differences in eRFS according to the positive numbers of these two independent risk factors. CONCLUSIONS: These findings suggest that it is important to consider laboratory abnormalities, particularly the De Ritis ratio and NLR, to predict disease recurrence following RNU in patients with clinically localized UUTUC.

Effects of 25- and 30-degree Trendelenburg positions on intraocular pressure changes during robot-assisted radical prostatectomy.

BACKGROUND: The objective of this study was to assess the effects of 25-degree and 30-degree Trendelenburg positions on intraocular pressure (IOP) changes during robot-assisted radical prostatectomy (RARP). MATERIALS AND METHODS: This prospective study involved a total of 30 consecutive patients undergoing RARP. All participants were randomly divided into two groups: Trendelenburg position with the head down at 25 degrees or 30 degrees. In addition to representative operative outcomes, IOP was measured at six discrete time points; Time 1 (T1): before induction of general anesthesia, patients in a horizontal supine position; T2: after induction of general anesthesia, patients in a horizontal supine position; T3: 1 hour after adopting the Trendelenburg position; T4: 2 hours after adopting the Trendelenburg position; T5: after pneumoperitoneum resolution in the Trendelenburg position; T6: anesthetized before awakening in a supine position. RESULTS: The total and console operative times, estimated blood loss, and intravenous fluid intake during RARP did not significantly differ between the two groups. While the IOP values measured at the same time points were similar between the two groups, the 25-degree Trendelenburg position significantly attenuated the IOP change from T1 to T3, T4, and T5 compared with those at 30 degrees. CONCLUSIONS: These findings suggest that RARP in the 25-degree Trendelenburg position may reduce the risks of position-related ophthalmic complications without increasing the difficulty of the surgical procedure.

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

OBJECTIVES: To evaluate the impact of metabolic syndrome on the early recovery of urinary continence after robot-assisted radical prostatectomy. METHODS: The present study included a total of 302 consecutive Japanese patients with clinically localized prostate cancer who underwent robot-assisted radical prostatectomy. In this study, postoperative urinary continence was defined as no leak or the use of a security pad. The continence status was assessed by interviews before and 1 and 3 months after robot-assisted radical prostatectomy. Metabolic syndrome was defined as follows: body mass index ≥25 kg/m2 and two or more of the following: hypertension, diabetes mellitus and dyslipidemia. The effect of the presence of metabolic syndrome on the continence status of these patients was retrospectively examined. RESULTS: A total of 116 (38.4%) and 203 (67.2%) of the 302 patients were continent at 1 and 3 months after robot-assisted radical prostatectomy, respectively. A total of 31 (10.3%) patients were judged to have metabolic syndrome. Despite the operative time being longer in patients with metabolic syndrome, no significant differences were observed in the remaining preoperative, intraoperative or postoperative variables between patients with or without metabolic syndrome. On multivariate logistic regression analysis, metabolic syndrome and the duration of hospitalization were significantly correlated with the 1-month continence status. Similarly, metabolic syndrome and estimated blood loss during surgery were independent predictors of continence rates at 3 months after robot-assisted radical prostatectomy. CONCLUSIONS: These findings suggest that the presence of metabolic syndrome could have a significant impact on the early recovery of urinary continence after robot-assisted radical prostatectomy.

Identification of risk factors predicting febrile neutropenia in patients with metastatic germ cell tumors receiving cisplatin-based combination chemotherapy.

OBJECTIVES: To identify clinical features and predictive factors of febrile neutropenia in Japanese patients with metastatic germ cell tumors undergoing cytotoxic chemotherapy. METHODS: Between April 2007 and May 2016, 86 consecutive Japanese patients with metastatic germ cell tumors were treated with cisplatin-based combination chemotherapy, including bleomycin, etoposide and cisplatin, and paclitaxel, ifosfamide and cisplatin. A total of 378 chemotherapy cycles administered for these 86 patients were retrospectively analyzed. RESULTS: During the 378 cycles, consisting of 212 for bleomycin, etoposide and cisplatin, and 166 for paclitaxel, ifosfamide and cisplatin, 81 episodes of febrile neutropenia (21.4%) developed in 34 patients (39.5%). Multivariate logistic regression analysis showed that low estimated glomerular filtration rate and albumin levels were independent risk factors for the development of febrile neutropenia. Furthermore, a significant difference in the incidence of febrile neutropenia was noted according to positive numbers of these two independent risk factors; that is, febrile neutropenia occurred in 13 of 171 courses in patients negative for any risk factors (7.6%), 44 of 155 courses in those positive for a single risk factor (28.4%) and 24 of 52 courses in those positive for two risk factors (46.2%). CONCLUSIONS: The incidence of febrile neutropenia in Japanese metastatic germ cell tumor patients receiving cisplatin-based combination chemotherapy appears to be higher than reported previously by studies in Western countries. When carrying out cytotoxic chemotherapy, special attention should be paid to patients with low estimated glomerular filtration rate and/or albumin levels considering the high probability of febrile neutropenia.

