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1.
IJU Case Rep ; 4(2): 69-73, 2021 Mar.
Article in English | MEDLINE | ID: mdl-33718807

ABSTRACT

INTRODUCTION: Treatment-related neuroendocrine prostate cancer, a rare and aggressive malignancy that emerges during androgen deprivation therapy characterized by low serum prostate-specific antigen concentrations, is challenging to monitor because it is associated with predominantly visceral and lytic bone metastases. CASE PRESENTATION: We describe the case of a 69-year-old man with treatment-related neuroendocrine prostate cancer in whom the treatment response could be monitored using whole-body diffusion-weighted magnetic resonance imaging in addition to serum concentrations of neuroendocrine markers. The patient responded well to platinum-based chemotherapy and achieved a complete response, as evidenced by these diagnostic modalities. CONCLUSION: Our case suggests that whole-body diffusion-weighted magnetic resonance imaging is useful in disease management for treatment-related neuroendocrine prostate cancer as well as the potential evaluation of mixed responses and treatment resistance.

2.
Cancer Immunol Immunother ; 69(5): 689-702, 2020 May.
Article in English | MEDLINE | ID: mdl-32030476

ABSTRACT

BACKGROUND: Increased expression of programmed cell death 1 ligand 1 (PD-L1) by tumor cells is thought to be a mechanism through which solid cancers promote immune tolerance. However, the association between PD-L1 expression and the prognosis of upper urinary tract urothelial carcinoma (UTUC) remains unknown. METHODS: We examined immunohistochemical PD-L1 expression and the tumor-infiltrating lymphocyte density (TILD) in 79 patients with UTUC who underwent nephroureterectomy. We classified the tumors into four types based on the combination of PD-L1 expression and TILD, and studied the clinicopathological characteristics of these four tumor types. RESULTS: Elevated expression of PD-L1 by tumor cells and a higher TILD were associated with a worse histological grade, higher pT stage, and higher peripheral blood neutrophil-to-lymphocyte ratio. Elevated expression of PD-L1 by tumor cells, a higher TILD, and type I, III, or IV tumors with elevated expression of either PD-L1 or TILD showed a positive correlation with poorer differentiation and local invasion. These three variables were associated with shorter progression-free survival and overall survival in univariate analysis, but only the latter was an independent determinant according to multivariate analysis. The patients who had type II tumors with lower PD-L1 expression and a lower TILD showed more favorable survival than the other three groups. CONCLUSIONS: These findings suggest that PD-L1 expression and TILs in the tumor microenvironment influence the progression of UTUC. Accordingly, it is important to understand the immunologic characteristics of the tumor microenvironment to develop more effective treatment strategies for this cancer.


Subject(s)
B7-H1 Antigen/metabolism , Carcinoma, Transitional Cell/pathology , Kidney Neoplasms/pathology , Lymphocytes, Tumor-Infiltrating/immunology , Ureteral Neoplasms/pathology , Adult , Aged , Aged, 80 and over , B7-H1 Antigen/immunology , Carcinoma, Transitional Cell/immunology , Carcinoma, Transitional Cell/surgery , Disease Progression , Female , Follow-Up Studies , Humans , Kidney/immunology , Kidney/pathology , Kidney/surgery , Kidney Neoplasms/immunology , Kidney Neoplasms/surgery , Male , Middle Aged , Neoplasm Grading , Nephroureterectomy , Prognosis , Progression-Free Survival , Retrospective Studies , Tumor Microenvironment/immunology , Ureter/immunology , Ureter/pathology , Ureter/surgery , Ureteral Neoplasms/immunology
3.
Int J Clin Oncol ; 25(3): 472-478, 2020 Mar.
Article in English | MEDLINE | ID: mdl-31440861

ABSTRACT

BACKGROUND: Previous studies indicated inverse relationships between body mass index (BMI), diabetes and prostate-specific antigen (PSA) concentration besides an established positive relationship between age and PSA. Other causal relationships between clinical parameters including hypertension, hepatic function, tests, lipid profile and PSA were also suggested. Thus, we incorporated these parameters all together into the analysis to identify possible determinants of PSA concentration to improve the accuracy of PSA tests. METHODS: Associations between PSA and the above-mentioned clinical parameters were examined among 14,486 men who visited our hospital for a routine health checkup, using linear regression analyses. RESULTS: Total of 1403 (9.7%) and 784 (5.4%) men were classified as diabetes and obesity, respectively. After adjusting age, significant PSA reductions were found in diabetic men, especially for men taking antidiabetics. Such association was seen when the diabetic status was represented by hemoglobin A1c (HbA1c) and fasting blood sugar (FBS) levels. That is, PSA levels were significantly reduced in men with higher HbA1c and FBS levels. Obesity was also associated with a reduction in PSA levels. Moreover, PSA levels were significantly decreased with increased ALT levels. CONCLUSIONS: PSA test results should be carefully interpreted especially for men with diabetes and obesity, in whom a substantial reduction in PSA concentration is likely to occur.


