The origin of idiopathic renal arteriovenous malformation with giant twin aneurysms.

A 50-year-old female patient who presented with intermittent gross hematuria was referred to our hospital. Three-dimensional computed tomography (3D-CT) revealed a left renal arteriovenous malformation (AVM). Because she declined to undergo additional therapy including surgical treatment, we observed the clinical course of renal AVM for 7 years using 3DCT. When the 3D-CT showed gradual enlargement of the aneurysms concurrent with the onset of clinical symptoms (cardiomegaly and hypertension), we performed simple left nephrectomy. After the operation, the cardiomegaly and hypertension returned to normal, and gross hematuria did not recur. Based on the macro-anatomical findings of the resected kidney and the observation of the natural course, this case strongly supported the hypothesis that the renal AVM had existed from birth and enlarged gradually to eventually produce the typical signs and symptoms.

Discontinuation of tamsulosin treatment in men with lower urinary tract symptoms: a pilot study.

OBJECTIVES: Since little investigation has been undertaken to determine if alpha1-blockers should be given continuously to sustain their efficacy, we conducted a pilot study to determine symptom change following discontinuation of tamsulosin after an initial improvement in symptoms in men with lower urinary tract symptoms (LUTS). PATIENTS AND METHODS: Thirty-three of 78 patients with mild-to-moderate prostate hyperplasia, who had symptom improvement according to the International Prostate Symptom Score (IPSS) to <10 or the quality of life (QOL) index to < or =3 after initial treatment with tamsulosin, were enrolled in this study. Subjective parameters (IPSS and QOL index) and objective parameters (maximum and mean urinary flow rates) were evaluated at baseline and after initial treatment, and 4, 8, 12 and 24 weeks after discontinuing tamsulosin. RESULTS: The rates of successful discontinuation of tamsulosin were high throughout the follow-up period, i.e., 80.6% at 4 weeks, 80.6% at 8 weeks, 80.0% at 12 weeks, and 68.9% at 24 weeks. Temporary worsening in both subjective and objective parameters was observed only at 4 weeks; however, these parameters recovered to almost post-treatment levels at 24 weeks. CONCLUSION: The present study suggests that continuous treatment is not always needed to maintain urinary symptom relief in a specific subset of patients who felt symptom improvement after initial treatment with tamsulosin.

Intraindividual variation in total and percent free prostate-specific antigen levels in prostate cancer suspects.

OBJECTIVES: To investigate intraindividual total and percent free serum prostate-specific antigen (PSA) in prostate cancer suspects and to understand the clinical implications. PATIENTS AND METHODS: Total and percent free PSA were measured using Tandem-R or chemiluminescent enzyme-linked immunoassay for a median of three times in 126 men. Prostate biopsies were performed in all patients; benign prostatic hyperplasia was diagnosed in 81 patients and prostate cancer in 45 patients. RESULTS: The overall mean coefficients of variation for total and percent free PSA were 16.10 +/- 11.94% and 15.45 +/- 15.91%, respectively. A significant correlation (p = 0.0056) was observed between the two variations. The variations in total and percent free PSA were related to none of such stratifications as baseline total PSA level, histology, age, or measurement interval, but for measurement interval on that for total PSA. CONCLUSION: Intraindividual variation in serum PSA should be considered in decision-making about performing prostate biopsies. Also, care should be taken in interpreting repeated percent free PSA measurements in order to enhance the specificity of total PSA, because it had a similar variation to total PSA variation.

Vascular endothelial growth factor-C (VEGF-C) expression predicts lymph node metastasis of transitional cell carcinoma of the bladder.

