Se Joong Kim

Risk Factors for Acute Prostatitis after Transrectal Biopsy of the Prostate

Purpose To investigate the incidence, clinical features, pathogenic bacteria, and risk factors associated with acute prostatitis after transrectal prostate biopsy. Materials and Methods We retrospectively reviewed the medical records of 923 transrectal ultrasound-guided needle biopsies of the prostate in 878 patients performed at our institution from June 2004 to May 2009. The indications for biopsy were generally serum prostate-specific antigen (PSA) elevation, abnormal findings on a digital rectal examination, or both. All biopsies were performed with the patient hospitalized except for 10 patients who refused to be hospitalized, and ciprofloxacin was administered as an antibiotic prophylaxis. The incidence, clinical features, pathogenic bacteria, and potential risk factors associated with acute prostatitis after prostate biopsy were evaluated. Results Acute prostatitis developed in 18 (2.0%) cases after prostate biopsy. Among them, 9 (1.0%) had bacteremia and 2 (0.2%) showed clinical features of sepsis. Of the total 50 urine or blood specimens sent for culture study, 27 (54.0%) specimens showed positive cultures, including E. coli in 25. Among the 27 culture-positive specimens, 26 (96.3%) were resistant to ciprofloxacin. Among the potential risk factors for acute prostatitis after prostate biopsy, biopsy performed as an outpatient procedure without a cleansing enema (p=0.001) and past history of cerebrovascular accident (p=0.048) were statistically significant. Conclusions Fluoroquinolone is effective as an antibiotic prophylaxis for transrectal prostate biopsy in most cases. The incidence of acute prostatitis after transrectal prostate biopsy was 2.0%, and almost all cases were caused by fluoroquinolone-resistant E. coli. A cleansing enema is recommended before transrectal prostate biopsy.

Prognostic Significance of Preoperative C-Reactive Protein Elevation and Thrombocytosis in Patients with Non-Metastatic Renal Cell Carcinoma

Purpose The aim of this study was to investigate the association of preoperative C-reactive protein (CRP) elevation and thrombocytosis with the prognosis of patients with non-metastatic renal cell carcinoma (RCC). Materials and Methods This was a retrospective review of the medical records of 177 patients (130 men and 47 women) with non-metastatic RCC who underwent a radical nephrectomy between March 2000 and May 2008 and for whom preoperative CRP and platelet data were available for analysis. Preoperative CRP elevation and thrombocytosis were compared with clinical and pathological variables. Results There were 38 patients with CRP elevation and 11 patients with thrombocytosis. The mean follow-up time was 48.3 months (median, 48.0; range, 13-111 months). Twenty-three patients (13.0%) developed metastases and six patients died during the follow-up period. CRP elevation was significantly correlated with anemia (p=0.001), T stage (p=0.004), grade (p=0.025), and metastasis (p<0.001). Thrombocytosis was significantly correlated with anemia (p=0.003), T stage (p=0.002), and metastasis (p=0.001). The univariate analysis identified anemia, CRP elevation, thrombocytosis, tumor histology subtype, tumor size, T stage, and grade as significant prognostic factors associated with recurrence-free survival, whereas the multivariate analyses showed that CRP elevation (p=0.033) and tumor size (p=0.007) were independent prognostic factors. Conclusions Preoperative CRP elevation and thrombocytosis were associated with a poorer prognosis and a higher recurrence rate in patients with non-metastatic RCC. Moreover, preoperative CRP elevation appeared to be an independent predictor of tumor recurrence and prognosis. Preoperative thrombocytosis, however, was not an independent prognostic factor for tumor recurrence and prognosis.

Differences in Tumor Characteristics and Prognosis in Newly Diagnosed Ta, T1 Urothelial Carcinoma of Bladder According to Patient Age

OBJECTIVES To evaluate the differences in tumor characteristics and prognosis according to age at presentation in patients with newly diagnosed Stage Ta, T1 urothelial carcinoma of the bladder. METHODS From 1998 to 2002, 1587 patients with newly diagnosed nonmuscle-invasive bladder cancer treated with transurethral resection were enrolled in this study. The median age was 63 years (range 21-98), and the median follow-up duration was 44 months (range 12-97). The study cohort was subdivided into 3 age groups: age < 60 years (group 1, n = 614), age > or = 60 but < 70 years (group 2, n = 566), and age > or = 70 years (group 3, n = 398). RESULTS Comparing the clinical and pathologic characteristics, the tumor size (chi(2)(trend) = 4.01, P = .045), multiplicity (chi(2)(trend) = 14.50, P < .001), T category (chi(2)(trend) = 17.11, P < .001), and tumor grade (chi(2)(trend) = 31.36, P < .001) tended to increase in the older age groups. The presence of carcinoma in situ and squamous differentiation, however, did not differ among the age groups (P > .05). The 5-year recurrence-free probability was 63.6%, 52.1%, and 43.9% for groups 1, 2, and 3, respectively (P < .001). The 5-year progression-free probability was 95.7%, 91.1%, and 84.2% for groups 1, 2, and 3, respectively (P < .001). CONCLUSIONS Stage Ta, T1 bladder urothelial carcinoma in the younger patients tended to be smaller, have fewer lesions, be less invasive, and have a more favorable tumor grade at the initial presentation. Furthermore, younger patients appeared to have a more favorable prognosis than older patients.

