Tendo Sato

Influence of 1 year of androgen deprivation therapy on lipid and glucose metabolism and fat accumulation in Japanese patients with prostate cancer

Background:We prospectively examined influence of androgen deprivation therapy (ADT) on lipid and glucose metabolisms in Japanese patients with prostate cancer.Methods:Patients with prostate cancer who were hormone-naive and scheduled to receive long-term ADT were recruited between 2011 and 2013. Body weight, abdominal circumference and blood testing associated with lipid and glucose metabolism were recorded every 3 months during 1 year of ADT. Computed tomography (CT) was performed to measure areas of subcutaneous and visceral fat before and after 1 year of ADT. ADT was limited to a luteinizing hormone-releasing hormone (LHRH) agonist with or without bicalutamide.Results:Of 218 patients registered, data were available from 177 patients who completed 1 year of ADT. Of these, CT was performed before and after 1 year of ADT in 88 patients. Median age was 75 years (range, 49–85 years). Median PSA before ADT was 16.7 ng ml−1 (range, 0.3–3316). Clinical stage was B (54.2%), C (23.2%) and D (20.9%). Mean increases in body weight and abdominal circumference after 1 year of ADT were 2.9 and 3.0%, respectively. Mean increases in total, low-density lipoprotein and high-density lipoprotein cholesterol and triglycerides were 10.6, 14.3, 7.8 and 16.2%, respectively. Mean increases in fasting blood sugar and hemoglobin A1c (HbA1c) were 3.9 and 2.7%, respectively. Lipid alterations were noted in patients without comorbidities, whereas changes in HbA1c were noted in patients with diabetes mellitus at baseline. These lipid and glucose alterations were prominent in the early ADT period. Both visceral and subcutaneous fat, as measured by CT, increased by >20%. The increase in subcutaneous fat was significantly greater than that in visceral fat (P=0.028).Conclusions:One year of ADT significantly changed lipid and glucose metabolism in Japanese patients with prostate cancer. Patient characteristics or comorbidities at baseline may be associated with ADT-induced metabolic changes.

Detection of Core2 β-1,6-N-Acetylglucosaminyltransferase in Post-Digital Rectal Examination Urine Is a Reliable Indicator for Extracapsular Extension of Prostate Cancer.

To identify appropriate candidates for aggressive treatment such as radical prostatectomy or radiation therapy of localized prostate cancer (PCa), novel predictive biomarkers of PCa aggressiveness are essential. Core2 β-1,6-N-acetylglucosaminyltransferase-1 (GCNT1) is a key enzyme that forms core 2-branched O-glycans. Its expression is associated with the progression of several cancers. We established a mouse IgG monoclonal antibody (mAb) against GCNT1 and examined the relationship of GCNT1 expression to the clinicopathological status of PCa. Paraffin-embedded PCa specimens were analyzed by immunohistochemistry for GCNT1 expression using a newly established mouse anti-GCNT1 mAb by ourselves. GCNT1-positive tumor showed significantly higher Gleason score and larger tumor volume. The number of GCNT1-positive cases was significantly lower in cases of organ-confined disease than in cases of extracapsular extension. GCNT1-negative tumors were associated with significantly better prostate-specific antigen (PSA)-free survival compared with GCNT1-positive tumors. Multivariate analysis revealed that detection of GCNT1 expression was an independent risk factor for PSA recurrence. We established new methods for GCNT1 detection from PCa specimens. Immunoblotting was used to examine post-digital rectal examination (DRE) urine from PCa patients. Over 90% of GCNT1-positive PCa patients with high concentrations of PSA showed extracapsular extension. In conclusion, GCNT1 expression closely associates with the aggressive potential of PCa. Further research aims to develop GCNT1 detection in post-DRE urine as a marker for PCa aggressiveness.

Preoperative butyrylcholinesterase level as an independent predictor of overall survival in clear cell renal cell carcinoma patients treated with nephrectomy.