Subject(s)
Diabetes Mellitus/blood , Hypertension/blood , Kallikreins/blood , Obesity/blood , Prostate-Specific Antigen/blood , Adult , Aged , Alanine Transaminase/blood , Blood Glucose/analysis , Body Mass Index , Glycated Hemoglobin/analysis , Humans , Lipids/blood , Liver Function Tests , Male , Middle Aged , Regression Analysis
4.
Open Heart ; 5(1): e000666, 2018.
Article in English | MEDLINE | ID: mdl-29344375

ABSTRACT

Objective: Renal cell carcinoma (RCC) is a hypervascular tumour due to high constitutive production of vascular endothelial growth factor (VEGF), which is activated by hypoxia-inducible factor (HIF). Elevated levels of cardiovascular peptides, including brain natriuretic peptide (BNP), have been reported in patients with cancer, regardless of whether they have overt cardiovascular disease. Furthermore, it has been demonstrated that hypoxia stimulates BNP production by an HIF-dependent manner. However, the clinical implications of such cardiovascular peptides in patients with RCC have not been assessed. Methods: In patients with clear cell RCC who underwent nephrectomy, we investigated the relationship between the serum level of BNP or N-terminal pro-BNP (NT-proBNP) and various clinicopathological characteristics, including serum VEGF and expression of BNP and HIF-2 alpha in the primary tumour. Results: Elevated preoperative serum levels of BNP, NT-proBNP and VEGF, as well as increased tumour expression of HIF-2 alpha, were associated with a worse performance status, local invasion, distant metastasis and shorter overall survival. HIF-2 alpha expression showed a positive correlation with the preoperative serum VEGF level, while there was no relation between the serum levels of BNP/NT-proBNP and VEGF or tumour expression of HIF-2 alpha. BNP expression was very low in both tumour tissues and normal kidney tissues. Serum levels of BNP, NT-proBNP and VEGF all decreased significantly after nephrectomy. Conclusions: Our findings suggested that the preoperative serum levels of BNP and NT-proBNP are markers of tumour progression, as well as indicators of subclinical functional and structural myocardial damage in patients with advanced RCC.

5.
Hinyokika Kiyo ; 63(7): 267-270, 2017 Jul.
Article in Japanese | MEDLINE | ID: mdl-28814706

ABSTRACT

A 26-year-old woman presented to our hospital with right costovertebral angle (CVA) pain. Ultrasonographyand computed tomography(CT) scan indicated right hydronephrosis, and MAG3 renogram showed an obstructed pattern in the right kidney. Enhanced CT scan revealed an ureteropelvic junction obstruction (UPJO) with an aberrant vessel. To clarifythe ureteropelvic junction (UPJ) structure in detail, we utilized 3D-CT with retrograde pyelography (RP), which further revealed the true pinhole ureteral stricture of UPJ unaffected bythe aberrant vessel.


Subject(s)
Ureteral Obstruction/diagnostic imaging , Adult , Female , Humans , Imaging, Three-Dimensional , Tomography, X-Ray Computed , Treatment Outcome , Ureteral Obstruction/surgery
6.
BMC Urol ; 17(1): 47, 2017 Jun 23.
Article in English | MEDLINE | ID: mdl-28645325

