Antimicrobial susceptibilities of Mycoplasma genitalium strains examined by broth dilution and quantitative PCR.

Only limited information regarding the antimicrobial susceptibilities of Mycoplasma genitalium is available because of difficulties in isolating M. genitalium strains from clinical specimens. Antimicrobial susceptibilities of 15 clinical isolates, 7 ATCC strains, and an early passage of the M30 strain were examined by the broth dilution method. Azithromycin, clarithromycin, sitafloxacin, and moxifloxacin were the most active drugs against M. genitalium, and their MIC(90)s were 0.002, 0.008, 0.125, and 0.125 mg/liter, respectively.

DNA repair gene hOGG1 codon 326 and XRCC1 codon 399 polymorphisms and bladder cancer risk in a Japanese population.

BACKGROUND: Bladder cancer is the most common urologic malignancy in the USA. Tobacco smoking generates oxidative DNA damage and induces bladder cancer. Base excision repair (BER) is a very important mechanism for repairing oxidative DNA damage. There are many enzymes involved in BER. Human oxoguanine glycosylase 1 (hOGG1) and X-ray repair cross-complementing 1 (XRCC1) are enzyme genes of BER. Actually, the hOGG1 codon 326 polymorphism was associated with the risk of lung oesophagus and stomach cancer. On the other hand, among several XRCC1 gene polymorphisms, codon 399 polymorphism was reported to reduce the risk of bladder cancer and raise the risk of lung cancer. METHODS: We examined the association between the genetic polymorphisms of hOGG1 codon 326 and XRCC1 codon 399 and bladder cancer risk. In this study, we recruited 251 bladder cancer cases and 251 healthy controls to evaluate the effect of hOGG1 codon 326 and XRCC1 codon 399 polymorphisms on bladder cancer. We detected genotypes by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. RESULTS: The frequencies of the hOGG1 codon 326 genotypes Cys/Cys was significantly higher in the cases than in the controls. Adjusted odds ratio (OR) was 1.85 (95% CI: 1.12-3.03; p = 0.02) compared with Ser/Ser, and was 2.05 (95% CI: 1.36-3.08; p = 0.01) compared with Ser/Ser + Ser/Cys. In addition, when evaluated with smoking status, the adjusted OR (Cys/Cys versus Ser/Ser + Ser/Cys) ran up to 2.78 (95% CI: 1.39-5.60; p < 0.01) among non-smokers. For the XRCC1 polymorphism, the Gln/Gln of XRCC1 codon 399 genotype was statistically higher in the controls than in the cases though compared with Alg/Alg + Alg/Gln. The adjusted OR was 0.45 (95% CI: 0.21-0.99; p = 0.05), and was lifted up to 0.37 (95% CI: 0.14-0.98; p = 0.05) among smokers. CONCLUSION: It is indicated that the hOGG1 codon 326 and XRCC1 codon 399 polymorphisms are risk factors of bladder cancer.

Activation of hepatocyte growth factor activator zymogen (pro-HGFA) by human kallikrein 1-related peptidases.

Hepatocyte growth factor activator (HGFA) is a serine protease and a potent activator of prohepatocyte growth factor/scatter factor (pro-HGF/SF), a multifunctional growth factor that is critically involved in tissue morphogenesis, regeneration, and tumor progression. HGFA circulates as a zymogen (pro-HGFA) and is activated in response to tissue injury. Although thrombin is considered to be an activator of pro-HGFA, alternative pro-HGFA activation pathways in tumor microenvironments remain to be identified. In this study, we examined the effects of kallikrein 1-related peptidases (KLKs), a family of extracellular serine proteases, on the activation of pro-HGFA. Among the KLKs examined (KLK2, KLK3, KLK4 and KLK5), we identified KLK4 and KLK5 as novel activators of pro-HGFA. Using N-terminal sequencing, the cleavage site was identified as the normal processing site, Arg407-Ile408. The activation of pro-HGFA by KLK5 required a negatively charged substance such as dextran sulfate, whereas KLK4 could process pro-HGFA without dextran sulfate. KLK5 showed more efficient pro-HGFA processing than KLK4, and was expressed in 50% (13/25) of the tumor cell lines examined. HGFA processed by these KLKs efficiently activated pro-HGF/SF, and led to cellular scattering and invasion in vitro. The activities of both KLK4 and KLK5 were strongly inhibited by HGFA inhibitor type 1, an integral membrane Kunitz-type serine protease inhibitor that inhibits HGFA and other pro-HGF/SF-activating proteases. These data suggest that KLK4 and KLK5 mediate HGFA-induced activation of pro-HGF/SF within tumor tissue, which may thereafter trigger a series of events leading to tumor progression via the MET receptor.

