Shinsuke Tasaki

Prognostic factors for upper urinary tract urothelial carcinoma after nephroureterectomy.

Introduction: The purpose of this study was to evaluate prognostic factors for patients with upper urinary tract urothelial carcinoma (UUT-UC) after nephroureterectomy and to seek a better way of finding more favorable clinical results for these patients. Patients and Methods: We retrospectively reviewed the medical records of 121 UUT-UC patients who underwent a nephroureterectomy at our institution, and analyzed the prognostic significance of various clinicopathological parameters for progression-free and disease-specific survival rates by using univariate and multivariate analysis. Results: A Cox proportional hazards model showed that extravesical tumor recurrence after surgery was an independent prognostic factor for disease-specific survival (p < 0.0001). An additional model showed that lymphovascular invasion (LVI) was one of the independent predictors of lower extravesical-recurrence-free survival rates (p = 0.0004). Our final finding was that pathological tumor stage and positive surgical margin were significantly associated with the presence of LVI (p < 0.0001 and p = 0.0029, respectively). Conclusions: We conclude that there is a high possibility of LVI in patients with large tumors. Our findings should be helpful in terms of determining whether or not to perform neoadjuvant chemotherapy for patients with large tumors, given the fact that we frequently find a severe reduction in renal function after nephroureterectomy.

Preoperative Risk Factors for Extraurothelial Recurrence in Patients with Ureteral Cancer Treated with Radical Nephroureterectomy

PURPOSEnRecent studies have suggested that lymph node dissection may improve the prognosis in patients with upper tract urothelial carcinoma. Therefore, patients who will benefit from lymph node dissection need to be selected before surgery. Because patients who have extraurothelial recurrence theoretically include those whose prognoses are improved by lymph node dissection, we conducted this study to determine the preoperative predictors of extraurothelial recurrence in patients with ureteral cancer.nnnMATERIALS AND METHODSnBecause it is not appropriate to categorize the preoperative radiologic findings of ureteral cancer and those of renal pelvic cancer using the same classification criteria, we focused on ureteral cancer. We reviewed preoperative factors in 70 patients with ureteral cancer treated with radical nephroureterectomy. Laboratory tests including inflammatory indices, tumor markers and estimated glomerular filtration rate, along with radiologic findings, were evaluated. Multivariate analyses were performed to determine independent factors predicting extraurothelial recurrence in patients with ureteral cancer.nnnRESULTSnPositive cytology, cT stage 3 or greater, length of ureteral cancer 3 cm or greater and estimated glomerular filtration rate less than 60 ml/minute/1.73 m2 were independent predictors of extraurothelial recurrence on multivariate analysis. When patients were stratified into 3 groups according to the number of risk factors, the 3-year extraurothelial recurrence-free survival rates were 95.2% in the low risk group, 75.8% in the intermediate risk group and 25.1% in the high risk group.nnnCONCLUSIONSnPositive cytology, cT stage 3 or greater, length of ureteral cancer 3 cm or greater and estimated glomerular filtration rate less than 60 ml/minute/1.73 m2 were preoperative predictive factors of extraurothelial recurrence in patients with ureteral cancer and lymph node dissection may be omitted for low risk patients.

Tumor necrosis is a strong predictor for recurrence in patients with pathological T1a renal cell carcinoma

Patients with pT1aN0M0 renal cell carcinoma (RCC) generally have good prognosis, and recurrence is rare. However, metastasis develops postoperatively in a small number of patients with pT1aN0M0 RCC. The present study was undertaken to identify predictors for recurrence in patients with pT1aN0M0 RCC. We reviewed the clinicopathological factors of 133 patients with pT1aN0M0 RCC who underwent radical or partial nephrectomy at the Department of Urology, National Defense Medical College (Saitama, Japan). Clinicopathological factors, including age, gender, tumor size, histological subtype, tumor grade, microvascular invasion, histological tumor necrosis, C-reactive protein levels and performance status were reviewed. These factors were compared between patients with and without postoperative recurrence. Recurrence-free survival (RFS) and cause-specific survival (CSS) rates were calculated using the Kaplan-Meier method. Univariate and multivariate analyses were performed to determine independent factors predicting recurrence in patients with pT1aN0M0 RCC. The 5-year RFS and CSS rates were 97.2 and 99.1%, respectively. When clinicopathological factors were compared between patients with and without recurrence, tumor size (P=0.0390) and percentage of tumor necrosis (P<0.0001) were significantly different between groups. All patients with recurrence had primary lesions ≥3 cm. By univariate analysis, tumor size (P=0.0379) and the presence of tumor necrosis (P=0.0319) were significant predictors for recurrence; tumor necrosis was also an independent predictor for recurrence (P=0.0143). In patients with pT1b tumors ≤5 cm (recurrence rate, 16.8%; n=48), the percentage of tumor necrosis was significantly higher in patients with recurrence compared with those without (P=0.0261). This suggests that tumor necrosis may be an important predictor for recurrence in small RCCs. Although recurrence is rare in pT1a RCC, the presence of tumor necrosis may be an important predictor for recurrence. Particularly, patients presenting with pT1a RCC with histological tumor necrosis should undergo careful follow-up.