The prognostic factors for the overall survival (OS) of clear cell renal cell carcinoma (ccRCC) patients treated with nephrectomy are not well defined. In the present study, we investigated the prognostic significance of preoperative butyrylcholinesterase (BChE) levels in 400 ccRCC patients undergoing radical or partial nephrectomy from 1992 to 2013 at our institution. Univariate and multivariate analyses were performed to determine the clinical factors associated with OS. Among the enrolled patients, 302 were diagnosed with organ-confined disease only (T1-2N0M0), 16 with lymph node metastases, and 56 with distant metastases. The median preoperative BChE level was 250 U/L (normal range, 168–470 U/L), and median follow-up period was 36 months. The 3-year OS rate in patients with preoperative BChE levels of ≥100 U/L was significantly higher than in those with levels of <100 U/L (89.3% versus 77.7%, P = 0.004). On univariate analysis, performance status; anemia; hypoalbuminemia; preoperative levels of BChE, corrected calcium, and C-reactive protein; and distant metastasis status were significantly associated with OS. Multivariate analysis revealed that preoperative BChE levels and distant metastasis status were significantly associated with OS. Our findings suggest a possible role of preoperative BChE levels as an independent predictor of OS after nephrectomy in ccRCC patients.

Impact of bacillus Calmette–Guérin therapy of upper urinary tract carcinoma in situ: comparison of oncological outcomes with radical nephroureterectomy

The clinical benefits of bacillus Calmette–Guérin (BCG) therapy for the management of upper urinary tract carcinoma in situ (CIS) remain unclear. We aimed to compare the efficacy and safety of BCG therapy for upper urinary tract CIS with those of radical nephroureterectomy (RNU). Of 490 patients with upper urinary tract carcinoma, we retrospectively reviewed the post-treatment course of 58 patients with upper urinary tract CIS who underwent either RNU (RNU group) or BCG therapy (BCG group). Efficacy and safety were compared between the RNU and BCG groups. Inverse probability treatment-weighted (IPTW)-adjusted multivariate Cox regression analysis was performed to identify the influence of BCG therapy on prognosis. The RNU and BCG groups included 20 and 38 patients, respectively. No significant difference was found in patients’ background, including age, sex, and performance status, between the groups. The reason underlying the selection of BCG therapy was bilateral CIS of the upper urinary tract (50%), solitary kidney (26%), unwillingness to undergo RNU (13%), and ineligibility for surgery (11%). The cytology became negative in 30 (79%) out of 38 patients after a 6-week course of BCG therapy, and 17 (57%) out of 30 patients remained negative. BCG-related adverse events (AEs) were observed in 92% of patients. The most common AE was cystitis (76%), followed by fever (50%). No significant differences were found in the progression-free, cancer-specific, and overall survivals between the RNU and BCG groups. IPTW-adjusted multivariate analysis revealed that BCG therapy did not worsen the prognosis of these patients. The limitations of our study were its retrospective design and small sample size. In conclusion, BCG therapy for upper urinary tract CIS might be a useful alternative for patient ineligible for RNU under careful observation for AEs.

The Impact of Preoperative Severe Renal Insufficiency on Poor Postsurgical Oncological Prognosis in Patients with Urothelial Carcinoma