Safety and feasibility of robot-assisted radical prostatectomy for clinically localized prostate cancer in elderly Japanese patients.

BACKGROUND: This study was conducted to assess the safety and feasibility of robot-assisted radical prostatectomy (RARP) for elderly Japanese (aged ≥ 70 years) patients with clinically localized prostate cancer (PCa). METHODS: From April 2012 to March 2016, a total of 302 consecutive patients with clinically localized PCa underwent RARP at our institute. In this series, 109 (36.1%) and 193 (63.9%) of the patients were divided into older (aged ≥ 70 years) and younger (aged <70 years) groups, respectively. The correlation between the categorized patient age and various clinicopathological factors, including preoperative characteristics, perioperative outcome, and urinary continence outcome after RARP, was retrospectively analyzed. RESULTS: Except for age and Gleason score at biopsy, there was no difference in the preoperative features between the two groups. A nonnerve-sparing RARP was performed more often in the younger group; however, other perioperative variables in the elderly group were comparable to those in the younger group. Similarly, the urinary continence rates at 1 month, 3 months, and 6 months after the surgery were equally favorable in the younger and older groups. CONCLUSION: RARP may be a reasonable therapeutic option for elderly patients with PCa and provides comparable perioperative and functional outcomes to those in younger patients.

Effect of Targeting Clusterin Using OGX-011 on Antitumor Activity of Temsirolimus in a Human Renal Cell Carcinoma Model.

BACKGROUND: It has not been well documented that the modulation of stress response mediates the efficacy of the mammalian target of rapamycin (mTOR) inhibitor in renal cell carcinoma (RCC). OBJECTIVE: The objective of this study was to investigate whether the activity of the mTOR inhibitor temsirolimus against RCC could be enhanced by OGX-011, an antisense oligodeoxynucleotide (ODN) targeting the stress-activated chaperone clusterin. METHODS: We investigated the efficacy of combined treatment with temsirolimus plus OGX-011 in a human RCC Caki-1 model focusing on the effects on apoptotic and autophagic pathways. RESULTS: Although clusterin expression was increased by temsirolims, additional treatment of Caki-1 with OGX-011 significantly inhibited clusterin upregulation (p < 0.05). Combined treatment of temsirolimus and OGX-011 synergistically enhanced the sensitivity of Caki-1 to temsirolimus (p < 0.01), reducing the IC50 by approximately 50 %. Apoptotic changes were marked in Caki-1 following combined treatment with a sublethal dose of temsirolimus and OGX-011, accompanying the significant downregulation of Mcl-1 (p < 0.05), but not with either agent alone. Furthermore, this combined treatment markedly blocked the temsirolimus-induced activation of autophagy in Caki-1 (p < 0.01). In-vivo systemic administration of temsirolimus plus OGX-011 significantly inhibited the growth of Caki-1 tumors compared with that of temsirolimus plus control ODN (p < 0.05). CONCLUSIONS: Silencing of clusterin using OGX-011 resulted in the further enhancement of proapoptotic activity as well as the marked attenuation of the autophagic pathway induced by temsirolimus in a human RCC model. Thus, the combined use of OGX-011 could be a promising strategy through the enhanced cytotoxic activity of temsirolimus against RCC.

De Ritis (aspartate transaminase/alanine transaminase) ratio as a significant predictor of recurrence-free survival in patients with upper urinary tract urothelial carcinoma following nephroureterectomy.