Usefulness of oral wash specimens for detecting Chlamydia trachomatis from high-risk groups in Japan.

Orogenital sex is recognized as a route for the transmission of Chlamydia trachomatis (CT) which thus causes male chlamydial urethritis. Patients with a pharyngeal CT infection have no gross lesions, but CT was tested by pharyngeal swabs. In this study, the usefulness of oral wash specimens for detecting CT was compared to that of swab specimens. In addition, oral wash specimens were also used to screen for CT pharyngeal infection. Eighteen female commercial sex workers in whom CT was detected from pharyngeal swabs were re-examined using both methods. The positive rate for CT was 44% by swabs and 61% by oral wash specimens. Forty-eight male students with CT-positive urine were also screened for pharyngeal CT infection. The positive rates were 6% by swabs and 10% by oral wash specimens. Our findings therefore indicate that oral wash specimens more effectively detected pharyngeal CT infection than pharyngeal swabs.

Clinical relevance of hepsin and hepatocyte growth factor activator inhibitor type 2 expression in renal cell carcinoma.

Cell surface proteolysis is important for the generation of bioactive proteins mediating tumor progression. Recent studies suggest that the membrane-anchored cell surface proteinases matriptase and hepsin have significant roles in tumors. We analyzed the expression and clinical relevance of matriptase and hepsin, and their inhibitors hepatocyte growth factor activator inhibitor type 1 (HAI-1) and type 2 (HAI-2) in 66 cases of conventional renal cell carcinomas (RCC). The mRNA level was evaluated in paired samples from tumor and non-tumorous renal tissues by real-time reverse transcription-polymerase chain reaction. As matriptase and hepsin potently activate the proform of hepatocyte growth factor (HGF), the expression of HGF and its receptor, c-Met, was also analyzed. Although upregulation of matriptase was observed occasionally in RCC, the expression level was not associated with prognostic parameters. Hepsin was downregulated in RCC, particularly in early stage disease, but upregulated in advanced stages. There was a trend of higher hepsin expression in RCC with distant metastasis, and Kaplan-Meier survival curves showed that high hepsin expression was associated with reduced overall survival (P<0.01, log-rank test). Moreover, multivariate analysis indicated that hepsin was an independent prognostic factor. Overexpression of HGF or c-Met also showed reduced overall survival. We also observed a tendency of low HAI-2 expression with reduced overall survival and a statistical association between high hepsin and low HAI-2 level. No associations were observed between matriptase and HAI-1 and HAI-2. Our findings suggest that the balance between hepsin and its inhibitor, HAI-2, may have prognostic value in RCC.

Isolation of Mycoplasma genitalium from first-void urine specimens by coculture with Vero cells.

