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We evaluated the feasibility and the benefits of total prostatectomy with suprapubic cystostomy drainage instead of a urethral Foley catheter. Of 65 consecutive total retropubic prostatectomies, 42 were carried out with the suprapubic cystostomy, and 23 with the urethral Foley catheter. Patients were asked postoperatively to complete a 5-cm visual analog scale on pain intensity related to the catheter and to urination after catheter removal. No problem related to cystostomy per se was observed. In the cystostomy group, over 85% and 69% of men perceived no urinary symptoms during catherization and no painful urination after catheter removal, respectively; whereas in the Foley group, 91% and 65% perceived those symptoms (P < 0.001 and P < 0.01, respectively). These findings suggest that urethral catheter-free prostatectomy is a good alternative to that with a urethral Foley catheter, and it gives patients an improved quality of early postoperative life.

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PURPOSE: We retrospectively evaluated the characteristics and long-term prognosis of incidentally detected renal cell carcinoma by health checkup. MATERIALS AND METHODS: From January 1987 to December 2005, 556 patients were treated for renal cell carcinoma in our department. Among them, 56 patients were detected by abdominal ultrasonography in health checkup of our health care center. We reevaluated the pathological stage according to 2002 TNM classification and tumor type of renal cell carcinoma according to 2004 World Health Organization histological classification. Survival analysis was determined by Kaplan-Meier's method and log-rank test. RESULTS: Of the patients, 50 were male and 6 were female. The age of the patients ranged 37 to 68 years old at diagnosis (median 54 years). The tumors were located in the right kidney in 22 patients and in the left kidney in 34. Pathologically T1a tumors were found in 40 patients (71%), T1b in 13 (23%), T2 in 2 (4%) and T3b in 1 patients (2%). One case of T3b had N2 and M1 disease. The followup time after the operation ranged 3 to 215 months (median 121 months). Seven patients died of renal cell carcinoma. One of the 7 patients in T1a disease died at 64 months, 4 in T1b at 47, 91, 119, 163 months, 1 in T2 at 39 months and 1 in T3b at 13 months, postoperatively. The cause specific 10-year survival rate was 97% for T1a disease and 57% for T1b (p < 0.01), respectively. CONCLUSION: Most of renal cell carcinomas were T1a disease, which were detected incidentally by health checkup. The cause specific survival rate was significantly higher for T1a disease than for T1b. Our data suggested that early detection was important for good prognosis. The abdominal ultrasonography was only method for detection in routine health checkup and should be broadly implemented.

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AIM: To overcome the disadvantages inherent in the standard surgical approach to the kidney, we introduced a novel surgical technique via a midline extraperitoneal approach. The surgical technique is not substantially different from that of the standard midline transperitoneal approach, except no entry is made into the peritoneal cavity. Although the peritoneum itself is extremely thin and fragile, the peritoneum together with underlying subperitoneal fascia can be dissected readily as a substantial layer, if the proper plane is dissected. Further medial mobilization of the peritoneal sac en bloc by pursuing the fusion fascia plane allows full exposure of the kidney, ureter and great vessels. This approach was adopted for consecutive 51 patients during a 10-month period in 2003. All operations, including 33 radical nephrectomies and 11 nephroureterectomies were completed successfully without significant technical difficulties and differences in operation time and estimated blood loss compared to the transperitoneal approach. No intra- or perioperative complication occurred. All patients did seem to have a much more comfortable postoperative period with minor pain and few abdominal complaint, and the clinical impression was that they resumed the physical activity and oral intake earlier than those after the transperitoneal approach (P = 0.056). There are no operation-related problems such as intra-abdominal adhesion or abdominal muscle weakness resulting in some deformity at 2-year or more follow up. This approach combines the advantages of the transperitoneal midline and extraperitoneal flank approach. Its use will undoubtedly reduce the complications inherent in the transperitoneal approach or the flank approach.

