In Ho Chang

Expression of resistin in the prostate and its stimulatory effect on prostate cancer cell proliferation

What’s known on the subject? and What does the study add?

Adjuvant Chemotherapy in the Management of pT3N0M0 Transitional Cell Carcinoma of the Upper Urinary Tract

Introduction: We investigate the efficacy of postoperative adjuvant chemotherapy for locally advanced, but lymph node negative, pathologic stage T3 transitional cell carcinoma (TCC) of the upper urinary tract. Patients and Methods: A retrospective study on 27 patients who had undergone radical nephroureterectomy with regional lymphadenectomy for pT3N0M0 primary upper urinary tract TCC at our institution from 1996 to 2001 was performed. Among the 27 patients, 16 also received adjuvant chemotherapy following surgery (adjuvant group), whereas the other 11 patients did not (nonadjuvant group). Results: Adjuvant and nonadjuvant therapy groups were not significantly different with respect to age, sex, performance status, tumor grade, and tumor location. Overall, 5 of the 16 patients (31%) in the adjuvant group and 4 of the 11 patients (36%) in the nonadjuvant group had recurrence of cancer at 40 months of follow-up. The two groups demonstrated no significant differences in recurrence-free survival (p = 0.794) and disease-specific survival (p = 0.783). Conclusions: Although it would be difficult to draw any definite conclusions from the results of our investigations, our data suggest that adjuvant therapy with traditional conventional chemotherapeutic regimens alone may not be effective as previously anticipated in significantly improving survival rates for locally advanced, but lymph node negative, TCC of the upper urinary tract.

The clinical significance in healthy men of the association between obesity related plasma hemodilution and tumor marker concentration.

PURPOSE We investigated the association between body mass index and the concentration of tumor markers including carcinoembryonic antigen, alpha-fetoprotein, the carbohydrate antigen 19-9 and prostate specific antigen, as well as the association between body mass index changes and tumor marker concentration changes in a population of healthy men. MATERIALS AND METHODS We evaluated data on 8,776 men screened for tumor markers (carcinoembryonic antigen, alpha-fetoprotein, carbohydrate antigen 19-9 and prostate specific antigen) at least 3 times annually during an annual examination from 2001 to 2007. We assessed the tumor marker test findings for a trend in the age, alanine aminotransferase and creatinine adjusted tumor marker concentration by body mass index. We used multivariate regression analysis to determine whether a change in body mass index was associated with a tumor marker concentration change over time using calculated tumor markers, body mass index, creatinine and alanine aminotransferase concentration change per year. RESULTS After adjusting for age, creatinine and alanine aminotransferase a higher body mass index was associated with lower prostate specific antigen (p for trend <0.001), carcinoembryonic antigen (p for trend <0.001) and carbohydrate antigen 19-9 (p for trend <0.001). On multivariate regression analysis each 1 kg/m(2) of body mass index gain per year was associated with a -0.011 ng/ml change in prostate specific antigen concentration, a -0.030 ng/ml change in carcinoembryonic antigen concentration and a -0.192 IU/ml change in carbohydrate antigen 19-9 concentration per year. CONCLUSIONS In this cohort of healthy men hemodilution from increased plasma volume may be responsible for the observed decreased tumor marker concentration in men with a higher body mass index. In addition, an increase in body mass index may predict a lower tumor marker concentration in an individual.

Relationship Between Serum Prostate-Specific Antigen Levels and Components of Metabolic Syndrome in Healthy Men

OBJECTIVES To assess the correlation between age, body mass index, systolic and diastolic blood pressure (BP), triglycerides, high-density lipoprotein (HDL), and fasting blood glucose (FBG) and the serum prostate-specific antigen (PSA) level and to determine the significant factors for predicting the serum PSA level in men with a low risk of prostate cancer. METHODS A total of 38 356 healthy male employees of the Korea Electric Power Corporation who were <60 years old and had a serum PSA level of <4 ng/mL were enrolled in this study from January 2002 to December 2006. Their BP, body weight, and body height were measured, and biochemical analyses of FBG, triglycerides, HDL, and serum PSA were performed. RESULTS The mean age +/- standard deviation was 44.38 +/- 7.90 years; the mean serum PSA level was 0.89 +/- 0.51 ng/mL; and the incidence of metabolic syndrome was 25.8%. On univariate analysis, significant correlations were noted between the serum PSA level and body mass index, diastolic BP, HDL, and FBG (P < .05). Multiple logistic regression analyses using 4 percentiles (10th, 25th, 75th, and 90th percentile) of the serum PSA level revealed trends for a positive association between older age and diastolic BP and the serum PSA level. The body mass index, HDL, and FBG correlated negatively with the serum PSA level. CONCLUSIONS These results suggest that the serum PSA level is significantly influenced by age and some components of the metabolic syndrome (obesity, diastolic BP, HDL, and FBG).

