Kyung Seok Han

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.

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.

Targeting Integrin-Linked Kinase Suppresses Invasion and Metastasis through Downregulation of Epithelial-to-Mesenchymal Transition in Renal Cell Carcinoma

Renal cell carcinoma (RCC) is the most common malignancy in the kidney. Antiangiogenic targeted therapies inhibit the progression of RCC, but have limited impacts on invasion or metastasis of tumor cells. Integrin-linked kinase (ILK) is a serine/threonine kinase implicated in the regulation of cell growth/survival, cell-cycle progression, epithelial–mesenchymal transition (EMT), invasion/migration, and angiogenesis. However, the role of ILK in RCC has not been evaluated. We investigated the role of ILK on cancer progression and metastasis and the therapeutic potential of ILK inhibition in RCC. Our investigation reveals that ILK is expressed at a low level in normal cells and low-stage RCC cells and is highly expressed in advanced and metastatic cells. Caki-1, a metastatic RCC cell line, showed higher expression of molecular EMT markers, including Snail and Zeb1, but decreased activity of GSK3β. Knockdown of ILK using small interference (si)-ILK minimally inhibited tumor proliferation and cell-cycle progression was not significantly affected. However, ILK knockdown suppressed the formation of stress fibers and focal adhesions and impeded phenotypic EMT markers, including cell migration and invasion, in Caki-1 and UMRC-3 cells. Finally, in vivo knockdown of ILK suppressed the progression, invasion, and metastasis of primary RCC in nude mice by downregulation of EMT markers (Snail, Zeb1, vimentin, and E-cadherin). Our results show that ILK may be essential for invasion and metastasis in RCC and regulates vimentin and E-cadherin expression by regulating the EMT-related transcription factors Snail and Zeb1. These results suggest that ILK may be a potential target in RCC. Mol Cancer Ther; 14(4); 1024–34. ©2015 AACR.

The efficacy of transureteroureterostomy for ureteral reconstruction during surgery for a non-urologic pelvic malignancy.

Of the many surgical options available for ureteral reconstruction during surgery for non‐urologic pelvic malignancies, the efficacy of transureteroureterostomy (TUU) was investigated.

A prospective evaluation of conventional cystography for detection of urine leakage at the vesicourethral anastomosis site after radical prostatectomy based on computed tomography

AIM To evaluate the diagnostic accuracy of conventional cystography for the detection of urine leakage at the vesicourethral anastomosis (VUA) site after radical prostatectomy based on computed tomography (CT) cystography. MATERIALS AND METHODS Patients who underwent radical prostatectomies at a single tertiary cancer centre were prospectively enrolled. Conventional cystography was routinely performed on postoperative day 7. Non-enhanced pelvic CT images were obtained after retrograde instillation of the same contrast material for a reference standard of urine leakage at the VUA site. Urine leakage was classified as follows: none; a plication abnormality; mild; moderate; and excessive. RESULTS One hundred and twenty consecutive patients were enrolled. Conventional cystography detected 14 urine leakages, but CT cystography detected 40 urine leakages, which consisted of 28 mild and 12 moderate urine leakages. When using CT cystography as the standard measurement, conventional cystography showed a diagnostic accuracy of 17.8% (5/28) for mild urine leakage and 75% (9/12) for moderate leakage. Of nine patients diagnosed with mild leakage on conventional cystography, four (44.4%) had complicated moderate urine leakages based on CT cystography, requiring prolonged catheterization. The sensitivity, specificity, positive and negative predictive values, and accuracy of conventional cystography were 35, 100, 100, 75.4, and 78.3%, respectively. CONCLUSIONS Conventional cystography is less accurate than CT cystography for diagnosing urine leakage at the VUA site after a radical prostatectomy. The present results suggest that CT cystography is a good choice for diagnostic imaging of urine leakage after radical prostatectomy.

Incidental Prostate Cancer Detected by Cystoprostatectomy in Korean Men

OBJECTIVES To determine the incidence and characteristics of incidental prostate cancer diagnosed by cystoprostatectomy (CPT) in Korean men. METHODS Thirty-six consecutive male patients scheduled to undergo CPT were prospectively enrolled. The CPT specimens were examined and the clinicopathologic characteristics of incidental cancers compared with those of T1c prostate cancers that had undergone radical prostatectomy. Complete transverse sections of the prostate were taken from the apex to the base at 4-mm intervals. RESULTS Of the 36 CPT patients, 18 (50%) had incidental prostate cancer. Most of the incidental tumors were confined to the prostate gland, except in 1 patient. Tumor involvement at the prostate apex was found in 3 patients (16.7%), and Gleason scores in 3 cases were 7 to 10. Median tumor volume was 0.08 cm(3) (range, 0.01 to 20.51 cm(3)), and a tumor volume of more than 0.5 cm(3) was identified in 5 patients. Of these incidental prostate cancers, 38.9% (19.4% of all CPT patients) were clinically significant. As compared with the 38 T1c prostate cancer patients, incidental prostate cancer patients were older, had a lower prostate-specific antigen level, a lower grade, smaller tumor volume, and were less likely to have multiple tumors. However, no significant differences were observed between these two groups with respect to apical tumor involvement or tumor confinement to the prostate (P >0.05 for each). CONCLUSIONS Incidental prostate cancers were diagnosed in 50% of CPT specimens, and 19.4% of these were clinically significant.