Impact of Sulfatase-2 on cancer progression and prognosis in patients with renal cell carcinoma.

Heparan sulfate-specific endosulfatase-2 (SULF-2) can modulate the signaling of heparan sulfate proteoglycan-binding proteins. The involvement of SULF-2 in cancer growth varies by cancer type. The roles of SULF-2 expression in the progression and prognosis of renal cell carcinomas (RCC) have not yet been fully clarified. In the present study, the expression levels of SULF-2 mRNA and protein in 49 clinical RCC samples were determined by RT-PCR and immunostaining. The existence of RCC with higher SULF-2 expression and lower SULF-2 expression compared to the adjacent normal kidney tissues was suggested. High SULF-2 expression was correlated with an early clinical stage and less invasive pathological factors. Low SULF-2 expression was correlated with an advanced stage and higher invasive factors. Three-year cancer-specific survival (CSS) for high SULF-2 RCC and low SULF-2 RCC were 100% and 71.4%, respectively (log-rank P = 0.0019), with a significantly shorter CSS observed in low SULF-2 RCC patients. The influence of SULF-2 expression level on Wnt/VEGF/FGF signaling, cell viability and invasive properties was examined in three RCC cell lines, Caki-2, ACHN and 786-O, using a SULF-2 suppression model involving siRNA or a SULF-2 overexpression model involving a plasmid vector. High SULF-2 expression enhanced Wnt signaling and Wnt-induced cell viability, but not cell invasion. In contrast, low levels of SULF-2 expression significantly enhanced both cell invasion and viability through the activation of VEGF/FGF pathways. RCC with lower SULF-2 expression might have a higher potential for cell invasion and proliferation, leading to a poorer prognosis via the activation of VEGF and/or FGF signaling.

The presence of antibodies against the AD2 epitope of cytomegalovirus glycoprotein B is associated with acute rejection after renal transplantation.

The aim of this study was to evaluate the association between antibodies against cytomegalovirus (CMV) glycoprotein B (gB) and acute rejection after transplantation. Seventy-seven consecutive renal transplant recipients in a D + /R+ setting were studied. Biopsy-proven rejection occurred in 35% of the recipients. Among these recipients, 85% had antibodies against CMV gB. The rate of acute rejection was significantly higher in recipients with antibodies against gB than in those without them. Antibodies against gB can be a useful predictor of acute rejection in renal transplant recipients in a D + /R+ setting.

New classification for men with lower urinary tract symptoms: cluster analysis using the International Prostate Symptom Score.

SUBJECTS AND METHODS: • Secondary analysis of anonymous data from 10,434 patients enrolled in a postmarketing surveillance study of tamsulosin in Japan was performed. Data were prospectively collected through the central register from men diagnosed with LUTS in 1100 medical institutions between October 2004 and March 2005. • Those who had received an α1-adrenoceptor antagonist within 1 week before the initial visit were excluded. • The survey items were International Prostate Symptom Score (IPSS), quality of life (QOL) score, and patient characteristics including age, bodyweight, body mass index, and LUTS-related comorbid conditions. • Data on IPSS items were used in a hierarchical cluster analysis (Ward's method). RESULTS: • Of 10,434 men with LUTS, 9910 were included in the analysis after 5% data trimming (524 patients). Five symptom clusters were identified and the symptom types of each cluster were examined. • The largest cluster (27%) consisted of patients with multiple severe symptoms, i.e. complaining of six or more symptoms with a mean score ≥2.8. In contrast, the second smallest cluster (13%) consisted of patients with minimal symptoms, i.e. complaining of essentially one or two symptom with a mean score ≤2.1. • The other three clusters were labelled based on their dominant symptoms. The clusters were weak stream (27%), storage symptoms (21%) and voiding symptoms (12%). • The storage symptoms group was older, and had more comorbidities. • The distribution of the QOL score was different among the clusters, and the percentage of patients who were very dissatisfied was highest in the multiple severe symptoms group and lowest in the minimal symptoms group. CONCLUSIONS: • Cluster analysis using the IPSS showed that men with LUTS can be classified into five characteristic symptom groups. • A new approach to symptom-based classification may be useful to elucidate the pathology of male LUTS and individualize the therapeutic strategy for affected patients, but further studies are needed.

Long-term administration of prazosin improves bladder storage function: results from a study in spontaneously hypertensive rats.

