Kazuhisa Hagiwara

Prognostic benefit of surgical management in renal cell carcinoma patients with thrombus extending to the renal vein and inferior vena cava: 17-year experience at a single center

BackgroundManagement of renal cell carcinoma (RCC) with tumor thrombus extending to the renal vein and inferior vena cava (IVC) is challenging. The aim of this study was to evaluate the benefit of surgical management in such patients.MethodsFrom February 1995 to February 2013, 520 patients were treated for RCC at Hirosaki University Hospital, Hirosaki, Japan. The RCC patients with tumor thrombus extending to the renal vein (n = 42) and IVC (n = 43) were included in this study. The records of these 85 patients were retrospectively reviewed to assess the relevant clinical and pathological variables and survival. Prognostic factors were identified by multivariate analysis. The benefit of surgical management was evaluated using propensity score matching to compare overall survival between patients who received surgical management and those who did not.ResultsRCC was confirmed by pathological examination of surgical or biopsy specimens in 74 of the 85 patients (87%). Sixty-five patients (76%) received surgical management (radical nephrectomy with thrombectomy). Distant metastasis was identified in 45 patients (53%). The proportion of patients with tumor thrombus level 0 (renal vein only), I, II, III, and IV was 49%, 13%, 18%, 14%, and 5%, respectively. The estimated 5-year overall survival rate was 70% in patients with thrombus extending to the renal vein and 23% in patients with thrombus extending to the IVC. Multivariate analysis identified thrombus extending to the IVC, presence of distant metastasis, surgical management, serum albumin concentration, serum choline esterase concentration, neutrophil-lymphocyte ratio, and Carlson comorbidity index as independent prognostic factors. In propensity score-matched patients, overall survival was significantly longer in those who received surgical management than those who did not.ConclusionsSurgical management may improve the prognosis of RCC patients with thrombus extending to the renal vein and IVC.

BK Virus–Associated Urothelial Carcinoma of a Ureter Graft in a Renal Transplant Recipient: A Case Report

BACKGROUND Urothelial carcinomas of ureter grafts in renal transplant patients are rare. Here we report our experience with a case of BK virus-associated urothelial carcinoma in a ureter graft. CASE REPORT A 47-year-old man developed chronic renal failure secondary to diabetes mellitus and started maintenance hemodialysis in September 2007. Two months later, the patient received a renal transplant from his 70-year-old mother. The patient developed BK virus-associated nephropathy 1 year after transplantation and presented with a decline in renal function and hydronephrosis in the transplanted kidney 4 years 6 months after transplantation. Cystoscopy and retrograde pyelography revealed an irregular filling defect in the ureter graft. Cytologic diagnosis of his urine revealed a high-grade urothelial carcinoma. Computerized tomography showed a cT2 ureteral tumor and no involvement of other organs. The patient subsequently underwent a transplant nephroureterectomy with bladder cuff resection. Histopathologic findings revealed a high-grade urothelial carcinoma, pT2, in the ureter graft with SV40-positive staining. The patient was closely observed without adjuvant chemotherapy therapy and remained disease free 1 year after surgery. Renal transplant recipients with BK virus infection are at high risk of developing urologic malignancies. Close attention is necessary to diagnose post-transplantation urologica malignancies as early as possible.

Preoperative chronic kidney disease predicts poor oncological outcomes after radical cystectomy in patients with muscle-invasive bladder cancer

Objective To evaluate the impact of preoperative chronic kidney disease (CKD) on oncologic outcomes in muscle-invasive bladder cancer patients who underwent radical cystectomy. Methods A total of 581 patients who underwent radical cystectomy at four medical centers between January 1995 and February 2017 were examined retrospectively. We investigated oncologic outcomes, including progression-free, cancer-specific, and overall survival (PFS, CSS, and OS, respectively) stratified by preoperative CKD status (pre-CKD vs. non-CKD). We performed a Cox proportional hazards regression analysis using inverse probability of treatment weighting (IPTW) to evaluate the impact of preoperative CKD on prognosis and developed the prognostic factor-based risk stratification nomogram Results Of the 581 patients, 215 (37%) were diagnosed with CKD before radical cystectomy. Before the background adjustment, PFS, CSS, and OS after radical cystectomy were significantly lower in the pre-CKD group compared to the non-CKD group. Background-adjusted IPTW analysis showed that preoperative CKD was significantly associated with poor PFS, CSS, and OS after radical cystectomy. The nomogram for predicting 5-year PFS and OS probability showed significant correlation with actual PFS and OS (c-index = 0.73 and 0.77, respectively). Conclusions Muscle-invasive bladder cancer patients with preoperative CKD had a significantly lower survival probability than those without CKD.OBJECTIVE To evaluate the impact of preoperative chronic kidney disease (CKD) on oncologic outcomes in muscle-invasive bladder cancer patients who underwent radical cystectomy. METHODS A total of 581 patients who underwent radical cystectomy at four medical centers between January 1995 and February 2017 were examined retrospectively. We investigated oncologic outcomes, including progression-free, cancer-specific, and overall survival (PFS, CSS, and OS, respectively) stratified by preoperative CKD status (pre-CKD vs. non-CKD). We performed a Cox proportional hazards regression analysis using inverse probability of treatment weighting (IPTW) to evaluate the impact of preoperative CKD on prognosis and developed the prognostic factor-based risk stratification nomogram. RESULTS Of the 581 patients, 215 (37%) were diagnosed with CKD before radical cystectomy. Before the background adjustment, PFS, CSS, and OS after radical cystectomy were significantly lower in the pre-CKD group compared to the non-CKD group. Background-adjusted IPTW analysis showed that preoperative CKD was significantly associated with poor PFS, CSS, and OS after radical cystectomy. The nomogram for predicting 5-year PFS and OS probability showed significant correlation with actual PFS and OS (c-index = 0.73 and 0.77, respectively). CONCLUSIONS Muscle-invasive bladder cancer patients with preoperative CKD had a significantly lower survival probability than those without CKD.

