Y chromosome haplogroup D2a1 is significantly associated with high levels of luteinizing hormone in Japanese men.

The association between the Y chromosome haplogroup D2 and risk of azoospermia and low sperm motility has been previously studied, and it was indicated that haplogroups DE (YAP lineage) are associated with prostate cancer risk in Japanese males. Our assumption had been that Y chromosome haplogroups may be associated with sex hormone levels, because sex hormones have been deemed responsible for spermatogenesis and carcinogenesis. In this study, we assessed the association between Y chromosome haplogroups and sex hormone levels, including those of testosterone, sex hormone-binding globulin (SHBG), follicle-stimulating hormone (FSH), luteinizing hormone (LH), inhibin-B, and calculated free testosterone (cFT), in 901 young men from the general Japanese population (cohort 1) and 786 Japanese men of proven fertility (cohort 2). We found that the haplogroup D2a1 was significantly associated with high LH levels in a combined analysis involving two cohorts (ß = 0.068, SE = 0.025, p = 0.0075), following correction for multiple testing. To date, this result is the first evidence that implicates Y chromosome haplogroups in an association with sex hormone levels.

Five cases of beta-ureidopropionase deficiency detected by GC/MS analysis of urine metabolome.

The clinical presentation of inborn errors of pyrimidine degradation varies considerably from asymptomatic to severe neurological illness. We have reported a method to screen for and make a chemical diagnosis of beta-ureidopropionase deficiency, leading to the discovery of the first asymptomatic case of this disease. In this method, the recovery of beta-ureidopropionate and beta-ureidoisobutyrate, the key biomarkers, was very high,and the adoption of GC/MS and targeted analysis enabled us to simultaneously obtain information related and unrelated to pyrimidine metabolism. The present study reports the results of a large-scale screening of 24,000 newborns using dried urine on filter paper. Identification of a total of four asymptomatic patients among newborns suggests the high incidence (1/6000) of this disease in Japan. While these newborns were asymptomatic, two additional cases detected at the age of 5 years as well as 3 months with this method for high-risk screening had autism and West syndrome, respectively.The key biomarkers and alpha-ureidobutyrate used as an internal standard were found to give not only their di-trimethylsilyl derivatives but also tri-trimethylsilyl derivatives, upon derivatization. The mass spectra and retention times of their tri-trimethylsilyl derivatives and data handling for quantification of the markers are presented.Identification of individuals with defects in pyrimidine metabolism would realize personalized medication in cancer chemotherapy with pyrimidine analogs such as 5-fluorouracil.

Prostate cancer incidence varies among males from different Y-chromosome lineages.

The incidence rate of prostate cancer in African-American males is two times higher than Caucasian men and ten times higher than Japanese men. The geographical specificity of Y haplogroups implies that males from different ethnic groups undoubtedly have various Y lineages with different Y-chromosomal characteristics that may affect their susceptibility or resistance to such a male-specific cancer. To confirm this hypothesis we studied the Y-chromosomal haplogroups of 92 Japanese prostate cancer patients comparing them with randomly selected 109 unrelated healthy Japanese male controls who were confirmed to be residents of the same geographical area. Males could be classified using three binary Y-chromosome markers (sex-determining region Y (SRY), YAP, 47z) into four haplogroups DE, O2b(*), O2b1, and untagged group. Our results confirmed that prostate cancer incidence varies among males from different Y-chromosome lineages. Males from DE and the untagged haplogroups are at a significantly higher risk to develop prostate cancer than O2b(*) and O2b1 haplogroups (P=0.01), odds ratio 2.17 and 95% confidence interval (1.16-4.07). Males from haplogroup DE are over-represented in the patient group showing a percentage of 41.3%. The underlying possible causes of susceptibility variations of different Y lineages for such a male-specific cancer tumorigenesis are discussed. These findings explain the lower incidence of prostate cancer in Japanese and other South East Asian males than other populations. To our knowledge, this is the first reliable study examining the association between prostate cancer and Y-chromosomal haplogroups, comparing prostate cancer patients with carefully selected matched controls.

Study of peroxisome proliferator-activated receptor (PPAR)-gamma in renal ischemia-reperfusion injury.