Isolation of Mycoplasma genitalium from clinical specimens remains difficult. We describe an improvement of the Vero cell coculture method in which the growth of M. genitalium was monitored by quantitative real-time PCR. Four new M. genitalium strains were isolated from six first-void urine specimens of male Japanese patients with urethritis. In two of them, only M. genitalium was detected: one also contained Ureaplasma urealyticum, and one contained Chlamydia trachomatis, Neisseria gonorrhoeae, U. urealyticum, and Ureaplasma parvum. In the specimens yielding isolates of M. genitalium, growth was documented by quantitative PCR after two to five passages in Vero cells. The complete isolation procedure from the initial inoculation to completion of single-colony cloning took about 1 year. Isolation of M. genitalium from urine specimens proved to be more difficult than from swab specimens. Due to the cytotoxic effect of urine, a procedure involving washing of the urinary sediment was introduced. Furthermore, prolonged storage of the urine specimens before culture was shown to be detrimental to the success of isolation, as shown by the lack of success in attempts to isolate M. genitalium from mailed urine specimens as well as by simulation experiments. High concentrations of penicillin G and amphotericin B were surprisingly inhibitory to the growth of wild-type M. genitalium strains, but penicillin G at 200 IU/ml and polymyxin B at 500 microg/ml could be used as selective antibiotics to avoid bacterial overgrowth in the Vero cell cultures.

[Yoke technique for severe proximal hypospadias].

UNLABELLED: PROPOSED: Various techniques have so far been reported for the repair of hypospadias, however, a one-stage procedure for the repair of severe proximal hypospadias still remains difficult to perform. We recently have begun to use the Yoke hypospadias repair technique for the treatment of severe proximal hypospadias. PATIENTS AND METHODS: As the chief surgeon, I performed a one-stage hypospadias repair on 40 proximal hypospadiac patients with severe fibrous chordee between July 1992 and December 2004. During the early period, eleven patients underwent urethroplasty by the Transverse Preputial Island Flap techinique (TPIF). Next, 10 patients underwent One-stage Urethroplasty with Parameatal Foreskin flap technique (OUPF IV). Finally, the most recent 19 had their hypospadias repaired by the Yoke technique. RESULTS: With the TPIF technique in the early periods, only 6 out of 11 patients underwent a successful repair (54.5%). With the OUPF IV technique, the success rate was only 60.0% (6 out of 10 cases). In contrast, 17 out of 19 cases treated by the Yoke technique in the most recent period had a successful repair, although proximal urethrocutaneous fistula and urethral stenosis occurred in one patient, respectively. A relatively high success rate was therefore obtained using the Yoke technique for the repair of severe proximal hypospadias. CONCLUSION: The Yoke techniques for the repair of hypospadias is therefore considered to be a safe and effective technique for the repair of proximal hypospadias because of the continuous skin flap of the ventral urethral plate and the prepuce with a blood supply from the circumferential vascular pedicle. We consider this technique to be very useful for the treatment of severe proximal hypospadias.

Expression and distribution of OCTN2 in mouse epididymis and its association with obstructive azoospermia in juvenile visceral steatosis mice.

AIM: L-carnitine, an essential cofactor for mitochondrial, beta-oxidation of long-chain fatty acids, is known to play important roles in sperm maturation and metabolism when spermatozoa pass and acquire motility in the epididymis. We reported that obstructive azoospermia occurred in the epididymis in the juvenile visceral steatosis (JVS) mice, which are OCTN2 dysfunction mice caused by mutations in the gene encoding OCTN2, have been used for animal models of primary systemic carnitine deficiency. The aim of present study is to investigate the expression of OCTN2 protein in the mouse epididymis and its relation between the localization of OCTN2 and obstructive azoospermia in JVS mice as animal models for human male infertility. METHODS: Animals used in this study were wild-type (C57BL/6 J) mice (n = 4) and JVS mice (n = 4). We made a specific polyclonal antibody against OCTN2 and examined immunohistochemically the localization of OCTN2 in the mouse epididymis. RESULTS: OCTN2 was localized on the apical membrane of the principal cells of distal corpus and cauda epididymides. Immunocytochemistry demonstrated that OCTN2 was localized on the surface of microvillus upon the principal cells. In JVS mice, immunoreactivity started in a region immediately distal to where the sperm obstruction occurred. CONCLUSIONS: Our results suggest that OCTN2 functions as a carnitine transporter between the epithelium and the lumen in distal corpus and cauda epididymides and provides a clue as to why obstructive azoospermia is induced in distal parts of epididymis.

Antibiotic susceptibility testing of Mycoplasma genitalium by TaqMan 5' nuclease real-time PCR.

