Masaharu Nishikido

An evaluation of Bosniak's radiological classification of cystic renal masses.

Objective To determine the clinical usefulness of Bosniaks classification of cystic renal masses, the differentiation of which remains difficult despite significant advances in diagnostic imaging.

Expression of Matrix Metalloproteinase-7 on Cancer Cells and Tissue Endothelial Cells in Renal Cell Carcinoma: Prognostic Implications and Clinical Significance for Invasion and Metastasis

Purpose: The expression of matrix metalloproteinase-7 (MMP-7) correlates with the malignant potential of various tumors and patient survival. We investigated the clinical and prognostic significance of MMP-7 expression in cancer cells and endothelial cells in human renal cell carcinoma (RCC). Experimental Design: We reviewed tissue samples of 156 patients with RCC who had undergone radical operation. MMP-7 expression was examined by immunohistochemistry. Sections containing MMP-7-positive vessels were also stained for CD34. The density of MMP-7-positive vessels was determined by a computer-aided image analysis system. Multivariate analysis was done to assess relevant variables for invasion, metastasis, and cause-specific survival. Results: The proportion of MMP-7-expressing tumor cells were significantly higher (P < 0.001) than that of normal cells. MMP-7-positive vessels were considered blood vessels based on staining for CD34, and their density was increased in tumor areas. The proportion of MMP-7-expressing cancer cells and density of MMP-7-positive vessels correlated with grade, pathologic tumor stage, and metastasis. Multivariate analysis showed that MMP-7 expression on cancer cells correlated with pathologic tumor stage only, whereas MMP-7-positive vessel density correlated with metastasis only. The elevated status of MMP-7 in cancer tissues was an independent predictor for cause-specific survival (odds ratio, 8.61; P = 0.040) by multivariate analysis. Conclusions: Our results showed that MMP-7 influences tumor progression by regulating invasion and angiogenesis. Multivariate analysis showed that MMP-7 status of cancer tissues was strong predictor of poor prognosis. Our results suggest that MMP-7 targeting treatment may be a potential target against RCC.

Systemic immune response after intravesical instillation of bacille Calmette–Guérin (BCG) for superficial bladder cancer

The mechanism of anti‐tumour activity by BCG is not known clearly. However, many studies suggest that immunological response is related to effectiveness of intravesical instillation of BCG in the therapy for superficial bladder carcinoma. Peripheral blood mononuclear cells (PBMC), urine and serum were obtained from patients with superficial carcinoma at various times during the course of BCG instillation. Urine of patients showed increased levels of IL‐1β, IL‐2, IL‐6, tumour necrosis factor‐alpha (TNF‐α), interferon‐gamma (IFN‐γ) and macrophage colony‐stimulating factor (M‐CSF) after BCG instillation. Levels of IL‐2 and IFN‐γ in the serum also increased after BCG instillation, but IL‐1β, IL‐6, TNF‐α and M‐CSF were not detectable. Maximal levels of IL‐2 and IFN‐γ in the urine or serum were shown after the fourth instillation. BCG‐induced killer cell activity in PBMC increased significantly after the third BCG instillation. These results suggest that BCG instillation involved not only local immunological efforts but also systemic immune responses. Tumour‐free patients produced higher BCG‐induced killer cell activity than tumour recurrence patients. BCG‐induced killer cell activity may be useful for monitoring the effectiveness of intravesical BCG instillation.

Outcome of surgery in cystic renal cell carcinoma.

