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In the present study, the association between clinicopathological parameters and α-actinin-4 (ACTN4) expression in bladder cancer specimens was evaluated, and the functional role of ACTN4 in bladder cancer cells was investigated. Immunohistochemistry using anti-ACTN4 antibody was performed in bladder cancer specimens (53 superficial and 42 muscle-invasive cases) from 95 patients who underwent radical cystectomy (n=46) or transurethral resection (TUR) only (n=49). We divided the levels of ACTN4 expression into 2 groups (low or high) by comparing the staining intensity in each specimen with that of the vascular endothelial cells in the same specimen, and we evaluated the correlations between these levels and pathological parameters, recurrence and prognosis. We also investigated the effects of ACTN4 suppression by siRNA on the invasive ability and proliferation of T24 and KU19-19 cells. High ACTN4 expression was significantly associated with higher tumor grade and higher pT stage. In patients with superficial bladder cancer treated only by TUR, the rate of intravesical recurrence did not differ significantly between patients with high ACTN4 expression and patients with low ACTN4 expression. In patients who had muscle‑invasive tumors and underwent radical cystectomy, high ACTN4 expression was associated with neither recurrence nor poor prognosis. Nonetheless, high ACTN4 expression was shown by a large percentage (81%) of patients with muscle-invasive bladder cancer and by a small percentage (17%) of patients with superficial bladder cancer. Furthermore, the leading edges of the invasive bladder cancer showed increased ACTN4 expression. ACTN4 suppression significantly reduced the number of invading bladder cancer cells but unexpectedly increased the proliferation of bladder cancer cells. ACTN4 suppression increased the phosphorylation of ERKs but not AKT or STAT3, suggesting that the increased proliferation due to ACTN4 suppression was mediated in part by the ERK pathway. ACTN4 expression may suppress the proliferation of bladder cancer cells and may produce conditions which facilitate cancer cell invasion.

Objectives Salvage urethroplasty after failed repair of traumatic urethral injury is a urological challenge, and we herein describe our experience with it. Methods From October 2010 to January 2012, five patients underwent salvage repair of failed urethroplasties for traumatic urethral injuries: three bulbar straddle injuries and two pelvic fracture urethral injuries. One of the three failed urethroplasties for bulbar straddle injuries was a stricture excision and primary anastomosis, and its failure was due to periurethral abscess formation. Another was an augmented anastomotic urethroplasty using buccal mucosa, and its failure was due to periurethral abscess formation. The third was a tube graft urethroplasty using buccal mucosa, and its failure was due to a stricture at the anastomotic site. Two failed urethroplasties for pelvic fracture urethral injuries were perineal anastomotic repairs combined with corporal separation and inferior pubectomy, and the failures of both were due to ischemic bulbar necrosis. The urethral gap lengths estimated from urethrograms ranged from 12 to 45 mm (mean = 26 mm). Results Urethroplasties in all patients with bulbar straddle injuries were salvaged by stricture excision and primary anastomosis with corporal separation, and urethroplasties in both patients with pelvic fracture urethral injuries were salvaged by abdominal transpubic perineal urethroplasty. Although the patients who underwent transpubic urethroplasty had transient pelvic girdle pain, no severe complications were observed. All patients were for 10 to 25 months postoperatively (mean = 16 months) able to void satisfactorily without additional treatment. Conclusions Failed urethroplasties for traumatic urethral injuries can be salvaged with a second reconstruction surgery. The procedure of choice for this salvage is anastomotic urethroplasty with techniques for tension-free anastomosis.

Introduction: Glucose-regulated protein 78 (GRP78), a chaperone for newly formed proteins during folding and glycosylation, is associated with resistance to apoptosis in some forms of cancer. We assessed GRP78 expression and its correlation with clinicopathological parameters and survival. Patients and Methods: Immunohistochemistry was performed using formalin-fixed, paraffin-embedded specimens: 128 primary renal cell carcinoma (RCC) specimens (120 conventional and 8 other cell types) and 9 metastatic specimens. GRP78 positivity was determined based on intensity of staining and percentage of cells stained. Correlation of GRP78 positivity with clinicopathological parameters including patients’ survival was evaluated. Results: A statistically significant association was found between GRP78 positivity and higher tumor grade (G3; p = 0.0002), lymphovascular invasion (positive; p Conclusions: There was a significant relationship between GRP78 expression levels and aggressiveness of RCC. Increased expression of GRP78 might be a useful parameter to predict shortened survival in patients with RCC.

A 73-year-old male patient with hypertension and hyperglycemia was referred to our hospital because of a diagnosis regarding his left adrenal tumor. Because the levels of urinary metanephrine and normetanephrine were elevated, and (131) I-MIBG scintigraphy showed intense uptake in the adrenal tumor, the tumor was diagnosed as a pheochromocytoma. An adrenalectomy was carried out. Severe polyuria, which was accompanied by a rapid decrease in central venous pressure, started 1 hour after the operation. Urine output of more than 8000 mL/day continued until the 16th postoperative day. Plasma antidiuretic hormone (ADH) levels were within the normal range. Plasma human atrial natriuretic peptide (hANP) and brain natriuretic peptide (BNP) were elevated postoperatively, and the elevation of these peptides was one possible cause for the severe polyuria. Because ADH levels in the tumor fluid were not elevated, the tumor was not an ADH-secreting tumor. Urinary β2-microglobulin was significantly elevated after the operation, thus suggesting that renal tubule dysfunction might also have been involved in the polyuria. However, the mechanism of polyuria after the resection of adrenal pheochromocytoma is not fully understood. Polyuria after the resection of adrenal pheochromocytoma is extremely rare, and the present subject is the second case to date.

We report a rare case of primary amelanotic malignant melanoma of the female urethra. A 58-year-old female with complaint of nodule on the external urethral meatus was referred to our hospital. Pathological diagnosis of the biopsy specimen from the nodule was malignant melanoma. Computed tomography of the chest and abdomen as well as bone scan showed no evidence of metastasis. Sentinel biopsy from the inguinal lymph nodes revealed no metastasis. Thereafter, the patient underwent radical urethrectomy, whose limits of resection were the bulbocavernosal muscles bilaterally, the arch of the pubic symphysis anteriorly, the anterior vaginal wall posteriorly, and the urethra up to the level of the bladder neck superiorly. The histopathological diagnosis was amelanotic malignant melanoma of the urethra. The patient had received six cycles of DAV-Feron (dacarbazine, nimustine, vincristine, and interferon-beta) in an adjuvant setting, and there is no sign of recurrence 25 months after operation.

The human Sept4/Bradeion GTPase (56Kda) is specifically expressed in colorectal cancer, malignant melanoma, prostate cancer and other urologic cancers such as renal cell carcinoma and bladder cancer. Significance of Bradeion is that, 1) 'all or none' expression, 2) no genetic alterations among patients, and 3) strong tissue-and cell type- specificity. This character satisfies the desired criteria as a target to monitor and control cancer. With the advent of current technology development in nano-scale, we have succeeded to develop the effective serum test for early diagnosis of cancer. Fluorescence correlation spectroscopy (FCS) can directly and quickly analyse protein-protein binding in a sample solution by reflecting the molecular weight of the labeled molecules. We present a novel and successful diagnostic methods by the quantitative detection of Sept4/Bradeion � the patients' serum using monoclonal antibodies. The resulting diagnostic efficacy was as follows; 100% (colorectal cancer), 89.0 % (prostate cancer), 92.3 % (renal cell carcinoma), and 89.0 % (bladder cancer). More importantly, the increased Bradeion titers decreased to the normal level after one week (polypectomy with colonoscope) to 3 weeks after surgical detection of the cancer.

