Yuma Waseda

Pathological Complete Response and Two-year Disease-free Survival in a Primary Gastric Choriocarcinoma Patient with Advanced Liver Metastases Treated with Germ Cell Tumor-based Chemotherapy: A Case Report

Choriocarcinoma is an early metastasizing and highly invasive tumor and characterized as a high-level human chorionic gonadotropin-secreting tumor. It normally arises in the gestational trophoblast, gonads and much less frequently in the stomach. Primary gastric choriocarcinoma appears to have a poor prognosis; especially with liver metastasis, the survival period is expected to be <1 month. This unfavorable clinical outcome is partly due to the lack of defined chemotherapy against primary gastric choriocarcinoma. We herein report a case of a 68-year-old male primary gastric choriocarcinoma patient with advanced liver metastases in which germ cell tumor-based chemotherapy achieved a pathological complete response and 2-year disease-free survival.

Utility of computed diffusion-weighted MRI for predicting aggressiveness of prostate cancer

To investigate the value of computed (c) diffusion‐weighted imaging (DWI) in assessing prostate cancer aggressiveness.

DWI as an Imaging Biomarker for Bladder Cancer

OBJECTIVE DWI has been increasingly applied in the management of bladder cancer. In this article, we discuss the role of DWI as an imaging biomarker for bladder cancer. CONCLUSION The DWI signal is derived from the motion of water molecules, which represents the physiologic characteristics of the tissue of interest. The emerging evidence highlights the utility of DWI for bladder cancer detection and characterization. DWI is a potentially useful tool to individualize treatment strategies.

A Case of Hereditary Persistence of α-Fetoprotein: Diagnostic Usefulness of the Subfraction Profile

α-Fetoprotein is a well-established tumor marker for non-seminomatous germ cell tumors. Elevated α-fetoprotein levels, however, result from a variety of clinical conditions. Hereditary persistence of α-fetoprotein is a rare benign disorder in which serum α-fetoprotein levels are persistently elevated, but there are no disabilities and symptoms. A 35-year-old man was diagnosed with pT1 testicular embryonal carcinoma. Post-orchiectomy α-fetoprotein levels remained persistently elevated without clinical or radiographic abnormalities. His mothers elevated α-fetoprotein levels confirmed the diagnosis of hereditary persistence of α-fetoprotein. Lens culinaris agglutinin-reactive α-fetoprotein fractions have been reported as a useful diagnostic marker for non-seminomatous germ cell tumors; in this patient, its measurement showed high non-reactive α-fetoprotein levels, which indicated the low probability of residual tumors. The present case represents the third case of hereditary persistence of α-fetoprotein in Japan, and the first in which the α-fetoprotein subfraction was evaluated.

MP15-04 NEW PREDICTIVE SCORING MODEL FOR RECURRENCE INCORPORATING BLADDER NECK INVOLVEMENT IN PATIENTS WITH NON-MUSCLE-INVASIVE BLADDER CANCER

INTRODUCTION AND OBJECTIVES: We previously reported that bladder neck involvement (BNI) was an independent risk factor for progression to muscle invasion in primary non-muscle-invasive bladder cancer (NMIBC) and we developed a new predictive scoring model for progression incorporating BNI (Fujii et al., Eur Urol 1998; Kobayashi and Fujii et al., Urol Oncol 2014). In the present study, we investigated the impact of BNI on recurrence in NMIBC, and developed a new predictive scoring model for recurrence incorporating BNI and assessed its predictive ability. METHODS: We enrolled a total of 589 Japanese patients who underwent transurethral resection for bladder tumors at a single center from 2001 to 2016, and who were pathologically diagnosed with Ta and T1 NMIBC. Exclusion criteria were: carcinoma in situ and patients with tumors located in the prostatic urethra. Multivariate Cox proportional hazards regression models using the Prentice-Williams-Peterson gap time model were generated to identify the independent predictors for recurrence. The predictive ability of our model was assessed using Harrell0s concordance index (c-index) and was compared with that of the EORTC and CUETO scoring models. RESULTS: Over a median follow-up period of 3.1 years, 258 patients (43.8%) experienced a total number of 475 recurrences, and the disease progressed in 37 patients (6.3%). The recurrence probability at 3 years was 49.7%. In 106 patients (18.0%) with current and prior history of BNI, subsequent recurrence probability at 3 years was 67.2%. Multivariate analysis revealed that history of BNI (HR 1.60, P < 0.001) along with histologic grade 2-3 (HR 1.53, P 1⁄4 0.020), multiple tumors of four or more (HR 1.37, P 1⁄4 0.016) and male (HR 1.30, P 1⁄4 0.043) were independent predictors of recurrence. Our scoring model of assigning 1 point to each risk variable represented higher c-index of 0.59 than the EORTC (0.57) and CUETO (0.50) models. Dividing patients into 3 groups according to their scores (0-1/2/3-4), recurrence rates increased as the score (P <0.001). CONCLUSIONS: This study showed that current and prior history of BNI is a significant risk factor for recurrence in NMIBC. Our scoring model incorporating BNI is an easy means of estimating recurrence risk and can be used to determine the appropriate management for individual patients. Source of Funding: none

