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Objective: To identify predictive factors for multifocal lesions in patients with upper tract urothelial carcinoma (UTUC)., Patients and Methods: Between June 1996 and September 2013, a cohort of 147 patients underwent radical nephroureterectomy at our institution. Univariate and multivariate logistic regression analyses were performed to identify clinical covariates significantly associated with the multifocal UTUC lesions and establish a model to predict its occurrence., Results: In the univariate analyses, estimated glomerular filtration rate, hydronephrosis, history of bladder cancer, hemoglobin level, and Brinkman index were significantly associated with multifocal lesions. In the multivariate analysis, hydronephrosis (P = .010), history of bladder cancer (P = .017), Brinkman index >100 (P = .014), and hemoglobin level <11 g/dL (P = .031) were independent predictive factors for multifocal lesions. Using these independent factors, we calculated the predictive probability of multifocal lesions and predicted their occurrence. The predictive probability of multifocal lesions strongly correlated with their observed rate (regression coefficient = 0.9999)., Conclusion: An improved understanding of UTUC has led to various clinical guidelines being revised to recommend less invasive interventions in appropriate cases. Hydronephrosis, history of bladder cancer, Brinkman index, and hemoglobin level are independent predictive factors for multifocal lesions of UTUC. Although this study has limitations and additional studies are required to validate our findings, this information may aid in appropriate patient selection for partial ureterectomy and may be effectively incorporated into clinical practice., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Objective: To investigate the clinical implication of preoperative serum total cholesterol (TC) level in patients with clear cell renal cell carcinoma (RCC)., Methods: The records of 364 patients with clear cell RCC who had undergone nephrectomy were retrospectively reviewed. The association among preoperative TC level, clinicopathologic factors, and oncological outcome in terms of cancer-specific survival (CSS) and recurrence-free survival period was analyzed by univariate and multivariate analyses., Results: As a continuous variable, lower serum TC level was found to be significantly associated with male sex, symptomatic tumor, advanced TNM stage, higher nuclear grade, microscopic venous invasion, poor Eastern Cooperative Oncology Group Performance Status, larger tumor size, elevated C-reactive protein level, and lower hemoglobin level. Univariate analysis showed that relatively lower preoperative serum TC level was associated with lower recurrence-free survival (P = .040) and CSS (P <.001) rates. Multivariate analysis indicated that in addition to pT stage, M stage, nuclear grade, and Eastern Cooperative Oncology Group Performance Status, serum TC level (hazard ratio, 0.988 per mg/dL; 95% confidence interval, 0.980-0.998; P = .019) was an independent predictor of CSS., Conclusion: Low preoperative serum TC level is associated with worse prognosis in patients with clear cell RCC. Consideration of preoperative serum TC level might thus provide additional prognostic information for patients with clear cell RCC., (Crown Copyright © 2014. Published by Elsevier Inc. All rights reserved.)

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., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Objectives: To evaluate the recurrence and progression in patients with non-muscle-invasive bladder tumors who remained tumor-free for at least 5 years, which should assist in the development of schedules of their follow-up evaluations. Non-muscle-invasive bladder tumors that recur or progress at a late time point are not rare., Methods: Between 1985 and 2002, 814 cases diagnosed with non-muscle-invasive bladder cancer were treated with transurethral resection. Of these 814 cases, 262 patients with no tumor recurrence for more than 5 years were included in the study. The median follow-up interval was 10.0 years., Results: During the follow-up period, 39 tumors (14.9%) showed tumor recurrence. The 5- and 10-year recurrence-free survival rates were 81.6% and 76.0%, respectively. There was no significant difference in tumor recurrence among the low-, intermediate-, and high-risk groups based on the current clinical guideline. Only the use of intravesical mitomycin C was determined to be a significant unfavorable risk factor for late recurrence. Five patients (1.9%) experienced stage progression, 3 of whom did not have metastases at the time of diagnosis of the progression but died because of bladder cancer disease., Conclusions: After a 5-year tumor-free period, even in the low-risk group, recurrence occurred at a late time point to a degree that was the same as that for the intermediate- and high-risk groups. Finally, some of the high-risk patients experienced late progression with a high degree of malignant behavior, suggesting longer follow-up is needed for each patient., (Copyright (c) 2010 Elsevier Inc. All rights reserved.)