BACKGROUND: To evaluate the prognostic significance of preoperatively assessed aspartate aminotransaminase (AST), alanine aminotransaminase (ALT), and the AST/ALT (De Ritis) ratio in patients with upper urinary tract urothelial carcinoma (UUTUC). METHODS: This study included a total of 109 consecutive patients with clinically localized UUTUC who underwent nephroureterectomy. Effects of preoperative levels of AST, ALT, and the De Ritis ratio in addition to conventional clinicopathological parameters on the extravesical recurrence-free survival (eRFS) in these 109 patients were retrospectively analyzed. RESULTS: Despite the lack of a significant correlation of AST or ALT with any of the factors examined in this study, the elevation of the De Ritis ratio was significantly correlated with several unfavorable parameters, including elderly age, high pathological stage, high tumor grade, and lymphovascular invasion. During the observation period of this series (median = 40.8mo), extravesical disease recurrence developed in 39 (35.8%) of the 109 patients, with a 5-year eRFS rate of 56.8%. Of several factors examined, the tumor location, De Ritis ratio, pathological stage, lymph node metastasis, tumor grade, lymphovascular invasion, surgical margin status, and adjuvant chemotherapy were shown to be significantly correlated with eRFS by univariate analysis. Of these, the De Ritis ratio, pathological stage, lymph node metastasis, and tumor grade were identified as independent predictors of eRFS on multivariate analysis. CONCLUSIONS: These findings suggest that preoperative assessment of the De Ritis ratio may provide useful information with respect to the clinical course of patients with clinically localized UUTUC who are scheduled to be treated with nephroureterectomy.

Irinotecan and nedaplatin as salvage therapy for patients with advanced germ cell tumors following intensive treatment with cisplatin-based combination chemotherapies.

BACKGROUND: To analyze the clinical outcomes of the irinotecan plus nedaplatin (IN) regimen in patients with advanced germ cell tumors (GCTs) refractory to cisplatin-based combination chemotherapies. METHODS: This study included a total of 20 consecutive advanced GCT patients who were categorized into intermediate- or poor-risk GCT groups according to the International Germ Cell Consensus Classification, and were judged to show refractory or relapsed disease after bleomycin, etoposide and cisplatin and cisplatin, ifosfamide and paclitaxel therapies. All 20 patients subsequently received IN therapy (irinotecan 100 mg/m(2) on days 1 and 15; nedaplatin 100 mg/m(2) on day 1) every 4 weeks. RESULTS: Following a median of 3 cycles of IN, 9 patients (45 %) achieved normalization of serum tumor markers. In addition, surgical resection of the residual tumors following IN was performed in 5 patients, of whom 4 were pathologically diagnosed with no viable cancer cells. At a median follow-up of 9 months, 11 patients (55 %) were alive, including 7 (35 %) with no evidence of disease, whereas the remaining 9 (45 %) died of disease progression. The median duration of overall survival after the introduction of IN to these 20 patients was 13.4 months. Severe hematological toxicities were observed in all patients, but were manageable. Although fatal treatment-related interstitial pneumonia occurred in 1 patient, other non-hematological toxicities were generally tolerable. CONCLUSIONS: Considering the markedly unfavorable characteristics of the included patients with advanced GCT who were intensively treated with cisplatin-based combination chemotherapies, IN could be regarded as having promising therapeutic activity with an acceptable toxicity profile.

UNC-51-like kinase 1 expression in radical nephrectomy specimens as a predicting factor of progression-free survival in patients with metastatic renal cell carcinoma treated with mammalian target of rapamycin inhibitors.

BACKGROUND: To analyze basal expression levels of multiple components in the autophagy pathway in radical nephrectomy specimens from patients with metastatic renal cell carcinoma (mRCC) treated with mammalian target of rapamycin (mTOR) inhibitors, to identify factors predicting susceptibility to these agents. METHODS: This study included 48 consecutive patients undergoing radical nephrectomy, who were diagnosed with mRCC and subsequently treated with either everolimus or temsirolimus. Expression levels of 5 major molecular markers involved in the signaling pathway associated with autophagy, including autophagy-related protein (Atg)5, Atg9, Beclin1, microtubule-associated protein light chain 3, and UNC-51-like kinase 1 (ULK1), were measured by immunohistochemical staining of primary renal cell carcinoma specimens. RESULTS: During the observation period of this study (median = 16.2 mo), 36 patients developed disease progression, with a median progression-free survival (PFS) period of 7.6 months. Of several factors examined, bone metastasis, liver metastasis, and ULK1 expression were shown to have significant effects on the response to mTOR inhibitors. PFS was significantly correlated with the expression level of ULK1 in addition to bone and liver metastases on univariate analysis. Of these significant factors, ULK1 expression and liver metastasis were independently associated with PFS on multivariate analysis. CONCLUSIONS: It may be useful to consider expression levels of potential molecular markers in the autophagy pathway, particularly ULK1, in addition to conventional parameters, when selecting patients with mRCC who are likely to benefit from treatment with mTOR inhibitors.