PURPOSE: It has been found that expression of vascular endothelial growth factor-C (VEGF-C) in several carcinomas is significantly associated with angiogenesis, lymphangiogenesis and regional lymph node metastasis. However, VEGF-C expression in bladder transitional cell carcinoma (TCC) has not yet been reported. To elucidate the role of VEGF-C in bladder TCC, we examined VEGF-C expression in bladder TCC and pelvic lymph node metastasis specimens obtained from patients who underwent radical cystectomy. METHODS: Eighty-seven patients who underwent radical cystectomy for clinically organ-confined TCC of the bladder were enrolled in the present study. No neoadjuvant treatments, except transurethral resection of the tumor, were given to these patients. The VEGF-C expressions of 87 bladder tumors and 20 pelvic lymph node metastasis specimens were examined immunohistochemically and the association between VEGF-C expression and clinicopathological factors, including angiogenesis as evaluated by microvessel density (MVD), was also examined. RESULTS: Vascular endothelial growth factor-C expression was found in the cytoplasm of tumor cells, but not in the normal transitional epithelium. Vascular endothelial growth factor-C expression was significantly associated with the pathological T stage (P = 0.0289), pelvic lymph node metastasis (P < 0.0001), lymphatic involvement (P = 0.0008), venous involvement (P = 0.0002) and high MVD (P = 0.0043). The multivariate analysis demonstrated that VEGF-C expression and high MVD in bladder TCC were independent risk factors influencing the pelvic lymph node metastasis. Moreover, the patients with VEGF-C-positive tumors had significantly poorer prognoses than those with the VEGF-C-negative tumors (P = 0.0087) in the univariate analysis. The multivariate analysis based on Cox proportional hazard model showed that the independent prognostic factors were patient age (P = 0.0132) and pelvic lymph node metastasis (P = 0.0333). CONCLUSION: The present study suggests that VEGF-C expression is an important predictive factor of pelvic lymph node metastasis in bladder cancer patients.

Vesicoureteral reflux after intravesical instillation of bacillus Calmette-Guérin against carcinoma in situ of the bladder.

We report a case of vesicoureteral reflux (VUR) 3 years after intravesical instillation of bacillus Calmette-Guérin (BCG, Tokyo 172 strain) against carcinoma in situ of the bladder. The present case suggests that a long-term careful follow-up is needed to detect not only tumor recurrences but also VUR as a late complication after intravesical BCG instillation.

[A case of advanced rhabdomyosarcoma of the spermatic cord who occurred epilepsy-like symptoms, but was completely responded to chemotherapy].

A 19-year-old man presented with left aggressive painless scrotal swelling. On the diagnosis of left intrascrotal tumor, left high orchiectomy with partial scrotal skin resection was performed. Pathological examination of the specimen and systemic metastasis survey revealed embryonal rhabdomyosarcoma of left spermatic cord with multiple lung metastasis (Intergroup Rhabdomyosarcoma Study Group IV). Systemic chemotherapy with etoposide (VP-16), cisplatin (CDDP), and ifosfamide (IFO) (VIP therapy) was started. Although epilepsy-like symptoms occurred at the first course of VIP therapy, these symptoms immediately improved by diazepam administration. These symptoms were thought to be due to the adverse effects of IFO. To our knowledge, there were little reports on epilepsy-like symptoms caused by IFO in Japan. On the other hand, his multiple lung metastasis disappeared after the second course of VIP therapy. Although IFO may be effective in rhabdomyosarcoma, the toxicity of various nervous systems may be discovered.

Primary cell preparation of human renal tubular cells for transcriptome analysis.

We initiated a toxicogenomics project using Affymetrix GeneChip((R)) HG-U133A and HG-U133B arrays harboring 45,000 probe sets representing more than 39,000 transcripts to analyze gene expression in primary cultures of human cells after exposure to chemicals that cause tissue toxicity. In order to assess the quality of the samples studied, we prepared primary human renal cortical cell cultures from surgically resected human kidney and evaluated the origin of the cells and the effects of cryopreservation. We analyzed the primary cultures using GeneChip and compared their expression patterns with those in the Novartis Research Foundation (GNF) Gene Expression Database. The comparison with the GNF database revealed that the gene expression pattern of the cultured cells was compatible with kidney cells, indicating that we had purified human renal cortical cells. Due to the purification procedure, the primary cultured cells could be a mixture of renal components; however, we identified the major population as renal proximal tubule cells by assessing gamma-GTP activity and Glut2 antigen expression. We compared gene expression in the cells before and after cryopreservation. The expression of 567 selected housekeeping genes was unchanged by cryopreservation (Pearson's correlation coefficient r = 0.980; p < 0.0001). The analysis of more than 39,000 transcripts after normalization revealed no significant changes in expression. These results indicate that our method is satisfactory for obtaining adequate primary cell cultures of renal origin and that gene expression was not significantly changed by cryopreservation.

Forced expression of cytidine deaminase confers sensitivity to capecitabine.