Mycoplasma genitalium is an important pathogen in male nongonococcal urethritis (NGU). Isolation of M. genitalium from clinical specimens by axenic culture is very difficult and time-consuming, and very few strains are available for antibiotic susceptibility testing. Primary isolation of M. genitalium by coculture with Vero cells improves the isolation rate significantly. However, some strains cannot be adapted to axenic culture. In this study, we determined the antibiotic susceptibility of M. genitalium strains grown in Vero cell culture with dilutions of antibiotics. Growth of M. genitalium was monitored by a quantitative PCR assay detecting a single-copy region of the mgpB adhesin gene. Growth inhibition in the presence of antibiotics was expressed as a percentage of the DNA load of controls grown in the absence of antibiotics. Eighteen strains were examined, including 6 new strains isolated from urethral swab specimens and 4 new strains isolated from urine specimens collected from Japanese men. Eight strains adapted to axenic culture were also tested by the conventional broth dilution method. The two methods had an acceptable correlation. Azithromycin was the most active drug against M. genitalium. Among the fluoroquinolones, moxifloxacin had the highest activity, with MICs ranging from 0.03 to 0.5 mg/liter, whereas ciprofloxacin and levofloxacin were considerably less active, with MICs ranging from 0.5 to 16 mg/liter and 0.25 to 4 mg/liter, respectively. MICs for tetracycline ranged from 0.125 to 4 mg/liter. This new method could increase the number of M. genitalium strains available for antibiotic susceptibility testing and significantly shorten the time from sampling to MIC results.

Expression of novel organic cation/carnitine transporter (OCTN2) in the mouse pancreas.

Among the organic cation transporters, OCTN2 is identified as the most important carnitine transporter owing to the ability to transport carnitine. Although the OCTN2 is previously found in various tissues, there have been no reports showing the OCTN2 in the pancreas. In this study, we examined the expression and localization of OCTN2 in the mouse pancreas by the aid of an in situ hybridization technique and immunohistochemistry with anti-OCTN2 antibody. As a result, the OCTN2 expression was found in the A-cells for the first time. OCTN2 was not expressed in B-cells, notwithstanding that the metabolism of long-chain fatty acids, which are transported into the mitochondria with the help of carnitine, was expected for fatty acid-stimulated insulin secretion. Thus, this study suggests the possibility of carnitine uptake in the pancreatic A-cells through OCTN2 and implies the presence of carnitine transporter(s) other than OCTN2 in the B-cell.

Effects of different alpha-1 adrenoceptor blockers on proximal urethral function using in vivo isovolumetric pressure changes.

The effects of different alpha-1 adrenoceptor blockers on the urethra and the cardiovascular system were evaluated using an in vivo isovolumetric intra-urethral pressure model in New Zealand white rabbits. The urethra of anesthetized male rabbits was cannulated through the bladder and secured at the vesico-urethral junction. The distal side of urethra under the pubic bone was also closed to allow measurement of the intra-urethral pressure. Both the intra-urethral pressure and the femoral arterial pressure were monitored. The effects of five different alpha-1 adrenoceptor blockers on the increases in both the intra-urethral pressure and blood pressure induced by phenylephrine were then examined. The inhibition rate of the alpha-1 adrenoceptor blockers prazosin, bunazosin, terazosin, alfuzosin and tamsulosin on the increase in intra-urethral pressure caused as a result of contraction by phenylephrine was 87.5 +/- 4.5% (mean +/- S.E.), 88.0 +/- 7.2%, 86.2 +/- 6.2%, 81.4 +/- 4.8% and 92.5 +/- 5.0% respectively. The potency ranking of these alpha-1 adrenoceptor blockers was tamsulosin > bunazosin > prazosin > terazosin > alfuzosin. Their inhibition rate of the arterial pressure increase induced by phenylephrine was 81.9 +/- 5.0%, 86.2 +/- 5.9%, 76.0 +/- 6.0%, 63.6 +/- 5.7% and 58.0 +/- 5.2% respectively, with a potency ranking of bunazosin > prazosin > terazosin > alfuzosin > tamsulosin. We therefore conclude that the alpha-1 adrenoceptor blockers bunazosin and prazosin have a more potent action on both the urethra and the vascular system. However, tamsulosin and alfuzosin displayed a marked blockade of the increased urethral pressure induced by phenylephrine, with much less of a blockade of arterial pressure. In the present study, tamsulosin has been shown to be the most sensitive and powerful of the alpha-1 adrenoceptor blockers on urethral smooth muscle.

