Yoshio Ohno

Pretreatment Neutrophil-to-Lymphocyte Ratio as an Independent Predictor of Recurrence in Patients With Nonmetastatic Renal Cell Carcinoma

PURPOSE We investigated the prognostic significance of the neutrophil-to-lymphocyte ratio to predict recurrence in patients with nonmetastatic renal cell carcinoma. MATERIALS AND METHODS We retrospectively reviewed the records of 192 patients with nonmetastatic renal cell carcinoma (T1-4N0M0) who underwent nephrectomy between 1986 and 2000. Mean followup was 93 months (range 6 to 232) months. We assessed the prognostic value of the pretreatment neutrophil-to-lymphocyte ratio, and other clinical and laboratory parameters on univariate and multivariate analysis. RESULTS Presentation mode, tumor stage, C-reactive protein, lymphocyte count and the neutrophil-to-lymphocyte ratio significantly correlated with recurrence-free survival on univariate analysis. The recurrence-free survival rate in patients with a neutrophil-to-lymphocyte ratio of less than 2.7 was 93.7% at 5 years and 79.8% at 10 years, significantly higher than the 77.9% and 58.4%, respectively, in patients with a ratio of 2.7 or greater (p = 0.0205). Multivariate analysis revealed that T stage and the neutrophil-to-lymphocyte ratio were independent predictors of recurrence. The 10-year survival rate in patients at low risk (T2 or less and neutrophil-to-lymphocyte ratio less than 2.7), intermediate risk (T2 or less and ratio 2.7 or greater, or T3 or greater and ratio less than 2.7) and high risk (T3 or greater and ratio 2.7 or greater) was 82.0%, 63.6% and 33.0%, respectively, which were significantly different. CONCLUSIONS An increased pretreatment neutrophil-to-lymphocyte ratio is an independent predictor of recurrence. The combination of T stage and the neutrophil-to-lymphocyte ratio can be used to stratify recurrence risk in patients with nonmetastatic renal cell carcinoma.

Prognostic value of neutrophil-to-lymphocyte ratio and establishment of novel preoperative risk stratification model in bladder cancer patients treated with radical cystectomy.

OBJECTIVE Preoperative prognostic factors in bladder cancer patients have not been fully established. This study was undertaken to investigate preoperative prognostic factors, including neutrophil-to-lymphocyte ratio (NLR), and to develop a novel prognostic factors-based risk stratification model for disease-specific survival (DSS) in bladder cancer patients treated with radical cystectomy (RC). METHODS We performed a retrospective analysis of 189 consecutive bladder cancer patients treated with RC at our institution. Prognostic value of the preoperative clinical and laboratory parameters were evaluated by univariate and multivariate Cox proportional hazard model analyses, and patients were stratified according to relative risks (RRs) for DSS. RESULTS One-, 3-, and 5-year DSS rates were 86.8%, 70.8%, and 61.7%, respectively. In univariate analysis, tumor size, clinical T stage, hydronephrosis, concomitance of carcinoma in situ, and some laboratory findings (hemoglobin [Hb] level, platelet count, C-reactive protein, neutrophil count, lymphocyte count, and NLR) were significantly associated with poor prognosis. In multivariate analysis, tumor size, hydronephrosis, Hb level, and NLR were independent factors for predicting poor prognosis. Patients were stratified into 3 risk groups: low (RR = 1.000-3.717), intermediate (RR = 4.149-9.315), and high (RR = 10.397-38.646). The differences among the groups were significant. CONCLUSIONS NLR was an independent prognostic factor, as were tumor size, hydronephrosis, and Hb levels, and the combination of these factors can stratify DSS risks in bladder cancer patients treated with RC. This information may be useful for identifying patients who might be candidates for clinical trials of multimodal treatment strategies, including innovative neoadjuvant treatments.

Followup of Neutrophil-to-Lymphocyte Ratio and Recurrence of Clear Cell Renal Cell Carcinoma

PURPOSE An increase in the pretreatment neutrophil-to-lymphocyte ratio is associated with poor prognosis for various cancers, including renal cell carcinoma. However, the clinical implication of a posttreatment change in the neutrophil-to-lymphocyte ratio in patients with cancer remains unclear. MATERIALS AND METHODS We reviewed the records of 250 patients with nonmetastatic clear cell renal cell carcinoma and analyzed associations among clinicopathological variables, the preoperative and postoperative neutrophil-to-lymphocyte ratio, and recurrence-free survival. RESULTS The 10-year recurrence-free survival rate for patients with a preoperative neutrophil-to-lymphocyte ratio of 2.7 or greater was significantly lower than that for those with a ratio of less than 2.7 (64.4% vs 83.7%, p = 0.0004). When combined with the postoperative ratio, patients with a preoperative ratio of 2.7 or greater could be further divided into 2 groups with a significantly different prognosis. The 10-year recurrence-free survival rate for patients with a preoperative neutrophil-to-lymphocyte ratio of 2.7 or greater and postoperative ratio of less than 2.7 was significantly lower than that for those with a preoperative and postoperative ratio of 2.7 or greater (52.0% vs 83.5%, p = 0.0487). The latter was similar to the 83.7% for patients with a preoperative ratio of less than 2.7. In patients with recurrence the ratio at recurrence was significantly increased compared with the postoperative ratio (mean ± SD 2.82 ± 1.63 vs 2.00 ± 0.90, p = 0.0090). Multivariate analysis showed that tumor size, pathological tumor stage and the neutrophil-to-lymphocyte ratio change (a combination of the preoperative and postoperative ratios) were independent predictors of recurrence. Using these 3 significant variables patients were stratified into low, intermediate and high risk groups, among which the recurrence-free survival rate significantly differed. CONCLUSIONS The posttreatment neutrophil-to-lymphocyte ratio change was a significant prognostic factor for recurrence as well as tumor size and pathological tumor stage in patients with clear cell renal cell carcinoma.