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BACKGROUND: We investigated the clinical efficacy and the prolongation of survival with combination therapy of estramustine phosphate (EMP) and endocrine therapy in untreated patients with progressive prostate cancer. METHODS: We randomly divided 57 patients with untreated stage D prostate cancer into two groups, an endocrine monotherapy group and a group receiving combination treatment, consisting of endocrine therapy plus EMP. Treatment was continued until deterioration. RESULTS: There were no significant differences in the improvement rating for subjective/objective symptoms or in progression-free survival between the two groups. However, overall survival was significantly prolonged in the combination therapy group (log-rank test, P = 0.0394; generalized Wilcoxon's test, P = 0.0145). In particular, overall survival was significantly prolonged, compared to that in the endocrine monotherapy group, in patients in the combination therapy group who were less than 74 years old, those with a performance status (PS) of 1 to 3, a pretreatment prostate-specific antigen (PSA) level of more than 20 ng/ml, moderately or poorly differentiated carcinoma, or a partial response (PR) based on the PSA level 12 weeks after the start of treatment. There was no significant difference in the incidence of side effects between the combination therapy and the endocrine monotherapy groups. CONCLUSION: A combination of EMP with endocrine therapy may be useful for initial treatment in younger patients (aged 73 or younger) and in patients at high risk of progressive prostate cancer.

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Obstructive nephropathy refers to the mechanical or functional changes in the urinary tract that interfere with normal urinary flow. Once obstruction is set, it leads to progressive renal damage that is mainly characterized with tubulointerstitial fibrosis. Here we reviewed the pathophysiology of urinary tract obstruction and indicated future therapeutic options. Following complete unilateral ureteral obstruction, there is a progressive fall in renal blood flow and glomerular filtration rate, and is a increase in intratubular pressure. These events activate the plasma and tissue renin-angiotensin systems (RAS). It has been proved that upregulated angiotensin II is one of the crucial factors those are responsible for the subsequent deleterious process. Angiotensin II induces transforming growth factor-beta, which causes overproduction of extracellular matrix (ECM) proteins like collagen, fibronectin, etc. The ECM proteins are dominantly accumulated in tubulointerstitium and result in deterioration of renal function. Along with the activation of the RAS, tissue ischemia and mononuclear leukocyte infiltration also modulate the fibrotic changes. The process from the RAS activation to renal fibrosis is observed not only in obstructive nephropathy but also in other renal diseases and is called the Final Common Pathway. Mechanical release of the obstruction is to perform in terms of the treatment, however, several promising pharmaceutical options are now under investigation.

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Tubulointerstitial fibrosis is a major cause of irreversible renal damage in the obstructed kidney. The effects of release of obstruction on the obstructed kidney are not clearly understood. We investigated the effects of the release of ureteral obstruction on renal fibrosis and the expression of fibrogenic factors. Rats underwent 5 day of unilateral ureteral obstruction (UUO). After release of obstruction by removing an encased rubber tube, changes in interstitial volume were morphologically evaluated and the mRNA expression of transforming growth factor-beta (TGF-beta), type IV collagen (collagen IV), and plasminogen activator inhibitor-1 (PAI-1) were examined by reverse transcription-polymerase chain reaction (RT-PCR) up to 28 days. Renal interstitial volume, collagen IV and PAI-1 mRNA gradually decreased from 7 days to 28 days after release of obstruction. However, increased expression of TGF-beta mRNA persisted up to 14 days, and then declined 28 days after release. In conclusion, obstruction-induced renal fibrosis was recovered with diminished expression of TGF-beta and collagen IV. Decreased PAI-1 expression in the post-obstructed kidney may contribute to the degradation of extracellular matrix proteins and recovery of tubulointerstitial fibrosis, at least partly, after release of ureteral obstruction.

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Waardenburg syndrome type 2 (WS2) is associated with heterozygous mutations in the gene encoding microphthalmia-associated transcription factor (MITF) and characterized by deafness and hypopigmentation due to lack of melanocytes in the inner ear and skin. Melanocyte-specific MITF isoform (MITF-M) is essential for melanocyte differentiation and is transcriptionally induced by Wnt signaling that is mediated by beta-catenin and LEF-1. Here we show that MITF-M transactivates its own promoter (M promoter) by interacting with LEF-1, as judged by transient expression assays and in vitro protein-protein binding assays, whereas no transactivation of the M promoter was detected with MITF-M alone or with the combination of MITF-M and dominant-negative LEF1 that lacks the beta-catenin-binding domain. This synergy depends on the three LEF-1-binding sites that are clustered in the proximal M promoter. Importantly, MITF-M recruited on the M promoter could function as a non-DNA-binding cofactor for LEF-1. Thus, MITF-M may function as a self-regulator of its own expression to maintain a threshold level of MITF-M that is required for melanocyte development. We suggest that MITF-M haploinsufficiency may impair the dosage-sensitive role of MITF-M or the correct assembly of multiple transcription factors, involving MITF-M, on the M promoter, which could account for dominant inheritance of WS2.