Tumor necrosis factor-alpha (TNF-alpha) is a vital component of the inflammatory process and its aberrant over-expression has been linked to numerous disease states. New treatment strategies have sought to reduce circulating TNF-alpha, either with neutralizing anti-TNF-alpha binding proteins such as etanercept or via drugs that inhibit de novo TNF-alpha synthesis like pirfenidone. In the present study, we examined the effects of both classes of drugs on secreted and cell-associated TNF-alpha produced by THP-1 cells. All of the tested drugs significantly reduced secreted levels of bioactive TNF-alpha following stimulation with LPS as measured by bioassay. However, etanercept-treated cells had approximately six-fold higher levels of cell-associated TNF-alpha compared with that of the LPS-alone treatment group. Surprisingly, LPS+infliximab treated cells did not increase cell-associated TNF-alpha relative to the LPS-alone treatment. Pirfenidone significantly reduced both secreted and cell-associated TNF-alpha levels. These drug-related differences in cell-associated TNF-alpha may have broad implications in the future for the therapeutic uses of anti-TNF-alpha drugs in the management of TNF-alpha diseases.

Objectives: To investigate the clinical significance of local assessment by endorectal magnetic resonance imaging (MRI) in prostate cancer patients with metastases., Methods: The local extent and tumor size were determined by endorectal MRI in 95 prostate cancer patients with metastases, and their clinical implications were assessed., Results: The maximum diameter and tumor volume significantly correlated with the local extent of disease but not with extent of disease (EOD) on bone scan. In univariate analyses, EOD, serum prostate-specific antigen level, serum alkaline phosphatase level, and hemoglobin level were significantly associated with disease-specific survival, whereas tumor size and local extent of primary lesions were not. In a multivariate analysis EOD on bone scan was a significant prognostic factor., Conclusions: Tumor size and local extent of the primary lesion estimated by endorectal MRI were not associated with disease-specific survival. Assessment of the primary lesion by endorectal MRI is of limited value in predicting the prognosis of prostate cancer patients with metastases.

Objectives: To evaluate the relationship between serum interleukin (IL)-6 and cachexia in patients with prostate cancer., Methods: Serum levels of IL-6, total protein, albumin, total cholesterol, and hemoglobin concentration were determined in 164 blood samples from patients with prostate cancer. The body mass index and performance status were also determined., Results: The serum total protein, albumin, and cholesterol levels, hemoglobin levels, and body mass index of the patients whose serum IL-6 level was 7 pg/mL or greater were significantly lower (P <0.05) than the corresponding values in patients with a serum IL-6 level of less than 7 pg/mL. The serum IL-6 level of patients with a serum albumin level of less than 3.5 g/dL, serum total protein level of less than 7.0 g/dL, serum total cholesterol level of less than 180 mg/dL, hemoglobin level of less than 11.0 g/dL, and body mass index of less than 21 kg/m2 were significantly greater (P <0.05) than the values in their respective counterparts. A significant correlation was found between the elevation of serum IL-6 and performance status (P <0.05). The mortality rate of patients with greater serum IL-6 levels was significantly greater than that of those with lower serum IL-6 levels in patients with untreated disease, patients in remission, and patients with relapse (all P <0.05)., Conclusions: These findings suggest that IL-6 may be one of the factors contributing to the complex syndrome of cachexia in patients with prostate cancer (all P <0.05).

Objectives: To determine the usefulness of alpha1-antichymotrypsin-prostate-specific antigen (PSA) complex (PSA-ACT)-based parameters in predicting bone metastasis in patients with prostate cancer., Methods: PSA-ACT, total PSA, free PSA, their volume-adjusted values, and alkaline phosphatase were evaluated in 220 consecutive patients with newly diagnosed prostate cancer., Results: Bone metastases were detected by bone scan in 27 (12.3%) of the 220 patients. The serum levels of PSA-ACT, total PSA, free PSA, PSA density, PSA adjusted for transition zone volume, PSA-ACT density, PSA-ACT adjusted for transition zone volume, alkaline phosphatase, PSA-ACT/PSA ratio, and Gleason score in patients with bone metastases were each significantly greater than in those without bone metastases. On receiver operating characteristic analyses, PSA-ACT had the greatest area under the curve (0.88), but the receiver operating characteristic curve demonstrated that the sensitivity and specificity of PSA-ACT were marginally better than those of total PSA at only a few selected cutoff points. At a sensitivity of 93% (2 patients with bone metastasis missed), unnecessary bone scans would have been avoided in 107 and 102 patients using a PSA-ACT cutoff value of 10 ng/mL and total PSA cutoff value of 11.5 ng/mL, respectively. Multivariate logistic regression analysis demonstrated that PSA-ACT and Gleason score were significant independent predictors of bone metastasis., Conclusions: PSA-ACT is as useful as total PSA for identifying patients with a low probability of having bone metastasis. PSA-ACT could replace PSA for predicting negative bone scans in a clinical setting in which PSA-ACT is used for monitoring and screening patients for prostate cancer.