A 62-year-old woman presented with right flank pain, and computed tomography (CT) showed bilateral adrenal tumors (right, 8 cm; left, 4 cm). There were no abnormal findings on physical examination, and adrenal hormone levels in serum and urine were within normal limits. Radiological studies showed a right adrenal tumor with intratumoral hemorrhage, a cystic tumor in the left adrenal gland, and no sign of distant metastasis. Because laboratory tests showed normal levels of adrenal hormones, we considered the tumors to be nonfunctioning adrenal tumors. The right adrenal tumor was surgically removed because it was thought to be malignant, and histological examination revealed that it was a leiomyosarcoma. Postoperative CT showed a pleural metastasis in the right chest wall. The patient received combination chemotherapy with cyclophosphamide, vincristine, adriamycin, and dacarbazine. The metastasis was also treated with radiofrequency ablation (RFA). Because the left adrenal tumor grew rapidly despite two courses of the chemotherapy, it too was surgically removed. After the operation, metastasis in the right iliac bone was treated with RFA and radiotherapy. Positron emission tomography detected bilateral femoral metastases, and these were treated with radiotherapy in combination with a low dose of cisplatin. A liver metastasis and a small metastasis in the left kidney were treated with RFA and a metastasis in the pancreatic tail was removed surgically. Sixteen months after the right adrenalectomy, the patient died due to systemic spread of the disease. Multiple local treatments including RFA, radiotherapy, and resection were effective for the local control of metastatic lesions of adrenal leiomyosarcoma.

Objectives To investigate the mechanism of gefitinib resistance in renal cell carcinoma (RCC) cells. Although epidermal growth factor receptor (EGFR) is frequently overexpressed in RCC, gefitinib, a tyrosine kinase inhibitor of EGFR, has only a limited antitumor effect on RCC. Methods The effects of gefitinib on the activation status of EGFR and kinases downstream in its signaling cascade were examined in three gefitinib-resistant RCC cell lines: SKRC-44, KU20-01, and 786-O. The changes in signaling cascades and cell survival that were induced by gefitinib in combination with either the phosphatidylinositol 3-kinase inhibitor LY294002 or the knockdown of Akt expression by transient transfection with Akt small interfering RNA were examined in 786-O cells. Results Gefitinib alone did not significantly reduce cell viability in any of the examined cell lines. Although in each line, the phosphorylation of EGFR and extracellular signal-regulated kinase was inhibited by 0.1 μM gefitinib, the phosphorylation of Akt was constitutive and was not inhibited by even 10 μM gefitinib. In 786-O cells, the phosphorylation of both extracellular signal-regulated kinase and Akt was inhibited by gefitinib used in combination with either LY294002 or the knockdown of Akt expression, and the viability of 786-O cells was suppressed significantly by gefitinib used in combination with LY294002 (P Conclusions Constitutively activated Akt might prevent the antitumor efficacy of gefitinib in renal cell carcinoma, and the therapeutic effectiveness of gefitinib might be improved by inhibiting Akt activation.

Objective: Renal cell carcinoma (RCC) with a high-nucleolar-grade component is considered to be an aggressive type of tumor. In the present study, we evaluated the impact of the presence of the worst-nucleolar-grade component and also tried to determine predictors for recurrence and prognosis in patients with the worst grade component. Methods: We evaluated 314 patients with RCC. A three-graded system was used for nucleolar grading, the patients were classified into four groups according to the presence of the worst nucleolar grade (Grade 3) and the occupancy of each grade, and clinicopathological factors and clinical outcomes were compared. In patients of Grade 3 components (Groups 1 and 2), factors influencing on prognosis and recurrence were evaluated by multivariate analysis. Results: There was no significant difference in clinicopathological factors between Group 1 (with Grade 3-dominant tumors) and Group 2 (with tumors in which Grade 1 or 2 was dominant and there were Grade 3 components). Neither did cause-specific survival or recurrence-free survival differ significantly between those two groups. In multivariate analysis, only distant metastasis was an independent predictor for prognosis in all patients with Grade 3 components. Moreover, an elevated C-reactive protein (CRP) level (≥1 mg/dl) was the only independent predictor of recurrence in NOMO patients. Conclusions: Regardless of dominancy, the presence of the worst grade component has a significant clinical impact in RCC patients. NOMO patients whose RCC has worst-grade components but whose CRP levels are < 1 are expected to have longer recurrence-free intervals and to survive longer than those whose CRP levels are higher.

Fatty acid synthase is a key enzyme in the de novo biosynthesis of fatty acids. Increased fatty acid synthase expression and its association with tumor aggressiveness and poor prognosis have been demonstrated in various human malignant tumors. We investigated fatty acid synthase expression in patients with renal cell carcinoma and its impact on clinicopathological parameters.Fatty acid synthase expression in 120 patients with renal cancer was examined by immunohistochemistry. The relationship between fatty acid synthase expression status and various clinicopathological parameters was analyzed. Survival analysis was performed using the log rank test and a Cox multivariate hazard model.Of 120 tumors 18 (15%) showed positive fatty acid synthase expression, which was significantly associated with advanced pathological T stage (pT3-4, p = 0.0009), regional lymph node metastasis (p = 0.0429), distant metastasis (p = 0.0042), higher histological grade (G3, p = 0.0017) and microvascular invasion (p = 0.0357). Patients with positive fatty acid synthase expression had significantly shorter cancer specific survival than those with negative FAS expression (p0.0001). Multivariate Cox proportional hazards model analysis demonstrated that positive fatty acid synthase expression was an independent predictor of shortened cancer specific survival (p = 0.0363, HR 3.736).Increased FAS expression could be an indicator of tumor aggressiveness and poor prognosis of renal cell carcinoma. Patients with fatty acid synthase positive tumors should be followed closely and carefully, and adjuvant therapy should be considered.

We developed and evaluated a photoacid generator (PAG)-bonded resist, a chemical amplified (CA) resist for decreasing line edge roughness (LER) and increasing sensitivity in extreme ultraviolet lithography (EUVL) and electron beam (EB) lithography. We investigated many samples to find an effective for the PAG-bonded resist. Under EB exposure, the LERs and resolutions of the PAG-bonded resist and PAG-blended resist which uses the same PAG and base polymer were compared. It was confirmed that the LER and resolution of the PAG-bonded resist are better than those of the PAG-blended resist. An LER of 3.5 nm in 75 nm line-and-space (L/S) and a resolution of 25 nm space were achieved. Under EUV exposure, a sensitivity of 5.0 mJ/cm2 was achieved.