Current treatment strategies for castration-resistant prostate cancer.

Prostate cancer is the most common cancer in men in United States and the fifth most common cancer in men in Korea. Although the majority of patients with metastatic prostate cancer initially respond to androgen deprivation therapy, almost all patients will eventually progress to develop castration-resistant prostate cancer (CRPC). Treatment options for CRPC remain limited. Prostate cancer was considered unresponsive to chemotherapy until the mid-1990s, when mitoxantrone combined with prednisone was shown to play a role in the palliative treatment of patients with CRPC. In 2004, two large randomized clinical trials demonstrated for the first time a small but significant survival advantage of docetaxel-based chemotherapy compared with mitoxantrone in patients with metastatic CRPC. Recently, cabazitaxel was shown to improve survival in patients with metastatic CRPC who progressed after docetaxel-based chemotherapy. Sipuleucel-T was also demonstrated to improve overall survival in patients with asymptomatic or minimally symptomatic metastatic CRPC. Along with mitoxantrone and docetaxel, cabazitaxel and sipuleucel-T are now approved for use in metastatic CRPC by the US Food and Drug Administration. There have been multiple early-phase clinical trials of various agents for the treatment of CRPC, and some are in phase III development. This review focuses on the key clinical trials of various treatment options of CRPC currently in use and under investigation.

Cyclooxygenase-2 and p53 expression as prognostic indicators in conventional renal cell carcinoma.

The aim of this study was to investigate the relationship of cyclooxygenase (COX)-2 and p53 expression with prognosis in patients with conventional renal cell carcinoma (RCC). Formalin-fixed, paraffin-embedded tissue sections of conventional RCC from 92 patients, who had undergone radical nephrectomy, were examined for COX-2 and p53 expression by immunohistochemistry and compared with clinicopathological variables. The COX-2 expression significantly correlated only with tumor size (p=0.049), whereas the p53 expression profoundly correlated with the TNM stage (p=0.024), M stage (p=0.001), and metastasis (synchronous or metachronous; p=0.004). The COX-2 overexpression did not significantly associate with p53 positivity (p=0.821). The survival rate of patients correlated with the p53 expression (p<0.0001) but not with the COX-2 expression (p=0.7506). Multivariate analyses indicated that tumor size, M stage, and p53 expression were independent prognostic factors for cancer-specific survival. The COX-2 expression was not an independent factor. These results show that the increased expression of p53 was associated with metastasis and a worse prognosis in conventional RCC, which suggests that p53 might have played an important role in the progression of conventional RCC. The increased expression of COX-2 was associated only with tumor size, but may not be an important prognostic factor in conventional RCC. No association was observed between COX-2 overexpression and p53 positivity in conventional RCC.

Inhibition of bladder cancer invasion by Sp1‐mediated BTG2 expression via inhibition of DNA methyltransferase 1

Significantly lower endogenous expression of B‐cell translocation gene 2 (BTG2) was observed in human muscle‐invasive bladder cancers (MIBC) than matched normal tissues and non‐muscle invasive bladder cancers (NMIBC). BTG2 expression was inversely correlated with increased expression of the DNA methyltransferases DNMT1 and DNMT3a in MIBC, but not NMIBC, suggesting a potential role for BTG2 expression in muscle invasion of bladder cancer. Over 90% of tumor tissues revealed strong methylation at CpG islands of the BTG2 gene, compared with no methylation in the normal tissues, implying epigenetic regulation of BTG2 expression in bladder carcinogenesis. By using EJ bladder cancer cells and the demethylating agent decitabine, transcription of BTG2 was shown to be up‐regulated by inhibiting DNMT1 expression via modification at CpG islands. DNMT1 binding to the BTG2 gene further regulated BTG2 expression by chromatin remodeling, such as H3K9 dimethylation and H3K4 trimethylation, and Sp1 activation. Induced BTG2 expression significantly reduced EJ cell tumorigenesis and invasiveness together with induction of G2/M arrest. These results demonstrate an important role for the BTG2/TIS21/PC3 gene in the progression of bladder cancers, and suggest that BTG2/TIS21/PC3 is a promising epigenetic target for prevention of muscle invasion in human bladder cancers.

Impact of Caveolin-1 Expression on the Prognosis of Transitional Cell Carcinoma of the Upper Urinary Tract

This study aimed to investigate the relationship of caveolin-1 expression with prognosis in patients with transitional cell carcinoma of the upper urinary tract (TCC-UUT). Formalin-fixed, paraffin-embedded tissue sections of TCC-UUT from 98 patients, who had undergone radical nephroureterectomy, were stained immunohistochemically using antibodies against caveolin-1. The expression pattern of caveolin-1 was compared with the clinicopathological variables. The caveolin-1 expression was significantly correlated with T stage (p<0.001) and grade (p=0.036). The survival rate of patients with caveolin-1 positive tumors was significantly lower than that of patients with caveolin-1 negative tumors (p<0.0001). The univariate analyses identified T stage, grade, and caveolin-1 expression as significant prognostic factors for cancer-specific survival, whereas the multivariate analyses indicated that T stage and caveolin-1 expression were independent prognostic factors. These results show that the increased expression of caveolin-1 is associated with tumor progression and poor prognosis in TCC-UUT, suggesting that caveolin-1 may play an important role in the progression of TCC-UUT.