Recent studies of ischemia-reperfusion (I/R) injury have focused on the function of neutrophils, the action mechanism of inflammatory cytokines. However, few reports have addressed peroxisome proliferator-activated receptor (PPAR)-gamma. PPAR-gamma is a ligand-activated transcriptional factor belonging to the steroid receptor superfamily. It plays a role in both adipocyte differentiation and tumorigenesis. We researched the expression of PPAR-gamma in renal I/R injury of the rat. Male Lewis rats were used. The right kidney was harvested and the left renal artery and vein were clamped at 90 minutes of ischemic time. Rats were killed at 0, 1.5, 3, 5, and 12 hours after reperfusion. PPAR-gamma expression was studied by immunohistostaining. PPAR-gamma expression was observed only on mesangial and endothelial cells of normal kidney. From 1.5 to 3 hours after reperfusion, PPAR-gamma expression gradually became stronger on mesangial and endothelial cells. PPAR-gamma expression was most intense on mesangial cells and endothelial cells at 3 hours after reperfusion. Twelve hours after reperfusion, necrosis extended throughout the ischemic kidney and nearly all the tubular epithelial cells were destroyed, but 12 hours after reperfusion PPAR-gamma expression gradually became weaker on mesangial and endothelial cells. PPAR-gamma was expressed in the rat model having renal I/R injury. Several hours after maximal of PPAR-gamma expression, maximal renal I/R injury was observed. These results may indicate a relationship between PPAR-gamma expression and renal I/R injury.

Occupational cancer genetics: infrequent ras oncogenes point mutations in lung cancer samples from chromate workers.

BACKGROUND: Chromium carcinogenicity and mutagenicity are no longer disputed. However, although chromium has various genetic effects that induce cancer, its mechanism of inducing lung cancer in humans is still not fully understood. p53, a tumor suppressor gene, was found to be infrequently mutated in samples of lung cancer in workers with long occupational exposure to chromium, suggesting other cancer-related genes to be targeted in such tumors. METHODS: To assess the contribution of the ras oncogenes in the pathogenesis of chromate-related lung cancer, we studied point mutations at the critical positions of codons 12, 13, and 61 of the Ha-ras and Ki-ras oncogenes in 38 lung cancer samples derived from Japanese patients who worked in the chromate industry for long periods. We used both radioactive isotope and non-radioisotope PCR-SSCP techniques. RESULTS: The results of this study demonstrated that activation of ras genes due to point mutations in chromate-related lung cancer is a rare event. CONCLUSIONS: Ras oncogenes activated by point mutations do not have a major role in the process of tumorigenesis of chromate-related lung cancer.

[A case of collecting duct carcinoma (Bellini duct carcinoma) producing carcinoembryonic antigen].

We report a case of collecting duct carcinoma (Bellini duct carcinoma) producing carcinoembryonic antigen (CEA). A 61-year-old man visited our hospital because of a left renal mass detected by ultrasonography in an other hospital. Computed tomography showed a low density tumor measuring about 3 cm in the left kidney. Angiography demonstrated a hypovascular tumor. The serum level of CEA was increased to 20 ng/ml. (normal < 7 ng/ml). Left radical nephrectomy was performed. Histological examination revealed collecting duct carcinoma with papillary growth (T1aN1M0). Cancer cells showed a positive immunohistochemical staining for CEA. Under a diagnosis of CEA-producing collecting duct carcinoma of the left kidney, the patient underwent systemic chemotherapy (M-VAC). The serum level of CEA decreased to the normal level after the nephrectomy, but six months postoperatively, metastatic bone tumor at the left pelvic bone was revealed on the plain film and at the same time, the CEA level was increased again.

Urine screening of five-day-old newborns: metabolic profiling of neonatal galactosuria.