Bacteria of preoperative urinary tract infections contaminate the surgical fields and develop surgical site infections in urological operations.

BACKGROUND: The risk factors for surgical site infection (SSI) following urological operations have not been clearly identified, although the presence of a preoperative urinary tract infection (UTI) is thought to be one risk factor. We studied potential risk factors to clarify when and how bacteria contaminate wounds and SSI develop. METHODS: Objects of the present study were patients with SSI after open urological operations that were performed at the Department of Urology, Miyazaki Medical College Hospital, University of Miyazaki, Kiyotake, Miyazaki, Japan, during the period between June 1999 and December 2000. Endourological operations, operations on children and short operations of less than 2 h duration were excluded. Patients were screened for the presence of UTI before the operation and subcutaneous swabs for culture were collected at the end of the operation by brushing with a sterile cotton-swab just before skin closure. RESULTS: Surgical site infections occurred in 20 of 134 patients. Bacteria from the subcutaneous swabs were detected in 15 (75.0%) of the patients with SSI. All patients received antimicrobial prophylaxis (AMP), but bacteria from the subcutaneous swabs of patients with SSI were less susceptible to the agents (20.0%). Preoperative UTI were observed in 11 (55.0%) of the patients with SSI. In these patients, four had the same species of bacteria detected from urine, swab and wound, three had the same species from swab and wound and one had the same species from urine and wound. CONCLUSIONS: Preoperative UTI was the most important risk factor for SSI following urological operations. It is most likely that the bacteria in the urine contaminated the surgical fields and the AMP resistant strains produced SSI.

Lack of evidence for the association of E-cadherin gene polymorphism with increased risk or progression of prostate cancer.

BACKGROUND: E-cadherin is an epithelial cell adhesion molecule, and decreased E-cadherin expression in human prostate cancer is associated with tumor grade and advanced clinical stage. A -160 C-->A polymorphism in the promoter region of E-cadherin has been shown to decrease gene transcription. This allelic variation may be a potential genetic marker that can help identify those individuals at higher risk for invasive/metastatic disease. MATERIALS AND METHODS: We studied the effect of E-cadherin gene polymorphism on prostate cancer susceptibility in a case control study of 219 prostate cancer patients and 219 male controls, to determine whether this polymorphism is a biomarker for the risk and how aggressive the disease is. RESULTS: The genotype frequencies in the prostate cancer group were C/C: 0.607, C/A: 0.352, A/A: 0.041, and in the control group C/C: 0.671, C/A: 0.301, A/A: 0.027. A significant difference between the two groups was not found (p = 0.34), and the adjusted OR for A/A genotype was not statistically significant (OR = 1.66, 95% CI 0.58-4.78). Subdividing prostate cancer according to tumor differentiation and stage, we found no association between E-cadherin polymorphism and poor differentiation and invasiveness of prostate cancer. CONCLUSIONS: These data do not support an association between the E-cadherin genotype and the occurrence or progression of prostate cancer in Japanese populations.

Hepatocyte growth factor activator inhibitor types 1 and 2 are expressed by tubular epithelium in kidney and down-regulated in renal cell carcinoma.