OBJECTIVES We retrospectively review patients treated for renal cell carcinoma at 19 institutes in collaboration with the Japanese Society of Renal Cancer, to clarify the risk factors for ipsilateral adrenal involvement (IADI). METHODS The clinicopathologic factors of the 30 patients with IADI were compared with those of the 926 control patients without IADI, and independent predictors for IADI were identified by multivariate analysis. RESULTS Preoperative computed tomography (CT) could detect 83.3% of the instances of synchronous ipsilateral adrenal metastasis. Patients with IADI had significantly larger primary tumors, higher pT stages and histologic grades, and higher percentages of upper pole involvement, microvascular invasion, spindle-cell-type tumors, lymph node metastasis (LNM), and distant metastasis (DM) outside the ipsilateral adrenal gland (IAd) than in control patients. Multivariate logistic regression analysis of clinical factors revealed that tumor size greater than 5.5 cm, pT stage of 3 or higher, LNM, and DM outside IAd, but not upper pole involvement, were significant predictors of IADI. CONCLUSIONS Tumor size greater than 5.5 cm, clinical T stage of 3 or higher (tumor for which pT stage of 3 or higher is suspected), LNM, and DM outside IAd seemed to be important preoperative indicators of IADI. These factors and CT findings would be useful preoperative indicators for ipsilateral adrenalectomy. Moreover, patients with renal cell carcinoma who have normal adrenal on CT, have a T1 tumor extending less than 5.5 cm, and have neither LNM nor DM are good candidates for adrenal-sparing nephrectomy.

OBJECTIVES Because lymphangiogenesis and lymphatic invasion are key steps to nodal involvement in various types of cancer, we examined the clinicopathologic significance of lymphangiogenesis and lymphatic invasion in renal cell carcinoma. METHODS Peritumoral lymphatics and intratumoral lymphatics (ITLs) from 106 patients with clear cell renal cell carcinoma specimens were immunostained with D2-40 antibody, which specifically recognizes the lymphatic-specific marker podoplanin. The clinicopathologic significance of the densities and presence of lymphatic vessels and lymphatic invasion (LVI) was evaluated, and the staining pattern of D2-40 was compared with that of CD34. RESULTS Peritumoral lymphatics were present in 100 patients (94.3%), and ITLs were present in only 20 (18.9%). LVI was present in 6 patients (5.7%), of whom 5 had concomitant microvascular invasion. Some lymphatic vessels were positive not only for D2-40, but also for CD34. The presence of ITLs and LVI were significantly associated with pathologic T stage (P

BACKGROUND Lymphatic invasion in radical prostatectomy specimens has been suggested to be an unfavorable prognostic factor in clinically localized prostate cancer. Lymphangiogenesis detected by antibodies specific for lymphatic endothelial cells has been associated with lymphatic invasion and lymph node metastasis in prostate cancer. This study was designed to examine whether lymphangiogenesis in prostate biopsy could predict lymphatic spread in radical prostatectomy specimens. METHODS Paraffin-embedded positive biopsy cores obtained from 99 patients who underwent radical prostatectomy at our institution were immunostained with D2-40 monoclonal antibody, which specifically recognizes lymphatic endothelium. The association between lymphatic parameters in prostate biopsy and pathological parameters in radical prostatectomy specimens was analyzed. RESULTS Peritumoral and intratumoral lymphatic (ITL) vessels were observed in 90 (90.9%) and 23 cases (23.2%). Average and maximal peritumoral lymphatic vessel density (PTLD) and the presence of ITL in positive biopsy cores were significantly associated with positive biopsy core rates (P = 0.0015 for average PTLD, P

In order to reduce line edge roughness and to increase sensitivity, PAG-bonded chemically amplified resist was developed and was evaluated in extreme ultraviolet lithography (EUVL) and electron beam (EB) lithography. We investigated various kinds of photo acid generators (PAGs) which are on the basis of the sulfonium salts to find the beneficial photo acid generator (PAG) for our designed PAG-bonded resist. It was confirmed that not only the structure of anion of PAG but also the structure of cation of PAG are important to achieve the resist specification. It is confirmed that by a selected PAG system, high E0 sensitivity was achieved under the EUV exposure. In addition, LER of 3.5 nm (3σ) was achieved by an EB writing tool.

OBJECTIVES Adoption of laparoscopic partial nephrectomy (LPN) has been limited by lack of reliable hemostatic techniques. We evaluated radiofrequency coagulation (RFC) in obtaining hemostasis during LPN for small renal masses. METHODS Over 4 years LPN was performed by a retroperitoneal approach in 11 patients with solitary, predominantly exophytic renal tumors. A retroperitoneal approach was used in all patients. The renal hilum was not exposed. RF energy was delivered to coagulate the lesion and a margin of normal parenchyma. Tumors were excised together with at least a 0.5-cm margin of normal parenchyma, with the use of ultrasonic shears. RESULTS Mean tumor size was 2.2 cm (range, 1.5 to 3.0). Mean operative time was 222 minutes (range, 130 to 305 minutes) and mean blood loss was 51 mL (range, 10 to 200 mL). During excision bleeding from the cut renal surface was minimal, and structure of the cortex and medulla still could be clearly distinguished after coagulation. No serious complications such as uncontrolled bleeding or urine leakage occurred. One patient had a thermal burn develop at the site of needle electrode insertion and hydronephrosis caused by pyeloureteral junction (PUJ) stricture. In follow-up, ranging from 8 to 53 months, no local recurrence or distant metastasis was detected by computed tomography. CONCLUSIONS Hemostatic capability of RFC is excellent, improving visibility and ease of operation during LPN, and eliminating need for hilar clamping. Further experience and advancement of RF technology will be needed for the application of this method to larger, centrally located tumors.

We developed a novel chemically amplified resist to increase sensitivity and reduce line edge roughness (LER) in extreme ultraviolet (EUV) lithography. This resist consists of a base resin of which a photochemical acid generator (PAG) is bonded to the side chain this is called the PAG-bonded resist. Under EUV exposure, an E0 sensitivity of 1.9 mJ/cm2 and a low outgassing pressure of 2.5×10-6 Pa were achieved. Resolution and LER were obtained by electron beam (EB) exposure. Under EB exposure, an LER of 2.1 nm (3σ) for a 100 nm line and space (L/S) pattern was achieved by the PAG-bonded base resin. In addition, we improved this resist and an LER of 4.0 nm (3σ) for a 50 nm L/S pattern was achieved under EB exposure. These results demonstrate that the novel resist system has a good advantage in terms of high sensitivity and low LER.

We studied the associations of lymphatic invasion and lymphatic vessel density around tumors with lymph node (LN) status in renal cell carcinoma (RCC) by immunohistochemical analysis using D2-40 antibody as a lymphatic marker. Surgically removed specimens from 76 cases with RCC, including 16 cases with LN metastasis, were used. Lymphatic vessel density around the tumor increased compared with normal kidneys but was not significant by LN status. Tumor size, tumor cell types, patterns of tumor growth, nuclear grade of tumor cells, venous invasion, lymphatic invasion, and primary tumor stage were predictive factors for LN metastasis. Based on multivariate regression analysis, only lymphatic invasion was an independent risk factor for LN metastasis. The immunohistochemical detection of lymphatics was useful for identifying the lymphatic invasion of RCC, and the presence of lymphatic invasion around RCC was an independent predictive factor for LN metastasis.