We determined urinary galactose and 4-hydroxyphenyllactic acid (4HPLA) in 4338 of 5-day-old newborns using a newly developed GC-MS screening method. Fifty-two infants were chemically diagnosed as having transient galactosuria based upon elevated urinary galactose levels (4.78-30.53 mg/mg creatinine, control 1.10 +/- 0.89 mg/mg creatinine). These infants did not excrete galactitol or galactonic acid into the urine, which is typical of hereditary galactosemia. Nearly 40% of the transient galactosuria was associated with immature infants (low birth weight or borne before 37 gestational weeks). Immature hepatic function is one explanation for neonatal transient galactosuria, but heterozygotes or the carriers of galactose degradation enzyme deficiencies were also suspected in some of the newborns, judging from the comparisons of urinary galactose and 4HPLA excretion between neonates and patients with galactosemia.

Pilot study of gas chromatographic-mass spectrometric screening of newborn urine for inborn errors of metabolism after treatment with urease.

Gas chromatographic-mass spectrometric (GC-MS) techniques for urinary organic acid profiling have been applied to high-risk screening for a wide range of diseases, mainly for inborn errors of metabolism (IEM), rather than to low-risk screening or mass screening. Using a simplified procedure with urease-pretreatment and the GC-MS technique, which allows simultaneous determination of organic acids, amino acids, sugars and sugar acids, we performed a pilot study of the application of this procedure to neonatal urine screening for 22 IEM. Out of 16,246 newborns screened, 11 cases of metabolic disorders were chemically diagnosed: two each of methylmalonic aciduria and glyceroluria, four of cystinuria, and one each of Hartnup disease, citrullinemia and alpha-aminoadipic aciduria/alpha-ketoadipic aciduria. The incidence of IEM was thus one per 1477, which was higher than the one per 3000 obtained in the USA in a study targeting amino acids and acylcarnitines in newborn blood spots by tandem mass spectrometry. Also, 227 cases were found to have transient metabolic abnormalities: 108 cases with neonatal tyrosinuria, 99 cases with neonatal galactosuria, and 20 cases with other transient metabolic disorders. Two hundred and thirty-eight cases out of 16,246 neonates (approximately 1/68) were thus diagnosed using this procedure as having either persistent or transient metabolic abnormalities.

Relationship between glutathione S-transferase M1 deficiency and urothelial cancer in dye workers exposed to aromatic amines.

PURPOSE: It is speculated that the susceptibility to urothelial cancer in dye workers who are exposed to aromatic amines is affected not only by occupational environmental factors but by host specific factors. We evaluated the interaction between glutathione S-transferase M1 gene deficiency and the occupational environmental factors associated with urothelial cancer. MATERIALS AND METHODS: The study included 137 workers who had prior exposure to dyestuff intermediates, of whom 36 had urothelial cancer. The prevalence of a glutathione S-transferase M1 gene polymorphism was investigated using polymerase chain reaction. The relationship between the glutathione S-transferase M1 0/0 gene and occupational environmental factors in the onset of urothelial cancer was examined by multivariate analysis. RESULTS: The prevalence of glutathione S-transferase M1 gene deficiency did not differ significantly between the urothelial cancer (21 cases, 58.3%) group and the cancer-free (47, 46.3%) group. It was estimated that 29.6% of the urothelial cancers in these dye workers was attributable to the glutathione S-transferase M1 0/0 gene. Analysis using multiple logistic models showed low predictive ability for urothelial cancer due to glutathione S-transferase M1 gene deficiency (p = 0.084, odds ratio 2.260, 95% confidence interval [CI] 0.904 to 5.652). A history of working in small factories (p = 0.000, odds ratio 7.404, 95% CI 2.854 to 19.206) and a long period of exposure (p = 0.016, odds ratio 5.051, 95% CI 1.371 to 18.612) significantly predicted cancer. CONCLUSIONS: We demonstrated a strong trend using the multiple logistic analysis of the contribution of glutathione S-transferase M1 gene polymorphism and occupational environmental factors. Therefore, the glutathione S-transferase M1 enzyme might have an important role in the detoxification of aromatic amine derived carcinogens. Occupational environmental factors, however, might contribute more than a glutathione S-transferase M1 gene deficiency to the occurrence of urothelial cancer among individuals exposed to aromatic amines, because of the extremely potent carcinogenicity of some occupational environmental factors.

Recurrence of primary superficial bladder cancer treated with prophylactic intravesical Tokyo 172 bacillus Calmette-Guérin: a long-term follow-up.