Ureteral Involvement Is Associated with Poor Prognosis in Upper Urinary Tract Urothelial Carcinoma Patients Treated by Nephroureterectomy: A Multicenter Database Study

BACKGROUND The prognostic significance of tumor location for patients with upper urinary tract urothelial carcinoma (UUT-UC) has been disputed. Several papers have reported that ureteral cancer is associated with worse prognosis. OBJECTIVE To investigate the prognostic significance of the presence of ureteral tumors in UUT-UC patients who underwent radical nephroureterectomy (RNU). DESIGN, SETTING, AND PARTICIPANTS In this multicenter retrospective study, 1068 eligible patients (median follow-up: 40 mo [interquartile range: 17-77 mo]) were divided into three groups based on tumor location: renal pelvic, ureteral, and both-regional (having both renal pelvic and ureteral tumors). The ureteral and both-regional groups were subsequently integrated into the ureteral involvement group to evaluate its prognostic impact. INTERVENTION All patients underwent RNU. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS The prognostic impact of tumor location on survival was analyzed. RESULTS AND LIMITATIONS The renal pelvic, ureteral, and both-regional groups consisted of 507 (47.5%), 430 (40.3%), and 131 (12.3%) patients, respectively. The ureteral and both-regional groups had a higher rate of lymphovascular invasion and lymph node metastasis compared with the renal pelvic group. The renal pelvic and both-regional tumors presented more frequently with locally advanced stages (pT3/T4) compared with the ureteral tumors. The 5-yr cancer-specific survival (CSS) and progression-free survival (PFS) rates of patients in the ureteral (70.5% and 66.7%, respectively) and both-regional groups (64.8% and 57.8%, respectively) were significantly worse than those in the renal pelvic group (81.9% and 78.1%, respectively). In a multivariate analysis, the presence of ureteral involvement was a significant prognostic factor for CSS (hazard ratio [HR]: 1.50; p=0.006) and PFS (HR: 1.35; p=0.023). This study is inherently limited by the biases associated with its retrospective and multicenter design. CONCLUSIONS The presence of ureteral involvement had a significant impact on the survival of surgically treated UUT-UC patients associated with a poor prognosis. PATIENT SUMMARY We demonstrated that the ureteral involvement was associated with poor survival compared with patients with renal pelvic tumor only in upper urinary tract urothelial patients treated by nephroureterectomy.

Predictive ability of renal cortex enhancement in dynamic computed tomography for residual renal function after nephroureterectomy: Comparison with 99mTc-diethylenetriaminopentacetic acid renography and validation study

To estimate postoperative residual renal function after radical nephroureterectomy for upper tract urothelial carcinoma using the preoperative dynamic computed tomography renal cortex enhancement ratio in comparison with the split kidney glomerular filtration rate measured by 99mTc‐diethylenetriaminopentacetic acid renography.

MP39-12 HIGHER SERUM C-REACTIVE PROTEIN LEVEL REPRESENTS THE IMMUNOSUPPRESSIVE TUMOR MICROENVIRONMENT IN PATIENTS WITH CLEAR CELL RENAL CELL CARCINOMA

METHODS: We profiled the expression and activation state of extracellular signal-regulated kinase (ERK), a critical effector of the MAPK signaling pathway, in 131 ex vivo biopsies from 39 clear cell RCC tumors and adjacent normal parenchyma after nephrectomy. We performed fine-needle aspirate (FNA) biopsies of grossly representative sections after bivalving the kidney. We performed nano-scale immunoassays (NIA) to quantify the absolute and relative abundances of the phospho-isoforms of ERK1/2 using the Peggy Sue instrument (Protein Simple). ERK1/2 was interrogated with a pan-ERK antibody. Expression levels of ERK levels were compared across samples by normalization to the levels of the ubiquitously expressed protein HSP70. RESULTS: ERK1 was infrequently activated, with most samples (69%) demonstrating no phosphorylation of ERK1. In contrast, ERK2 demonstrated phosphorylation in the majority of the samples. Two distinct mono-phosphorylated ERK2 isoforms were detected (pERK2a and pERK2b), with relative abundances ranging from 0-58% and 1-57%, respectively. The relative abundance of dual-phosphorylated ERK2 (ppERK2) ranged from 0-26%. The overall ITH of ERK2 activation was low (average standard deviation [SD] 6%) compared with the difference in ERK2 activation among the 39 tumors (SD 5% 22%). CONCLUSIONS: The abundance and activation of ERK1/2 can be measured from scant FNAs of RCC using novel proteomic methods. We found little ITH of ERK, which suggests that protein ITH is generally less than functional heterogeneity among tumors. These data suggest that a single renal mass biopsy may accurately measure the activity of relevant signaling pathways within a tumor, which may facilitate future precision medicine approaches.