We developed and evaluated PAG bonded resist which is chemically amplified (CA) resist to reduce line edge roughness (LER) in extreme ultraviolet lithography (EUVL). Under electron beam (EB) exposure, it is compared that LER and resolution of photo acid generator (PAG) bonded resist and PAG blended resist which using same PAG and base polymer. It was found that LER and resolution of PAG bonded resist are better than that of PAG blended resist. LER of 3.5 nm in 75 nm L/S and resolution of 25 nm space were achieved. Under EUV exposure, sensitivity of 5.0 mJ/cm2 is achieved.

Aim: C-reactive protein (CRP) elevation is reportedly a prognostic factor in patients with renal cell carcinoma (RCC). Thrombocytosis has recently been reported also to be a prognostic factor in RCC and, like CRP, to be related to inflammatory cytokines such as interleukin-6. The aim of this study was to evaluate the importance of both thrombocytosis and CRP elevation in tumor recurrence and prognosis for patients with RCC. Methods: The clinical records of 178 patients who underwent radical nephrectomy were reviewed. Thrombocytosis was defined as a platelet count ≥350 000/mm3, and CRP elevation was defined as a CRP level ≥1.0 mg/dL. Disease-free survival and cause-specific survival rates were calculated. Independent predictors for recurrence and prognosis were determined. Results: Patients with thrombocytosis and patients with elevated CRP levels had significantly higher pathological T stage, clinical stage, tumor size, histological grade, and percentage of microvascular invasion than did patients without THC and patients with CRP levels

Prostate-specific membrane antigen (PSMA) is a membrane-bound antigen expressed on the surface of prostate cancer cells, and this paper describes the use of an antibody against PSMA for targeting gene therapy. We coupled anti-PSMA monoclonal antibody with poly-L-lysine and then incubated it with plasmids. These complexes were then transfected with cationic liposomes into cells. The transfection efficiency of anti-PSMA- liposome complex was higher than that of normal IgG-liposome complex in PSMA-positive LNCaP cells. Furthermore, anti-PSMA-liposome complex containing a suicide gene, thymidine kinase, demonstrated a selective growth-inhibitory effect on LNCaP cells in vitro, but did not exert a significant effect on PSMA-negative cells. In an in vivo xenograft model of LNCaP cells in nu/nu mice, we administered the complexes via the tail vein. Judging on the basis of both 5-bromo-4-chloro-3-indolyl-beta-D-galactopyranoside (X-Gal) staining and luciferase assay findings, a significant enrichment of plasmid DNA was observed in LNCaP xenografts with anti-PSMA-liposome complex in comparison with normal IgG-liposome complex. However, the distribution of plasmid DNA did not change substantially in any other organs including the liver, kidney, lung, and spleen. Moreover, in suicide gene therapy, anti-PSMA-liposome complex exerted a significant inhibitory effect on the growth of LNCaP xenograft, in contrast to normal IgG-liposome complex.

Leptin, an adipocyte derived cytokine that is closely associated with obesity, was recently shown to be involved in carcinogenesis and cancer progression. Because obesity is a significant risk factor for renal cell carcinoma, we investigated the link between leptin and the development of renal cell carcinoma.Associations between preoperative serum leptin levels and leptin receptor expression in tumor specimens and various clinicopathological parameters were analyzed in 57 patients with renal cell carcinoma.Serum leptin levels were 1.2 to 16.2 ng/ml (mean 4.5). Of 57 tumors 22 (38.6%) demonstrated high leptin receptor expression. Serum leptin levels were significantly higher in patients with vs without tumor specimen venous invasion (p = 0.030) and higher in patients with high vs low leptin receptor expression (p = 0.019). There were significant associations between high leptin receptor expression and the presence of venous invasion (p = 0.013), histological type (p = 0.0076) and regional lymph node metastasis (p = 0.047). Of 42 patients with N0M0 disease those with serum leptin 5.0 ng/ml or more had significantly shorter progression-free survival than patients with lower levels (p = 0.0043). Multivariate Cox proportional hazards model analysis demonstrated that higher serum leptin was an independent predictor of progression-free survival (p = 0.0406).Leptin and leptin receptor could have a key role in the invasion of renal cell carcinoma and they could be valuable predictors of progression.

28歳の男性. 2003年5月, 以前から指摘されていた左内シャント動脈瘤をネコに咬まれ受傷した. 左前腕部の腫脹, 熱感, 疼痛のため当科を受診した. 来院時, 動脈瘤の直上に2箇所の咬傷を認め, 内シャントは完全に閉塞していた. 蜂窩織炎の疑いで緊急入院となった. amikacin, piperacillin, clindamycinを併用し, γ-グロブリンを投与した. 後日, 創培養からパスツレラが検出されたためpanipenem/betamipronとminocyclineの併用に変更した. 炎症反応は改善傾向にあったが, 22病日に動脈瘤が突然破裂した. 用手的に圧迫止血し, 緊急に内シャント動脈瘤切除を施行した. 28病日に左肘部に内シャントを再建し, 維持透析を行っている. ネコ咬傷後のパスツレラ感染症は増加しているが, シャント感染をきたした報告例は世界初と思われる.

BACKGROUND Angiotensin II (AII) type 1 receptor (AT1R) antagonists are used widely as antihypertensive agents, and long-term AT1R blockade may have a protective effect against cancer. We previously demonstrated that specific AT1R blockade with candesartan, an AT1R antagonist, inhibited vascular endothelial growth factor (VEGF) production and dramatically decreased lung metastasis of renal cancer by inhibiting tumor angiogenesis. This study was then undertaken to investigate the effects of AT1R blockade using candesartan in prostate cancer (PCa). METHODS We first determined whether hormone-independence is associated with tumor angiogenesis and AT1R expression. Accordingly, we postulated that AT1R blockade may affect angiogenesis in androgen-independent PCa rather than in androgen-dependent PCa, and investigated the effects of AII and candesartan on PCa cell lines and a tumor xenograft model. RESULTS A human hormone-refractory PCa (HRPC) and C4-2 androgen-independent PCa cell line showed significantly higher expression of VEGF, MVD, and AT1R than did human androgen-dependent PCa and an LNCaP androgen-dependent PCa cell line. In vitro, AII and candesartan did not directly affect the proliferation of LNCaP and C4-2 cells, but candesartan significantly suppressed VEGF production in C4-2 cells. In vivo, candesartan significantly suppressed VEGF expression, serum PSA concentration and tumor growth (1.1 ± 0.2, 45.0 ± 17.6 ng/ml, 235.8 ± 37.4 mm3) in C4-2 xenografts in castrated mice, compared with the controls (2.4 ± 0.6, 376.7 ± 74.2 ng/ml, 830.8 ± 147.6 mm3). CONCLUSIONS Candesartan exerted preventive effects on HRPC, rather than on androgen-sensitive PCa, through the inhibition of tumor angiogenesis. Prostate 67:41–49, 2007. © 2006 Wiley-Liss, Inc.