BACKGROUND: Long-term results after transurethral resection (TUR) and prophylactic intravesical Tokyo 172 bacillus Calmette-Guérin (BCG) therapy for primary superficial bladder cancer were analyzed by multivariate analysis, and factors affecting the recurrence of bladder tumors after this therapy were examined. METHODS: One-hundred and forty-one consecutive patients with primary superficial bladder cancer who consulted the Department of Urology at Wakayama Medical College and affiliated hospitals between May 1985 and May 1990 were studied. Tokyo strain BCG was given intravesically (80 mg in 40 ml saline) weekly for 6 weeks. RESULTS: The 5-year cumulative recurrence-free rate by the Kaplan-Meier method was 0.702 in 141 patients with primary superficial bladder cancer. The 5-year recurrence-free function using the proportional hazard model was 0.743. Using the Cox proportional hazard model, variables that significantly contributed to recurrence after intravesical BCG included female sex, tumor size less than 1 cm in diameter, and T1 tumor stage. Patient age, tumor type, multiplicity, tumor grade, and concomitant carcinoma in situ did not contribute to recurrence. CONCLUSION: Long-term results showed that prophylactic intravesical Tokyo strain BCG after TUR for primary superficial bladder cancer is also effective in preventing the recurrence of bladder cancer, and the biologic behavior of superficial bladder cancer other than stage T1 tumor may be altered after intravesical BCG.

PCNA and p53 in urinary bladder cancer: correlation with histological findings and prognosis.

BACKGROUND: This study aimed to immunohistochemically examine the expression of proliferating cell nuclear antigens (PCNA) and p53 protein in transitional cell carcinomas (TCC) of the urinary bladder, and to investigate possible correlations of this expression with the tumor grade or stage, tumor recurrence, and prognosis of the disease. MATERIALS AND METHODS: The immunohistochemical status of the PCNA and p53 proteins were determined on paraffin-embedded sections from 128 patients with TCC of the urinary bladder, using PC-10 and DO7 as the primary antibodies. Positive stainings were represented by scores (Labeling Index; LI, %) calculated as the percent of positive cells among all neoplastic cells counted. The findings were compared to the patients' histopathological features. Patients who underwent transurethral resection were divided into groups with "low" and "high" scores for PCNA and p53, respectively, and the tumor recurrence rate was compared among the groups. Patients who underwent total cystectomy were similarly divided into "low" and "high" score groups, and survival rates of the groups were compared. RESULTS: PCNA expression was observed in 66 of 128 patients (51.6%), with a mean labeling index of 26.6%. Overexpression of p53 was observed in 65 of 128 patients (50.8%), with a mean labeling index of 35.3%. There were significant correlations of the PCNA and p53 indices with both histological grade and stage of the tumor. In the TUR group, there were no statistically significant differences in recurrence rate between the groups with high or low scores for either PCNA or p53. In the total cystectomy group, there was a significant correlation between survival rate and positive staining for PCNA, but not for p53. The relationship between 2 parameters, PCNA and p53 scores, was not significant (linear correlation coefficient, r = 0.67). CONCLUSIONS: PCNA and p53 status in transitional cell carcinomas of the urinary bladder is related to the histopathological findings. We also suggest that immunohistochemical staining for PCNA provides significant clinical information which may be useful in the initial selection of therapy. However, overexpression of p53 does not appear to represent an independent prognostic marker in bladder tumors.

Gas chromatographic-mass spectrometric metabolic profiling of patients with fatal infantile mitochondrial myopathy with de Toni-Fanconi-Debré syndrome.

The metabolic profiles of three patients with fatal infantile mitochondrial myopathy with de Toni-Fanconi-Debré syndrome were studied by simultaneous analysis, after urease treatment of urinary organic acids, carbohydrates, polyols and amino acids using gas chromatography/mass spectrometry (GC/MS). All three patients persistently showed lactic aciduria, phosphaturia, glucosuria and generalized amino aciduria. This abnormal urinary metabolic profile was observed before the onset of any clinical symptoms, indicating that chemical diagnosis may be done presymptomatically. In one patient, the concentration of lactate increased in parallel with the severity of the clinical condition, whereas the urinary levels of 3-hydroxybutyrate, amino acids and glucose fluctuated and showed only a general tendency to increase with the clinical course. The above results suggest that simultaneous GC/MS analyses, without fractionation, of urinary metabolites facilitate not only the early chemical diagnosis either before or after the first onset, but also follow-up studies, providing an important index for the evaluation of the severity and clinical course in patients with this disorder.

