Ho Kyung Seo

Lymphovascular Invasion in Transurethral Resection Specimens as Predictor of Progression and Metastasis in Patients With Newly Diagnosed T1 Bladder Urothelial Cancer

PURPOSE We evaluated the clinical significance of lymphovascular invasion in transurethral resection of bladder tumor specimens in patients with newly diagnosed T1 urothelial carcinoma of the bladder. MATERIALS AND METHODS Enrolled in the study were 118 patients with newly diagnosed T1 urothelial carcinoma of the bladder who underwent transurethral resection of bladder tumor between 2001 and 2007. Patient records were retrieved from a prospectively maintained bladder cancer database. We evaluated the correlation between lymphovascular invasion and other clinicopathological features, and the impact of lymphovascular invasion on disease recurrence, disease progression and metastasis. RESULTS Lymphovascular invasion was histologically confirmed in 33 patients (28.0%). While lymphovascular invasion correlated with tumor grade (p = 0.002), it was not associated with gender, age, bladder tumor history, tumor size, multiplicity or concomitant carcinoma in situ. Recurrence, progression and metastasis developed in 45 (38.1%), 19 (16.1%) and 10 patients (8.5%), respectively. Univariate analysis showed that lymphovascular invasion was marginally associated with recurrence and significantly associated with progression (p = 0.011) and metastasis (p = 0.019). Multivariate Cox proportional hazards analysis revealed that recurrence was significantly associated with lymphovascular invasion (p = 0.029), and with bladder tumor history (p <0.001), tumor size (p = 0.031) and multiplicity (p = 0.043). Lymphovascular invasion was the only independent prognostic factor associated with progression (p = 0.016). CONCLUSIONS In patients with newly diagnosed T1 urothelial carcinoma of the bladder lymphovascular invasion in transurethral resection of bladder tumor specimens predicts disease progression and metastasis.

Pretreatment assessment of tumor enhancement on contrast-enhanced computed tomography as a potential predictor of treatment outcome in metastatic renal cell carcinoma patients receiving antiangiogenic therapy.

Tumor vascularity is a potential predictor of treatment outcomes in metastatic renal cell carcinoma (mRCC), and contrast enhancement of tumors in computed tomography (CT) is correlated significantly with microvessel density. In this study, the authors investigated whether tumor enhancement in contrast‐enhanced CT (CECT) is useful for predicting outcomes in patients with mRCC who are receiving antiangiogenic therapy.

Methotrexate, vinblastine, doxorubicin and cisplatin combination regimen as salvage chemotherapy for patients with advanced or metastatic transitional cell carcinoma after failure of gemcitabine and cisplatin chemotherapy

We investigated the safety and efficacy of a methotrexate, vinblastine, doxorubicin and cisplatin (M-VAC) combination regimen as second-line chemotherapy for patients with advanced or metastatic transitional cell carcinoma who failed first-line gemcitabine and cisplatin (GC) chemotherapy. Thirty patients who had progressed or relapsed after GC chemotherapy as first-line treatment were enrolled in this study. The major toxicities were neutropaenia and thrombocytopaenia. A grade 3 or 4 neutropaenia occurred in 19 (63.3%) and a grade 3 or 4 thrombocytopaenia developed in nine patients (30.0%). There were no life-threatening complications during the study. The overall response was 30%. A complete response was achieved in two patients (6.7%) and a partial response in seven (23.3%). The overall disease control rate was 50%. Seven out of 16 patients who had responded previously to GC responded to M-VAC, while 2 out of 14 who had not responded to GC responded to M-VAC. The median response duration was 3.9 months and the median progression-free survival was 5.3 months. The median overall survival was 10.9 months. M-VAC showed encouraging efficacy and reversible toxicities in patients who had progressed after GC chemotherapy and, especially, M-VAC appears to be a reasonable option as a sequential treatment regimen in patients who responded previously to GC chemotherapy.

Results of repeated transurethral resection for a second opinion in patients referred for nonmuscle invasive bladder cancer: the referral cancer center experience and review of the literature.