OBJECTIVES To review cases of cystic renal cell carcinoma treated surgically at our institution and define their clinical and histopathologic features. METHODS Between 1986 and 1998, 21 patients with cystic renal cell carcinoma were treated surgically. Cystic renal cell carcinoma was categorized using Hartmans classification. RESULTS Histopathologic examination demonstrated cystic necrosis in 11 patients, multilocular cystic renal cell carcinoma in 9, and unilocular cystic renal cell carcinoma in 1 patient. Tumors were incidentally found during an evaluation of unrelated disease or a general health checkup in 14 patients (67%). The mean tumor size was 5.6 cm (range 0.5 to 12) for cystic necrosis and 5.4 cm (range 2 to 9) for multilocular cystic renal cell carcinoma. All 9 cases of multilocular cystic renal cell carcinoma were of the clear cell type and tumor grade 1. The mean follow-up period was 65 months (range 9 to 141). The 5-year disease-specific survival rates for multilocular cystic renal cell carcinoma and cystic necrosis were 100% and 80%, respectively. CONCLUSIONS The prognosis for patients with cystic renal cell carcinoma is better than that for patients with solid tumors. In particular, the prognosis of multilocular cystic renal cell carcinoma is excellent. Multilocular cystic renal cell carcinoma represents a distinct subtype of renal cell carcinoma that can be completely cured by surgery.

The diagnostic value of bone scan in patients with renal cell carcinoma.

PURPOSE Bone scan is performed as part of the evaluation of bone metastasis. We assessed the diagnostic value of bone scan in patients with renal cell carcinoma. MATERIALS AND METHODS Bone scan was performed at presentation in 205 patients with confirmed renal cell carcinoma. Abnormal hot areas were further evaluated by x-ray, computerized tomography or surgery. RESULTS Of the 56 patients (27%) with an abnormal bone scan 32 (57%) had osseous metastatic lesions. Overall bone metastasis was present in 34 of the 205 patients (17%). Bone scan had 94% sensitivity and 86% specificity. Of the 124 patients with clinically localized, stages T1-2N0M0 disease exclusive of bone metastasis 6 (5%) had bone metastasis only, whereas 28 of 81 (35%) with locally advanced or metastatic disease had bone metastasis, including 12 (35%) who complained of bone pain and 19 (56%) who presented with other symptoms due to local tumor growth or metastasis at other sites. Three patients (9%) were asymptomatic. There was osseous metastasis without other metastasis, enlarged regional lymph nodes or bone pain in 7 patients, including 1 with stage T1b (2% of all with that stage), 2 with stage T2 (5%), 1 with stage T3a (4%), 1 with stage T3b (6%), 1 with stage T3c (14%) and 1 with stage T4 (6%) disease. CONCLUSIONS Bone scan may be omitted in patients with stages T1-3aN0M0 tumors and no bone pain because of the low proportion of missed cases with bone metastasis.

Predictive values of acute phase reactants, basic fetoprotein, and immunosuppressive acidic protein for staging and survival in renal cell carcinoma.

OBJECTIVES To determine the clinical significance and predictive value of three acute phase reactants (erythrocyte sedimentation rate, C-reactive protein, and ferritin), as well as basic fetoprotein (BFP) and immunosuppressive acidic protein, in patients with renal cell carcinoma. METHODS Erythrocyte sedimentation rate, C-reactive protein, ferritin, BFP, and immunosuppressive acidic protein levels were measured in 92 patients with renal cell carcinoma diagnosed in 1989 to 1999. The levels were compared with the clinical stage and nuclear grade, and their predictive values of survival were evaluated statistically. RESULTS All markers, with the exception of BFP, correlated with each other and with the clinical stage and nuclear grade. BFP did not correlate with the acute phase reactants. The log-rank test revealed that the levels of C-reactive protein, immunosuppressive acidic protein, and ferritin significantly influenced survival. Multivariate stepwise analysis identified ferritin as the only independent and significant prognostic marker (hazard ratio = 5.624, P = 0.001). However, when age, sex, clinical stage, and nuclear grade were entered into the same analysis, only clinical stage was an independent marker of prognosis. CONCLUSIONS The results of our study demonstrated that serum ferritin is the most useful marker among five tested factors for staging and predicting survival, although the clinical stage is the best parameter that predicts the prognosis of patients with renal cell carcinoma accurately.

Lymphangiogenesis and angiogenesis in conventional renal cell carcinoma: association with vascular endothelial growth factors A to D immunohistochemistry.