PURPOSE: Hepatocyte growth factor (HGF) and its receptor MET have been implicated in kidney development and renal cell carcinoma (RCC) progression. HGF is secreted as an inactive proform and it must be activated to initiate MET signaling. HGF activator (HGFA) activates pro-HGF in injured tissue. We evaluated the expression of HGFA and its endogenous inhibitors HAI-1 and HAI-2 in normal kidney and RCC. MATERIALS AND METHODS: We examined the gene expression of HGFA, HAI-1, HAI-2, HGF and MET in a normal kidney by laser captured microdissection, followed by reverse transcriptase-polymerase chain reaction. We also quantified the mRNA levels of these proteins in 14 RCC cases by real-time reverse transcriptase-polymerase chain reaction. RESULTS: HAI-1 and HAI-2 were abundant in the normal kidney. The uriniferous tubules showed the highest levels of HAI-1 and HAI-2 mRNA. HGFA was hardly detectable in the normal kidney. However, in the kidney with RCC a low but distinct level of HGFA mRNA became detectable in the tumor and adjacent renal tissue. The HAI-1 mRNA level was significantly and consistently down-regulated in RCC relative to normal tissue. HAI-2 mRNA was also significantly low in the advanced stage of RCC. MET was up-regulated in most cases of RCC. CONCLUSIONS: HAI-1 and HAI-2 were expressed in renal tubular epithelial cells. The expression of the 2 HAIs was significantly down-regulated in RCC, whereas HGFA expression was enhanced in the diseased kidney, suggesting an imbalance between HAI and its target proteinases, including HGFA, in favor of proteinase activities in RCC.

A randomized controlled trial of short-term versus long-term prophylactic intravesical instillation chemotherapy for recurrence after transurethral resection of Ta/T1 transitional cell carcinoma of the bladder.

PURPOSE: In a prospective randomized controlled study, we investigated the optimal schedule for intravesical instillation of epirubicin for maximizing its effect on prophylaxis and disease progression after transurethral resection of newly diagnosed Ta/T1 bladder cancer. MATERIALS AND METHODS: The patients were instilled with epirubicin (30 mg/30 ml in normal saline) within 24 hours after transurethral resection and then randomized into 2 groups after a definite histopathological diagnosis of Ta/T1 bladder cancer. One group of 77 patients received 19 intravesical instillations of epirubicin in the year after transurethral resection (group 1). The second group of 73 patients received 9 intravesical instillations of epirubicin during the 3 months after transurethral resection (group 2). Nonrecurrence rates and toxicity were compared. RESULTS: In the followup period, 10 group 1 patients (13.0%) and 23 group 2 patients (31.5%) had recurrent disease. The 3-year nonrecurrence rate was 85.2% in group 1, whereas it was 63.9% in group 2. The nonrecurrence rate of group 1 was significantly higher than that of group 2 throughout the observation period (p = 0.005). The incidence and severity of toxicity were not significantly different between the 2 groups. CONCLUSIONS: Our study indicates that long-term instillation of epirubicin is more effective than short-term instillation in preventing recurrence after transurethral resection of Ta/T1 bladder cancer.

Cytochrome P450 (CYP) 1A2, sulfotransferase (SULT) 1A1, and N-acetyltransferase (NAT) 2 polymorphisms and susceptibility to urothelial cancer.

PURPOSE: Arylamines are suspected to be the primary causative agent of urothelial cancer in tobacco smoke. In the human liver, arylamines are N-hydroxylated by a cytochrome P450 (CYP)1A2-catalyzed reaction, which produces a substrate for O-esterification that can be catalyzed by N-acetyltransferases (NAT) or sulfotransferases (SULT). Recently, several polymorphisms of CYP1A2, SULT1A1, and NAT2 that affect their activities have been reported. METHODS: In this study, 306 Japanese patients with urothelial transitional cell carcinoma and 306 healthy controls were compared for frequencies of CYP1A2, SULT1A1, and NAT2 genotypes. RESULTS: The frequencies of NAT2 intermediate or slow acetylator genotype were significantly higher in the urothelial cancer patients than in the healthy control subjects [odds ratio (OR) = 1.49, 95% confidence interval (95% CI) 1.06-2.09, OR = 3.23, 95% CI 1.72-6.08, respectively]. Stratifying by amount of smoking, among subjects who consumed >33.5 pack-years and carried the SULT1A1 *1/*1 or NAT2 slow acetylator genotype, the OR was 1.73 (95% CI 1.01-2.97) whereas it was 7.31 (95% CI 1.90-28.05) in non-smokers who carried the homozygous wild genotype, respectively. The relationships between CYP1A2, SULT1A1, and NAT2 polymorphisms and clinical findings including tumor differentiation, stage, and recurrence rate were analyzed. Only associations between NAT2 genotype and pathological findings were admitted, and the higher OR of NAT2 intermediate and slow acetylator genotype was more likely to present to a low-grade tumor (G1) among heavy-smokers. CONCLUSIONS: Our results suggest that SULT1A1 *1/*1 and NAT2 slow acetylator genotypes might modulate the effect of carcinogenic arylamines contained in tobacco smoke, and that the modulation of NAT2 intermediate and slow acetylator genotype has a tendency to present a higher risk for highly differentiated tumors among heavy-smokers.