Wisteria floribunda Agglutinin and Its Reactive-Glycan-Carrying Prostate-Specific Antigen as a Novel Diagnostic and Prognostic Marker of Prostate Cancer

Wisteria floribunda agglutinin (WFA) preferably binds to LacdiNAc glycans, and its reactivity is associated with tumor progression. The aim of this study to examine whether the serum LacdiNAc carrying prostate-specific antigen–glycosylation isomer (PSA-Gi) and WFA-reactivity of tumor tissue can be applied as a diagnostic and prognostic marker of prostate cancer (PCa). Between 2007 and 2016, serum PSA-Gi levels before prostate biopsy (Pbx) were measured in 184 biopsy-proven benign prostatic hyperplasia patients and 244 PCa patients using an automated lectin-antibody immunoassay. WFA-reactivity on tumor was analyzed in 260 radical prostatectomy (RP) patients. Diagnostic and prognostic performance of serum PSA-Gi was evaluated using area under the receiver-operator characteristic curve (AUC). Prognostic performance of WFA-reactivity on tumor was evaluated via Cox proportional hazards regression analysis and nomogram. The AUC of serum PSA-Gi detecting PCa and predicting Pbx Grade Group (GG) 3 and GG ≥ 3 after RP was much higher than those of conventional PSA. Multivariate analysis showed that WFA-reactivity on prostate tumor was an independent risk factor of PSA recurrence. The nomogram was a strong model for predicting PSA-free survival provability with a c-index ≥0.7. Serum PSA-Gi levels and WFA-reactivity on prostate tumor may be a novel diagnostic and pre- and post-operative prognostic biomarkers of PCa, respectively.

Risk-stratified surveillance and cost effectiveness of follow-up after radical cystectomy in patients with muscle-invasive bladder cancer

Background The recurrence risk stratification and the cost effectiveness of oncological surveillance after radical cystectomy are not clear. We aimed to develop a risk stratification and a surveillance protocol with improved cost effectiveness after radical cystectomy. Results Of 581 enrolled patients, 175 experienced disease recurrences. The pathology-based protocol presented significant differences in recurrence-free survival between normal- and high-risk patients, but the medical expense was high, especially in normal-risk (≤pT2pN0) patients. Cox regression analysis identified six factors associated with recurrence-free survival. Risk score-based 5-year follow-up was significantly more cost effective than the pathology-based protocol. Materials and Methods We retrospectively evaluated 581 patients with radical cystectomy for muscle-invasive bladder cancer at 4 hospitals. Patients with routine oncological follow-up were stratified into normal- and high-risk groups by a pathology-based protocol utilizing pT, pN, lymphovascular invasion, and histology. Cost effectiveness of the pathology-based protocol was evaluated and a risk-score-based protocol was developed to optimize cost effectiveness. Risk-scores were calculated by summing risk factors independently associated with recurrence-free survival. Patients were stratified by low-, intermediate-, and high-risk score. Estimated cost per one recurrence detection by the pathology and by risk-scores were compared. Conclusions Risk-score-stratified surveillance protocol has potential to reduce over-evaluation after radical cystectomy without adverse effects on medical cost.

Efficacy and Safety of Silodosin and Dutasteride Combination Therapy in Acute Urinary Retention due to Benign Prostatic Hyperplasia: A Single-Arm Prospective Study

This study aimed to assess the efficacy of combination therapy with dutasteride and silodosin in patients with acute urinary retention (AUR) caused by benign prostatic hyperplasia (BPH). Eighty consecutive patients with a first episode of AUR were enrolled in this study. All patients received silodosin 8 mg and dutasteride 0.5 mg daily. Trial without catheter (TWOC) was attempted every 2 weeks until 12 weeks after the initiation of medication. The primary endpoint was the rate of catheter-free status at 12 weeks. Voided volume (VV), postvoid residual urine (PVR), uroflowmetry, International Prostatic Symptoms Score (IPSS), and quality of life due to urinary symptoms (IPSS-QOL) were also measured. All patients were followed up for more than 12 weeks and were included in this analysis. The success rate of TWOC at 12 weeks was 88.8%. VV and maximum urinary flow rate were significantly higher at 2, 4, 8, and 12 weeks compared with the time of AUR (P < 0.001). IPSS and IPSS-QOL were significantly lower at 2, 4, 8, and 12 weeks compared with the time of AUR (P < 0.001). In conclusion, a combination of dutasteride and silodosin therapy may be effective and safe for patients with AUR due to BPH.