OBJECTIVES: To investigate the effects of long-term administration of the α(1) -adrenoceptor antagonist prazosin on afferent inputs from the lower urinary tract (LUT). METHODS: Twenty female spontaneously hypertensive rats (SHR) were randomized to receive a 4-week course of prazosin (0.12 mg/kg per day) or vehicle; 10 female Wistar-Kyoto (WKY) rats were given vehicle. Prazosin or vehicle was administered via an osmotic pump. The effect of prazosin on urodynamic parameters was determined by continuous cystometry in conscious animals. After cystometry, rats were killed and c-fos expression in the dorsal horn of the L6 spinal cord was measured by immunohistochemistry. RESULTS: The bladder contraction interval was significantly shorter in untreated SHR compared with WKY rats (2.36 ± 0 vs 4.27 ± 0.12 min, respectively; P < 0.05) and cystometric capacity was decreased significantly in SHR compared with WKY rats. L6 spinal cord c-Fos expression was also significantly greater in SHR than WKY rats. The administration of prazosin significantly increased the micturition interval (4.07 ± 0.58 min; P < 0.05) and bladder capacity, but it did not affect micturition pressure. In SHR, the number of c-Fos-positive neurons was significantly lower following the administration of prazosin compared with vehicle. CONCLUSIONS: Increased afferent input from the LUT may induce an increase in urinary frequency in SHR. Furthermore, long-term administration of prazosin can exert inhibitory effects on afferent pathways from the LUT during the storage phase. Reductions of afferent input can result in increased bladder capacity and increased micturition interval.

Development of a new compact intraoperative magnetic resonance imaging system: concept and initial experience.

BACKGROUND: Magnetic resonance imaging (MRI) during surgery has been shown to improve surgical outcomes, but the current intraoperative MRI systems are too large to install in standard operating suites. Although 1 compact system is available, its imaging quality is not ideal. OBJECTIVE: We developed a new compact intraoperative MRI system and evaluated its use for safety and efficacy. METHODS: This new system has a magnetic gantry: a permanent magnet of 0.23 T and an interpolar distance of 32 cm. The gantry system weighs 2.8 tons and the 5-G line is within the circle of 2.6 m. We created a new field-of-view head coil and a canopy-style radiofrequency shield for this system. A clinical trial was initiated, and the system has been used in 44 patients. RESULTS: This system is significantly smaller than previous intraoperative MRI systems. High-quality T2 images could discriminate tumor from normal brain tissue and identify anatomic landmarks for accurate surgery. The average imaging time was 45.5 minutes, and no clinical complications or MRI system failures occurred. Floating organisms or particles were minimal (1/200 L maximum). CONCLUSION: This intraoperative, compact, low-magnetic-field MRI system can be installed in standard operating suites to provide relatively high-quality images without sacrificing safety. We believe that such a system facilitates the introduction of the intraoperative MRI.

Does body habitus of patients affect operative difficulty during retroperitoneal laparoscopic radical nephrectomy?

BACKGROUND AND PURPOSE: Because of the limited working space available during retroperitoneal laparoscopic radical nephrectomy (LRN), the body habitus of the patient is likely to affect the risk of operative difficulties. This study sought to determine whether anthropometric measurements based on CT and abdominal radiography could be used to predict operative difficulties during retroperitoneal LRN. PATIENTS AND METHODS: Between August 2004 and January 2012, 96 consecutive patients with preoperative CT and abdominal radiography examinations underwent retroperitoneal LRN for a T(1) or T(2) stage renal tumor at our institution. The association between anthropometric measurements and demographics of patients and operative duration, estimated blood loss (EBL), and perioperative complications were retrospectively analyzed. Multivariate analysis was performed, and P<0.05 was considered significant. RESULTS: Anterior perirenal fat distance (P=0.016) and distance from the 12th rib to the iliac crest (P=0.038) were independently associated with operative duration. Only anterior perirenal fat distance (P=0.001) was independently associated with EBL. No intraoperative complications and reoperations occurred. The occurrence or severity of postoperative complications was not significantly associated with anthropometric measurements. Body mass index ≥25.0 kg/m(2) was not significantly associated with operative difficulties. CONCLUSION: The anterior perirenal fat distance and the distance from the 12th rib to the iliac crest can be used to predict operative difficulties during retroperitoneal LRN.

Humanised antihuman IL-6R antibody with interferon inhibits renal cell carcinoma cell growth in vitro and in vivo through suppressed SOCS3 expression.

Interleukin-6 (IL-6), one of the proinflammatory cytokines, is considered to be one of the factors associated with poor prognosis of patients with renal cell carcinoma (RCC). Suppressor of cytokine signalling-3 (SOCS3) is rapidly up-regulated by IL-6 and a negative regulator of cytokine signalling. SOCS3 not only suppresses cytokine-mediated JAK/STAT signalling, but also sustains MAPK pathways. In our study, among the RCC cell lines, IL-6 mRNA expression was the highest in the 786-O cells, which also showed the highest level of SOCS3 mRNA expression under the condition of interferon stimulation. In contrast, ACHN cells had the lowest expression of both IL-6 and SOCS3 mRNA under the same condition. Our study is undertaken to evaluate the effect of humanised antihuman IL-6 receptor (IL-6R) antibody, which completely neutralises IL-6 activity, in RCC cell proliferation and its effect on signalling pathways. IL-6R antibody, tocilizumab, significantly suppressed cell proliferation in 786-O cells with interferon stimulation. Western blot analysis revealed that the tocilizumab enhanced the interferon-induced phosphorylation of STAT1 and inhibited SOCS3 expression and the phosphorylation of both STAT3 and ERK. In contrast, the IL-6 inhibited STAT1 phosphorylation, enhanced STAT3 phosphorylation and accelerated cell proliferation in ACHN cells. The in vivo effects of combination therapy with tocilizumab and interferon showed significant suppression of 786-O tumour growth in a xenograft model. Morphological observation of the tumours revealed the apoptosis, invasion of inflammatory cells and fibrosis. These findings suggest that combination therapy using an antihuman IL-6R antibody with interferon may represent a novel therapeutic approach for the treatment of RCC.