Purpose: We clarified whether adenovirus mediated intramuscular gene transfer of soluble vascular endothelial growth factor receptor 1 (sFlt-1) can inhibit lung metastasis of renal cell carcinoma. Materials and Methods: We constructed the adenovirus vector AdsFlt-1, which expresses soluble Flt-1 protein. Functional validation of the vector was determined by HUVEC (in vitro human umbilical vein endothelial cell) proliferation inhibition assay. The efficacy of AdsFlt-1 was tested in a Renca murine renal cell carcinoma lung metastasis model. BALB/c mice were injected with Renca cells, followed by the intramuscular administration of AdsFlt-1 24 hours later. Lung specimens were harvested 17 days later and the number of lung metastases was counted. Immunohistochemical analysis of the specimen for angiogenesis and apoptosis was done. Results: Treatment with adenovirus expressed sFlt-1 inhibited HUVEC proliferation. The intramuscular administration of AdsFlt-1 significantly inhibited lung metastasis of Renca cells. Immunohistochemical analysis of the lung specimen showed fewer neovessel formations and more apoptotic cells in AdsFlt-1 treated tumors in mice. Conclusions: The intramuscular administration of AdsFlt-1 effectively inhibited lung metastasis in a murine model of renal cell carcinoma. Because of the simplicity of this therapy, it may well be useful as an effective adjuvant therapy for renal cell carcinoma.

Suicide gene therapy has potential for the treatment of prostate cancer under conditions of androgen deprivation. We show here that the combination of promoter/enhancer of prostate-specific membrane antigen (PEPM) and the Cre-loxP system is a good method to express a suicide gene, namely herpes virus thymidine kinase (TK), in prostate cancer cells. We have examined this system in a castration model in vivo, in comparison with a prostate-specific antigen promoter/enhancer system (PP). In the castrated mice, the tumor luciferase activity with the combination of the PEPM plus the Cre-loxP system was about 50 times greater than that with the control GL3 plasmid. A similar increase was observed in non-castrated mice. In contrast, the luciferase activity of the plasmid PP was decreased significantly in tumors from castrated mice as compared with tumors from non-castrated control mice. Regarding the therapeutic effect, the combination plasmid PEPM-Cre plus CMV-loxP-TK exhibited a strong inhibitory effect on tumor growth in the castrated mice, as in the non-castrated mice. In contrast, PP-TK plasmid did not show any significant growth inhibition in the castrated mice. These findings indicate that the combination of PEPM and Cre-loxP system may have a good treatment effect under androgen ablation conditions in vivo, and our system may therefore be applicable to patients who have previously received androgen deprivation therapy.

ZD1839 or Iressa (AstraZeneca, Macclesfield, United Kingdom) is an orally active, selective epidermal growth factor receptor tyrosine kinase inhibitor. We evaluated the antitumor activity of ZD1839 in human renal cell carcinomas (RCC).Six established human RCC lines and surgical specimens from 10 patients with RCC were used. Protein expression was detected by Western blotting and/or immunohistochemistry. The concentrations of vascular endothelial growth factor and interleukin-8 in the supernatants were measured by enzyme-linked immunosorbent assay. Cell cycle progression and the apoptotic ratio were evaluated by flow cytometry. In vitro angiogenesis was measured using human umbilical vascular endothelial cells by capillary-like network formation analysis. In vivo SKRC-49 cells injected subcutaneously into athymic nude mice were treated with various doses of ZD1839 orally. The effect of ZD1839 on tumor xenografts angiogenesis was evaluated by immunohistochemistry using CD34 Ab.Epidermal growth factor receptor was activated in all RCC lines and over expressed in 7 of 10 RCC specimens (70%) compared with adjacent normal renal tissues. Treatment of SKRC-49 cells with ZD1839 (0.1 to 10 microM) for 48 hours resulted in the accumulation of cells in the G1 phase and a 30% to 50% decrease in cellular proliferation compared with untreated controls (p0.01). The tumor xenograft study confirmed that ZD1839 (50 to 100 mg/kg daily) significantly inhibited SKRC-49 tumor growth compared with controls within 3 weeks after treatment (p0.01). Vascular endothelial growth factor and interleukin-8 production was significantly decreased in ZD1839 treated SKRC-49 cells compared with untreated controls (p0.01). Treatment of human umbilical vascular endothelial cells with SKRC-49 supernatants treated with ZD1839 for 11 days resulted in an approximate 80% decrease in tubule formation compared with untreated controls (p0.01). Immunohistochemical assays showed that ZD1839 treatment resulted in a significant decrease in CD34 positive neovessels compared with controls in SKRC-49 xenografts.These results suggest that the antitumor activity of ZD1839 appears to derive not only from direct inhibition of cell proliferation, but also from the inhibition of tumor angiogenesis in RCC.

We determined whether the novel nuclear factor kappa B activation inhibitor dehydroxymethylepoxyquinomicin (DHMEQ), which is derived from epoxyquinomicin C, affects renal inflammatory responses in unilateral ureteral obstruction.DHMEQ (8 mg./kg.) was administered to rats 1 day after unilateral ureteral obstruction and every day thereafter. Kidneys were harvested at day 7 after unilateral ureteral obstruction. Tissue nuclear factor kappa B activity and transforming growth factor-beta were determined by electrophoretic mobility shift assay and bioassay using mink lung epithelial cells, respectively. Renal tubular proliferation and apoptosis were detected by immunostaining proliferating cellular nuclear antigen and the TUNEL (Intergen, Purchase, New York) assay, respectively. Leukocyte infiltration was detected by immunostaining for CD45. Fibrosis was assessed by measuring tissue hydroxyproline content.Unilateral ureteral obstruction for 7 days significantly activated nuclear factor kappa B, induced tubular apoptosis, proliferation and interstitial fibrosis in the obstructed kidney of the control group compared with their unobstructed counterparts (30.3 +/- 4.5 nuclei per high power field versus 1.7 +/- 0.4, 25.7 +/- 3.3 nuclei per high power field versus 3.2 +/- 0.4 and 6.2 +/- 0.3 micromol. hydroxyproline per gm. tissue versus 3.4 +/- 0.1, respectively). Conversely daily administration of DHMEQ (8 mg./kg.) significantly inhibited nuclear factor kappa B activation and decreased mean tubular apoptosis (9.5 +/- 2.1 nuclei per high power field), proliferation (10.2 +/- 2.4 nuclei per high power field) and interstitial fibrosis (4.9 +/- 0.4 micromol. hydroxyproline per gm. tissue) in the obstructed kidney.Specific inhibition of nuclear factor kappa B can prevent inflammatory renal responses, suggesting that targeting nuclear factor kappa B activation may be feasible for preventing inflammatory kidney diseases.