Performance status as a significant prognostic predictor in patients with urothelial carcinoma of the bladder who underwent radical cystectomy.

OBJECTIVES: To assess the significance of performance status as a prognostic factor after radical cystectomy for urothelial carcinoma of the bladder. METHODS: The present study included 730 consecutive patients with urothelial carcinoma of the bladder who underwent radical cystectomy. Clinicopathological outcomes in these patients were analyzed focusing on the impact of performance status, which was assessed using the Karnofsky Performance Status scale before surgery. Patients were classified into groups with Karnofsky Performance Status ≥90 and ≤80. RESULTS: A total of 561 (76.8%) and 169 (23.2%) patients were judged to have Karnofsky Performance Status ≥90 and ≤80, respectively. During a mean of 52.0 months, disease recurrence and mortality occurred in 257 (35.2%) and 249 (34.1%) patients, respectively, and the 5-year recurrence-free and overall survival rates were 64.1 and 65.3%, respectively. There were significant differences in age, hemoglobin, albumin, estimated glomerular filtration rate, pathological T stage and nodal involvement between the Karnofsky Performance Status ≥90 and ≤80 groups. Multivariate analysis showed independent impacts of Karnofsky Performance Status, pathological T stage, nodal involvement and lymphovascular invasion on recurrence-free survival, as well as independent impacts of Karnofsky Performance Status, age, body mass index, hemoglobin, pathological T stage, nodal involvement and lymphovascular invasion on overall survival. CONCLUSIONS: The results suggest a significant association between impaired performance status and unfavorable prognosis in patients with urothelial carcinoma of the bladder undergoing radical cystectomy.

Enhanced Sensitivity to Sunitinib by Inhibition of Akt1 Expression in Human Castration-resistant Prostate Cancer PC3 Cells Both In Vitro and In Vivo.

OBJECTIVE: To investigate whether antitumor activity of sunitinib is enhanced by silencing Akt1 in a human castration-resistant prostate cancer PC3 model. MATERIALS AND METHODS: We initially established PC3 in which the expression vector containing a short hairpin ribonucleic acid targeting Akt1 was introduced (PC3/sh-Akt1). Changes in various phenotypes of PC3/sh-Akt1 after treatment with sunitinib were compared with those of PC3 transfected with control vector alone (PC3/C) both in vitro and in vivo. RESULTS: When cultured in the standard medium, in vitro growth of PC3/sh-Akt1 was almost similar to that of PC3/C. However, compared with PC3/C, PC3/sh-Akt1 showed a significantly higher sensitivity to sunitinib, accompanying impaired phosphorylation of p44/42 mitogen-activated protein kinase, downregulation of Bcl-2, and upregulation of Bax. In addition, treatment with sunitinib significantly suppressed the migration ability of PC3/sh-Akt1 compared with that of PC3/C. In vivo, administration of sunitinib induced the significantly marked growth inhibition of PC3/sh-Akt1 compared with that of PC3/C, and apoptotic index in PC3/sh-Akt1 tumor in mice treated with sunitinib was significantly greater than that in PC3/C tumor. CONCLUSION: Combined treatment with Akt1 inhibitor and sunitinib could be a promising therapeutic approach for men with castration-resistant prostate cancer.

Expression Profile of Autophagy-related Markers in Localized Prostate Cancer: Correlation With Biochemical Recurrence After Radical Prostatectomy.