BACKGROUND AND PURPOSE We evaluated the results of a second transurethral resection (TUR) performed in patients referred after an initial TUR for nonmuscle invasive bladder cancer. PATIENTS AND METHODS From April 2001 to January 2008, patients who were referred for a second opinion and who underwent a second TUR at our institution were included in this study. Patients who had noninvasive bladder cancer and received the second TUR less than 8 weeks after the initial TUR were included in this analysis. The presence of residual tumor and changes of stage or grade from the two different TUR procedures were recorded and analyzed. RESULTS Fifty-six patients were evaluated in this study. The initial TUR specimens included the muscularis propria layers in 17 cases (30.4%), while the second opinion TUR specimens included the proper muscle layers in 47 cases (83.9%). Residual tumor was present in 16 of 25 (64.0%) patients with T(a) bladder cancer and in 20 of 30 (66.7%) patients with T(1) bladder cancer. Overall upstaging by the second TUR occurred for 9 patients (16.1%). Of 25 patients with T(a) bladder cancer, the second TUR confirmed the lamina propria invasion in one (4.0%) and muscle invasion in one (4.0%). The second TUR confirmed the muscle invasion in 7 of 30 (23.3%) patients with T(1) bladder cancer. Nine patients (16.1%) had their treatment strategy changed. CONCLUSION The previous results and our experiences suggest that a second TUR is recommended to reduce the chance of residual tumor and staging error because of nonstandardized TUR in the patients referred to an academic or referral center for a second opinion, irrespective of previous tumor stage.

Prostate stem cell antigen mRNA in peripheral blood as a potential predictor of biochemical recurrence in high-risk prostate cancer.

To determine whether the presence of prostate stem cell antigen (PSCA) mRNA in peripheral blood can predict biochemical recurrence (BCR) after radical prostatectomy in patients with high‐risk prostate cancer.

Overexpression of ERG and Wild-Type PTEN Are Associated with Favorable Clinical Prognosis and Low Biochemical Recurrence in Prostate Cancer

Objectives The aim of this study was to investigate the expression of two commonly altered genes ERG and PTEN in prostate cancer (PC) and evaluate their prognostic significance. Despite conflicting published results, TMPRSS2-ERG gene fusion and PTEN loss are generally considered unfavorable markers for PC progression. Materials and Methods Of the 762 prostatic adenocarcinoma specimens obtained from radical prostatectomy, 613 without neoadjuvant hormone therapy were included in tissue microarrays for quantitatively assessment of ERG and PTEN expression via immunohistochemistry. Statistical analysis of the association between such expression and clinicopathological parameters, including clinical prognosis, was performed with a p-value of <0.05 considered significant. Results During a median follow-up period of 44.0 months, 132 (21.5%) patients developed biochemical recurrence (BCR). ERG overexpression and PTEN loss were observed in 145 (23.7%) and 253 (41.3%) cases, respectively. BCR-free survival was significantly better in patients with ERG overexpression (p=0.005), but unfavorable among those with PTEN loss (p=0.142). Sub-group analysis revealed that patients with PTEN loss and negative ERG expression had the worst BCR-free survival outcome (p=0.021). Furthermore, multivariate analysis identified prostate-specific antigen level (≥10 ng/mL), Gleason score (>6), pathologic T stage (≥T3), positive surgical margin, and extraprostatic capsule extension as significant risk factors for BCR (p<0.05). Conclusions Our results indicated that ERG overexpression was associated with favorable BCR-free survival after radical prostatectomy for PC, whereas PTEN loss was with unfavorable outcomes.

The outcome with ureteric stents for managing non-urological malignant ureteric obstruction

To investigate the clinical outcome using ureteric stents to manage ureteric obstruction in advanced non‐urological malignancies.