STAT3 inhibition by WP1066 suppresses the growth and invasiveness of bladder cancer cells

Signal transducer and activator of transcriptionxa03 (STAT3) regulates the expression of genes mediating cell survival, proliferation and angiogenesis and is aberrantly activated in various types of malignancies, including bladder cancer. We examined whether it could be a novel therapeutic target for bladder cancer using the STAT3 inhibitor WP1066. In T24 and UMUC-3 bladder cancer cells, 5xa0µM WP1066 prevented the phosphorylation of STAT3 and 2.5xa0µM WP1066 decreased cell survival and proliferation significantly (P<0.01). WP1066 also induced apoptosis accompanied by the suppression of the expression of Bcl-2 and Bcl-xL in T24 cells. Moreover, the covered area in a wound and the number of cells invading through a Matrigel chamber decreased significantly (P<0.01) when cells were treated with WP1066. The activities of MMP-2 and MMP-9 were also decreased by treatment with 10xa0µM WP1066. Our results revealed that using WP1066 to inhibit the STAT3 signaling pathway suppressed the viability and invasiveness of bladder cancer cells effectively and could be a novel therapeutic strategy against bladder cancer.

Clinical outcomes of percutaneous radiofrequency ablation for small renal cancer

Partial nephrectomy is the treatment of choice for small renal cell carcinoma (RCC) from the perspective of cancer management and renal function. However, when patients with RCC are of advanced age, exhibit severe comorbidities, including cardiovascular and pulmonary diseases, or have hereditary RCC, ablative therapies, including radiofrequency ablation (RFA) and cryoablation are useful treatment options. In the present study, the clinical outcomes of percutaneous RFA for treating small RCC were evaluated. Between December 2005 and March 2015, 40 patients (41 renal tumors in total) underwent RFA and a total of 50 sessions of RFA were performed. The average tumor size was 2.5 cm. A total of 18 tumors were exophytic and 23 were parenchymal. Of the 41 tumors, 85.4% were completely ablated by initial RFA and the rate of complete ablation following reablation for residual viable lesions was 95.1%. Local recurrence-free survival following complete ablation was 84.2% at 3 years. A patient with a 4.7 cm RCC tumor rapidly progressed following four RFA treatments until complete ablation was achieved. The metastasis-free survival rate following initial RFA was 95.7% at 3 years. The RCC-specific survival was 100% (mean follow-up, 38 months). Adverse events occurred in five sessions (10%); however, only 1 patient with arteriovenous fistula required intervention (transarterial embolization). The mean hospital stay following RFA was 3.2 days. The mean decrease in estimated glomerular filtration rate following RFA was 2.7%. The results of the present study indicate that percutaneous RFA was an effective treatment for small RCCs with respect to management of cancer, minimal invasiveness and minimal loss of renal function, particularly in patients for whom surgery would be a high risk and those at increased risk of deterioration of renal function.

Docosahexaenoic acid inhibits the phosphorylation of STAT3 and the growth and invasion of renal cancer cells

Docosahexaenoic acid (DHA) has a variety of anti-tumor activities. The present study examined the anti-tumor activity of DHA in renal cancer cells and its underlying mechanisms of action. The effects of DHA on the viability and proliferation of the human renal cancer cell lines Caki-1 and 786-O were examined by an MTS assay and cell counting. In addition, cell cycle distribution and cell apoptosis were analyzed by flow cytometry and Annexin V staining, and modulation of cell mobility and invasiveness was assessed by wound healing and Matrigel invasion assays. Effects of DHA on intracellular signaling pathways were also analyzed by western blotting. It was observed that DHA significantly reduced the viability and proliferation of Caki-1 and 786-O cells (P<0.01). Specifically, there were increases in the sub-G1 and G2/M cell populations, as well as the percentages of cells exhibiting Annexin-positive and propidium-iodide-negative staining. In addition, the covered area in a wound and the number of cells invading through a Matrigel chamber decreased when Caki-1 or 786-O cells were treated with DHA. Phosphorylation of epidermal growth factor receptor was also upregulated following DHA treatment, while phosphorylation of signal transducer and activator of transcription 3 and Akt was downregulated. Collectively, these data suggest that DHA may be useful in the treatment of renal cell carcinoma.

Prediction of Biochemical Recurrence after Radical Prostatectomy Using Peritumoral Lymphatic Vessel Density in Biopsy Specimens in Patients with Localized Prostate Cancer

Introduction: Lymphatic invasion has been associated with biochemical recurrence (BCR), and many patients with postoperative elevation of prostate-specific antigen (PSA) develop distant metastases within several years. We previously found peritumoral lymphatic vessel density (PTLD) in biopsy cores to be an independent predictor of lymphatic invasion in radical prostatectomy specimens, so we speculate that PTLD parameters in biopsy specimens could also be independent predictors of BCR after surgery. Patients and Methods: We obtained positive biopsy cores from 110 patients who underwent radical prostatectomy at our institution. Biopsy cores were immunostained with the D2-40 monoclonal antibody, which specifically and selectively detects lymphatic endothelium. We evaluated differences between the BCR-free survival rates and used univariate and multivariate analyses to detect independent predictors of BCR. Results: The results of a Cox proportional hazards model showed that lymphatic invasion in prostatectomy specimens was one of the independent postoperative prognostic factors for BCR (p = 0.0338). An additional model showed that one PTLD parameter, maximal PTLD, was among the independent preoperative predictors of lower BCR-free survival rates (p = 0.0200). Conclusions: Information about PTLD in prostate biopsy specimens could be helpful for selecting patients as radical prostatectomy candidates, and patients with high PTLD values should be carefully monitored after surgery.