OBJECTIVE: To evaluate the expression of multiple molecular markers involved in autophagy, a cellular degradation pathway for the clearance of damaged or superfluous proteins and organelles, in localized prostate cancer (PC) to clarify the prognostic significance of these markers in patients undergoing radical prostatectomy (RP). METHODS: Expression levels of 5 autophagy markers, including autophagy-related gene 5, autophagy-related gene 9, Beclin1, microtubule-associated protein light chain 3, and UNC-51-like kinase 1 (ULK1), in RP specimens from 160 consecutive patients with clinically localized PC were measured by immunohistochemical staining. RESULTS: Of these 5 markers, ULK1 expression was significantly correlated with the incidence of biochemical recurrence (BR). On univariate analysis, ULK1 expression, serum prostate-specific antigen level, pathologic stage, Gleason score, seminal vesicle invasion, and surgical margin status were identified as significant predictors of BR. All these significant factors except for seminal vesicle invasion were independently associated with BR on multivariate analysis. Furthermore, significant differences in BR-free survival according to the positive numbers of these 5 independent risk factors were noted, that is, BR occurred in 2 of 33 patients negative for risk factors (6.1%), 20 of 76 patients positive for 1 or 2 risk factors (26.3%), and 38 of 51 patients positive for ≥3 risk factors (74.5%). CONCLUSION: Collectively, these findings suggest that measurement of expression levels of potential autophagy markers, particularly ULK1, in RP specimens, in addition to conventional parameters, may contribute to the accurate prediction of BR after RP for localized PC.

Expression pattern of autophagy-related markers in non-metastatic clear cell renal cell carcinoma: association with disease recurrence following radical nephrectomy.

PURPOSE: To evaluate the expression of multiple molecular markers associated with autophagy, a cellular degradation pathway for the clearance of damaged or superfluous proteins and organelles, in clear cell renal cell carcinoma (CCRCC) in order to identify the prognostic significance of these markers in patients undergoing radical nephrectomy. METHODS: Expression levels of five markers, including autophagy-related gene 5 (Atg5), Atg9, Beclin 1, microtubule-associated protein light chain 3 (LC3), and UNC-51-like kinase 1 (ULK1), in radical nephrectomy specimens from a total of 100 patients with non-metastatic CCRCC were measured by immunohistochemical staining. RESULTS: All the five markers were significantly correlated with some pathological factors reflecting an aggressive phenotype, including the pathological T stage, tumor grade, and microvascular invasion. During the follow-up period of this series (median 58.0 months), disease recurrence developed in 41 of the 100 patients, with a 5-year recurrence-free survival (RFS) rate of 61.3%. On univariate analysis, expression levels of Atg5 and Beclin 1, in addition to the pathological T stage, microvascular invasion, and preoperative CRP level, were identified as significant predictors of disease recurrence. Of these factors, the expression of Beclin 1 and preoperative CRP level were independently correlated with RFS on multivariate analysis. CONCLUSION: These findings suggest that the combined assessment of expression levels of autophagy-associated markers, particularly Beclin 1, in radical nephrectomy specimens with conventional prognostic parameters, would contribute to the precise prediction of postoperative disease recurrence in patients with non-metastatic CCRCC.

Significance of 4E-binding protein 1 as a therapeutic target for invasive urothelial carcinoma of the bladder.

BACKGROUND: To evaluate the expression of multiple molecular markers involved in the mammalian target of rapamycin (mTOR) signaling pathway in human muscle-invasive bladder cancer (BC) and to assess the therapeutic efficacies of mTOR inhibitors in human BC KoTCC-1 cells. METHODS: Expression levels of 5 markers, including PTEN, phosphorylated (p)-Akt, p-mTOR, p-p70 ribosomal S6 kinase, and p-4E-binding protein 1 (4E-BP1), were measured in radical cystectomy specimens from 49 patients with muscle-invasive BC by immunohistochemical staining. We then analyzed the effects of treatment with temsirolimus or Ku-0063794, a dual inhibitor of mTOR complex 1 (C1) and mTOR complex 2 (C2), on changes in the growth and expression profiles of 5 mTOR-associated markers in KoTCC-1 cells. RESULTS: During the follow-up period of this study, disease recurred in 27 patients (55.1%), and of several factors examined, the expression level of p-4E-BP1 in addition to the pathological T stage was independently related to recurrence-free survival on multivariate analysis. Although the growth of KoTCC-1 cells was inhibited by both temsirolimus and Ku-0063794 in dose-dependent manners, treatment with Ku-0063794 resulted in a marked decrease in the expression of p-4E-BP1 in KoTCC-1 cells compared with that with temsirolimus. Furthermore, the growth-inhibitory effect of both mTOR inhibitors was shown to be proportional to the expression levels of p-4E-BP1. CONCLUSIONS: The phosphorylation status of 4E-BP1 appeared to be correlated with the prognosis of patients with muscle-invasive BC following radical cystectomy as well as the sensitivities of BC cells to mTOR inhibitors; therefore, the inactivation of 4E-BP1 using Ku-0063794 may be a promising novel approach for muscle-invasive BC.