Identification of Immunohistochemical Factors That Predict the Synchronous or Metachronous Development of Bladder Tumors in Patients with Upper Urinary Tract Tumors

Objective: To identify markers that predict the synchronous or metachronous development of bladder cancer in patients with upper urinary tract (UUT) tumors. Materials and Methods: Between March 2001 and December 2005, we identified 38 consecutive patients who had been histologically diagnosed as having transitional cell carcinoma in the renal pelvis and ureter. These patients were divided into 2 groups (n = 19 per group): group 1 patients with metachronous or synchronous bladder cancer, and group 2 patients with UUT tumors only. We analyzed the differences between the 2 groups with respect to the expression of various biomarkers (p53, Rb, Ki-67, PTEN, and bcl-2) and in terms of clinical parameters. Results: The 2 groups differed significantly in terms of multiplicity (p = 0.029), papillary configuration (p = 0.001), the presence of lymphovascular emboli (p = 0.019), and Ki-67 overexpression (p = 0.029) in UUT tumors. Multivariate analysis revealed that Ki-67 overexpression in UUT tumor tissues significantly predicts bladder cancer development (HR 6.440; 95% CI 1.121–37.014; log rank p = 0.037). Conclusion: Ki-67 overexpression in UUT tumor tissues was found to be an independent predictor of the development of bladder cancer in UUT tumor patients.

Haplotype Analysis of Prostate Stem Cell Antigen and Association With Prostate Cancer Risk

PURPOSE Prostate stem cell antigen has become a promising target as a potential biomarker for prostate cancer, but to our knowledge there are no reports of a genetic variation of the PSCA gene associated with prostate cancer risk. We determined the potential association between specific variations of the PSCA gene and prostate cancer in Korean men. MATERIALS AND METHODS In this hospital based, case-control study 194 patients newly diagnosed with histologically confirmed prostate cancer were enrolled. Visitors for cancer screening served as healthy controls. We genotyped 12 PSCA gene single nucleotide polymorphisms in 194 cases and 169 healthy controls. RESULTS Men with the rs1045531 AA genotype were at higher risk for prostate cancer than those with the CC genotype. Individuals with the CCCAGGTACGG haplotype were at significantly increased risk for prostate cancer. When considering clinical factors, rs3736001, which is a nonsynonymous cDNA single nucleotide polymorphism (Glu39Lys), showed an association with prostate specific antigen 10 ng/ml or greater and prostate cancer risk. CONCLUSIONS Men with the rs1045531 AA genotype of PSCA were at higher risk for prostate cancer. On haplotype analysis CCCAGGTACGG and CGA haplotype carriers showed a significant association with prostate cancer risk. To our knowledge this is the first report of PSCA genetic variation associated with prostate cancer risk.

Prognostic value of p53 and Ki-67 expression in intermediate-risk patients with nonmuscle-invasive bladder cancer receiving adjuvant intravesical mitomycin C therapy.

OBJECTIVES To analyze the prognostic values of p53 and Ki-67 expression in intermediate-risk patients with nonmuscle-invasive bladder cancer who were treated with adjuvant intravesical mitomycin C. METHODS From 2001 to 2006, 129 patients with nonmuscle-invasive bladder cancer who had undergone transurethral resection and adjuvant intravesical mitomycin C therapy. Patients with primary, single, Stage TaG1 lesions and those with T1G3 or carcinoma in situ lesions were excluded. The expression of p53 and Ki-67 was measured by immunohistochemistry on tissue sections after transurethral resection. The clinical and pathologic data were collected in a prospectively maintained bladder cancer database program. RESULTS The mean follow-up period was 48.6 months (range 6.1-96.0). Of the 129 patients, 61 (47.3%) developed recurrence and 15 (11.6%) developed progression to muscle-invasive disease. The expression of p53 was not associated with the patient outcomes, but Ki-67 overexpression was related to progression-free survival on univariate analysis (relative risk 4.38, 95% confidence interval 1.48-13.01, P = .006). On multivariate analysis, Ki-67 overexpression was significantly associated with progression-free survival (relative risk 3.40, 95% confidence interval 1.04-11.05, P = .042). In the patients with Ki-67 overexpression, the 1- and 5-year progression-free survival rate was 98.0% and 73.9%, respectively. When the combination of p53 and Ki-67 expression was assessed in the multivariate model, the simultaneous overexpression of p53 and Ki-67 did not predict for progression-free survival (adjusted relative risk 1.16; 95% confidence interval 0.21-6.20, P = .863). CONCLUSIONS These results suggest that Ki-67 expression can identify a subset of intermediate-risk patients with nonmuscle-invasive bladder cancer in whom intravesical mitomycin C therapy could be effective.