A giant prostatic hyperplasia treated by open surgery.

We report a rare case of giant prostatic hyperplasia treated by open surgery. A 70-year-old man was suffering from macrohematuria. Computed tomography revealed a markedly enlarged prostate measuring 580 mL. The serum prostate-specific antigen level was 9.430 ng/mL. Prostatic biopsy showed benign prostatic hyperplasia. We perfomed retropubic open prostatectomy, since macrohematuria continued and he was also suffering from lower urinary tract symptoms. The adenoma was completely enucleated in one piece. The removed specimen was 13 × 11 × 6 cm in size and weighed 475 g. Histological examination also demonstrated prostatic fibromuscular hyperplasia. This is the 15th-heaviest adenoma ever reported in English-language journals. Transurethral surgical techniques or other minimally invasive approaches are performed for patients with small to medium-sized prostates. However, open surgery is recommended for markedly enlarged prostatic hyperplasia.

Laparoscopic nephrectomy, ex vivo angioplasty, and renal autotransplant for a renal artery aneurysm: a case report.

We describe in this report the case of a renal aneurysm in a 42-year-old woman. The aneurysm measured 27 mm in diameter, and was sited at the first bifurcation of the renal artery. We performed laparoscopic nephrectomy, ex vivo angioplasty and renal autotransplant to avoid ischemic damage to the kidney during reconstruction. The patient recovered and was discharged from the hospital without any complications. Hence, we suggest these treatments can be effectively done in patients with complex renal aneurysms.

Does periprostatic local anesthesia for prostate biopsy affect the operative difficulty of open radical prostatectomy? A prospective randomized trial.

OBJECTIVES: Periprostatic local anesthesia for transrectal ultrasound (TRUS)-guided prostate biopsy requires additional needle punctures and injection of local anesthetics into the periprostatic area. This study sought to determine the influence of periprostatic local anesthesia on the surgical difficulty of open radical prostatectomy (RP). PATIENTS AND METHODS: A total of 241 consecutive patients who underwent TRUS-guided prostate needle biopsy were randomized to receive either periprostatic nerve block (Anesthesia group; n=120) or no anesthesia (Control group; n=121). After diagnosing localized prostate cancer, patients who underwent open RP without neoadjuvant androgen deprivation therapy were evaluated as to whether perioperative nerve block affected operative duration, estimated blood loss (EBL), positive margin rate or complications. RESULTS: Twenty-one patients in the Anesthesia group and 19 patients in the Control group were investigated in the current study. In assessing the patients who underwent open RP with or without periprostatic nerve block, no significant differences in operative duration, EBL, positive margin rate or complications were seen between groups. CONCLUSION: Periprostatic nerve block does not appear to affect perioperative outcomes after open RP.

The Association between Severity of Atherosclerosis and Lower Urinary Tract Function in Male Patients with Lower Urinary Tract Symptoms.

OBJECTIVES: The present study was undertaken to investigate the association between the severity of atherosclerosis and lower urinary tract function in male patients with lower urinary tract symptoms. METHODS: Male patients with lower urinary tract symptoms were examined with routine investigation. The severity of atherosclerosis was assessed by ultrasound examination of carotid artery. Patients were divided into two groups: control group and atherosclerosis group. The voiding function and storage function were compared between the two groups. RESULTS: A total of 50 men (69.9 ± 9.1 years [mean ± standard deviation]) entered the study. There was no significant difference in age distribution (control group: 68.7 ± 7.6 years; atherosclerosis group: 72.5 ± 9.7 years) and prostate volume (control group: 26.5 ± 17.3 mL; atherosclerosis group: 22.2 ± 11.0 mL) between the two groups. In the voiding parameters, maximum flow rate in the atherosclerosis group (13.4 ± 5.5 mL/s, P < 0.05) was significantly lower than that in the control group (16.7 ± 7.7 mL/s). Postvoid residual urine volume showed no significant difference between the two groups. In the storage parameters, voided volume was significantly reduced in the atherosclerosis group (161.8 ± 46 mL, P < 0.05), as compared to control group (201.1 ± 78 mL). Moreover, daytime frequency was 7.13 ± 3.02 times in the control group, and significantly higher in the atherosclerosis group (8.75 ± 2.50 times, P < 0.05). CONCLUSION: Development of atherosclerosis impairs both voiding and storage function independently of age, suggesting atherosclerosis leads to lower urinary dysfunction.