Tissue or tumor specific gene delivery is crucial for achieving successful results in suicide gene therapy. Prostate specific antigen (PSA) promoter is known to be highly specific in prostate tissue but its promoter activity is much weaker than that of constitutive viral promoters. In the current study we enhanced PSA promoter activity by combining it with the Cre-loxP system. We also applied this system to adenovirus mediated suicide gene therapy with the cytosine deaminase (CD) gene.The Cre-loxP DNA recombination system was used to enhance PSA promoter. A plasmid with the PSA promoter-enhancer combination was constructed to drive Cre recombinase. Another plasmid contained the cytomegalovirus promoter-loxP-flanked stop signal-luciferase gene. LNCaP human prostate cancer cells were co-transfected with these 2 plasmids and luciferase activity was measured to assess promoter activities. Adenoviral vectors with the CD suicide gene were constructed in similar fashion and tested in LNCaP cells in in vitro/in vivo prostate cancer models.Promoter activity of the combined PSA promoter/enhancer and Cre-loxP system was 3 times stronger than that of PSA promoter/enhancer alone. It was further enhanced 7-fold in the presence of testosterone. Application of this system to CD suicide gene therapy by adenoviral vectors inhibited subcutaneous LNCaP tumor growth in nude mice.Combining the Cre-loxP system with PSA promoter/enhancer amplified promoter activity and was found to inhibit the growth of PSA producing prostate cancer cells in vivo.

To enhance the efficacy of suicide gene therapy for prostate cancer under androgen deprivation, we designed a promoter system that consists of the prostate-specific membrane antigen (PSMA) promoter / enhancer (PEPM) and Cre-loxP DNA recombination system. We constructed two kinds of plasmids. One plasmid contains a Cre recombinase (Cre) under the control of PEPM and the other expresses CMV-lox-luciferase / herpes simplex virus thymidine kinase (TK). In PSMA-positive LNCaP cells, the promoter activity of the PEPM-Cre plus CMV-lox-luciferase demonstrated 800-fold greater activity compared with that of the PSMA promoter alone. However, no enhancement of the promoter activity was observed in the PSMA-negative cells. Furthermore, in contrast to prostate specific antigen promoter / enhancer (PP), the promoter activity of PEPM did not decrease when the LNCaP cells were cultured in charcoal-stripped fetal bovine serum (CFBS). In an in vitro gene therapy model with LNCaP cells, the cell growth inhibition in the presence of ganciclovir (GCV) was more evident in the cells transfected with the PEPM-Cre plus CMV-lox-TK than in the cells with the PP-TK, and the difference in efficacy between the two plasmids was more remarkable when the cells were maintained in CFBS medium. The therapeutic effect of PEPM-Cre plus CMV-lox-TK was also observed in xenografted LNCaP cells on nude mice when the plasmids were directly injected into tumors and GCV was administered intraperitoneally. These findings indicate that the combination of the PSMA promoter / enhancer and the Cre-loxP system can enhance the PSMA promoter activity even under androgen ablation conditions and can exert its anti-tumor effect both in vitro and in vivo.

We determined whether the cyclooxygenase-2 inhibitor etodolac affects renal tubular damage and interstitial fibrosis in unilateral ureteral obstruction.Etodolac (10 mg./kg.) was administered to rats 1 day before unilateral ureteral obstruction and every day thereafter. Kidneys were harvested at day 14 after unilateral ureteral obstruction. Tissue transforming growth factor-beta and prostaglandin E2 were measured by bioassay using mink lung epithelial cells and enzyme linked immunosorbent-sandwich assay. Renal tubular proliferation and apoptosis were detected by immunostaining with proliferating cellular nuclear antigen and by terminal deoxynucleotidyl transferase mediated deoxyuridine triphosphate nick end labeling, respectively. Cyclooxygenase-2 expression was detected by immunohistochemistry. Fibrosis was assessed by measuring collagen deposition in trichrome stained slides.Bioassay showed that in the control group obstructed kidneys contained significantly higher mean transforming growth factor-beta1 than unobstructed kidneys (79.1 +/- 8.3 versus 33.6 +/- 4.2 ng./gm. tissue) and etodolac significantly decrease the mean value in obstructed kidneys (46.2 +/- 10.0 ng./gm. tissue). Assay demonstrated that obstructed control kidneys had significantly more mean tubular apoptosis than their unobstructed counterparts (26.6 +/- 5.4 versus 2.2 +/- 1.4 nuclei per high power field) and etodolac significantly decreased mean renal tubular apoptosis in the obstructed kidneys (16.2 +/- 1.9 nuclei per high power field). In addition, immunostaining with proliferating cellular nuclear antigen showed that obstructed kidneys in the control group had significantly more mean renal tubular proliferation than unobstructed kidneys (9.8 +/- 3.4 versus 3.9 +/- 0.1 per high power field) and etodolac significantly increased mean proliferating renal tubule in the obstructed kidneys (24.9 +/- 4.3 per high power field). Control obstructed kidneys had significantly more fibrosis and prostaglandin E2 production, which were also significantly blunted by etodolac.The cyclooxygenase-2 inhibitor etodolac significantly reduces tissue transforming growth factor-beta, resulting in decreased tubular damage and interstitial fibrosis. This finding suggests that etodolac is a promising agent for preventing renal tissue damage in unilateral ureteral obstruction.

The bacteriophage P1-derived Cre-loxP system is a powerful and versatile tool for in vivo DNA recombination. It is widely used in gene targeting research. The combination of the Cre-loxP system and a specific promoter enables conditional "knockout" of a target gene in a particular tissue or cell type. It has also made it possible to delete genes in adult animals that are essential for embryogenesis. This system is also used to enhance tissue- or tumor-specific promoter activities that are useful for gene therapy of certain types of cancer. It is expected that this simple and effective system will be further utilized in various research applications.

We determined whether tranilast, the anti-allergic agent N-(3, 4-dimethoxyciannamoyl)-anthranilic acid, would diminish renal transforming growth factor-beta (TGF-beta) levels in unilateral ureteral obstruction and concomitantly affect renal tubular apoptosis and proliferation in that condition.Tranilast (150 mg./kg.) was administered to rats 1 day before unilateral ureteral obstruction and each day thereafter. Kidneys were harvested day 14 after unilateral ureteral obstruction. Tissue TGF-beta was measured by bioassay using mink lung epithelial cells. Renal tubular proliferation and apoptosis were detected by immunostaining proliferating cell nuclear antigen and the terminal deoxynucleotidyl transferase mediated deoxyuridine triphosphate nick end labeling assay, respectively. Fibrosis was assessed by measuring collagen deposition with trichrome stained slides.TGF-beta bioassay showed that obstructed kidneys in controls contained significantly higher mean TGF-beta plus or minus standard deviation than unobstructed kidneys in controls (73.7 +/- 13.6 versus 14.1 +/- 5.5 pg./mg. tissue) and tranilast significantly decreased tissue TGF-beta in obstructed kidneys (15.9 +/- 4.8 pg./mg. tissue). The terminal deoxynucleotidyl transferase mediated deoxyuridine triphosphate nick end labeling assay demonstrated that obstructed kidneys in controls had significantly more mean tubular apoptosis than the unobstructed counterparts (36.6 +/- 6.7 versus 5.8 +/- 5.5 nuclei per high power field) and tranilast significantly decreased mean renal tubular apoptosis in obstructed kidneys (16.2 +/- 1.7 nuclei per high power field). In addition, immunostaining proliferating cell nuclear antigen showed that obstructed kidneys in controls had significantly more mean renal tubular proliferation than unobstructed kidneys (20.7 +/- 3.4 versus 6.2 +/- 2.1 per high power field) and tranilast significantly increased proliferating renal tubules in obstructed and unobstructed kidneys (26.5 +/- 8.3 and 14.5 +/- 3.4 per high power field, respectively). Control obstructed kidneys exhibited significantly more fibrosis, which was also blunted by tranilast.Tranilast significantly decreases tissue TGF-beta, resulting in a reduction in tubular apoptosis and an increase in tubular proliferation. This finding suggests that tranilast is a promising agent for preventing renal tubular damage in unilateral ureteral obstruction.