ABSTRACT

BACKGROUND: Many urologic surgeons refer to biopsy core details for decision making in cases of localized prostate cancer (PCa) to determine whether an extended resection and/or lymph node dissection should be performed. Furthermore, recent reports emphasize the predictive value of prostate-specific antigen density (PSAD) for further risk stratification, not only for low-risk PCa, but also for intermediate- and high-risk PCa. This study focused on these parameters and compared respective predictive impact on oncologic outcomes in Japanese PCa patients. METHODS: Two-hundred and fifty patients with intermediate- and high-risk PCa according to the National Comprehensive Cancer Network (NCCN) classification, that underwent robot-assisted radical prostatectomy at a single institution, and with observation periods of longer than 6 months were enrolled. None of the patients received hormonal treatments including antiandrogens, luteinizing hormone-releasing hormone analogues, or 5-alpha reductase inhibitors preoperatively. PSAD and biopsy core details, including the percentage of positive cores and the maximum percentage of cancer extent in each positive core, were analyzed in association with unfavorable pathologic results of prostatectomy specimens, and further with biochemical recurrence. The cut-off values of potential predictive factors were set through receiver-operating characteristic curve analyses. RESULTS: In the entire cohort, a higher PSAD, the percentage of positive cores, and maximum percentage of cancer extent in each positive core were independently associated with advanced tumor stage ≥ pT3 and an increased index tumor volume > 0.718 ml. NCCN classification showed an association with a tumor stage ≥ pT3 and a Gleason score ≥8, and the attribution of biochemical recurrence was also sustained. In each NCCN risk group, these preoperative factors showed various associations with unfavorable pathological results. In the intermediate-risk group, the percentage of positive cores showed an independent predictive value for biochemical recurrence. In the high-risk group, PSAD showed an independent predictive value. CONCLUSIONS: PSAD and biopsy core details have different performance characteristics for the prediction of oncologic outcomes in each NCCN risk group. Despite the need for further confirmation of the results with a larger cohort and longer observation, these factors are important as preoperative predictors in addition to the NCCN classification for a urologic surgeon to choose a surgical strategy.


Subject(s)
Prostate-Specific Antigen/blood , Prostatectomy/standards , Prostatic Neoplasms/blood , Prostatic Neoplasms/pathology , Robotic Surgical Procedures/standards , Aged , Biopsy, Large-Core Needle/methods , Biopsy, Large-Core Needle/standards , Cohort Studies , Humans , Male , Middle Aged , Predictive Value of Tests , Prostatectomy/methods , Prostatic Neoplasms/surgery , Retrospective Studies , Risk Factors , Robotic Surgical Procedures/methods , Treatment Outcome
7.
Urol Case Rep ; 11: 47-49, 2017 Feb.
Article in English | MEDLINE | ID: mdl-28149748

ABSTRACT

We report a rare case of extravasation of urine, which may be associated with bilateral complete ureteral duplication, vesicoureteral reflux (VUR), and benign prostatic hyperplasia (BPH). A 71-year-old male presented with a complaint of right abdominal pain. An extravasation of urine was noted, and was improved by indwelling urethral catheterization. Transurethral resection of the prostate and the endoscopic subureteral injection of dextanomer/hyaluronic acid were performed for the treatment of BPH and VUR, respectively. The post-surgery recovery was successful.

9.
BMC Cancer ; 15: 1097, 2015.
Article in English | MEDLINE | ID: mdl-25784113

ABSTRACT

BACKGROUND: The relationship between the clinicopathological features and molecular changes associated with standardized uptake value (SUV) determined by Positron emission tomography (PET) with [18F] fluorodeoxyglucose (18F-FDG PET) in human renal cell carcinoma (RCC) has not been elucidated. On the other hand, overactivation of the phosphatidylinositol 3'kinase (PI3K), serine/threonine kinase Akt, and mammalian target of rapamycin (mTOR) pathway has been detected in a variety of human cancers, including RCC. So far, little is known about the relationship between the SUV and these proteins in human RCC. Thus, it is important to study the relevance of SUV with clinicopathological features in human RCCs from a molecular point of view. METHODS: Seventy-seven consecutive patients with RCC who underwent nephrectomy and pretreatment determination of the maximum SUV (SUVmax) by 18F-FDG PET were analyzed. We investigated the relationship between the SUVmax, phosphorylated-Akt (Ser-473) (pAkt(Ser-473)), phosphorylated-Akt (Thr-308) (pAkt(Thr-308), and phosphorylated-S6 ribosomal protein (Ser-235/236) (pS6) protein levels in the primary tumor and various clinicopathological features. RESULTS: The average SUVmax of the primary tumor was 6.9 (1.5 to 40.3). A higher SUVmax was correlated with higher expression of pAkt(Ser-473), pAkt (Thr-308), and pS6 protein in the primary tumor. A higher SUVmax and increased expression of pAkt (Ser-473), pAkt (Thr-308), and pS6 of the primary tumor was associated with less tumor differentiation, a higher pT stage, regional lymph node involvement, microscopic vascular invasion, and distant metastasis, as well as with early relapse following radical nephrectomy in patients who had localized or locally advanced RCC without distant metastasis (cTanyNanyM0) and with shorter overall survival in all patients. CONCLUSIONS: A higher SUVmax on 18F-FDG PET is associated with elevated tumor levels of pAkt and pS6 protein and with aggressive behavior and metastatic potential of RCC, as well as with early relapse following radical nephrectomy and shorter overall survival. These findings suggest that SUVmax may be useful for predicting the biological characteristics of RCC.