Effects of a KiSS-1 peptide, a metastasis suppressor gene, on the invasive ability of renal cell carcinoma cells through a modulation of a matrix metalloproteinase 2 expression

Although effects of a metastasis suppressor gene, KiSS-1, have been postulated to be mediated by its receptor, hOT7T175, the mechanism of such effects remains unknown. This study was designed to evaluate the mechanism of how KiSS-1 works and to assess effects of a synthesized truncated KiSS-1 protein on the invasive ability of renal cell carcinoma (RCC) cells. Four RCC cell lines, Caki-1, KU19-20, RSP and RSM, were investigated to determine mRNA expressions of KiSS-1, its receptor, hOT7T175, matrix metalloproteinases (MMPs) and MMP inhibitors. While all cell lines demonstrated hOT7T175 mRNA expressions, only Caki-1 had KiSS-1 transcripts. A synthesized truncated KiSS-1 peptide, metastin (45-54), produced a marked suppression of the invasive ability in KU19-20 cells, which were deficient for KiSS-1 transcripts, but not in Caki-1 cells. Metastin (45-54) also increased the ability of KU19-20 cells to attach to collagen 4. Both MMP-2 mRNA levels and protein production were significantly decreased only in KU19-20 cells by metastin (45-54). In conclusion, metastin (45-54) may have potential therapeutic use by suppressing the motility and invasive ability of RCC cells which possess hOT7T175 with either a negative expression or very low expression level of KiSS-1 through, at least in part, the down-regulation of MMP-2.

Impact of Tumor Size on Renal Function and Prediction of Renal Insufficiency After Radical Nephrectomy in Patients With Renal Cell Carcinoma

PURPOSE From the perspective of oncological and functional outcomes partial nephrectomy is considered standard surgery for small renal tumors 4 cm or less. However, radical nephrectomy is commonly done for small tumors. It is important to predict postoperative renal function in patients to choose the most optimal surgical procedure. MATERIALS AND METHODS We retrospectively reviewed the records of 271 patients treated with radical nephrectomy for renal cell carcinoma. Associations of tumor size and clinical variables with renal function were analyzed. RESULTS Preoperatively the mean ± SD glomerular filtration rate was 74.38 ± 17.70 ml per minute/1.73 m(2) and 56 patients (20%) had renal insufficiency (glomerular filtration rate less than 60 ml per minute/1.73 m(2)). The mean decrease in the glomerular filtration rate after radical nephrectomy was 24.2 ± 12.40 ml per minute/1.73 m(2) (31.5% ± 15%). Of 215 patients with a preoperative glomerular filtration rate of 60 ml per minute/1.73 m(2) or greater 165 (77%) had new onset renal insufficiency. Age, tumor size, preoperative glomerular filtration rate and hypertension were significantly associated with new onset renal insufficiency. Multivariate analysis revealed that age 60 years or greater, tumor size 7 cm or less and the preoperative glomerular filtration rate were independent risk factors for new onset renal insufficiency (p <0.05). Finally, we developed a predictive model for new onset renal insufficiency after radical nephrectomy. CONCLUSIONS Tumor size 7 cm or less, age 60 years or greater and a decreased preoperative glomerular filtration rate were significant risk factors for new onset renal insufficiency in patients treated with radical nephrectomy. Partial nephrectomy might be considered an option according to the risk of postoperative renal insufficiency, especially in elderly patients with a tumor of 7 cm or less.

Development and internal validation of a nomogram predicting extracapsular extension in radical prostatectomy specimens

Objectives:  To present a nomogram predicting the side‐specific probability of extracapsular extension (ECE) in radical prostatectomy (RP) specimens.

