Hidehiko Yoshii

Impact of thrombocytosis and C-reactive protein elevation on the prognosis for patients with renal cell carcinoma.

Aim: C‐reactive protein (CRP) elevation is reportedly a prognostic factor in patients with renal cell carcinoma (RCC). Thrombocytosis has recently been reported also to be a prognostic factor in RCC and, like CRP, to be related to inflammatory cytokines such as interleukin‐6. The aim of this study was to evaluate the importance of both thrombocytosis and CRP elevation in tumor recurrence and prognosis for patients with RCC.

Impact of Postoperative C-Reactive Protein Level on Recurrence and Prognosis in Patients With N0M0 Clear Cell Renal Cell Carcinoma

PURPOSE Preoperative C-reactive protein is a strong predictor of recurrence and prognosis in patients with renal cell carcinoma while postoperative C-reactive protein reportedly predicts survival in patients with metastatic renal cell carcinoma. We evaluated the impact of postoperative C-reactive protein on recurrence and prognosis in patients with N0M0 clear cell renal cell carcinoma. MATERIALS AND METHODS We defined increased preoperative C-reactive protein as 1 mg/dl or greater and postoperative C-reactive protein normalization as at least 1 postoperative measurement of less than 0.3 mg/dl. We reviewed the records of 263 patients with N0M0 clear cell renal cell carcinoma who underwent nephrectomy, and in whom preoperative and postoperative C-reactive protein values were available. We used multivariate analysis to identify independent factors predicting recurrence and prognosis. We also evaluated C-reactive protein at recurrence and its impact on survival. RESULTS Increased preoperative C-reactive protein and nonnormalization of postoperative C-reactive protein were associated with worse clinicopathological factors. Postoperative C-reactive protein nonnormalization, increased preoperative C-reactive protein, microvascular invasion and histological tumor necrosis were independent predictors for recurrence. Risk stratification using these factors effectively predicted the possibility of recurrence. Anemia, thrombocytosis and postoperative C-reactive protein nonnormalization were independent predictors of overall survival. Postoperative followup revealed recurrence in 50 patients. The 3-year survival rate in patients with C-reactive protein 0.3 mg/dl or greater at recurrence was significantly lower than that in patients with less than 0.3 mg/dl at recurrence (47.3% vs 81.6%). CONCLUSIONS Nonnormalization of postoperative C-reactive protein is a strong predictor of recurrence and prognosis. Patients with C-reactive protein 0.3 mg/dl or greater at recurrence might not survive as long as those with C-reactive protein less than 0.3 mg/dl at recurrence.

Glucose-Regulated Protein 78 Positivity as a Predictor of Poor Survival in Patients with Renal Cell Carcinoma

Introduction: Glucose-regulated protein 78 (GRP78), a chaperone for newly formed proteins during folding and glycosylation, is associated with resistance to apoptosis in some forms of cancer. We assessed GRP78 expression and its correlation with clinicopathological parameters and survival. Patients and Methods: Immunohistochemistry was performed using formalin-fixed, paraffin-embedded specimens: 128 primary renal cell carcinoma (RCC) specimens (120 conventional and 8 other cell types) and 9 metastatic specimens. GRP78 positivity was determined based on intensity of staining and percentage of cells stained. Correlation of GRP78 positivity with clinicopathological parameters including patients’ survival was evaluated. Results: A statistically significant association was found between GRP78 positivity and higher tumor grade (G3; p <0.0001), advanced T stage (≧pT3; p = 0.0002), lymphovascular invasion (positive; p <0.0001), regional nodal involvement (≧N1; p = 0.0086), and distant metastases at presentation (M1; p = 0.001). Positivity of GRP78 expression was significantly associated with shorter disease-specific survival and shorter progression-free survival. Cox proportional hazard model showed that strong GRP78 positivity was an independent predictor of shortened progression-free survival in N0M0 RCC patients. Conclusions: There was a significant relationship between GRP78 expression levels and aggressiveness of RCC. Increased expression of GRP78 might be a useful parameter to predict shortened survival in patients with RCC.