Captopril is known to inhibit the growth of renal cancer but the mechanism involved has been unclear. The current study elucidates the mechanism of captopril induced inhibition of the growth of the Renca mouse renal cancer cell line involving transforming growth factor-beta, which is known to be a growth inhibitory cytokine in epithelial cells and tissues.Transforming growth factor-beta in conditioned medium was measured by bioassay. Levels of transforming growth factor-beta and transforming growth factor-beta type II receptor expression messenger RNA were determined by reverse transcriptase-polymerase chain reaction and flow cytometry. Cell viability was determined by bromodeoxyuridine (BrdU) incorporation and tetrazolium bromide assay.Captopril (0.01 to 1 mM.) showed no significant effect on transforming growth factor-beta synthesis or transforming growth factor-beta messenger RNA in Renca cells. On the other hand, 1 mM. captopril significantly inhibited Renca cell growth. Reverse transcriptase-polymerase chain reaction and flow cytometry showed that 1 mM. captopril up-regulated type II receptor expression.These findings suggest that captopril restores transforming growth factor-beta type II receptor expression and inhibits the growth of Renca cells by increasing their sensitivity to transforming growth factor-beta.

BACKGROUND/PURPOSE Twenty-two institutes have organized Keio University Prostate Cancer Study Group to study clinical efficacy and safety of Leuprolide acetate (Leuplin) for the treatment of advanced prostate cancer (clinical stage D1 and D2). Cotreatment of Leuplin and Estramustine phosphate disodium (Estracyt) has been performed to investigate its clinical efficacy. MATERIALS AND METHODS One hundred and two cases of advanced prostate cancer were treated either with Leuplin alone (group I), Leuplin and Estracyt (group II) or Estracyt alone (group III). After 12 weeks treatment, clinical effects against subjective symptoms (pain, voiding difficulty, performance status and body weight), serum testosterone level, tumor size and serum PSA level were examined to investigate short-term effect of each treatment. The treatment had been continued for 24 months and the treatment effects including progression free survival and overall survival were analyzed. RESULTS Clinical efficacy after 12 weeks treatment were examined among 97 cases (group I; 35 cases, group II; 36 cases, group III; 26 cases). The background of those patients in each group was statistically equal. Treatment effects against subjective symptoms and serum testosterone level statistically revealed no significant difference among 3 groups. Treatment effects against primary tumor, bone metastatic lesion, lymphnode metastatic lesion and serum PSA level were investigated and anti-tumor effect was characterized by total efficacy rate (complete remission rate plus partial remission rate) of each treatment group. Treatment efficacy rates for each lesion and PSA demonstrated no statistical difference among 3 treatment groups. Total efficacy rate of group I, II and III were 88.2%, 84.0% and 78.3%, respectively, which statistically revealed no significant difference. Total efficacy rate of each group after completing 24 months treatment was; group I 80.0%, group II 55.6% and group III 83.3%, which statistically showed no significant difference among 3 treatment groups. The median day for progression free survival of group I, II and III were 661, 731 and 517, respectively. The overall survival rate of group I, II and III after completing 24 months treatment were 77.5%, 83.0% and 72.4%, respectively. Both progression free survival rates and overall survival rates revealed no significant difference among 3 groups. Side effects during 24 months treatment were seen in 8.6% of group I, 47.2% of group II and 26.9% of group III, and these occurrence rates were significantly different among the groups (p = 0.0013). CONCLUSION Although number of the cases had not been able to continue the treatment for their side effects, the statistical characterization demonstrated that cotreatment of Leuplin and Estracyt had no greater treatment effect than monotreatment of each drug.

The authors present a case of renal oncocytoma with numerous intracytoplasmic lumina in a 45-year-old woman, with an emphasis on the ultrastructural findings of so-called oncoblasts. The tumor was located in the upper pole of the left kidney, measuring about 3.3 cm in diameter. Histologically, it was composed of solid nests or acinar growths of so-called oncocytic tumor cells with numerous intracytoplasmic lumina and scattered foci of so-called oncoblasts. The luminal surface was positive for Hale's colloidal iron stain. A very small number of glycogen-containing cells were found scattered in a few nests. Immunohistochemically, tumor cells were positive for cytokeratin and epithelial membrane antigen, but negative for vimentin and carcinoembryonic antigen. The Ki-67 labeling index was 1.2%. All of the Ki-67-positive cells were oncocytes. So-called oncoblasts were negative for Ki-67. Ultrastructural examination revealed that the predominant tumor cells had cytoplasm packed with round mitochondria and the mitochodria had lamellar long cristae. So-called oncoblasts showed scant cytoplasm with a moderate number of small mitochondria. Some of them showed pyknosis which can be regarded as mitochondrial involution. The authors believe that so-called oncoblasts are damaged or involuted oncocytes rather than precursors of oncocytes.

Adult Wilms' tumor (AWT) is a rare disease. We investigated the clinical characteristics and the outcome of four patients with AWT treated by nephrectomy followed by radiation therapy and/or chemotherapy (protocol of the Fourth National Wilms' Tumor Study). Serum levels of lactic dehydrogenase (LDH), immunosuppressive acidic protein (IAP), and C-reactive protein (CRP) were above normal in all four patients. Two of three patients with unfavorable histology (UFH) had stage III or IV disease and died within 14 months of diagnosis while undergoing the chemotherapy. The other patient with UFH had a stage II tumor, which was treated with tumor-bed irradiation, and has survived for 26 months after nephrectomy. One patient with a stage I tumor and favorable histology also received chemotherapy, but she subsequently developed multiple metastases, and died 70 months after nephrectomy. Radiotherapy for metastases had palliative effects on osseous pain and tumor growth. The clinical results of the chemotherapy for AWT were poor. Analysis of more cases is needed to indicate whether or not the conventional chemotherapeutic regimen for Wilms' tumor in children requires modification to improve the outcome in AWT.