Subject(s)
Carcinoma, Renal Cell/diagnostic imaging , Fluorodeoxyglucose F18 , Kidney Neoplasms/diagnostic imaging , Positron-Emission Tomography/methods , Proto-Oncogene Proteins c-akt/metabolism , Radiopharmaceuticals , Ribosomal Protein S6 Kinases/metabolism , Adult , Aged , Aged, 80 and over , Blotting, Western/methods , Carcinoma, Renal Cell/enzymology , Carcinoma, Renal Cell/pathology , Female , Humans , Immunohistochemistry , Kidney Neoplasms/enzymology , Kidney Neoplasms/pathology , Male , Middle Aged , Phosphorylation
10.
Biomed Res Int ; 2014: 396064, 2014.
Article in English | MEDLINE | ID: mdl-25089268

ABSTRACT

To clarify the role of serum soluble T cell regulatory molecules in clear cell renal cell carcinoma (CCRCC), we measured the serum levels of soluble interleukin-2 receptor (sIL-2R), soluble B7-H3 (sB7-H3), and soluble cytotoxic T lymphocyte associated antigen-4 (sCTLA-4) in 70 CCRCC patients and 35 healthy controls. We investigated correlations between the serum levels of these soluble T cell regulatory molecules and the pathological grade, clinical stage, and prognosis of CCRCC. We also assessed the relations among each of these soluble molecules. As a result, the serum level of sIL-2R was significantly higher in CCRCC patients than in healthy controls (P < 0.05). In addition, elevation of serum sIL-2R was significantly correlated with the clinical stage (P < 0.001), and the survival of patients with high sIL-2R levels was shorter than that of patients with low sIL-2R levels (P < 0.05). Furthermore, the serum level of sB7-H3 was also significantly correlated with the clinical stage (P < 0.05), while the sIL-2R and sB7-H3 levels showed a positive correlation with each other (R = 0.550, P < 0.0001). These results indicate that the serum level of sIL-2R reflects tumor progression in CCRCC patients. In addition, the possibility was suggested that the IL-2/IL-2R and B7-H3 pathways may be involved in the progression of CCRCC.


Subject(s)
Adenocarcinoma, Clear Cell/pathology , Carcinoma, Renal Cell/pathology , Gene Expression Regulation, Neoplastic , Liver Neoplasms/pathology , T-Lymphocytes, Regulatory/cytology , Adult , Aged , B7 Antigens/blood , CTLA-4 Antigen/blood , Case-Control Studies , Disease Progression , Female , Humans , Immune System , Interleukin-2/blood , Male , Middle Aged , Prognosis , Receptors, Interleukin-2/blood , Young Adult
11.
BMC Cancer ; 14: 412, 2014 Jun 07.
Article in English | MEDLINE | ID: mdl-24908363

ABSTRACT

BACKGROUND: Activation of Rho, one of the small GTPases, and its major downstream target Rho-kinase (ROCK) promotes the development and metastasis of cancer. We previously showed that elevation of Rho and ROCK expression was associated with tumor invasion, metastasis, and an unfavorable prognosis in patients with urothelial cancer of the bladder or upper urinary tract. METHODS: We investigated the effects of a ROCK inhibitor on the growth, migration, and apoptosis of bladder cancer cells. We also examined phosphorylation of RhoA (RhoA activity) by measuring its GTP-bound active form and assessed the expression of ROCK to explore the underlying molecular mechanisms. RESULTS: Lysophosphatidic acid (LPA) and geranylgeraniol (GGOH) induced an increase of cell proliferation and migration in association with promotion of RhoA activity and upregulation of ROCK expression. The ROCK inhibitor fasudil (HA-1077) suppressed cell proliferation and migration, and also induced apoptosis in a dose-dependent manner. HA-1077 dramatically suppressed the expression of ROCK-I and ROCK-II, but did not affect RhoA activity. CONCLUSIONS: These findings suggest that ROCK could be a potential molecular target for the treatment of urothelial cancer.