Involvement of Epstein-Barr virus expression in testicular tumors.

PURPOSE: Because orchitis has been described as a symptom of infectious mononucleosis which is caused by Epstein-Barr virus (EBV), a human tumor virus, we tried to ascertain the relationship between EBV and testicular tumors. MATERIALS AND METHODS: Sixteen seminomas, 11 embryonal carcinomas and 25 nonmalignant control testes were examined for persistence and expression of the EBV genome. To detect expression of EBV, mRNA in situ hybridization and immunofluorescence staining by monoclonal antibodies were performed. To confirm the EBV genome in testes, we used nested polymerase chain reaction (PCR). RESULTS: Messenger RNA in situ hybridization showed that all 27 seminomas and embryonal carcinomas expressed EB viral RNA, but the 25 nonmalignant testes did not. Monoclonal antibody staining showed EBV-related nuclear antigen (EBNA) 2 and latent membrane protein (LMP) 1 expression in testicular tumors. Nested polymerase chain reaction detected the EBV genome in normal testes as well as in testicular tumors. CONCLUSIONS: These results suggest that EBV is related to testicular tumors.

Factors affecting the occurrence of urothelial tumors in dye workers exposed to aromatic amines.

BACKGROUND: Past studies have analyzed individual jobs in dyestuff factories, materials manufactured and handled, age at exposure, and the duration of exposure in factories as factors related to the occurrence of urothelial tumors. None of these studies was based on long-term observation, and the factors involved in the occurrence of urothelial tumors remain controversial. In this study, various factors that may affect the occurrence of urothelial tumors in dye workers were assessed by multivariate analysis. METHODS: Three hundred and sixty-three workers in nine member factories of the Dyestuff Industrial Cooperative Association were included the study. Factory A is a large dyestuff chemical factory in Wakayama City with 218 dye workers. The other eight smaller factories employ a total of 145 dye workers. Correlations of tumor occurrence with a variety of factors, such as dyestuff intermediates manufactured and handled, types of job in the factory, age at the beginning of occupational exposure, and the duration of exposure were examined by multivariate analysis using multiple logistic models. RESULTS: Urothelial tumors were found in 58 (16.0%) of the 363 dye workers in the nine member factories of the Cooperative Association examined in the present study. The incidence in workers in Factory A, 5.5% (12 patients), was significantly (P < 0.01) lower than the overall incidence, while that in the eight small factories, 31.7% (46 patients), was significantly (P < 0.01) higher than the overall incidence. The risk factors significantly related to tumor occurrence in the 363 dye workers were benzidine (odds ratio, 8.302) as a dyestuff intermediate, manufacturing work (odds ratio, 4.631), and a long period of exposure (odds ratio, 1.018). Correlations of the tumor occurrence with the various factors were examined by multivariate analysis using multiple logistic models. In the total of 363 workers, benzidine as an intermediate (P < 0.05), manufacturing work (P < 0.01) and the duration of exposure (P < 0.01) were found to have contributed to the urothelial tumor occurrence. In Factory A, benzidine as an intermediate (P < 0.01) and duration of exposure (P < 0.05) contributed significantly to tumor occurrence. CONCLUSIONS: 1) The manufacturing and handling of benzidine and duration of exposure contribute significantly to the occurrence of occupational urothelial tumor, the former more strongly than the latter; 2) the contribution of different job types to tumor occurrence may be dependent upon the industrial health and safety practices in each factory.

[Prostate specific antigen in patients with prostatic cancer--clinical usefulness of its measurement with sensitive enzyme immunoassay, TOSOH II PA assay].