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PURPOSE: The efficacy and toxicity of two-drug therapy (etoposide and cisplatin, EP) in patients with metastatic germ cell tumors were investigated. PATIENTS AND METHODS: Between December 1996 and November 1999, 18 patients with metastatic germ cell tumors (6 seminomas and 12 non-seminomas, Stage II 8, Stage IIIA 2, Stage IIIB 6, Stage IIIC 2) were treated by 3-5 cycles of induction chemotherapy regimen (EP). Etoposide and cisplatin were administrated in doses of 100 mg/m2 and 20 mg/m2, respectively, on days 1 to 5 and then repeated from day 21. After tumor markers obtained normal levels, one or two additional cycles of EP were continued. Patients showing evidence of residual tumor mass underwent debulking surgery as early as possible. RESULTS: At the end of EP therapy, 4 (22%) of the 18 patients achieved complete remission and 14 patients (78%) showed partial remission. Seven patients of partial remission were treated by excision of residual abnormalities: 6 had pathologically necrotic debris in the resected specimen and 1 had teratoma, and these 7 patients all achieved complete remission. Four other patients achieving partial remission were followed without surgical excision and have had no evidence of disease progression. Remaining three patients achieving partial remission received salvage chemotherapy with or without adjunctive surgery, resulted in complete remission in 2 patients and partial remission in 1 patient. EP demonstrated to have less treatment-related toxicity compared with that of EBP. Follow up studies ranging from 12 to 47 months (median, 29.6) showed that one patient experienced a relapse from complete remission at 13 months and was salvaged by chemotherapy and surgery. Finally, thirteen patients (72%) who achieved complete remission are alive and disease-free and 5 patients (28%) showing partial remission are alive with negative tumor markers and no evidence of relapse. CONCLUSION: These results suggests that EP is an efficacious and less toxic first line regimen for good-prognosis patients with metastatic germ cell tumors.

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BACKGROUND: The incidence of prostate cancer increases with age and latent cancer is common in older men. But clinical prostate cancer is rare in men aged < 50 years. METHODS: Between 1988 and 2000, we studied seven cases of prostate cancer in men aged under 50 years. The clinicopathological results included: the first sign or symptom; prostate-specific antigen (PSA) at the time of diagnosis; existence of abnormal digital rectal examination (DRE); the differentiation of the cancer and Gleason score; and the outcome of treatment. RESULTS: Six cases were diagnosed as stage D2. One case was diagnosed as stage B2 and the patient underwent radical prostatectomy. None of the cases were detected by mass screening. The PSA at diagnosis was < 10 ng/mL in only one case and that patient underwent radical prostatectomy. Six cases were diagnosed pathologically as poorly differentiated adenocarcinoma. The only patient who survived more than 5 years underwent radical prostatectomy. CONCLUSION: Six of seven cases of prostate cancer were detected at advanced stage. Only one case was thought to be curable and this patient's cancer was detected by chance occult blood test. Because young prostate cancer patients are potential candidates for radical prostatectomy and the sensitivity of PSA might be higher in young men, high-risk groups could be screened by PSA.

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BACKGROUND: The present study examined adrenal metastasis resulting from renal cell carcinoma (RCC), with the aim of assessing the need for routine ipsilateral adrenalectomy during radical nephrectomy. METHODS: Ipsilateral and contralateral adrenal metastases were investigated in 256 patients with RCC who had undergone radical nephrectomy from 1977 to 1996 at the Tohoku University School of Medicine. RESULTS: Twelve of the 256 patients (4.7%) had adrenal metastasis. Ten of these 12 patients had progressed to disseminated disease with very poor prognosis. Two patients who had solitary adrenal metastases remained disease-free for 21 and 7 years. Four patients showed metastases to the contralateral adrenal gland. Adrenal metastases in seven of 12 patients were identified by pre- or postoperative computed tomography (CT), and in another five macroscopically during surgery. CONCLUSIONS: Adrenalectomy was regarded as a possible curative treatment for patients with solitary adrenal metastasis. However, the incidence of this kind of metastasis was minimal and contralateral adrenal metastases may occur in RCC cases. We therefore believe that adrenalectomy should only be performed if radiographic evidence reveals metastases in the adrenal gland or if gross disease is present at the time of nephrectomy.