A Possible Relationship Between Testosterone and Lower Urinary Tract Symptoms in Men

PURPOSE In this study we searched for possible associations between serum testosterone levels and the severity of lower urinary tract symptoms in men. MATERIALS AND METHODS In 278 patients with a mean age of 62 years blood levels of total testosterone, albumin, sex hormone-binding globulin, fasting glucose, fasting insulin and high sensitivity C-reactive protein were measured. Free testosterone, bioavailable testosterone and homeostasis model assessment of insulin resistance were calculated. Prostate volume was measured by transrectal ultrasonography and the severity of lower urinary tract symptoms was assessed using the International Prostate Symptom Score. RESULTS Calculated free testosterone and bioavailable testosterone were negatively related to International Prostate Symptom Score total scores and subscores (voiding symptoms) after adjusting for age, prostate volume, high sensitivity C-reactive protein and homeostasis model assessment of insulin resistance (p <0.05). In addition, calculated free testosterone and bioavailable testosterone were significantly related to the presence of severe lower urinary tract symptoms (International Prostate Symptom Score 20 or greater) using unadjusted and adjusted models (p <0.05), although the odds ratio of bioavailable testosterone was lower than that of calculated free testosterone on multivariate analysis. High sensitivity C-reactive protein was negatively correlated with serum total testosterone (r = -0.128, p = 0.038) and bioavailable testosterone (r = -0.126, p = 0.041), and homeostasis model assessment of insulin resistance was negatively correlated with serum total testosterone (r = -0.236, p <0.001), calculated free testosterone (r = -0.179, p = 0.003) and bioavailable testosterone (r = -0.162, r = 0.007). However, no significant correlation was found between high sensitivity C-reactive protein or homeostasis model assessment of insulin resistance, and International Prostate Symptom Score total scores, voiding symptoms scores and storage symptoms scores. CONCLUSIONS Our findings support the favorable role of endogenous testosterone in lower urinary tract function and suggest that testosterone deficiency may be a pathophysiological mechanism connecting lower urinary tract symptoms and the metabolic syndrome in men.

Association between serum prostate-specific antigen level, liver function tests and lipid profile in healthy men

To assess the association between serum prostate‐specific antigen (PSA) level and age, liver function tests (LFTs) including alkaline phosphatase (ALP), total bilirubin (TB), lipid profile (total cholesterol, TC, triglycerides, TG, high‐density lipoprotein, HDL) and fasting blood sugar (FBS), and to determine the significant factors for predicting the serum PSA level in men with a low risk of having prostate cancer.

Role of the mTOR Pathway in the Progression and Recurrence of Bladder Cancer: An Immunohistochemical Tissue Microarray Study

Purpose Numerous trials have been conducted to develop new treatment regimens for superficial and invasive bladder cancer, because there is an urgent need to identify novel agents to prevent the recurrence and progression of these cancers. We evaluated the prognostic and biological significance of mTOR pathway-related markers in patients with bladder cancer who had undergone transurethral resection of their bladder tumors and radical cystectomy. Materials and Methods We retrieved 208 bladder cancer specimens collected from patients between 1989 and 2007 and constructed a tissue microarray comprising 208 tumor samples and 25 benign urothelium samples. Immunohistochemical staining was performed for mTOR, phosphorylated (phos) S6, and phos4E-BP1. The pattern, percentage, and intensity of staining for all three markers were evaluated. Results The median age at diagnosis of the patient cohort was 67 years (range: 29-87 years), and the median follow-up was 72 months (range: 1-257 months). The expression of phos4E-BP1 was higher in the bladder cancer cohort than in the benign cohort, whereas phosS6 expression was lower in the bladder cancer cohort than in the benign cohort. The expression of phosS6 was significantly higher in high-grade bladder cancer (p<0.01). There was a significant positive correlation between the H-scores of mTOR and phos4E-BP1 (coefficient of correlation, r=0.37, p<0.01) as well as between the H-scores of mTOR and phosS6 (r=0.17, p<0.05). In the multivariate analysis, strong phosS6 expression predicted shorter progression (p<0.01; hazard ratio [HR], 2.516) and disease-specific survival (p<0.01; HR, 2.396) but not overall survival (p=0.112), whereas strong phos4E-BP1 expression was a predictor of disease-specific survival (p<0.05; HR, 2.105). Moreover, strong phosS6 expression predicted shorter recurrence-free (p<0.05) and progression-free (p<0.05) survival in the superficial bladder cancer cohort. Conclusions Our results demonstrate that mTOR pathway activation, as assessed by phos4E-BP1 phosphorylation, is related to bladder cancer tumorigenesis and that S6 protein phosphorylation is associated with a high level of disease recurrence and progression and poor cancer-specific survival.