Subject(s)
1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine/analogs & derivatives , Apoptosis/drug effects , Cell Movement/drug effects , Protein Kinase Inhibitors/pharmacology , rho-Associated Kinases/antagonists & inhibitors , 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine/pharmacology , Cell Line, Tumor , Cell Proliferation/drug effects , Humans , Immunohistochemistry , Tumor Stem Cell Assay , Urinary Bladder Neoplasms/metabolism , Urologic Neoplasms/metabolism
12.
BMC Urol ; 14: 43, 2014 May 29.
Article in English | MEDLINE | ID: mdl-24886065

ABSTRACT

BACKGROUND: Gleason pattern 3 less often has molecular abnormalities and often behaves indolent. It is controversial whether low grade small foci of prostate cancer (PCa) on biopsy could avoid immediate treatment or not, because substantial cases harbor unfavorable pathologic results on prostatectomy specimens. This study was designed to identify clinical predictors for classical and redefined insignificant cancer on prostatectomy specimens in Japanese men with favorable pathologic features on biopsy. METHODS: Retrospective review of 1040 PCa Japanese patients underwent radical prostatectomy between 2006 and 2013. Of those, 170 patients (16.3%) met the inclusion criteria of clinical stage ≤ cT2a, Gleason score (GS) ≤ 6, up to two positive biopsies, and no more than 50% of cancer involvement in any core. The associations between preoperative data and unfavorable pathologic results of prostatectomy specimens, and oncological outcome were analyzed. The definition of insignificant cancer consisted of pathologic stage ≤ pT2, GS ≤ 6, and an index tumor volume < 0.5 mL (classical) or 1.3 mL (redefined). RESULTS: Pathologic stage ≥ pT3, upgraded GS, index tumor volume ≥ 0.5 mL, and ≥ 1.3 mL were detected in 25 (14.7%), 77 (45.3%), 83 (48.8%), and 53 patients (31.2%), respectively. Less than half of cases had classical (41.2%) and redefined (47.6%) insignificant cancer. The 5-year recurrence-free survival was 86.8%, and the insignificant cancers essentially did not relapse regardless of the surgical margin status. MRI-estimated prostate volume, tumor length on biopsy, prostate-specific antigen density (PSAD), and findings of magnetic resonance imaging were associated with the presence of classical and redefined insignificant cancer. Large prostate volume and short tumor length on biopsy remained as independent predictors in multivariate analysis. CONCLUSIONS: Favorable features of biopsy often are followed by adverse pathologic findings on prostatectomy specimens despite fulfilling the established criteria. The finding that prostate volume is important does not simply mirror many other studies showing PSAD is important, and the clinical criteria for risk assessment before definitive therapy or active surveillance should incorporate these significant factors other than clinical T-staging or PSAD to minimize under-estimation of cancer in Japanese patients with low-risk PCa.


Subject(s)
Biopsy, Large-Core Needle/statistics & numerical data , Organ Size , Prostatectomy/statistics & numerical data , Prostatic Neoplasms/pathology , Prostatic Neoplasms/surgery , Tumor Burden , Adult , Aged , Humans , Japan , Male , Middle Aged , Prognosis , Reproducibility of Results , Risk Assessment , Sensitivity and Specificity
13.
Onco Targets Ther ; 7: 289-95, 2014.
Article in English | MEDLINE | ID: mdl-24627641