MP71-15 PREDICTIVE ABILITY OF RENAL CORTEX ENHANCEMENT IN DYNAMIC CT FOR RESIDUAL RENAL FUNCTION AFTER NEPHROURETERECTOMY: COMPARATIVE STUDY WITH RENOGRAPHY

INTRODUCTION AND OBJECTIVES: Systemic inflammation is a common host reaction to cancer progression. Serum level of buttyrylcholinesterase (BChE) have been reported to reflect the presence of inflammation and other clinical conditions. BChE is an alphaglycoprotein found in the nervous system and liver. Its serum level is reduced in many clinical conditions, such as liver damage, injury, infection, and malignant disease. We retrospectively evaluated the potential prognostic significance of buttyrylcholinesterase before chemotherapy as an independent predictor of overall survival in patients with advanced upper-tract urothelial cancer. METHODS: We treated seventy-four patients (52 men and 22 women) with advanced upper-tract urothelial cancer (UTUC) at our clinic between August 2004 and December 2015. The average age was 69.3 (43e89), and average eGFR was 50.5 (11.6e99.3) ml/minute/1.73m2. Mean observation periodwas 24.0 (3e96) months. Levels of serumBChE (normal range 168-470 U/L) were measured 1 week before chemotherapy. The average serum level of BChE were 240.6 U/L (53-509). The patients received 2 courses of GCarbo consisted of 800mg/m2 gemcitabine on days 1, 8, and 15 and carboplatin (AUC 4) on day 2. If this regimen was effective, another 2 courses of GCcarbo was performed. If this regimen did not induce any tumor size reduction, we switched to 2 courses of GCarboD (D; 70mg/m2) treatment as second-line treatment. RESULTS: GCarbo regimen yielded 5 cases (6.8%) of CR, 32 (43.2%) of PR, and the average duration of response of 11.4 (2e29) months. GCarboD treatment was administered in 21 cases, and yielded 2 (9.5%) PR and a duration of response was 31.5(7-50) months. The median over-all survival period was 14.3 months. When analyzed by serum BChE level, the over-all survival were 22.0 months in the BChE >168 U/L group and 12.0 months in the BChE <168 group (p1⁄40.036). The level of serum BChE showed no association with treatment effect. CONCLUSIONS: Serum BChE level before chemotherapy may have the potential to predict over-all survival in patients with advanced upper-tract urothelial cancer.

MP16-18 OPTIMAL COMBINATION OF MRI-TARGETED BIOPSY AND SYSTEMATIC BIOPSY FOR MEN WITH SUSPICION OF PROSTATE CANCER

INTRODUCTION AND OBJECTIVES: Magnetic resonance imaging (MRI)-targeted prostate biopsy (MRBX) is an effective biopsy procedure for with suspicion of prostate cancer on MRI. However, some significant cancer (SC) is missed using MRBX. Use of systematic prostate biopsy (SBX) for negative areas on MRI to detect SC missed by MRBX is not established for this indication. In this study, we aimed to explore the optimal combination of SBX and MRBX in these patients. METHODS: Between 2014 and 2015 at our institution, 271 men underwent MRBX with or without SBX based on prebiopsy multiparametric 1.5T MRI. Of these, 52 were excluded from the analysis because of PSA levels>40 ng/ml, obvious clinical T3-4 disease or biopsy with an insufficient number of cores for severe comorbidity. The remaining 219 men who underwentMRBXandSBXinonesessionaccording toourbiopsyprotocolwere enrolled in this study. MRBX was performed under cognitive or MRI/transrectal ultrasound fusion. Using MRBX, four-core samples for one suspicious lesiononMRIwereperformed.TheSBXprotocolwasa transperineal18-core biopsy.SCwasdefinedasclinical stageT2borgreater,biopsyGleasonscore of 4+3orgreater, ormaximumcancer lengthof 5mmorgreater.Cancerother thanSCwasdefinedas indolent cancer (IC). SC thatwasnot detected or that wasdetectedas ICusingMRBX,but thatwasdetectedasSCusingSBXwas defined as MRBX-missed SC. The frequency of MRBX-missed SC was investigated. A SBX protocol that could sufficiently detect MRBX-missed SC with a minimum number of sampling cores was determined. RESULTS: The median PSA was 7.5 ng/ml, and one/two suspicious lesions were observed in 204/15 patients, respectively, using MRI. The detection rate of any cancer or SC using both MRBX and SBX was 76%or 61%, respectively. Frequency ofMRBX-missed SC to overall SC was 13% (21/135). MRBX results in MRBX-missed SC patients was no cancer in 8 and IC in 13. Of 21 MRBX-missed cancer, a maximum of 10, 13, 15, 17, 19, 20 and 21MRBX-missed SCwere detected using 2, 4, 6, 8, 10, 12and14SBXsamplingcores, respectively.Whenweset theSC detection rate using both MRBX and the transperineal 18-core SBX at 100%, aminimum of 6 sampling cores in SBX (in addition to MRBX) were required to detect 95% of overall SC as SC. The six SBX sampling locationswere bilateral transperineal anterior, posterior and far lateral sites. CONCLUSIONS: The combination of transperineal 6-core SBX and MRBX could be an optimal biopsy strategy that strikes a balance between SC detectability and sampling number for men with suspicion of prostate cancer on MRI.