So Ushijima

A Comparison of Cooling Methods for Laparoscopic Partial Nephrectomy

OBJECTIVES To evaluate appropriate cooling methods in laparoscopic partial nephrectomy. METHODS Under general anesthesia, 21 porcine kidneys were exposed retroperitoneoscopically. Ice slush (500 g) was put into the retroperitoneal cavity after renal vascular clamping. Renal parenchymal temperature was measured by a thermometer. Seven kidneys were cooled only by ice slush (group I). In seven kidneys, 200 mL of 4 degrees C saline was infused around the kidney 45 minutes after vascular clamping (group II). In seven kidneys, 4 degrees C saline was irrigated continuously through a 5F ureteral catheter, which was inserted into the ureter (group III). RESULTS In group I, 21 minutes after vascular clamping, the lowest temperature achieved was 13.2 degrees C, and at 47 minutes the temperature exceeded 20 degrees C. In group II, the lowest temperature achieved was 13.0 degrees C 23 minutes after vascular clamping, and at 59 minutes the temperature exceeded 20 degrees C. In group III, the lowest temperature of 10.6 degrees C was achieved at 27 minutes, and at 79 minutes the temperature exceeded 20 degrees C. CONCLUSIONS In complicated cases of laparoscopic partial nephrectomy, cooling with both ice slush and ureteral catheter irrigation was thought to be effective. When the renal collecting system is opened, an additional infusion of cooled water may also be effective.

Gene therapy with TRAIL against renal cell carcinoma

Tumor necrosis factor–related apoptosis-inducing ligand (TRAIL) induces apoptosis in cancer cells. However, TRAIL is not toxic against most normal cells. We have accordingly examined by in vivo electroporation whether TRAIL induces apoptosis in renal cell carcinoma. In addition, combination treatment with TRAIL and 5-fluorouracil (5-FU) against renal cell carcinoma was also investigated. The NC65 renal cell carcinoma line was used as a target. pCAGGS TRAIL was injected into the NC65 tumors in the right flanks of severe combined immunodeficient mice. Tumors were pulsed with the CUY21 electroporator. Electroporation was done once on day 0 or thrice on days 0, 2, and 4. Apoptosis was determined by terminal deoxyribonucleotide transferase–mediated nick-end labeling assay. When TRAIL gene therapy using in vivo i.t. electroporation was done once only, the growth of NC65 tumors was not inhibited. However, when TRAIL gene therapy was done thrice, growth suppression of the NC65 tumors was observed. Transfection of the TRAIL gene by in vivo electroporation induced apoptosis in NC65 tumors. When NC65 cells were treated with TRAIL gene therapy in combination with 5-FU, stronger growth suppression was obtained. TRAIL gene therapy did not induce liver dysfunction in severe combined immunodeficient mice. This study shows that TRAIL gene therapy induced growth suppression and apoptosis in NC65 tumors without severe side effects, and that combination treatment of NC65 cells with TRAIL gene therapy and 5-FU resulted in higher antitumor activity. These findings suggest that TRAIL gene therapy and/or 5-FU may be effective against renal cell carcinoma without harmful toxic effects. [Mol Cancer Ther 2006;5(9):2165–71]

Four-Dimensional Ultrasonography for Dynamic Bladder Shape Visualization and Analysis During Voiding

Objective. The purpose of this study was to describe initial applications of 4‐dimensional ultrasonography (4DUS) for visualizing dynamic change in 3‐dimensional (3D) bladder shape as well as for analyzing intravesical volume and diameters during voiding. Methods. In 15 healthy volunteers and 5 patients with lower urinary tract symptoms, 4DUS images of the bladder during voiding were obtained by transabdominal 4DUS and compared with the outcome of uroflowmetry. Changes of intravesical volume as well as diameters in axial, coronal, and sagittal planes were measured and analyzed in comparison with uroflow data. Results. Dynamic 3D visualization of the bladder shape was feasible in all 20 men. Multiplanar display of 4DUS showed dynamic 3D images of the bladder during voiding to be simultaneously visualized in the axial, coronal, and sagittal planes. The change and decrease rate in intravesical volume calculated by 4DUS data had significant correlation with the average flow rate (P = .02) and the maximum flow rate (P = .04), respectively. Among the 3 diameters, the change of coronal diameter was significantly most correlated with change of the intravesical volume (P < .0001). The change in coronal diameter, which was observed in patients with urinary disturbance, had a significant difference compared with those observed in control subjects (P = .01). Conclusions. Monitoring of voiding with 4DUS was feasible in healthy men and patients with lower urinary tract symptoms. Four‐dimensional ultrasonography has the potential to be a novel noninvasive urodynamic modality to visualize dynamically the lower urinary tract during voiding and to improve pathophysiologic understanding of voiding.