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BACKGROUND: The incidence and clinical features of bilateral germ cell testicular tumor (GCTT) in the Japanese population are not fully characterized. We examined the incidence, clinical features, management and outcome, sexual status, hormonal environment, implication of androgen replacement, and human leukocyte antigen (HLA) typing of bilateral GCTT. METHODS: We treated nine consecutive patients with bilateral GCTT from 1980 through to 1999, and reviewed their hospital and clinic charts. Testosterone, luteinizing hormone, follicle stimulating hormone, dehydroepiandrosterone, and dehydroepiandrosterone-sulfate were measured in bilateral orchiectomized patients. Human leukocyte antigen typing was assessed with peripheral lymphocyte. RESULTS: The incidence of bilateral GCTT against the total number of patients with GCTT was 9/274 (3.3%). The median age of the first tumor was 29 (range 21-75) years. Three cases were synchronous and the remaining six cases were metachronous. In the case of metachronous tumor, the median interval between first and contralateral tumor was 8 (range 2-25) years. Standard treatment was defined as surveillance policy in stage I, chemotherapy for higher stages of non-seminoma, and radiotherapy for stage II seminoma. Human leukocyte antigen typing was examined for seven cases. Five cases were positive for HLA-A24. The incidence of HLA-A24 in bilateral GCTT was identical to that of the Japanese population. The relapsing incidence of stage I disease with surveillance policy was almost identical to unilateral GCTT. A 74-year-old patient with stage II seminoma died of the disease at 1.3 years. The other eight patients remained well without any evidence of recurrence at a median follow-up period of 78 (range 12-204) months. Four patients with bilateral orchiectomy did not require androgen replacement without easy fatigability. Sexual status was conserved using androgen replacement. CONCLUSIONS: Long-term follow-up, as long as 25 years, is recommended for contralateral relapse. Some patients with bilateral orchiectomy do not require androgen replacement. The significance of HLA-A24 for bilateral testicular tumor is equivocal in the Japanese population.

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PURPOSE: We performed ultrasonography and (99m)technetium dimercaptosuccinic acid (DMSA) renal scan in infants with unilateral hydronephrosis during followup and after pyeloplasty to examine the correlation of ultrasound hydronephrosis grade with the severity of renal cortical damage and assess the recovery of renal function in the obstructed kidneys after surgery. MATERIALS AND METHODS: We studied 80 boys and 19 girls with unilateral hydronephrosis detected in the first year of life, including 75 (76%) in whom it was detected prenatally. Ultrasound images were graded according to the Society for Fetal Urology grading system. The severity of renal cortical damage was assessed by DMSA renal scan. Absolute function of the right and left kidneys was estimated by DMSA uptake and relative DMSA uptake was calculated by the formula, relative uptake = uptake in obstructed kidney/total uptake in right and left kidneys x 100%. RESULTS: On ultrasonography grades 1 to 4 hydronephrosis were diagnosed in 9, 21, 19 and 50 kidneys, respectively. On DMSA renal scan cortical damage was detected in 10 kidneys (53%) with grade 3 and 49 (98%) with grade 4 hydronephrosis but not in kidneys with grade 1 or 2 disease. Dysfunction in the obstructed kidney, defined as relative DMSA uptake less than 40%, was noted in 13 patients with grade 4 hydronephrosis. Relative DMSA uptake significantly increased after successful pyeloplasty compared with preoperative uptake (44% +/- 2% versus 40.1% +/- 2%, p <0.01). CONCLUSIONS: Ultrasound grading of hydronephrosis correlates with the severity of cortical damage or the decrease in renal function on DMSA renal scan. Differential renal function on DMSA renal scan may be a useful and less invasive tool for determining surgical indications and examining changes in renal function after surgery.

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PURPOSE: The plasminogen activator (PA)-plasmin system has been shown to influence turnover of the extracellular matrix in various tissues. We examined the alteration of plasminogen activator inhibitor-1 (PAI-1) and tissue-type plasminogen activator (t-PA) in kidneys with unilateral ureteral obstruction in rats. MATERIALS AND METHODS: Female rats that underwent ligation of the left ureter were sacrificed 12 hours, 1, 5 or 10 days later. The expressions of PAI-1 and t-PA was determined by reverse transcription-polymerase chain reaction and immunohistochemical studies in the obstructed and contralateral kidneys in each group. RESULTS: Control kidneys showed no PAI-1 messenger (m)RNA expression. After days 1 through 10 of unilateral ureteral obstruction the amount of PAI-1 mRNA significantly increased in obstructed compared with contralateral kidneys (p <0.01). Meanwhile, slight polymerase chain reaction products of t-PA were observed in control kidneys. After 12 hours through 10 days of unilateral ureteral obstruction, t-PA mRNA in obstructed and contralateral kidneys was significantly elevated compared with in control kidneys (p <0.05). No significant difference in t-PA was observed in the obstructed and contralateral kidneys in each group. Immunoreactivity to PAI-1 and t-PA was identified in obstructed kidneys. CONCLUSIONS: PAI-1 and t-PA are up-regulated in obstructed rat kidneys. Our results indicate that the PA-plasmin system has a role in the process of matrix accumulation and degradation during rat obstructive nephropathy.