OBJECTIVE: Cytidine deaminase (CDD) is involved in the metabolism of new pyrimidine analogues, capecitabine (N(4)-pentyloxycarbonyl-5'-deoxy-5-fluorocytidine) and gemcitabine (2',2'-difluorodeoxycytidine). The purpose of the present study was to directly examine the role of CDD in tumor cells themselves in mediating the sensitivity to capecitabine compared with gemcitabine. METHODS: The human bladder cancer cell line T24 was transfected with human CDD2 cDNA by the lipofectin method. RESULTS: Transfection of CDD2 cDNA did not change the levels of thymidine phosphorylase, dihydropyrimidine dehydrogenase and thymidylate synthase (TS) but increased the CDD activity significantly (p < 0.01). Forced expression of CDD made T24 sensitive to 5'-deoxy-5-fluorocytidine (5'DFCR) in vitro and capecitabine in vivo, but resistant to gemcitabine both in vitro and in vivo. Tetrahydrouridine, a specific CDD inhibitor, abrogated the changes in the in vitro sensitivity to 5'DFCR and gemcitabine by transfection of CDD2 cDNA. Transfection of CDD2 cDNA resulted in a significant increase in cellular 5-fluorouracil level (p < 0.01) and inhibition of TS activity (p < 0.01) after treatment with 5'DFCR in vitro. CONCLUSIONS: The present study clearly showed direct evidence for the contribution of CDD in tumor cells themselves to the sensitivities to capecitabine and gemcitabine.

Giant stercoral stone and catheterization difficulty.

An unusual case of giant calcification in the midline of the pelvis is reported herein. An 84-year-old male, whose urination was managed by clean intermittent self-catheterization (CIC), presented with catheter insertion difficulty. The patient had a history of transurethral operations for benign prostatic hyperplasia and small bladder stones. Kidney, ureter and bladder (KUB) X-ray of post-enhanced computed tomography (CT) suggested a giant ball-shaped calcification in the bladder. A recurrent bladder stone was suspected. However, pelvic CT scan revealed that the giant calcification was, in fact, situated in the rectum. Thus, a diagnosis of giant stercoral stone was made. After the stone was removed manually, the patient had no difficulty in inserting the catheter. His prior complaint may have been caused by urethral bladder neck obstruction due to the giant stercoral stone.

[Clinical evaluation of hot flushes developing during endocrine therapy for prostate carcinoma].

OBJECTIVE: There are few clinical investigations on the hot flushes that develop during endocrine therapy for prostate cancer in Japan, although there are many reports in the Western countries. Therefore, we evaluated the incidence of hot flushes and the association between hot flushes and clinical characteristics of prostate cancer patients receiving endocrine therapy. PATIENTS AND METHODS: Sixty-eight prostate cancer patients receiving endocrine therapy (LH-RH analog (group LH-RHA); 22 patients, LH-RHA + non-steroidal antiandrogen (group LH-RHA + NSAA); 20 patients, LH-RHA + steroidal antiandrogen (group LH-RHA + SAA); 8 patients, LH-RHA + estramustine phosphate (group LH-RHA + EP); 1 patient, bilateral orchiectomy (group O); 5 patients, O + non-steroidal antiandrogen (group O + NSAA); 11 patients, and O + steroidal antiandrogen (group O + SAA); 1 patient) were evaluated by a fixed questionnaire. The incidence of the hot flush, the association between hot flushes and the clinical factors, as well as the therapy of hot flushes including SAA and Kampo therapy were analyzed. RESULTS: The overall incidence of hot flushes was 37% (36% in group LH-RHA, 45% in group LH-RHA + NSAA, 13% in group LH-RHA + SAA, 0% in group LH-RHA + EP, 20% in group O, 45% in group O + NSAA, 100% in group O + SAA). No significant association between the hot flushes and the clinical factors of the patients was observed. On the other hand, in 3 of 4 patients treated by SAA, hot flushes improved after 4 weeks. In 2 of 3 patients treated by Kampo, hot flushes improved after 4 weeks. CONCLUSION: Hot flushes are the major side effect of endocrine therapy for Japanese prostate cancer patients. SAA and Kampo are thought to be effective for treatment of hot flushes.

Quantitative analysis of thymidine phosphorylase and dihydropyrimidine dehydrogenase in renal cell carcinoma.