Anterior perirectal fat tissue thickness is a strong predictor of recurrence after high‐intensity focused ultrasound for prostate cancer

Objective:  To evaluate if and why obesity affects the clinical outcome in patients undergoing high‐intensity focused ultrasound (HIFU) treatment for prostate cancer (CaP).

Increased expression of α-actinin-4 is associated with unfavorable pathological features and invasiveness of bladder cancer

In the present study, the association between clinicopathological parameters and α-actinin-4 (ACTN4) expression in bladder cancer specimens was evaluated, and the functional role of ACTN4 in bladder cancer cells was investigated. Immunohistochemistry using anti-ACTN4 antibody was performed in bladder cancer specimens (53 superficial and 42 muscle-invasive cases) from 95 patients who underwent radical cystectomy (n=46) or transurethral resection (TUR) only (n=49). We divided the levels of ACTN4 expression into 2 groups (low or high) by comparing the staining intensity in each specimen with that of the vascular endothelial cells in the same specimen, and we evaluated the correlations between these levels and pathological parameters, recurrence and prognosis. We also investigated the effects of ACTN4 suppression by siRNA on the invasive ability and proliferation of T24 and KU19-19 cells. High ACTN4 expression was significantly associated with higher tumor grade and higher pT stage. In patients with superficial bladder cancer treated only by TUR, the rate of intravesical recurrence did not differ significantly between patients with high ACTN4 expression and patients with low ACTN4 expression. In patients who had muscle‑invasive tumors and underwent radical cystectomy, high ACTN4 expression was associated with neither recurrence nor poor prognosis. Nonetheless, high ACTN4 expression was shown by a large percentage (81%) of patients with muscle-invasive bladder cancer and by a small percentage (17%) of patients with superficial bladder cancer. Furthermore, the leading edges of the invasive bladder cancer showed increased ACTN4 expression. ACTN4 suppression significantly reduced the number of invading bladder cancer cells but unexpectedly increased the proliferation of bladder cancer cells. ACTN4 suppression increased the phosphorylation of ERKs but not AKT or STAT3, suggesting that the increased proliferation due to ACTN4 suppression was mediated in part by the ERK pathway. ACTN4 expression may suppress the proliferation of bladder cancer cells and may produce conditions which facilitate cancer cell invasion.

Adrenomedullin Increases Renal Nitric Oxide Production and Ameliorates Renal Injury in Mice With Unilateral Ureteral Obstruction

PURPOSE We evaluated the effects of adrenomedullin (Peptide Institute, Minoh-shi, Osaka, Japan) on mediators, including nitric oxide and transforming growth factor-beta, and parameters of renal injury in a murine unilateral ureteral obstruction model. MATERIALS AND METHODS Three study groups of control, adrenomedullin treated and adrenomedullin plus L-NAME treated BALB/C mice, respectively, underwent left unilateral ureteral obstruction. A 24-hour urine sample was collected to measure urinary NO(2)/NO(3) 1 day before unilateral ureteral obstruction and kidneys were harvested on postoperative day 14. Tubulointerstitial damage markers were evaluated by immunohistochemistry. Tissue transforming growth factor-beta was determined by enzyme-linked immunosorbent assay. Endothelial and inducible nitric oxide synthase immunolocalization was also determined. RESULTS Urinary NO(2)/NO(3) was significantly higher in the adrenomedullin group than in controls, confirming increased renal nitric oxide production. Immunohistochemistry showed increased endothelial nitric oxide synthase in vascular endothelial cells in the adrenomedullin group but tissue transforming growth factor-beta did not significantly differ in controls vs the adrenomedullin group. Interstitial collagen deposition and fibroblasts in the obstructed kidney were significantly decreased in the adrenomedullin group. The number of leukocytes and apoptotic cells in the obstructed kidney were significantly decreased by adrenomedullin. Renal injury amelioration resulting from adrenomedullin was blunted by the nitric oxide synthase inhibitor L-NAME. CONCLUSIONS Adrenomedullin increased renal nitric oxide, and suppressed tubular apoptosis, interstitial fibrosis and inflammatory cell infiltration in mice with unilateral ureteral obstruction. The renoprotective peptide adrenomedullin may be useful for that condition.