E-cadherin gene polymorphism and risk of urothelial cancer.

The E-cadherin is important in cell-cell adhesion and in the development and maintenance of the epithelial phenotype. A -160C-->A polymorphism in the promoter region of E-cadherin has been shown to decrease gene transcription. This allelic variation may be a potential genetic marker that can help identify those individuals at higher risk for invasive/metastatic disease. We studied the effect of E-cadherin gene polymorphism on urothelial cancer susceptibility in a case control study of 314 urothelial cancer patients and 314 age-sex matched controls, to determine whether this polymorphism is a biomarker for the risk and how aggressive the disease is. The frequency with which the subjects carried E-cadherin A/A genotype was significantly higher in the urothelial cancer patients than in the healthy control subjects (OR=2.32, 95% CI 1.03-5.22). Subdividing urothelial cancer according to tumor differentiation and stage, we found no association between E-cadherin polymorphism and poorly-differentiation and invasiveness of urothelial cancer. Furthermore, no significant association between E-cadherin polymorphism and recurrence rate of urothelial cancer patients was found. The present study demonstrates for the first time that E-cadherin A/A genotype may be associated with susceptibility to urothelial cancer, but not with the progression of disease.

Primary adenocarcinoma arising from a paraurethral cyst in a female patient.

A very rare case of primary adenocarcinoma arising from a paraurethral cyst in a 63-year-old woman is reported. Initially she was diagnosed as having a simple paraurethral cyst because of absent communication with the urethra. The resected paraurethral cyst was histologically associated with adenocarcinoma. We also performed chemotherapy composed of methotrexate, vinblastine, Adriamycin and cisplatin because of lymph node metastasis. Our treatment, however, was not effective and the patient died of systemic metastases.

Genetic polymorphisms ofCYP2A6 andCYP2E1 with tobacco smoking is not associated with risk of urothelial cancer.

OBJECTIVES: To elucidate the association between genetic polymorphisms ofCYP2a6 andCYP2E1 and urothelial cancer susceptibility. METHODS: A total of 137 Japanese patients with urothelial cancer and 217 Japanese healthy controls, frequency-matched for age and gender, were selected. The polymorphisms ofCYP2A6 andCYP2E1 were analyzed by PCR-RFLP, and cigarette smoking histories were obtained through interviews RESULTS: The frequency ofCYP2A6 homozygote deletion genotype was 2.9% in the patients, compared with 3.2% in the controls (OR=0.84, 95% CI 0.24-2.96). The frequencies ofCYP2E1 C1/c2 andC2/c2 were 27.7% and 4.4% in the patients, compared with 35.5% and 6.0% in the controls (OR=0.68, 95% CI 0.42-1.09, OR=0.67, 95% CI 0.24-1.84, respectively). No statistically significant differences were observed when theCYP2A6 homozygote deletion genotype and theCYP2E1 genotypes were examined relative to smoking status. CONCLUSIONS: Our data indicate that neither a relationship between genetically impaired nitrosamine metabolism and tobacco-smoking consumption, nor urothelial cancer risk related to theCYP2A6 deletion genotype andCYP2E1 Rsa I genotype was found in Japanese population.