目的: 透析患者, 特に後天性多嚢胞腎 (ACDK) 症例に発生した腎細胞癌 (RCC) の臨床病理学的特徴を明らかにするために, 調査対象患者, 腎嚢胞の種類, 透析期間, 腫瘍の病理所見, そして患者の予後について検討を加えた.方法: 507施設にアンケート調査を行い, 嚢胞性腎疾患に合併したRCCで腎摘除術を受けている223例を集計した. その中から, 62例のACDK (5721例の腎癌の1.08%) を中心に, 慢性透析を受けている患者71名を今回の検討の対象とした. またアンケートの対象と同一期間中に, 一般人に発症したRCCで我々が治療した33症例を対照群とした.結果: 透析患者におけるRCCの83%がACDKに合併していた. ACDK症例のRCCの55.7%がpT 2で, わずか1.7%に手術時転移が認められた. 腎癌死に限定した場合の5年生存率は対照群の生存率より有意に良好であった.組織学的検討では, 構築型に関して48.3%が胞巣型, 13.1%が腺管型, 21.3%が乳頭型であり, 細胞型に関しては57.4%が淡明細胞亜型, 21.3%が顆粒細胞亜型であった. 細胞型では顆粒細胞亜型, 組織型では腺管型あるいは乳頭型の割合が対照RCCに比べ高い傾向を示した. 透析期間が判明している69症例 (ACDK 61例, その他の腎嚢胞8例) の組織学的検討でも, これらの細胞および組織型の増加は, 透析期間が10年を超える症例で明らかであった.

At the time of donor nephrectomy, congenital abnormalities of the inferior vena cava was discovered. A 56-year-old woman was worked up preoperatively and no abnormalities were found. Abdominal aortography was normal. At the time of operation, the inferior vena cava was located to the left and anterior to the abdominal aorta. In the renal hilus, the location of the renal artery and vein was reversal. We thought the ideas of operation and could successfully performed renal transplantation using donor kidney with congenital abnormalities of the inferior vena cava.

慢性腎不全の緊急血液透析導入時の一時的なブラッドアクセスとして使用されるウロキナーゼ・コーティング・カテーテル (UKカテーテル) のカテーテルトラブルについて, Shaldon型ダブル・ルーメン・カテーテル (DLカテーテル) と比較検討した. 対象は大腿静脈にUKカテーテルを挿入し血液透析を導入したUK群65名 (男性36名, 女性29名) とDLカテーテルを使用したDL群124名 (男性71名, 女性53名) である. UK群65名に対し87本のカテーテルを使用し, 合計653回の透析を行った. 1人あたりの透析回数は3-24回 (平均10.0回) で留置期間は5-52日間 (平均20.3日) であった. 合計653回の透析中22回 (3.3%) に合併症を認めた (患者65名中12名). 一方DL群124名は170本のカテーテルを使用し, 合計1474回の透析を行った. 1人あたりの透析回数は2-35回 (平均11.9回) で留置期間は3-92日間 (平均26.4日) であった. 合計1474回の透析中56回 (3.9%) に合併症を認めた (患者124名中56名). 内訳はUK群は血流不全が16回 (透析1回あたり2.4%), 発熱は3回 (0.45%), 自然抜去は1回 (0.15%) であった. また, 透析中にカテーテル自体の破損を2回 (0.30%) 認めた. DL群は発熱が27回 (1.83%) と最も多く, 次いで血流不全が21回 (1.42%), 出血および血腫が4回 (0.27%), その他, 自然抜去が4回 (0.27%) であった. 両群間でカテーテル合併症の発生頻度に有意差を認めなかった. 個々の合併症では発熱の発生頻度だけがDL群のほうがUK群より有意に高かった (P

We investigated whether the cell growth and apoptosis of multiple cytokine-producing bladder cancer cells can be regulated by nuclear factor kappaB (NF-kappaB). The bladder cancer cell line KU-19-19, obtained from a 76-year-old man who demonstrated marked leukocytosis, produces multiple cytokines and demonstrates autocrine growth by granulocyte colony-stimulating factor (G-CSF). Electrophoretic mobility shift assay (EMSA) revealed that NF-kappaB was activated in KU-19-19 but not in other bladder cancer cell lines (KU-1, KU-7, or T-24, respectively). The inhibition of NF-kappaB DNA-binding activity with adenovirus vectors expressing the stable form of the NF-kappaB inhibitor IkappaBalpha (multiplicity of infection [MOI] of 10) inhibited growth and induced apoptosis of KU-19-19, but not KU-1, KU-7, or T-24. The production of several cytokines was suppressed significantly in KU-19-19 by this gene delivery. Although dexamethasone (10 microM) could also suppress cytokine production, it did not induce dramatic cell death in KU-19-19 because it could not inhibit NF-kappaB activation stably and strongly. These results suggest that NF-kappaB activation maintains the cell viability as well as regulates cytokine production in cytokine-producing cancer cells and therefore these in vitro experiments support a rationale for preclinical in vivo studies to demonstrate growth inhibition in established tumors.

Renal myxomas are rare neoplasms. Only three cases have been convincingly diagnosed as renal myxoma. Here we report an additional case. The case was a 36-year-old man and he was discovered incidentally at the regular health-check for chronic hepatitis B. Computed tomography showed 8 cm low-density tumor in the lower pole of the left kidney. The tumor was slightly enhanced by contrast agents. Magnetic resonance imaging revealed the tumor as low intensity on T1-weighted imaging and high intensity on T2-weighted images. The tumor was enhanced by gadrinium enhancement homogeneously. The resected kidney contained semitranslucent, gelatinous, tan mass within the lower pole of the kidney. The microscopic examination showed the typical appearance of a myxoma, which consisted of large amounts of myxoid material containing a few uniformly scattered spindle cells The tumor cells showed immunoreactivity for vimentin but not for S-100 protein, epithelial membrane antigen, cytokeratin, alpha smooth muscle actin.

We compared cytokine levels in fluid from renal cysts with and without renal cell carcinoma.Fluid was aspirated from 18 renal cysts without (benign) and 21 with renal cell carcinoma (malignant). Serum from patients with renal cell carcinoma and healthy controls was collected and cytokines were measured by enzyme-linked immunosorbent assay.Interleukin-6 (IL-6) and basic fibroblast growth factor concentrations were higher in malignant than benign cysts or serum (p0.006). Epidermal growth factor levels were significantly higher in malignant cysts and serum than in benign cysts (p0.01). IL-6 levels in malignant cysts positively correlated with the erythrocyte sedimentation rate (R=0.80) and C-reactive protein (R=0.86), and they were higher in grade 3 than in grade 2 tumors. Basic fibroblast growth factor levels were significantly higher in malignant cysts associated with hypervascular than hypovascular tumors (p=0.029).Cytokine levels in aspirated fluid may help to identify malignant renal cysts and indicate the characteristics of coexisting tumors.

A 77-year-old Japanese woman was admitted to our hospital complaining of small urinary volume. Physical examination revealed a light red, edematous, pyriform mass, approximately 7 cm in diameter at the vulva. An orifice posterior to the base of the mass was catheterized and 20 ml of urine was obtained. Roentgenograms of contrast material injection to the orifice demonstrated a space of 20 ml. A diagnosis of complete inversion of the bladder was made. Under epidural anesthesia, attempts were made to reduce the mass through the urethra. The manual reduction proved to be difficult, but was successful by manual compression of the bladder wall and squeezing it back through the urethra, which took approximately 60 minutes. Complete transurethral inversion of the bladder is so rare that not much of the pathogenesis is clarified. In our patient, senility, obesity, multiple labor and surgeries are assumed to have resulted in laxity of the pelvic wall which would be one of the major risk factors for this condition.