ABSTRACT

BACKGROUND: Renal cell carcinoma (RCC) with sarcomatoid differentiation is invasive, refractory to treatment, and has a higher mortality. Therefore, systemic therapy is still challenging, and the curative resection of localized or locally advanced RCC with sarcomatoid differentiation is very important. Axitinib is a potent and selective second-generation vascular endothelial growth factor receptor tyrosine kinase inhibitor with improved safety and tolerability. Axitinib is generally recommended as second-line therapy for advanced RCC because the phase III axitinib versus sorafenib in advanced RCC (AXIS) trial demonstrated that it achieved longer progression-free survival than sorafenib in patients with metastatic RCC after failure of an approved first-line regimen. METHODS: We present a 73-year-old man who had a large (13 cm in diameter) right RCC with sarcomatoid differentiation that directly invaded the duodenum and inferior vena cava. The patient presented with gastrointestinal bleeding, was unable to eat solid food, and had become emaciated. Thus, his classification was poor risk with anemia, hypercalcemia, and poor performance status, according to the Memorial Sloan-Kettering Cancer Center criteria. He seemed unlikely to survive if radical nephrectomy, cavotomy with thrombectomy, and pancreatoduodenectomy were performed. To reduce the tumor burden and potential operative complications, we administered axitinib as first-line neoadjuvant therapy. RESULTS: Six weeks of treatment reduced the tumor burden without causing severe toxicities. Subsequently, radical right nephrectomy, cavotomy with thrombectomy, and pancreatoduodenectomy were performed successfully. The pathological treatment effect of axitinib was grade 2 (two-thirds necrosis). The resected tumor showed a heterogeneous reaction for phosphorylated Akt (Ser-473) by Western blotting and immunohistochemistry, indicating that parts of the tumor were sensitive to axitinib and other parts were not. CONCLUSION: Axitinib might be promising as preoperative or neoadjuvant therapy for locally advanced RCC (>cT3b or >cTanyN1).

14.
Clin Genitourin Cancer ; 12(5): e197-203, 2014 Oct.
Article in English | MEDLINE | ID: mdl-24674784

ABSTRACT

INTRODUCTION/BACKGROUND: Castration-resistant prostate cancer remains a therapeutic challenge, even after establishing the survival benefits of docetaxel chemotherapy. Metronomic chemotherapy stabilizes various cancers through antiangiogenic and immunomodulatory effects. We evaluate the activity of metronomic oral cyclophosphamide chemotherapy in metastatic CRPC patients, and assess predictive factors for clinical outcomes. PATIENTS AND METHODS: Twenty-four patients with metastatic CRPC received an oral cyclophosphamide and dexamethasone regimen. Of those, 11 patients (45.8%) had been exposed and resistant to previous docetaxel chemotherapy. Six patients had refused to receive docetaxel chemotherapy, and 7 patients could not receive the therapy because of deteriorated performance status. All patients had already shown resistance to continuous dexamethasone therapy. Demographic and clinical data were collected prospectively. RESULTS: A total of 16 patients (66.7%) experienced a reduction in PSA levels, and PSA decrease ≥ 50% was observed in 8 patients (33.3%). The median PSA progression-free and overall survival were 5.0 months and 19.0 months, respectively. The favorable PSA decrease had no associations with the progression-free and overall survival, but 7 patients (29.2%) in whom response had exceeded 8 months achieved long overall survival of 28 months in median. None of the patients discontinued therapy because of the presence of toxicities. CONCLUSION: Metronomic cyclophosphamide is an active and well tolerated chemotherapy and can be an option for metastatic CRPC patients. The benefit of this regimen could not always be evaluated according to a favorable PSA decrease; thus, we must identify the predictive factors of response other than known clinical factors.


Subject(s)
Antineoplastic Agents, Alkylating/therapeutic use , Antineoplastic Agents, Hormonal/therapeutic use , Cyclophosphamide/therapeutic use , Dexamethasone/therapeutic use , Prostatic Neoplasms, Castration-Resistant/drug therapy , Aged , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Cyclophosphamide/adverse effects , Dexamethasone/adverse effects , Disease-Free Survival , Docetaxel , Drug Resistance, Neoplasm , Humans , Male , Prospective Studies , Prostate-Specific Antigen/blood , Prostatic Neoplasms, Castration-Resistant/mortality , Prostatic Neoplasms, Castration-Resistant/pathology , Taxoids/therapeutic use , Treatment Outcome
15.
BMC Cancer ; 13: 509, 2013 Oct 30.
Article in English | MEDLINE | ID: mdl-24168110