Objectives: To investigate the clinical efficacy of a caudal block compared with periprostatic local anesthesia for transrectal ultrasound-guided multicore prostate needle biopsy., Methods: A total of 100 patients who had undergone initial prostate biopsy using a systematic five-region biopsy by a single operator were investigated. The patients were randomly divided into two groups, with each group receiving a different anesthetic modality before biopsy. Group 1 received periprostatic local anesthesia and group 2 received a caudal block. Both groups received 10 mL 1% lidocaine before biopsy. A 10-point visual analog scale was used to assess patient pain and anxiety. The duration between anesthesia induction and the beginning of the biopsy was measured., Results: Patients who received local anesthesia (group 1) reported significantly less pain immediately after biopsy, with an average score of 1.1 compared with 2.1 in group 2 (caudal block, P = 0.01). Both groups were comparable regarding age, prostate-specific antigen level, digital rectal examination findings, prostate size, number of biopsy cores, level of prebiopsy anxiety, body mass index, and histologic findings. Group 1 required a significantly shorter period of anesthesia (198.5 seconds) than did group 2 (594.5 seconds, P <0.0001). No anesthetic-related side effects occurred in either group., Conclusions: The results of our study have shown that the caudal block provides less effective anesthesia than periprostatic local anesthesia with the same dose of lidocaine for prostate biopsy. We have concluded that local anesthesia is a safe, simple, and rapid method of pain relief during prostate biopsy.

Objectives: To evaluate the association of signal transducer and activator of transcription 3 (STAT3) with the invasiveness and aggressiveness of localized prostate cancer., Methods: Paraffin-embedded specimens from 92 patients with clinically localized prostate cancer who underwent radical prostatectomy without neoadjuvant treatment were analyzed by immunohistochemistry using two antibodies: anti-phospho-specific STAT3 (p-STAT3) antibody, which recognized only activated STAT3, and anti-total STAT3 antibody, which recognized both activated and inactivated STAT3. The patients were separated into one of four groups according to the percentage of the cells with positive nuclear staining using a 0 to 3+ scoring system. The associations between the immunostaining and invasiveness and aggressiveness of clinically localized prostate cancer were analyzed., Results: Pathologically, 66 patients (71.7%) had organ-confined disease. Of the 92 tumors examined, 8, 20, 23, and 41 showed staining patterns for p-STAT3 of 0, 1+, 2+, and 3+, respectively. In addition, 0, 3, 2, and 87 tumors showed staining patterns for STAT3 of 0, 1+, 2+, and 3+, respectively. The staining patterns for p-STAT3 correlated significantly with pathologic stage, Gleason score, and extracapsular extension. No significant correlation was found between p-STAT3 immunostaining and microvascular invasion, perineural invasion, or seminal vesicle invasion. Patients with 3+ immunostaining of p-STAT3 had a significantly greater biochemical prostate-specific antigen failure rate than those with 2+ or less immunostaining., Conclusions: Increased p-STAT3 immunoreactivity showed a highly invasive and aggressive potential in patients with localized prostate cancer treated with radical prostatectomy. This suggests that STAT3 signaling contributes to the invasiveness and aggressiveness of prostate cancer.

Objectives: To assess the value of endorectal magnetic resonance imaging (MRI) for detecting the tumor site, tumor size, and disease extent in patients with localized prostate cancer., Methods: The MRI findings were compared with the histopathologic findings of radical prostatectomy specimens in 95 patients., Results: The histologic examination revealed 186 cancer foci. Endorectal MRI detected 109 cancer foci. The accuracy, sensitivity, and positive predictive value of endorectal MRI for detecting tumor foci greater than 1.0 cm in diameter was 79.8%, 85.3%, and 92.6%, respectively; the corresponding value for detecting tumor foci smaller than 1.0 cm was 24.2%, 26.2%, and 75.9%, respectively. The maximal tumor diameter on endorectal MRI correlated with that shown by histologic examination for tumors larger than 1.0 cm in diameter. However, it did not correlate significantly with the histologic diameter of tumors smaller than 1.0 cm. The accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of endorectal MRI was 74.7%, 57.1%, 82.1%, 57.1%, and 82.1%, respectively, for the detection of extracapsular extension and was 75.8%, 62.1%, 81.8%, 60.0%, and 83.1%, respectively, for local staging., Conclusions: The results of the present study suggest that endorectal MRI is useful for predicting local extension, as well as tumor site and tumor size, of cancer foci greater than 1.0 cm in diameter.