Impact of Changing Trends in Medical Therapy on Surgery for Benign Prostatic Hyperplasia Over Two Decades

Purpose Following the introduction of medical therapy for benign prostatic hyperplasia (BPH), we determined the effect of the change in trends in medical therapy on the indication and outcome of surgical intervention for BPH. Materials and Methods We compared the basic characteristics of, weight of resected tissue of, transfusions in, and postoperative complications of patients who underwent surgery between 1985 and 1989 (before the advent of medical therapy for BPH), between 1995 and 1999 (when medical therapy was developed and became widely used as alternative treatment), and between 2005 and 2009 (when medical therapy superseded surgical intervention to become first-line treatment and when combination therapy became widely adopted). Results At our institution, the mean age and BMI of patients increased over the past two decades (p<0.001). Hypertension, operation history, and other comorbidities also increased significantly (p<0.001, p=0.005, and p<0.001, respectively). The indications for surgery in 1985 to 1989, 1995 to 1999, and 2005 to 2009 were as follows: acute urinary retention in 34.7%, 20.2%, and 15.1% of patients and symptomatic deterioration in 61.1%, 72.3%, and 73.0% of patients, respectively. Prostate volume and the weight of resected tissue increased from 34.4±14.5 ml to 61.3±32.4 ml and from 7.2±6.4 g to 10.8±7.6 g, respectively, over two decades. Patients who underwent surgery in 2005 to 2009 had their catheters removed earlier (p<0.001). Secondary hemorrhage within four postoperative weeks and repeat transurethral resection of the prostate within 1 year decreased significantly (p=0.03 and p=0.003, respectively). No statistically significant change in impaired detrusor contractility was found (p=0.523). Conclusions Although patients who underwent surgery were older after widespread use of medical therapy for BPH, advancements in surgical techniques have benefitted these patients.

Association between metabolic syndrome and chronic kidney disease in the Korean population.

Aim:  We performed a retrospective study to examine the association between the metabolic syndrome (MS) and risk for the development of chronic kidney disease (CKD).

Significance of Cancer Involvement at the Ureteral Margin Detected on Routine Frozen Section Analysis during Radical Cystectomy

Introduction: We investigated the clinical significance of preoperatively-unsuspected ureteral involvement of cancer detected on intraoperative frozen section analysis of ureteral margins during radical cystectomy. Patients and Methods: We performed a retrospective study of 115 patients who received radical cystectomy for locally-advanced but node-negative transitional cell carcinoma of the bladder between 1995 and 2002 by reviewing their records. Results: Of 115 total patients, 5 (4.3%) demonstrated carcinoma in situ at the ureteral margin with 2 of 5 having a positive margin on final pathologic analysis. Meanwhile, only 3 of 115 total patients (2.6%) later showed upper urinary tract recurrence at a median interval of 30 months after cystectomy. And all 3 patients had intramural or juxtavesical ureter involvement of disease (p = 0.006), while not demonstrating carcinoma in situ in ureteral margins resected during cystectomy. On multivariate analysis, only the stage and grade of bladder cancer along with pathologic feature of vascular invasion were observed to be independent prognostic predictors of disease-specific survival. Conclusions: Cancer involvement of the distal ureteral margin detected through intraoperative frozen section analysis may not be a significant factor regarding upper tract recurrence and survival of patients with locally-advanced bladder cancer after radical cystectomy. Upper tract recurrence may be more prone to occur in patients with cancer involvement at the intramural or juxtavesical ureter.