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.

Clinical Impact of the Presence of the Worst Nucleolar Grade in Renal Cell Carcinoma Specimens

OBJECTIVE Renal cell carcinoma (RCC) with a high-nucleolar-grade component is considered to be an aggressive type of tumor. In the present study, we evaluated the impact of the presence of the worst-nucleolar-grade component and also tried to determine predictors for recurrence and prognosis in patients with the worst grade component. METHODS We evaluated 314 patients with RCC. A three-graded system was used for nucleolar grading, the patients were classified into four groups according to the presence of the worst nucleolar grade (Grade 3) and the occupancy of each grade, and clinicopathological factors and clinical outcomes were compared. In patients of Grade 3 components (Groups 1 and 2), factors influencing on prognosis and recurrence were evaluated by multivariate analysis. RESULTS There was no significant difference in clinicopathological factors between Group 1 (with Grade 3-dominant tumors) and Group 2 (with tumors in which Grade 1 or 2 was dominant and there were Grade 3 components). Neither did cause-specific survival or recurrence-free survival differ significantly between those two groups. In multivariate analysis, only distant metastasis was an independent predictor for prognosis in all patients with Grade 3 components. Moreover, an elevated C-reactive protein (CRP) level (>or=1 mg/dl) was the only independent predictor of recurrence in N0M0 patients. CONCLUSIONS Regardless of dominancy, the presence of the worst grade component has a significant clinical impact in RCC patients. N0M0 patients whose RCC has worst-grade components but whose CRP levels are <1 are expected to have longer recurrence-free intervals and to survive longer than those whose CRP levels are higher.

A Case of Vesicocutaneous Fistula to the Thigh

We report a case of vesicocutaneous fistula to the thigh that developed 7 years after an injury to the pelvis. A 34-year-old male patient was referred to our hospital because of a water-soluble yellow exudate from his left thigh. A urinary fistula was suggested by the results of an intravenous indigo carmine injection. Intravenous pyelography and computed tomography revealed the presence of a bladder deformation and a fistula originating at the ventral bladder wall and leading down to the left thigh. The patient underwent fistulectomy and partial cystectomy. To the best of our knowledge, no previous reports of vesicocutaneous fistula to the thigh have been published.

Erythropoietin production in renal cell carcinoma and renal cysts in autosomal dominant polycystic kidney disease in a chronic dialysis patient with polycythemia: A case report

In patients undergoing chronic hemodialysis (HD), erythropoietin (EPO) production from the kidney generally decreases and renal anemia develops. Patients without anemia, but with high serum EPO (sEPO) levels are rare among HD patients. The current study presents the case of a 67-year-old female HD patient with autosomal dominant polycystic kidney disease (ADPKD) and renal cell carcinoma (RCC), manifesting polycythemia with elevated sEPO levels. A radical nephrectomy was performed, which diminished the polycythemia, but the sEPO levels remained high. To determine the origin of the EPO production, immunohistochemistry was performed to detect EPO in the RCC and the renal cysts of the surgically resected kidney. In addition, the sEPO and EPO levels in a renal cyst were determined by enzyme immunoassay. EPO expression was demonstrated in RCC and cyst epithelial cells using immunohistochemistry, revealing extremely high EPO levels in the cyst fluid. Due to the remission of polycythemia following the nephrectomy, EPO production from the resected kidney appeared to have been the cause of the polycythemia. Positive EPO staining of the renal cysts in the resected polycystic kidney and sustained sEPO elevation following nephrectomy led to the hypothesis of EPO production in the renal cysts of the contralateral polycystic kidney. Although the postoperative EPO level was higher than the normal range, the hematocrit (Hct) level gradually decreased and recombinant human EPO was required again three months following the nephrectomy. Eight months after the nephrectomy, the Hct level was 30.2% with the use of rHuEPO. In conclusion, EPO production from RCC and renal cysts in ADPKD appeared to cause polycythemia in the HD patient.