Contrast media enhancement reduction predicts tumor response to presurgical molecular-targeting therapy in patients with advanced renal cell carcinoma

Background and Objective A quantitative tumor response evaluation to molecular-targeting agents in advanced renal cell carcinoma (RCC) is debatable. We aimed to evaluate the relationship between radiologic tumor response and pathological response in patients with advanced RCC who underwent presurgical therapy. Results Of 34 patients, 31 underwent scheduled radical nephrectomy. Presurgical therapy agents included axitinib (n = 26), everolimus (n = 3), sunitinib (n = 1), and axitinib followed by temsirolimus (n = 1). The major presurgical treatment-related adverse event was grade 2 or 3 hypertension (44%). The median radiologic tumor response by RECIST, Choi, and CMER were −19%, −24%, and −49%, respectively. Among the radiologic tumor response tests, CMER showed a higher association with tumor necrosis in surgical specimens than others. Ki67/MIB1 status was significantly decreased in surgical specimens than in biopsy specimens. The magnitude of the slope of the regression line associated with the tumor necrosis percentage was greater in CMER than in Choi and RECIST. Materials and Methods Between March 2012 and December 2016, we prospectively enrolled 34 locally advanced and/or metastatic RCC who underwent presurgical molecular-targeting therapy followed by radical nephrectomy. Primary endpoint was comparison of radiologic tumor response among Response Evaluation Criteria in Solid Tumors (RECIST), Choi, and contrast media enhancement reduction (CMER). Secondary endpoint included pathological downstaging, treatment related adverse events, postoperative complications, Ki67/MIB1 status, and tumor necrosis. Conclusions CMER may predict tumor response after presurgical molecular-targeting therapy. Larger prospective studies are needed to develop an optimal tumor response evaluation for molecular-targeting therapy.

Neoadjuvant chemohormonal therapy followed by robot-assisted and minimum incision endoscopic radical prostatectomy in patients with high-risk prostate cancer: comparison of perioperative and oncological outcomes at single institution

PurposeOptimal management strategies for patients with high-risk prostate cancer (PCa) have not been established. This study aimed to estimate the impact of surgical procedures on perioperative and oncological outcomes in patients with high-risk PCa who received neoadjuvant chemohormonal therapy (CHT) prior to radical prostatectomy (RP).MethodsIn this retrospective study, we focused on patients with high-risk PCa who received neoadjuvant CHT followed by RP. The enrolled patients were divided into the following two groups according to surgical procedure: the robot-assisted RP (RARP) group and minimum incision endoscopic RP (MIE-RP) group. The primary endpoint was biochemical recurrence-free survival (BRFS).ResultsA total of 522 high-risk PCa patients were enrolled in this study. The median operating time was significantly shorter in the MIE-RP group than in the RARP group. The median estimated blood loss was significantly lower in the RARP group than in the MIE-RP group. The rates of positive surgical margins (PSMs) were not statistically significant in either group. During the follow-up period, biochemical recurrence (BCR) without clinical recurrence occurred in 60 (23.9%) patients in the MIE-RP group and 5 (1.8%) in the RARP group. The 5-year BRFS rate was 76.5% in the MIE-RP group and 97.6% in the RARP group (P < 0.001). On multivariate analysis, RARP, PSM, pathological T stage, and initial prostate-specific antigen were significantly associated with BCR.ConclusionsNeoadjuvant CHT with subsequent RARP may decrease the risk of BCR when compared to MIE-RP.

Relationship between oxidative stress and lower urinary tract symptoms: results from a community health survey in Japan

To investigate the relationship between oxidative stress and lower urinary tract symptoms (LUTS) in a community‐dwelling population.

MP16-13 CLINICAL BENEFIT OF PRESURGICAL AXITINIB THERAPY IN RENAL CELL CARCINOMA PATIENTS WITH THROMBUS EXTENDING TO INFERIOR VENA CAVA

of patients had progressive disease (PD). Median PFS was 5.5 months and median OS was 18.0 months. Among all patients analyzed for Tcell response, five showed vaccine-induced (VI) T-cell responses against at least one HLA class I-restricted TUMAP and two patients with responses to multiple TUMAPs (Figure 1). The T-cell response rate in this study was similar to our previous study in Europe and US. Interestingly, two of the immune responders were of HLA-A*0206 phenotype, a HLA suballele rarely occurring in Europe and US but common in Japan. CONCLUSIONS: This study showed safety and tolerability of IMA901 vaccination and immune responses in Japanese RCC patients.