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BACKGROUND: Two types of transitional bladder carcinoma have been distinguished based on macroscopic morphology: type A papillary carcinomas, with papillomatous surface outgrowth without infiltration into muscular layer, and type B nodular carcinomas, with a nonpapillomatous surface appearance, most of which display infiltrative growth through muscular layer, and some of which display lymphatic or blood-borne metastasis. However, there is no specific predictor at early stages for later invasive and metastatic clinical outcome of patients with type B tumors. METHODS: The study included 1) glycosphingolipid (GSL) composition of type A and B tumors; 2) histologic and immunohistologic patterns of nodular (type B) bladder carcinoma from 44 patients based on a special sampling procedure termed whole-layer core biopsy (WLCB) using the antisialosyl-Le(x) (anti-SLe(x); SLe(x): NeuAcalpha3Galbeta4[Fucalpha3]GlcNAcbeta3Galbeta4GlcCer) SNH3 antibody or other antibodies; 3) comparison of the incidence of metastasis in patients with SNH3 positive versus SNH3 negative primary tumors and of 5-year survival curves; 4) comparison of bladder carcinoma cell lines from tumors with high versus low malignancy in terms of expression patterns of SLe(x), SLe(a), and other carbohydrates, E-selectin dependent adhesion, and transcript levels of five fucosyltransferases. RESULTS: Anti-SLe(x) monoclonal antibody (mAb) SNH3 staining of WLCB samples from 44 type B tumors showed that the majority of tumors (n = 31 patients) were SNH3 positive and the minority (n = 13 patients) were SNH3 negative. SNH3 positive patients had more lymph node or blood-borne metastasis and lower 5-year and 7-year survival rates, as indicated by Kaplan-Meier curves (P = 0.001). Staining of samples with other antibodies, including FH6 and CA19-9, was not correlated with long-term survival. Determination of GSL composition in extracts showed that SLe(x) ganglioside was present in all three patients with nodular tumors but absent in all three patients with papillary tumors tested. Bladder carcinoma cell lines from invasive tumors that maintained their metastatic properties were SNH3 positive, showed high levels of alpha1,3-fucosyltransferase VI (FT-VI) and FT-VII, and displayed E-selectin dependent adhesion. Cell lines from noninvasive tumors or normal bladder epithelia were negative for SNH3 reactivity, FT-VI, and FT-VII, and E-selectin dependent adhesion. CONCLUSIONS: SLe(x) expression in primary bladder carcinoma, defined by the mAb SNH3, is a predictor of invasive and metastatic outcome. No other carbohydrate epitope examined to date has equal prognostic value.

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BACKGROUND: The present study provides data from clinical experience with gamma-knife radiosurgery (GK) in patients with brain metastasis from renal cell carcinoma (RCC) and shows the value of this less invasive treatment modality. METHODS: Forty-two patients received GK. Twenty of the 42 cases had multiple brain metastases. Extracranial metastases were observed in the lung (38 cases), bone (12 cases), liver (9 cases), lymph node (5 cases) and skin (6 cases). RESULTS: Neurological symptoms seen in 40 patients were rapidly improved after GK in 32 patients (80%). Magnetic resonance imaging (MRI) evaluation after GK in 32 patients showed the disappearance of brain tumor in 9 patients (28%). Complete response was obtained by GK in tumors up to 30 mm in diameter. Repeated GK for newly developed lesions was conducted in 11 patients. Extracranial tumor resection was conducted in 7 cases (lung: 3, skin: 2, liver: 1, adrenal: 1). Chemo-radiotherapy or immunotherapy was effective in 8 cases (lung: 5, liver: 2, bone: 1). The actual one-, two- and three-year survival rates were 44.9%, 16.8%, and 11.2%, respectively. The median survival time was 12.5 months. In univariate analysis, the patients with successfully treated extracranial metastases had significantly better prognosis. In multivariate analysis, the patients with Karnofsky performance scale (KPS) > or = 80%, who were treated by GK more than once and obtained complete response (CR) or partial response (PR) by GK, had significantly better prognosis. CONCLUSION: Gamma-knife radiosurgery for RCC is an effective non-invasive modality of treatment. It offers a high local control rate and an improved quality of life and survival rate.

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