ABSTRACT

BACKGROUND: The system L amino acid transporter (LAT) has an important role in the transport of various amino acids, and there have been reports about the relation of this system to cancer. Although LATs are highly expressed in the kidneys, little is known about their influence on human renal cancer. METHODS: To clarify the role of LATs in human clear cell renal cell carcinoma (RCC), we investigated the expression of mRNAs for LAT1, LAT2, LAT3, LAT4, and 4F2hc in clear cell RCC tissues. The mRNAs of these five genes were analyzed by the real-time reverse transcription polymerase chain reaction in matched sets of tumor and non-tumor tissues obtained at operation from 82 Japanese patients with clear cell RCC. We also measured phosphorylated S6 ribosomal protein (Ser-235/236) proteins levels in 18 paired tumor and non-tumor tissues of the patients by Western blotting. RESULTS: Expression of LAT1 mRNA was significantly increased in tumor tissue compared with non-tumor tissue, while expression of LAT2 and LAT3 mRNAs was reduced. There was no difference in the expression of LAT4 and 4F2hc mRNAs between tumor and non-tumor tissues. Increased expression of LAT1 mRNA was associated with less differentiated tumors, local invasion, microscopic vascular invasion, and metastasis. Kaplan-Meier survival analysis showed that a higher serum LAT1 mRNA level was associated with a shorter overall survival time. Phosphorylated S6 ribosomal protein levels were associated with metastatic potential. LAT1 mRNA levels positively correlated with phosphorylated S6 ribosomal protein proteins levels in primary tumors. CONCLUSIONS: These findings suggest that LAT1 mRNA is related to the invasive and progressive potential of clear cell RCC.


Subject(s)
Carcinoma, Renal Cell/genetics , Carcinoma, Renal Cell/pathology , Gene Expression , Kidney Neoplasms/genetics , Kidney Neoplasms/pathology , Large Neutral Amino Acid-Transporter 1/genetics , Adult , Aged , Aged, 80 and over , Carcinoma, Renal Cell/mortality , Female , Follow-Up Studies , Humans , Kidney Neoplasms/mortality , Male , Middle Aged , Neoplasm Grading , Neoplasm Invasiveness , Neoplasm Metastasis , Neoplasm Staging , Phosphorylation , Prognosis , RNA, Messenger/genetics , Ribosomal Protein S6/metabolism
16.
Urol Int ; 90(3): 369-72, 2013.
Article in English | MEDLINE | ID: mdl-23076029

ABSTRACT

We present a case of renal metanephric adenoma (MA) mimicking papillary renal cell carcinoma (PRCC) on computed tomography (CT). In the present case, double-phase enhanced CT showed a hypovascular right renal tumor with gradual and prolonged enhancement. The renal tumor was surgically removed. Histological examination of the resected specimen showed renal MA. Although the radiological features of renal MA have been described by some authors, only a few reports have mentioned the pattern of enhancement on multiphase enhanced CT. The pattern of enhancement of a renal tumor is likely to be correlated with its pathological features. Since renal MA is thought to be genetically related to PRCC, these two tumors are likely to demonstrate similar radiological features, so that differentiating between them becomes difficult. In patients with a hypovascular renal mass that shows gradual and prolonged enhancement on multiphase enhanced CT, the diagnosis of renal MA should be considered.


Subject(s)
Adenoma/diagnostic imaging , Carcinoma, Renal Cell/diagnostic imaging , Kidney Neoplasms/diagnostic imaging , Tomography, X-Ray Computed , Adenoma/surgery , Biopsy , Diagnosis, Differential , Female , Humans , Kidney Neoplasms/surgery , Middle Aged , Nephrectomy , Predictive Value of Tests
17.
Clin Auton Res ; 23(2): 67-72, 2013 Apr.
Article in English | MEDLINE | ID: mdl-23099558

ABSTRACT

PURPOSE: The present study aimed to reveal the neurological origin of lower urinary tract symptoms (LUTS) in routine urological examination. METHODS: We retrospectively analyzed 70 cases to identify cases in which the neurologist and/or urologist suspected the relation between neurological diseases and LUTS. The compromised neurological areas were categorized into brain and spinal cord based on the appearance time of LUTS and presence/absence of disease specificity. We classified the lesion site based on the imaging result and the neurologic finding. We compared LUTS appearance time: from LUTS appearance till the first visit to urologist (first visit urologist) and from the aforementioned visit till the neurological diagnosis confirmation (neurological diagnosis). Finally, we conducted a detailed investigation of the surgical cases, as well as those with urodynamic studies (UDS) performed prior to the neurological examination. RESULTS: The neurological diseases involved 31 cases (44 %) of multiple system atrophy, 11 (16 %) of multiple sclerosis, and 4 (6 %) of Parkinson's disease. Associated symptoms comprised gait disturbance (38) and lower limb dysesthesia (20), while no associated symptoms were observed in 13 (19 %). Both the periods proved significantly shorter for spinal cord disease. Urological surgeries were performed in 10 cases (14 %). UDS findings revealed 10 cases of decrease in bladder compliance, and 15 of detrusor underactivity; no normal cases were observed. CONCLUSIONS: Consideration of detailed medical history, enforcement of UDS, and closer cooperation between urologists and neurologists are required to ascertain early and correct diagnosis, and to avoid unnecessary surgery.