OBJECTIVES Lymphangiogenesis is associated with tumor progression in various cancers and is regulated by vascular endothelial growth factors (VEGFs). However, little is known about the pathologic roles of lymphangiogenesis in renal cell carcinoma (RCC). We investigated the relationships between various clinicopathologic features and lymphangiogenesis, angiogenesis, and expression of VEGFs in RCC. METHODS The TNM stage and grade of 107 conventional RCC were reviewed. Lymph vessel density (LVD) and microvessel density (MVD) were measured by quantitative immunohistochemistry using anti-D2-40 antibody and anti-CD34 antibody, respectively. Expression levels of VEGF-A, B, C, and D were examined by immunostaining. RESULTS D2-40-positive lymphatic vessels were detected mainly in the peritumoral area. However, no significant difference was found between LVD in peritumoral areas of the RCC tissues and the normal kidney (P = 0.238). Intratumoral D2-40-positive lymphatic vessels were detected in only six specimens, and neither intratumoral nor peritumoral LVD correlated with the clinicopathologic features. VEGF-A expression correlated with MVD (r = 0.50, P <0.001), but not with LVD, and was also associated with pT stage, the presence of metastasis, and tumor grade. No other members of the VEGF family showed any correlation with LVD, MVD, or the clinicopathologic features. CONCLUSIONS Lymphangiogenesis seems to play a minimal role in the progression of human RCC. Only VEGF-A, but not B, C, or D, was associated with the histopathologic features and MVD of RCC.

Erectile dysfunction in hemodialysis patients with diabetes mellitus: Association with age and hemoglobin A1c levels

Abstract  Aim:  Erectile dysfunction (ED) is common in patients with diabetes mellitus (DM) as well as those undergoing hemodialysis (HD). The purpose of this study is to investigate the frequency and severity of ED in HD patients with DM and those without DM. In addition, we examined the relationship between erectile function and several risk factors, including presence of DM and hemoglobin A1c levels in HD patients.

Renal cell carcinoma with solitary metachronous metastasis to the urinary bladder

We report a case of renal cell carcinoma with solitary metachronous metastasis to the urinary bladder occurring 6 years after radical nephrectomy. The patient was treated with partial cystectomy and survived for 60 months. Other cases like this one were reviewed in published reports, and the 3-year survival rate for patients with this type of cancer with solitary metastasis to the urinary bladder was found to be 80%. The follow-up duration of our case was the longest in the published studies. We suggest that urinary bladder metastasis of renal cell carcinoma should be resected because no effective treatment for metastatic renal cell carcinoma is available. A good prognosis may be expected, especially in patients with solitary metastasis to the urinary bladder.

Multicenter Phase II Trial of S-1 in Patients With Cytokine-Refractory Metastatic Renal Cell Carcinoma

PURPOSE This phase II multicenter trial was conducted to evaluate the activity and safety of S-1 in Japanese patients with metastatic renal cell carcinoma (mRCC). We also examined the relation between response and mRNA expression levels of enzymes involved in the metabolism of fluorouracil (FU). METHODS Patients with mRCC who had received nephrectomy in whom cytokine-based immunotherapy was ineffective or contraindicated were studied. S-1 was administered orally at 80-, 100-, or 120-mg daily, assigned according to body surface area, on days 1 to 28 of a 42-day cycle. The primary end point was the objective response rate. The mRNA expression levels of FU-related enzymes were measured by reverse-transcriptase polymerase chain reaction in formalin-fixed, paraffin-embedded specimens of tumors obtained at nephrectomy. RESULTS A total of 45 eligible patients were enrolled. Eleven (24.4%) of 45 patients had partial responses to S-1, and 28 (62.2%) had stable disease. Median progression-free survival was 9.2 months. The severity of most adverse events was mild to moderate. The most common grade 3/4 drug-related adverse events were neutropenia (8.9%) and anorexia (8.9%). The expression level of thymidylate synthase (TS) mRNA was significantly lower in patients who responded to treatment (t-test, P = .048), and progression-free survival was significantly longer in patients whose TS mRNA expression levels were below the median value, as compared with those with higher levels (log-rank test, P = .006). CONCLUSION S-1 is active against cytokine-refractory mRCC. Quantification of TS mRNA levels in tumors before treatment may facilitate prediction of the response of mRCC to S-1.