OBJECTIVE: The purpose of the present study was to clarify the clinicopathological significance of both thymidine phosphorylase (TP) and dihydropyrimidine dehydrogenase (DPD) in renal cell carcinoma (RCC) based on a quantitative analysis of RCC patients. METHODS: Levels of TP and DPD in RCC and/or uninvolved renal tissues from 65 RCC patients were measured by enzyme-linked immunosorbent assay. RESULTS: The TP level and TP/DPD ratio were significantly higher in RCC than in adjacent uninvolved renal tissues (p < 0.0001). There was no significant difference in DPD levels between RCC and uninvolved renal tissues. The ratio of the highest to the lowest level was 623 in TP level, 28.9 in DPD level, and 985 in TP/DPD ratio. In the univariate analysis, patient's age (p = 0.04), tumor stage (p < 0.0001), tumor size (p = 0.007), TP expression (p = 0.03), and DPD expression (p = 0.04) were significantly associated with increased risk of death. Multivariate analysis showed that patient's age, tumor stage, and TP expression were independent prognostic factors. CONCLUSIONS: TP and DPD in RCC provide prognostic information although DPD was not an independent prognostic factor. The present finding of a wide range in these enzyme expressions in RCC suggests that a certain subpopulation with a high TP/DPD ratio has potential responsiveness to fluoropyrimidines, especially 5'-deoxy-5-fluorouridine and capecitabine.

Elevated serum progastrin-releasing peptide (31-98) level is a predictor of short response duration after hormonal therapy in metastatic prostate cancer.

BACKGROUND: The neuroendocrine (NE) pathway has been attracting attention as a mechanism for the androgen-independent progression because the neuropeptide provokes tumor growth and inhibits apoptosis under androgen-deprived milieu in prostate cancer cells. On the basis that serum progastrin-releasing peptide (ProGRP) is elevated in patients with advanced disease stage, we examined the prognostic value of the neuropeptide. METHODS: Serum ProGRP status was determined with an enzyme-linked immunosorbent assay (ELISA) in 460 men with benign and malignant prostatic diseases, chronic renal failure, and healthy controls. Seventy patients with metastatic prostate cancer including four patients (5.7%) with NE carcinoma who underwent hormonal therapy were enrolled in the prognostic analyses by Cox proportional hazards model. RESULTS: The serum status steadily shifted toward predominant expression of ProGRP with the progression of prostate cancer into metastatic and androgen-independent stages. Univariate analysis revealed that the deteriorated performance status (PS) and extent of bony disease (EOD), and high serum alkaline phosphatase (ALP), serum ProGRP, and nadir prostate-specific antigen (PSA) levels were associated with a lower progression-free survival (PFS) rate (P < 0.005). Multivariate analysis demonstrated that PS, serum ProGRP, and nadir PSA held an independent predictive value for PFS (P < 0.05), and all correlated with bone-related factors. Serum ProGRP was the most significant predictor among pre-treatment factors in this model (P = 0.0094). CONCLUSIONS: The neuropeptide precursor ProGRP is a distinct serum marker that is useful to know the NE milieu and provides prognostic information in patients with advanced prostate cancer. Standard therapy for metastatic prostate cancer may make progress when further studies will clarify the causative link between serum ProGRP level and androgen-independent disease progression.

Giant bladder diverticulum due to previous bullet injury: findings of gadolinium-enhanced magnetic resonance imaging.

Non-obstructive acquired giant bladder diverticulum is rare. An 84-year-old man presented with difficulty in urination. Radiological examinations including pelvic magnetic resonance imaging, urethrocystography and urethrocystoscopy demonstrated a giant bladder diverticulum with normal infravesical urinary tract. The patient had a past history of gunshot bladder injury and underwent surgical removal of the bullet. The giant bladder diverticulum was thought to be associated with the injury or the operation.

A deserosalized muscle layer covering method for antireflux ureteroileostomy: a preliminary clinical trial.