Subject(s)
Lower Urinary Tract Symptoms/diagnosis , Lower Urinary Tract Symptoms/etiology , Nervous System Diseases/complications , Nervous System Diseases/diagnosis , Adolescent , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Retrospective Studies , Young Adult
19.
J Magn Reson Imaging ; 31(3): 625-31, 2010 Mar.
Article in English | MEDLINE | ID: mdl-20187206

ABSTRACT

PURPOSE: To evaluate the diagnostic ability of diffusion-weighted imaging (DWI) and dynamic contrast-enhanced imaging (DCEI) in combination with T2-weighted imaging (T2WI) for the detection of prostate cancer using 3 T magnetic resonance imaging (MRI) with a phased-array body coil. MATERIALS AND METHODS: Fifty-three patients with elevated serum levels of prostate-specific antigen (PSA) were evaluated by T2WI, DWI, and DCEI prior to needle biopsy. The obtained data from T2WI alone (protocol A), a combination of T2WI and DWI (protocol B), a combination T2WI and DCEI (protocol C), and a combination of T2WI plus DWI and DCEI (protocol D) were subjected to receiver operating characteristic (ROC) curve analysis. RESULTS: The sensitivity, specificity, accuracy, and area under the ROC curve (Az) for region-based analysis were: 61%, 91%, 84%, and 0.8415, respectively, in protocol A; 76%, 94%, 90%, and 0.8931, respectively, in protocol B; 77%, 93%, 89%, and 0.8655, respectively, in protocol C; and 81%, 96%, 92%, and 0.8968, respectively in protocol D. ROC analysis revealed significant differences between protocols A and B (P = 0.0008) and between protocols A and D (P = 0.0004). CONCLUSION: In patients with elevated PSA levels the combination of T2WI, DWI, DCEI using 3 T MRI may be a reasonable approach for the detection of prostate cancer.


Subject(s)
Algorithms , Gadolinium DTPA , Image Interpretation, Computer-Assisted/methods , Magnetic Resonance Imaging/methods , Prostatic Neoplasms/diagnosis , Subtraction Technique , Aged , Aged, 80 and over , Contrast Media , Humans , Image Enhancement/methods , Male , Middle Aged , Reproducibility of Results , Sensitivity and Specificity
20.
BJU Int ; 105(11): 1519-25, 2010 Jun.
Article in English | MEDLINE | ID: mdl-19912185

ABSTRACT

OBJECTIVE: To investigate the influence of the revised Gleason grading system (GGS, revised at a consensus conference organized by the International Society of Urological Pathology in 2005) on prediction of prognosis for patients with prostate cancer with bone metastasis. PATIENTS AND METHODS: Prostatic needle biopsy specimens from 113 patients with prostate cancer with bone metastasis were scored using the conventional GGS (CGGS), modified global GGS (MGGGS), and modified highest GGS (MHGGS). The patients were divided into two groups (Gleason score < or = 7 and > or = 8) using each grading system. Prostate-specific antigen failure-free survival after hormone therapy (HT) was estimated retrospectively. The Cox proportional hazard method was used for univariate and multivariate analysis. RESULTS: Patients with a Gleason score of < or = 7 had a significantly longer remission than patients with a score of > or = 8 according to each GGS. However, the better prognosis patients were detected more precisely by the CGGS and MGGGS than the MHGGS. Multivariate analysis showed that the CGGS and MGGGS were significant prognostic indicators for the outcome of HT after adjustment for other prognostic factors. CONCLUSIONS: These results suggest that the CGGS and MGGGS are more useful than the MHGGS as prognostic indicators for HT. Further evaluation in larger series is needed to define its clinical usefulness.


Subject(s)
Adenocarcinoma/secondary , Bone Neoplasms/secondary , Prostatic Neoplasms/pathology , Adenocarcinoma/blood , Adult , Aged , Aged, 80 and over , Bone Neoplasms/blood , Disease-Free Survival , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Prognosis , Prostate-Specific Antigen/metabolism , Prostatic Neoplasms/blood
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