BACKGROUND The impact of preoperative renal impairment severity on prognosis in urothelial carcinoma remains unelucidated. OBJECTIVE To evaluate the impact of severe preoperative renal insufficiency on oncological outcomes in patients with urothelial carcinoma who underwent radical cystectomy or nephroureterectomy. DESIGN, SETTING, AND PARTICIPANTS A total of 1066 patients with urothelial carcinoma who underwent radical cystectomy or nephroureterectomy at six medical centres from February 1995 to November 2017 were retrospectively examined. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Oncological outcomes, stratified using preoperative estimated glomerular filtration rate (eGFR≥60, 45≤eGFR<60, and eGFR<45ml/min/1.73m2), were investigated. Inverse probability of treatment weighting (IPTW)-adjusted Cox proportional hazard regression analysis was performed to evaluate the impact of preoperative eGFR on prognosis. RESULTS AND LIMITATIONS Of 610 patients with muscle-invasive bladder cancer (MIBC), 80 (13%) had severe renal insufficiency (eGFR<45ml/min/1.73m2). Of 456 patients with upper tract urothelial carcinoma (UTUC), 101 (22%) had severe renal insufficiency. Significant differences were noted in background and prognosis among the patients with preoperative eGFR≥60, 45≤eGFR<60, and eGFR<45ml/min/1.73m2. Findings of IPTW-adjusted Cox regression analysis demonstrated that preoperative eGFR<45ml/min/1.73m2 was significantly associated with poor postsurgical recurrence-free, cancer-specific and overall survival rates in patients with either MIBC or UTUC. CONCLUSIONS Patients with urothelial carcinoma with preoperative eGFR<45ml/min/1.73m2 had a significantly lower survival probability than those without. PATIENT SUMMARY In this report, we found that preoperative severe renal insufficiency (estimated glomerular filtration rate<45ml/min/1.73m2) had higher risk for relapse and lower survival probability. Close attention is necessary when urothelial carcinoma patients have severe renal insufficiency before radical cystectomy or nephroureterectomy.

Slow Gait Speed and Rapid Renal Function Decline Are Risk Factors for Postoperative Delirium after Urological Surgery.

Objectives The aim of this study was to identify risk factors associated with postoperative delirium in patients undergoing urological surgery. Methods We prospectively evaluated pre- and postoperative risk factors for postoperative delirium in consecutive 215 patients who received urological surgery between August 2013 and November 2014. Preoperative factors included patient demographics, comorbidities, and frailty assessment. Frailty was measured by handgrip strength, fatigue scale of depression, fall risk assessment, and gait speed (the timed Get-up and Go test). Postoperative factors included types of anesthesia, surgical procedure, renal function and serum albumin decline, blood loss, surgery time, highest body temperature, and complications. Uni- and multivariate logistic regression analyses were performed to assess pre- and postoperative predictors for the development of postoperative delirium. Results Median age of this cohort was 67 years. Ten patients (4.7%) experienced postoperative delirium. These patients were significantly older, had weak handgrip strength, a higher fall risk assessment score, slow gait speed, and greater renal function decline compared with patients without delirium. Multivariate analysis revealed slow gait speed (>13.0 s) and rapid renal function decline (>30%) were independent risk factors for postoperative delirium. Conclusions Slow gait speed and rapid renal function decline after urological surgery are significant factors for postoperative delirium. These data will be helpful for perioperative patient management. This study was registered as a clinical trial: UMIN: R000018809.

Long-term effects of Bacilles Calmette-Guerin perfusion therapy for elderly patients with upper urinary tract urothelial carcinoma in situ.

404 Background: According to several guidelines, the standard therapy for carcinoma in situ (CIS) of the upper urinary tract is total nephroureterectomy. However, it is difficult to determine a treatment strategy for elderly patients. Bacillus Calmette-Guerin (BCG) therapy has already been established as a treatment for non-muscle invasive bladder cancer. However, although there are several reports indicating the effectiveness of BCG perfusion therapy for the upper urinary tract CIS, it has not been established yet. We conducted a retrospective study to assess the long-term effects of BCG perfusion therapy for the upper urinary tract CIS for elderly patients. Methods: We treated 34 patients with upper urinary tract CIS at our clinic between August 2004 and March 2015. 29 patients (22 men and 7 women) with the age of 65 years or older were enrolled. 11 subjects had the entire urinary tract CIS, 8 had bilateral, 10 had unilateral CIS of the upper urinary tract. The average period of observation was 45.5 mon...