Expression profile of epithelial-mesenchymal transition markers in non-muscle-invasive urothelial carcinoma of the bladder: correlation with intravesical recurrence following transurethral resection.

OBJECTIVES: To evaluate the expression of molecular markers involved in epithelial-mesenchymal transition (EMT), a key process mediating the progression of malignant tumors, in non-muscle-invasive urothelial carcinoma of the bladder (NMIUCB) to clarify the significance of these markers as predictors of intravesical recurrence in patients treated with transurethral resection (TUR). MATERIALS AND METHODS: Expression levels of 13 EMT markers, including E-cadherin, N-cadherin, ß-catenin, γ-catenin, fibronectin, matrix metalloproteinase (MMP)-2, MMP-9, Slug, Snail, TWIST, vimentin, ZEB1, and ZEB2, in TUR specimens obtained from 161 consecutive patients with NMIUCB were measured by immunohistochemical staining. RESULTS: Of these 13 markers, significant differences in the incidence of intravesical recurrence were noted according to expression levels of E-cadherin, N-cadherin, MMP-2, MMP-9, and TWIST. Univariate analysis also identified expression levels of E-cadherin, N-cadherin, MMP-2, MMP-9 and TWIST, in addition to the tumor size, pathological T category, and concomitant carcinoma in situ, as significant predictors of intravesical recurrence-free survival. Of these significant factors, expression levels of E-cadherin, MMP-9, and TWIST; tumor size; and concomitant carcinoma in situ appeared to be independently associated with intravesical recurrence-free survival on multivariate analysis. Furthermore, there were significant differences in recurrence-free survival according to positive numbers of these 5 independent risk factors (i.e., positive for 0 or 1 factor vs. positive for 2 factors vs. positive for 3 or more factors). CONCLUSIONS: Consideration of expression levels of EMT-associated markers in TUR specimens, in addition to conventional prognostic parameters, would contribute to the accurate prediction of intravesical recurrence following TUR for NMIUCB.

Preoperative differentiation between benign and malignant renal masses smaller than 4 cm treated with partial nephrectomy.

BACKGROUND: The aim of this study is to accurately differentiate between benign and malignant small renal masses (SRMs) prior to surgery. METHODS: The study included 144 patients with SRMs <4 cm suspected to be renal cell carcinoma (RCC) based on several imaging examinations, who subsequently underwent partial nephrectomy. Clinicopathological data were analyzed based on the preoperative findings obtained from enhanced computed tomography (CT) as follows: group 1 showing a typical imaging pattern for clear cell RCC (CCRCC), and group 2 showing an imaging pattern atypical of CCRCC. We then evaluated the association between clinicopathological characteristics and pathological diagnosis in order to identify factors which can predict the pathological diagnosis. RESULTS: Based on the criteria, 102 (70.8 %) and 42 (29.2 %) patients were classified into group 1 and group 2, respectively. The only independent factor identified to predict the final pathological diagnosis of the 144 patients was preoperative CT findings. Only 7 (6.9 %) patients were pathologically diagnosed with benign tumors in group 1; however, 13 (31.0 %) of the 42 patients in group 2 appeared to have pathologically confirmed benign tumors. A younger age and lower body mass index (BMI) in group 2 were shown to be independently associated with benign histology on multivariate analysis. CONCLUSIONS: The proportion of patients with benign tumors was comparatively high in those with CT findings atypical for CCRCC; therefore, other clinical parameters, such as age and BMI, should be considered when determining therapeutic strategies for patients with such SRMs.

Efficacy and tolerability of TIP (paclitaxel, ifosfamide and cisplatin) incorporated into induction chemotherapy for patients with intermediate- or poor-risk metastatic germ cell tumors.