Objectives: To investigate the expression of activator protein-2 (AP-2) in renal cell carcinoma (RCC) by immunohistochemistry. Three AP-2 isoforms alpha (alpha), beta (beta), and gamma (gamma) are known to exhibit a highly homologous structure; however, their functions are considered to be different. AP-2 has been implicated to play a role in carcinogenesis, as well as in the development of the kidney., Methods: The expression of the three AP-2 isoforms, alpha, beta, and gamma, was determined in 58 patients with RCC by immunohistochemistry. Epidermal growth factor receptor and erbB2 expression in 42 patients with RCC was also evaluated to investigate the correlation with AP-2 isoforms., Results: AP-2 isoforms are differentially expressed in normal renal tubules. Of 58 RCC tissue specimens, 15 (25.9%) demonstrated nuclear and cytoplasmic expression of AP-2alpha. Clear cell RCC had a significantly greater rate of AP-2alpha expression than the nonclear subtypes (14 of 41 clear versus 1 of 17 nonclear subtypes). Of the 58 specimens, 8 (13.8%) showed nuclear staining for AP-2beta; notably, localized small cases had a significantly greater rate of nuclear staining for AP-2beta (5 of 13 in pT1a versus 3 of 45 in pT1b or greater). In addition, only 2 cases (3.5%) demonstrated nuclear staining for AP-2gamma. Epidermal growth factor receptor and erbB2 expression did not correlate with expression of the AP-2 isoforms., Conclusions: AP-2 isoforms were differentially expressed in RCC, as well as in the adult normal kidney. AP-2alpha was dominantly expressed in clear cell RCC. AP-2beta expression was observed in the low-stage subtypes of RCC, and this transcription factor may be related to early carcinogenesis.

Objective: The distribution of the two estrogen receptors (ER-alpha, ER-beta) in human prostate tissue have not been fully clarified, so the present study investigated the mRNA expression of the receptors to explain the broad spectrum of estrogen activity in prostate cancer., Materials and Methods: Four human prostate cancer cell lines (LNCap, JCA-1, DU-145 and PC-3) and 24 pairs of untreated prostate cancer tissue and noncancerous tissue from resected prostate glands were subjected to RT-PCR testing., Results: Both LNCap and JCA-1 expressed the mRNA of both receptors, but DU-145 and PC-3 only expressed ER-beta mRNA. In the human prostate tissue samples, 20 of the 24 prostate cancer tissues expressed ER-alpha, and 23 of the 24 expressed ER-beta. Of the 24 noncancer tissues, 14 expressed ER-alpha mRNA and 17 expressed ER-beta mRNA. The incidence of ER-beta mRNA expression between the paired cancer and noncancer tissues was statistically significantly different (p<0.05)., Conclusions: A higher incidence of ER-beta mRNA expression in untreated prostate cancer tissues was observed. Furthermore, the absence of ER-alpha mRNA and the presence of ER-beta mRNA expression in hormone-independent and/or untreated prostate cancer cells leads to a tentative speculation of the mechanism of the hormone refractory feature of prostate cancer.

Objectives: To assess the prognostic significance of alkaline phosphatase (ALP) flare in 114 patients with metastatic prostate cancer treated with endocrine therapy., Methods: ALP flare was defined as a transient increase of the serum ALP level to 120% or more of the pretreatment value after the initiation of endocrine therapy, followed by a subsequent decrease., Results: Univariate analysis demonstrated that patients with poorly differentiated adenocarcinoma, an extent of disease of 2 or greater, a serum ALP level above twice the upper limit of normal, a serum prostate-specific antigen level greater than 100 ng/mL, an ALP flare, and a hemoglobin level of 12 g/dL or less had a significantly lower survival rate than their respective counterparts. Multivariate Cox's proportional hazards model analysis demonstrated that tumor histologic features and ALP flare were significant prognostic indicators for survival., Conclusions: The results of the present study suggest that the tumor histologic features and the ALP flare are significant prognostic indicators for survival in patients with metastatic prostate cancer treated with endocrine therapy.

We report a case of primitive neuroectodermal tumor (PNET) arising from the retroperitoneal cavity. Because of infiltration, the tumor was excised en bloc with the left kidney. Despite postoperative adjuvant chemotherapy and local radiation therapy, the tumor recurred and the patient died of the disease 3 months postoperatively. Serum levels of neuron-specific enolase (NSE) correlated with those of lactate dehydrogenase (LDH), and it is suggested that monitoring NSE and LDH is useful in evaluating tumor recurrence. The clinical course and the treatment of this aggressive tumor are reviewed.