Production of erythropoietin and multiple cytokines by metanephric adenoma results in erythrocytosis

This is the first report of direct evidence that metanephric adenoma cells produce erythropoietin and other types of cytokines, which may be the cause of the high incidence of erythrocytosis in patients with this tumor. The purpose of the study was to establish a metanephric adenoma cell line in vitro from nephrectomized tumor tissue in order to investigate the ability of metanephric adenoma cells to produce erythropoietin and other types of cytokines. The tumor tissue was obtained from a 16‐year‐old boy who had developed metanephric adenoma with erythrocytosis and was served for cell culture. Significantly high concentrations of erythropoietin, granulocyte–macrophage colony‐stimulating factor (GM‐CSF), granulocyte–colony‐stimulating factor (G‐CSF), interleukin‐6 (IL‐6), and IL‐8 were detected in the cell culture supernatant. Southern hybridization showed specific positive signals for GM‐CSF, G‐CSF, IL‐6, IL‐8 and erythropoietin. The number of chromosomes was 46‐XY without any structural abnormalities in cytogenetic analysis of the cultured cells.

Prediction of biochemical recurrence after robot-assisted radical prostatectomy: analysis of 784 Japanese patients.

To examine biochemical recurrence after robot‐assisted radical prostatectomy in Japanese patients, and to develop a risk stratification model for biochemical recurrence.

Pneumatosis intestinalis and hepatic portal venous gas in a patient receiving sorafenib

A 77-year-old woman with fever, lower leg edema and general malaise was referred to the Tokyo Medical University Hospital. She had undergone a left nephrectomy for renal tuberculosis and a subtotal gastrectomy for a gastric ulcer at ages 19 and 42 years, respectively. An abdominal computed tomography (CT) scan showed a 7.8-cm right renal mass and a thrombus in the inferior vena cava (Fig. 1a). Magnetic resonance imaging confirmed a right renal tumor, with a thrombus extending into the right atrium through the renal vein (Fig. 1b). No lymph node or distant metastasis was noted. We diagnosed the condition as renal cell carcinoma (stage T3c N0 M0). The laboratory findings showed anemia (blood hemoglobin level, 9.1 g/dL), and elevated serum creatinine (1.85 mg/dL) and C-reactive protein levels (5.4 mg/dL). The remaining examination result was unremarkable. She refused to undergo a nephrectomy and thrombectomy, because the procedures were invasive and postoperative hemodialysis induction is required. Therefore, a 400-mg/day sorafenib treatment was initiated. No adverse effects were observed during the initial 2 weeks; subsequently, the sorafenib dosage was increased to 600 mg/day. A total of 20 days after the treatment initiation, she complained of general malaise. Sorafenib was withdrawn because an elevated level of serum creatinine and thrombocytopenia were also observed. Three days thereafter, she suddenly experienced abdominal pain and vomiting. The abdominal radiograph showed massive small and large bowel dilation. At this time, her body temperature, blood pressure, and pulse rate were 35.8°C, 105/46 mmHg and 83 b.p.m., respectively. The laboratory test results showed no significant elevation of leukocyte count (4300/mL), but an increased C-reactive protein level (4.5 mg/dL) was recorded. The abdominal CT scan showed a distended small bowel and intestinal submucosal gas, indicative of pneumatosis intestinalis (PI) and massive hepatic portal venous gas (PVG; Fig. 1c,d). Although intestinal tract necrosis was suspected, arterial embolism or free air was not detected. An emergency operation was not possible given the rapid deterioration of her general condition. The patient died 17 h after the symptoms developed. PI is a pathological condition defined by the infiltration of gas into the wall of the gastrointestinal tract, and has

Clinical efficacy and prognostic factors of tumor progression in Japanese patients with advanced renal cell carcinoma treated with sorafenib

OBJECTIVE Result of clinical trial for registration purpose is often difficult to generalize because of its limited population in number and inclusion criteria. METHODS To understand the efficacy of sorafenib under daily medical practice, we retrospectively investigated therapeutic outcomes of 175 Japanese patients with advanced renal cell carcinoma treated with sorafenib at 15 centers. RESULTS The objective response rate and disease control rate were 15.4 and 77.1%, respectively, being similar to those in the Phase II study in Japanese patients (19.4 and 73.6 months). Any tumor shrinkage was observed with 53% of patients, while tumor control without growth was in 61%. Lung lesions were more sensitive to sorafenib than other lesions, in terms of any tumor shrinkage (54%) and the extent of maximal shrinkage, while tumor control was better in lymph node metastases (77%) than in lung (69%). Liver was worse in any tumor shrinkage (35%), tumor control (55%) and the extent of tumor growth. Slightly, shorter median overall survival of 21.1 months compared with Phase II clinical trial (25.3 months) is likely to be attributable to different patient population, because median overall survival was improved to 26.4 months when the population was matched to that in Phase II trial. Univariate and multivariate analyses identified prognostic factors for worse overall survival, including intermediate and poor Memorial Sloan-Kettering Cancer Center risk, Eastern Cooperative Oncology Group performance status ≥1, the presence of non-clear cell component and the presence of liver metastasis. CONCLUSIONS In conclusion, the present study confirmed the efficacy of sorafenib in the real-world setting on advanced renal cell carcinoma.