Prognostic Significance of Substaging according to the Depth of Lamina Propria Invasion in Primary T1 Transitional Cell Carcinoma of the Bladder

Purpose To evaluate the prognostic significance of the depth of lamina propria invasion in primary T1 transitional cell carcinoma (TCC) of the bladder. Materials and Methods We retrospectively reviewed the medical records of 183 patients with primary T1 TCC of the bladder who had undergone transurethral resection (TUR) at our institution. Substaging was defined according to the depth of lamina propria invasion as follows: T1a, superficial invasion of lamina propria; T1b, invasion into the muscularis mucosa (MM); T1c, invasion beyond the MM but not to the muscularis propria. The prognostic significance of various clinicopathological variables for recurrence and progression was analyzed. Results Of the 183 patients, substaging was T1a in 119, T1b in 57, and T1c in 7 patients. The recurrence rate was 32.8% for T1a and 40.6% for T1b/c, but there was no significant difference between the two groups. The progression rate was significantly different between the two groups: 5.8% in T1a and 21.9% in T1b/c (p=0.003). The cancer-specific mortality rate was also significantly different: 4.2% in T1a and 14.0% in T1b/c (p=0.036). In the univariate analysis, microscopic tumor architecture was the only significant prognostic factor for recurrence. In the univariate and multivariate analysis concerning progression, depth of lamina propria invasion and concomitant carcinoma in situ were significant prognostic factors. Conclusions Substaging according to the depth of lamina propria invasion in primary T1 TCC of the bladder was an independent prognostic factor for progression. This suggests that substaging would be helpful for guiding decisions about adjuvant therapies and follow-up strategies.

Practice Patterns of Korean Urologists for Screening and Managing Prostate Cancer according to PSA Level

Purpose There are still debates on the benefit of mass screening for prostate cancer (PCA) by prostate specific antigen (PSA) testing, and on systemized surveillance protocols according to PSA level. Furthermore, there is a paucity of literature on current practice patterns according to PSA level in the Korean urologic field. Here, we report the results of a nationwide, multicenter, retrospective chart-review study. Materials and Methods Overall 2122 Korean men (>40 years old, PSA >2.5 ng/mL) were included in our study (from 122 centers, in 2008). The primary endpoint was to analyze the rate of prostate biopsy according to PSA level. Secondary aims were to analyze the detection rate of PCA, the clinical features of patients, and the status of surveillance for PCA according to PSA level. Results The rate of prostate biopsy was 7.1%, 26.3%, 54.2%, and 64.3% according to PSA levels of 2.5-3.0, 3.0-4.0, 4.0-10.0, and >10.0 ng/mL, respectively, and the PCA detection rate was 16.0%, 22.2%, 20.2%, and 59.6%, respectively. At a PSA level >4.0 ng/mL, we found a lower incidence of prostate biopsy in local clinics than in general hospitals (21.6% vs. 66.2%, respectively). A significant proportion (16.6%) of patients exhibited high Gleason scores (≥8) even in the group with low PSA values (2.5-4.0 ng/mL). Conclusion We believe that the results from this nationwide study might provide an important database for the establishment of practical guidelines for the screening and management of PCA in Korean populations.

Prognostic Factors in Transitional Cell Carcinoma of the Upper Urinary Tract after Radical Nephroureterectomy

Purpose The aim of this study was to evaluate the prognostic factors for survival in patients treated surgically for transitional cell carcinoma of the upper urinary tract (UUT-TCC). Materials and Methods We retrospectively reviewed the medical records of 87 patients (64 men and 23 women, mean age of 62.2 years) with UUT-TCC who had undergone radical nephroureterectomy at our institution between June 1994 and June 2009. The median follow-up period was 32 months. The prognostic significance of various clinicopathological variables for recurrence-free and cancer-specific survival was analyzed by using univariate and multivariate analysis. Results Of the total 87 patients, 21 patients (24.1%) developed local recurrence or distant metastasis and 16 patients (18.4%) died of disease during the follow-up period. The 5-year recurrence-free and cancer-specific survival rates were 74.6% and 75.2%, respectively. In the univariate analysis, hydronephrosis, T stage, N stage, and lymphovascular invasion (LVI) were significant prognostic factors for recurrence-free and cancer-specific survival. In the multivariate analysis, T stage and LVI were independent prognostic factors for recurrence-free and cancer-specific survival. Conclusions The T stage and LVI are independent prognostic factors for recurrence-free and cancer-specific survival in patients with UUT-TCC treated by radical nephroureterectomy. These findings would be helpful for guiding decisions about adjuvant therapies and the surveillance interval.