The objective of this study was to analyze the clinical outcomes of TIP (paclitaxel, ifosfamide and cisplatin) incorporated into induction chemotherapy for patients with metastatic germ cell tumor (GCT) characterized by unfavorable clinical features. This study included 37 patients, who were categorized into intermediate- or poor-risk GCT according to the International Germ Cell Consensus Classification (IGCCC). All 37 patients received two cycles of bleomycin, etoposide and cisplatin (BEP) followed by several cycles of TIP. Following treatment with TIP, 25 patients achieved the normalization of serum tumor markers. In addition, surgical resection of the residual tumors following TIP was performed in 17 patients who were pathologically diagnosed with no viable cancer cells. At a median follow-up of 36 months, 31 patients were alive, including 27 with no evidence of disease, whereas the remaining six died of disease progression. The 5-year disease-free survival (DFS) and overall survival (OS) rates in these 37 patients were 72.9 and 85.3%, respectively. Despite the lack of a significant predictor of OS, univariate analysis identified the presence of a choriocarcinoma element and IGCCC as significant predictors of DFS, of which only the presence of a choriocarcinoma element appeared to be independently associated with DFS. In this series, treatment-related death did not occur, although 27 patients had at least one adverse event corresponding to grade 3 ≤. Collectively, it would be of worth to pursue the significance of the early incorporation of TIP into induction chemotherapy for patients with intermediate- or poor-risk metastatic GCT in the future.

Significance of circulating matrix metalloproteinase-9 to tissue inhibitor of metalloproteinases-2 ratio as a predictor of disease progression in patients with metastatic renal cell carcinoma receiving sunitinib.

OBJECTIVES: To assess the significance of circulating matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) as predictors of disease progression in patients with metastatic renal cell carcinoma (mRCC) receiving sunitinib. MATERIALS AND METHODS: Circulating levels of MMP-2, MMP-9, TIMP-1, and TIMP-2 in sera from 52 patients with mRCC treated with sunitinib were measured at the baseline and on the first day of each treatment cycle until progression using enzyme-linked immunosorbent assays. RESULTS: The baseline level of MMP-9 in nonresponders to sunitinib was significantly higher than that in responders, whereas the baseline level of TIMP-2 in nonresponders was significantly lower than that in responders. However, there were no significant differences in the serum levels of MMP-2 and TIMP-1 between responders and nonresponders. The serum MMP-9/TIMP-2 ratio at the baseline in nonresponders was also significantly higher than that in responders. Univariate analysis showed that the MMP-9/TIMP-2 ratio, but not MMP-9 and TIMP-2 levels, was significantly correlated with progression-free survival, and the MMP-9/TIMP-2 ratio, in addition to the Memorial Sloan-Kettering Cancer Center classification and C-reactive protein level, appeared to be independently associated with progression-free survival on multivariate analysis. Furthermore, despite the lack of significant differences in the serum levels of MMP-9 and TIMP-2 between the baseline and the time of progression, the MMP-9/TIMP-2 ratio at the time of progression was significantly elevated compared with the baseline ratio. CONCLUSIONS: An imbalance between the serum MMP-9 and TIMP-2 levels could be a novel biomarker to predict disease progression in patients with mRCC under treatment with sunitinib.

Long-term changes in renal function outcomes following radical cystectomy and urinary diversion.

BACKGROUND: We analyzed long-term changes in the renal function of patients undergoing radical cystectomy and urinary diversion (UD). METHODS: This study included 169 patients who underwent radical cystectomy and UD (42, cutaneous ureterostomy; 40, ileal conduit; 87, neobladder substitution), and were followed for at least 60 months (median 106 months). Renal deterioration was defined as a >25 % decrease in the estimated glomerular filtration rate (eGFR) relative to that prior to surgery. We determined the associations between several parameters and postoperative renal deterioration. RESULTS: Despite the significantly younger age and more favorable renal function of patients with neobladder substitution than of those with other types of UD, no significant differences were observed in the remaining preoperative clinical parameters among the three different UD groups. The mean eGFR of the 169 patients decreased from 69.6 to 55.9 mL/min/1.73 m(2), and renal deterioration was observed in 24 (57.1 %), 20 (50.0 %) and 34 (39.0 %) patients in the cutaneous ureterostomy, ileal conduit and neobladder substitution groups, respectively. Multivariate analysis of several parameters identified the presence of baseline hypertension and an episode of acute pyelonephritis, but not the type of UD, as significant predictors of postoperative renal deterioration. CONCLUSIONS: The incidence of renal deterioration was comparatively high following radical cystectomy, irrespective of the type of UD. Special attention should be paid to the long-term preservation of renal function in these patients, particularly those with hypertension and/or episodes of acute pyelonephritis.