Evaluation of autonomic malfunction in idiopathic normal pressure hydrocephalus

ObjectiveThe autonomic nervous system plays an important role in urinary disturbance which is one of the main symptoms of idiopathic normal pressure hydrocephalus (iNPH); thus, the focus of the present study was to identify the autonomic function parameters that would be useful as clinical indicators of iNPH.MethodsThe subjects consisted of 18 iNPH patients (group N) and 31 normal controls (group C). Before and after a lumbar puncture test, they were examined for CVR-R and total heart rate. A power spectral analysis of R–R interval variability of their 24-hour Holter ECGs was also done. High frequency (HF) was an indicator of parasympathetic activity, while the low to high frequency ratio (L/H) was used as an indicator of sympathetic activity. Urinary incontinence was evaluated using the overactive bladder symptom score (OABSS) questionnaire and bladder capacity. Correlations between the above indicators and clinical indicators of iNPH, such as the mini-mental state examination and the Evans index, were examined.ResultsThe HF values (ms2) were 190.3 in group C and 237.2 in group N; the difference was statistically significant. In group N, the HF value after the lumbar puncture test was lower (160.3) than the value before the lumbar puncture test, confirming that the increased parasympathetic state returned to a near normal level after CSF drainage. A significant positive correlation was noted only between the pre-lumbar puncture HF value and the OABSS.ConclusioniNPH is associated with increased parasympathetic activity, and the lumbar puncture test and shunt surgery may correct this autonomic imbalance to near normal levels.

Significant relationship of time-dependent uroflowmetric parameters to lower urinary tract symptoms as measured by the international prostate symptom score

Aims: The aim of the present paper is to elucidate the possible involvement of time‐dependent parameters as obtained by uroflowmetry in the manifestation of lower urinary tract symptoms (LUTS) in elderly patients.

Human testis specific protein: a new member of aldo-keto reductase superfamily.

Human testis specific protein, HTSP, was identified initially by the search of the Expressed Sequence Tag database, followed by the screening of human testis cDNA library. Among various organs examined, the HTSP transcripts were detected only in the testis, not in other reproductive organs such as vas deferens and prostate. No cross-hybridizing signal was detected in the testis of mouse or rat, indicating that this gene is specifically expressed in the human testis. We isolated four isoforms, HTSP1, 2, 3 and 4. Screening of the high throughput genomic sequence database indicated the localization of the HTSP gene in chromosome 10. Thus, HTSP isoforms were generated by alternative splicing of a single gene. HTSP4, the longest gene product, was composed of 307 amino acids and shared 56% identity to mouse vas deferens protein as well as human aldose reductase in amino acid levels. Bacterially expressed recombinant HTSP protein showed small but significant activity towards 9,10-phenanthrenequinone among the putative substrates so far tested. Accordingly, HTSP is a new member of the aldo-keto reductase superfamily with as yet unidentified function.

CNPY2 promoted the proliferation of renal cell carcinoma cells and increased the expression of TP53

Renal cell carcinoma (RCC) is the most common type of kidney cancer. However, the mechanisms underlying the progression of the disease are not well understood. The data in this report suggest that canopy FGF signaling regulator 2 (CNPY2) is a promoter of RCC progression. We found that CNPY2 significantly promoted growth of RCC cells and upregulated TP53 gene expression. Although TP53 is widely known as a tumor suppressor, in RCC TP53 promoted tumor cell growth. A typical p53 target gene, CDKN1A, was upregulated by both p53 and CNPY2 in RCC cells, suggesting that CNPY2 increased the expression level of TP53. Consistent with these results, CNPY2 and TP53 expression levels were positively correlated in RCC patients. These findings suggested that CNPY2 promoted cancer cell growth in RCC through regulating TP53 gene expression.

