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

前立腺生検標本におけるGCNT1の発現は悪性度の指標になり得る

掲載誌 Biochemical and Biophysical Research Communications, 170(1), p.150-156, 2016 http://www.sciencedirect.com/science/article/pii/S0006291X1630011

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

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

Core2 β-1,6-<i>N</i>-acetylglucosaminyltransferase-1 expression correlates with prostate cancer progression.

<p>(<b>A</b>) Biosynthetic pathways for <i>O</i>-glycans. (<b>B</b>) PCa specimens were incubated with an anti-core2 β-1,6-<i>N</i>-acetylglucosaminyltransferase-1 (GCNT1) monoclonal antibody (mAb), followed by a horseradish peroxidase (HRP)-conjugated secondary antibody. Counterstaining was performed using hematoxylin. GCNT1-positive cancer cells are brown. (<b>C</b>) Prostate-specific antigen-free survival periods were compared between GCNT1-positive and GCNT1-negative specimens. Survival was analyzed using Kaplan-Meier curves.</p

Prostate-specific antigen concentration and core2 β-1,6-<i>N</i>-acetylglucosaminyltransferase-1 expression predict extracapsular extension of prostate cancer.

<p>(<b>A</b>) Prostate-specific antigen (PSA) concentration and (<b>B</b>) Core2 β-1,6-<i>N</i>-acetylglucosaminyltransferase-1 (GCNT1) expression levels were significantly higher in prostate cancer (PCa) patients with extracapsular extension than in patients with organ-confined disease. (<b>C</b>) Receiver-operator characteristic curve analysis of PSA and GCNT1 revealed that the area under the curve of PSA was 0.7455 and GCNT1 was 0.7614. (<b>D</b>) Risk stratification was established using PSA and GCNT1 to predict the outcome of local PCa. Double negative (DN)-risk (PSA < 7.52 ng/mL, GCNT1< 79.36 pg/mg), single positive (SP)-risk (PSA > 7.52 ng/mL or GCNT1 > 79.36 pg/mg) and double positive (DP)-risk (PSA > 7.52 ng/mL and GCNT1 > 79.36 pg/mg) patients are compared.</p

Logistic regression analyses of risk factors for extracapsular extension of prostate cancer.

<p>^a; pre-treatment prostate-specific antigen</p><p>^b; Gleason score</p><p>CI, confidence interval; GCNT1, core2 β-1,6-<i>N</i>-acetylglucosaminyltransferase-1; HR, hazard ratio; PSA, prostate-specific antigen</p><p>Logistic regression analyses of risk factors for extracapsular extension of prostate cancer.</p

Univariate and multivariable analyses of risk factors for prostate-specific antigen recurrence.

<p>^a, pre-treatment prostate-specific antigen</p><p>^b, Gleason score</p><p>^c, cancer existence at the resected margin</p><p>^d, perineural invasion</p><p>^e, extracapsular extension</p><p>CI, confidence interval; GCNT1, core2 β-1,6-<i>N</i>-acetylglucosaminyltransferase-1; HR, hazard ratio; PSA, prostate-specific antigen.</p><p>Univariate and multivariable analyses of risk factors for prostate-specific antigen recurrence.</p