PURPOSE: To achieve complete protection of the upper urinary tract in patients with a neobladder we designed and clinically applied the deserosalized muscle layer covering method, a new antireflux ureteroileal reimplantation technique in which the terminal ureter is implanted in the muscle layer of the ileum. We present the operative procedure and preliminary results. MATERIALS AND METHODS: We created an orthotopic ileal neobladder after radical cystectomy in 5 patients with invasive bladder cancer. The ureters were reimplanted into the reservoir using the deserosalized muscle layer covering method. The functional outcome of this procedure was evaluated by radiological studies. RESULTS: No patients died during the perioperative period and no reimplanted ureters showed ureteral reflux or ureteral stricture during the observation period. Video cystometrograms demonstrated the complete prevention of reflux during the voiding and storage phases. CONCLUSIONS: The deserosalized muscle layer covering method provided a nonobstructed unidirectional flow of urine in all renal units examined in this study. The efficacy of this method was proved during short-term followup.

Immunohistochemical study of bcl-2, p53 and Ki-67 expressions in collecting duct carcinoma of the kidney. Five cases and review of the literature on bcl-2, p53 and Ki-67 expressions in renal cell carcinoma and transitional cell carcinoma.

OBJECTIVES: This study was designed to examine the expressions of bcl-2, p53 and Ki-67 antigen in collecting duct carcinoma (CDC) of the kidney by an immunohistochemical method. METHODS: The diagnosis of CDC was based on the criteria proposed by Srigley and Eble. The clinical courses of 5 CDC cases examined in this study suggested that 3 cases were low grade and 2 cases high grade. The expressions of bcl-2, p53 and Ki-67 antigen were evaluated in paraffin-embedded surgical specimens using anti-bcl-2 and anti-p53 antibodies and Ki-67 antigen, respectively. RESULTS: The expression of bcl-2 was recognized in 3 of 5 cases (60%), p53 expression also in 3 of 5 cases (60%). The Ki-67 labeling index was 7.46 +/- 7.40 (mean +/- SD). CONCLUSIONS: It was suggested that there were two clinical types in CDC; the expression of bcl-2 did not correlate with the CDC patients' clinical courses and the cellular proliferation, and p53 expression was recognized in the CDC patients with highly cellular proliferation.

De-serosalized muscle layer covering method for antireflux ureteroileostomy: a new operative technique and pressure study with ureterometry at the ureteroileal anastomotic site in dogs.

PURPOSE: In pursuit of a more effective antireflux ureteroileostomy with a lower postoperative complication rate we performed a new operative technique and evaluated intraureteral pressure with ureterometry to examine the mechanism of antireflux function. MATERIALS AND METHODS: A total of 11 beagle dogs were used in this study. A 3 x 2 cm. section of the ileal serosa was removed, the severed ureter was directly anastomosed to the de-serosalized area and 1 cm. of terminal ureter and the direct anastomotic site were covered with the de-serosalized ileal wall. The bladder was augmented with the ileum containing the ureter. Postoperative evaluations were performed monthly and ureterometry of the reimplanted ureter was done 6 months postoperatively. RESULTS: Complete reflux prevention and a low stricture rate were achieved with this procedure. Direct ureteroileal anastomosis caused stricture in 1 of the 11 ureters but the covering procedure to prevent ureteral reflux caused no ureteral strictures. When the bladder was empty, ureteral closure pressure at the intramural portion of the ureter was low. At the phase of high intravesical pressure ureteral closure pressure at the intramural ureter was as high as intravesical pressure. CONCLUSIONS: The de-serosalized muscle layer covering method prevented ureteral reflux completely with a low stricture rate. The antireflux function of this method seems to depend on the flexibility of the terminal ureter covered with the de-serosalized ileal wall. Reflux prevention in the low intravesical pressure phase seems to be due to extension of the ileal wall.

Isoliquiritigenin suppresses pulmonary metastasis of mouse renal cell carcinoma.

Isoliquiritigenin is a chalcone isolated from licorice and shallots. The ability of isoliquiritigenin to suppress metastasis was examined in a pulmonary metastasis model of mouse renal cell carcinoma. Isoliquiritigenin significantly reduced pulmonary metastasis, without any weight loss or leukocytopenia. Isoliquiritigenin suppressed in vitro proliferation of carcinoma cells, potentiated nitric oxide production by lipopolysaccharide-stimulated macrophages, and facilitated cytotoxicity of splenic lymphocytes in vitro. These findings suggest activation of macrophages, activation of cytotoxicity of lymphocytes, and direct cytotoxicity as possible mechanisms of metastasis suppression by isoliquiritigenin. In addition, isoliquiritigenin prevented severe leukocytopenia caused by administration of 5-fluorouracil.