Androgen suppresses testicular cancer cell growth in vitro and in vivo

Silencing of androgen receptor (AR)-meditated androgen signaling is thought to be associated with the development of testicular germ cell tumors (TGCTs). However, the role of the androgen/AR signal in TGCT development has not been investigated. In this study, we show that the androgen/AR signal suppressed the cell growth of seminomas (SEs), a type of TGCT, in vitro and in vivo. Growth of SE cells was suppressed by DHT treatment and reduction of androgen levels by surgical castration promoted cancer cell growth in an in vivo xenograft model. Tryptophan hydroxylase 1 (TPH1), the rate limit enzyme in serotonin synthesis, was one of the genes which expression was reduced in DHT-treated SE cells. TPH1 was highly expressed in SE cancer tissues compared with adjacent normal tissues. Activation of androgen/AR signaling in SE cells reduced the expression of TPH1 in SE cells, followed by the reduction of serotonin secretion in cell culture supernatant. These results suggested that silencing of androgen/AR signaling may cause initiation and progression of SE through increase in TPH1 gene expression level.

PD40-04 COMMUNITY-BASED PROSTATE CANCER SCREENING IN JAPAN: PREDICTING FACTORS FOR POSITIVE REPEAT BIOPSY.

population. Methods: A total of 50 207 men over 55 years-of-age have participated in a prostate cancer screening program in Otokuni, Kyoto, Japan for 12 years. Transperineal systematic biopsy was carried out in case of positive digital rectal examination (DRE) or positive transrectal ultrasonography (TRUS) or a prostate-specific antigen (PSA) value greater than 10.0 ng/mL. For those with a PSA level from 4.1 to 10.0 ng/mL, and negative DRE and TRUS findings, biopsy was indicated only when PSA density (PSAD) was greater than 0.15. The same indication was applied for the repeat biopsy. Results: A repeat biopsy after an interval of more than 2 years was carried out in 140 patients and was positive in 50 (36%) patients. The PSA value at the diagnosis of cancer declined from the initial value in six (12%) patients. On multivariate logistic regression analysis, PSA velocity (PSAV) as well as PSAD and DRE findings at latest screening were independent predictors for positive repeat-biopsy outcome. The odds ratio (95% confidence intervals) of PSAV >0.48, latest PSAD >0.33 and positive latest DRE were 4.17 (1.05–18.5), 4.15 (1.31–14.0), and 3.62 (1.06–13.2), respectively. A combination of three variables defined as positive if any of these were positive, reduced 31% of unnecessary biopsies while missing 8% of low volume, low grade cancers. Conclusions: A combination of latest PSAD, PSAV and positive DRE at latest screening might help to reduce unnecessary repeat biopsies in high-risk patients with an initial negative biopsy.

MP20-12 PREDICTIVE VALUE OF TUMOR CONTACT LENGTH ON MAGNETIC RESONANCE IMAGING FOR EXTRACAPSULAR EXTENSION OF PROSTATE CANCER

for overall detection rate of PCa and histological analysis of each Likert group (5,4,3), TB, SB and RARP samples according to Gleason score. Results determined diagnostic accuracy of biopsy samples in comparison to definitive histological diagnosis. RESULTS: 67/79 (84.1%) patients had TB positive for PCa, with a second lesion positive in 17/79 cases. Gleason score of TB and SB was equivalent in 29 (36.7%). Gleason score was higher in TB and SB in 15 (19%) and 35 (44%) cases, respectively. TB was benign in 14 patients. Gleason score at biopsy and RARP were equivalent in 49 (52.7%) cases but higher in RARP and biopsy in 10 and 34 cases, respectively. TB was PCa positive in 38/41 (92.7%) Likert 5 lesions. 2/3 remaining patients had PCa positive SB in an identical region to TB. 21/ 27 (77.8%) Likert 4 lesions had TB positive PCa, 3/6 remaining cases had PCa positive SB in an identical region to TB. TB was positive in 9/ 11 (81.8%) of Likert 3 lesions with SB negative in the remaining 2 patients. The correlation between mpMRI-TPFB-RARP was positive for 97.6% Likert 5, 88.9% Likert 4 and 85.7% Likert 3 lesions. mpMRI identified a suspicious lesion confirmed on RARP in 74 patients (93.7%). 2/5 patients with a negative correlation had a second MRI lesion that corresponded to RARP. CONCLUSIONS: The results of our analysis demonstrate the accuracy of mpMRI and the reliability of TB taken during TPFB in confirming PCa when compared to SB and definitive histological diagnosis.