A CASE OF METASTATIC BLADDER UROTHELIAL CARCINOMA WHOSE DISEASE WAS CONTROLLED FOR A RELATIVE LONG PERIOD BY MULTIDISCIPLINARY TREATMENT INCLUDING RADIATION TO A LUNG METASTASIS AND MULTIPLE COURSES OF CHEMOTHERAPY

A 67-year-old woman complained of urinary frequency and gross hematuria. She was referred to our hospital with the diagnosis of bladder tumor. Transurethral resection of the bladder tumor (TURBT) was performed and pathological diagnosis was urothelial carcinoma (G2>G3) with muscular invasion. Because she hoped bladder preservation therapy, she received two courses of M-VAC (methotrexate, vinblastine, doxorubicin and cisplatin) therapy, one course of arterial infusion chemotherapy, and chemoradiotherapy with cisplatin. After those therapies she underwent 4 times of TURBT and two courses intravesical BCG therapy. However, solitary lung metastasis appeared 19 months after the initial TURBT. Multidisciplinary treatments including 25 courses of various multiagent chemotherapies, radiation therapy to the lung metastasis and surgical resection of a urethral recurrence were performed. Although a localized radiation pneumonitis was developed, the lung metastasis appeared to be controlled for 26 months after the radiation therapy to the lung. Bilateral ureteral and renal pelvic tumors appeared after the radiation therapy. Severe bleeding was occurred from renal pelvic tumors several times and she needed the hospital stay 2 times. Active bleeding stopped after the administration of chemotherapy each time. Although she died of occlusive jaundice due to the liver metastasis, she had been alive due to the multidisciplinary treatment for 67 months after lung metastasis appearance with relatively good performance status.

CLINICAL ANALYSIS ABOUT PERCUTANEOUS NEEDLE BIOPSY FOR RENAL MASSES

(Objective) We investigated the efficacy and safety of percutaneous renal mass biopsy retrospectively. (Methods) A retrospective review was performed of 44 patients (46 renal masses) who received ultrasound and/or computed tomography guided percutaneous biopsy of a solid renal mass between April 2004 and December 2012 in National Defense Medical College Hospital. (Results) The median renal mass size was 45 (range 15-140) mm with a median of 2 (1-5) cores taken. Thirteen masses were biopsied for differential diagnosis between RCC and other malignancies (or benign renal tumors), 11 were biopsied for differential diagnosis between RCC and renal pelvic urothelial carcinoma, 10 unresectable masses were biopsied to confirm the diagnosis pathologically before starting medication, and 12 small masses were biopsied before radio-frequency ablation. Of the initial 46 biopsies, 38 (82.6%) were diagnostic. The median lesion sizes in the diagnostic and nondiagnostic biopsy specimens were 45 (15-140) mm and 43 (17-128) mm. The median numbers of diagnostic and nondiagnostic cores were 2 (1-5) and 1.5 (1-4). These size and core number differences between the diagnostic and nondiagnostic biopsy specimens are not statistically significant. Of initial nondiagnostic 8 masses, 3 masses that were performed repeat biopsy resulted in determined diagnosis finally. There were mild postprocedural hematomas not requiring blood transfusion. There was no tumor dissemination after renal mass biopsy. (Conclusions) Percutaneous biopsy of renal masses is a safe procedure that provides diagnostic information.

Clinical implication of ectopic liver lipid accumulation in renal cell carcinoma patients without visceral obesity

Fatty liver has emerged as a prognostic marker of cancer, so we investigated the impact of ectopic lipid accumulation in liver on the clinical outcome for patients with renal cell carcinoma (RCC). The records of 230 consecutive patients who had undergone surgery for RCC were reviewed, and liver lipid accumulation was estimated from the attenuation in unenhanced preoperative CT images. The median liver CT values of patients with G3 tumors was lower than that of patients with G1–2 tumors (Pu2009=u20090.0116), that of patients with pT3–4 tumors was lower than that of patients with pT1–2 tumors (Pu2009=u20090.0336), and that of patients with visceral obesity defined as a visceral fat areau2009≥u2009100u2009cm2 was lower than that of patients without visceral obesity (Pu2009<u20090.0001). In patients without visceral obesity the median liver CT values of patients with pT3–4 tumors was lower than that of patients with pT1–2 tumors (Pu2009=u20090.0401), that of patients with metastasis was lower than that of patients without metastasis (Pu2009=u20090.026), and fatty liver was associated with shorter overall survival (Pu2009=u20090.0009). Ectopic lipid accumulation in liver thus seems to be a predictor of aggressive forms of RCC.