The TOSOH II PA (AIA-PACK PA in the U.S.A.) monoclonal immunoenzyme assay was used and the clinical usefulness of prostate specific antigen (PSA) was evaluated in 39 men with prostatic cancer and 32 men with benign prostatic hyperplasia (BPH) confirmed pathologically. We evaluated the lower limit of detection in this assay by the mean PSA level plue 3 standard deviations in 5 separate experiments with a zero control sera as well as the mean PSA level minus 3 standard deviations in 5 separate experiments with serial dilutions of a known concentration of PSA. PSA concentrations of 0 to 0.25 ng/ml could not be distinguished from the zero control. Therefore, we set the lower limit of detection for the assay as 0.25 ng/ml. At our laboratory, the normal standard value was determined by the mean PSA level plus 3 standard deviations in 79 healthy men as 2.3 ng/ml. Of patients that underwent radical cystoprostatectomy for bladder cancer, all had PSA levels less than 0.25 ng/ml, while only 6% had PAP levels less than 0.11 ng/ml, the lower limit of detection in the TOSOH II PAP assay. We compared TOSOH II PA with Markit PA, a commonly used assay in Japan. Although there was a close linear correlation (r = 0.90) between the TOSOH II PA and Markit PA, the difference of slope in the linear regression lines was great, it was thought due to anti-PSA antibodies in each assay recognizing different epitopes of PSA in the blood.(ABSTRACT TRUNCATED AT 250 WORDS)

The effects of intravesical chemoimmunotherapy with epirubicin and bacillus Calmette-Guérin for prophylaxis of recurrence of superficial bladder cancer: a preliminary report.

The effects of intravesical chemoimmunotherapy with epirubicin and bacillus Calmette-Guérin (BCG) for prophylaxis of recurrence of superficial bladder cancer (pTa, pT1) were investigated in 29 patients aged a median of 70 years between January of 1991 and May of 1993. The patients received intravesical instillation of 40 mg epirubicin immediately after transurethral resection (TUR) of the bladder cancer. At 1 week after TUR, 80 mg Tokyo-strain BCG was instilled into the bladder once a week for 6 weeks. Thereafter, the patients were followed by cystoscopy and urinary cytology at 3-month intervals until recurrence was detected. Of the 29 patients, 28 had no evidence of disease over a mean follow-up period of 20 months. The 1 case of recurrence occurred at 3 months after TUR and that patient died of cancer progression. The simple recurrence rate was 3.5% after therapy. According to the person-years method, the number of recurrent tumors per 100 patient-months was 0.17. The cumulative nonrecurrence rate determined for all cases was 96.5% at 30 months. Adverse reactions, including urinary frequency, urgency, and miction pain, among others, were observed in 27 patients (93%). Only 1 patient was withdrawn from the treatment because of severe bladder-irritation symptoms due to the BCG instillation. The intravesical chemoimmunotherapy with epirubicin and BCG seemed to be effective for prophylaxis of recurrence of superficial bladder cancer.

Results of adjuvant chemotherapy for invasive uroepithelial cancer.

Between June 1982 and July 1990, 55 patients (41 with bladder cancers and 14 with renal pelvic or ureteral cancers) who had undergone radical extirpative surgery and/or node dissection for pathological stage pT2-4 and/or nodal disease received adjuvant chemotherapy consisting of cisplatin alone or in combination with other agents. In all, 26 of the bladder-cancer patients also received preoperative chemotherapy consisting of arterial infusion of cisplatin, mitomycin C, and Adriamycin. Adjuvant chemotherapy was performed according to the following protocol. Between June 1982 and July 1987, 30-50 mg/m2 cisplatin either alone or in combination with Adriamycin and 5-fluorouracil (CAF) was given to 35 patients in an induction and maintenance setting for 1 year. After July 1987, short-course cisplatin (70 mg/m2) or cisplatin, etoposide, and Adriamycin combination chemotherapy (CVA) was given to 20 patients. Of the 55 patients, 38 are alive and show no evidence of disease, three are alive with disease, 13 have died of their disease, and 1 has died of an unrelated cause. The 5-year survival of all patients was 65.1%. The survival of the 20 patients who were treated after July 1987 was better than that of the 35 patients who were treated before June 1987. Local recurrence and/or distant dissemination occurred in 16 patients, 13 of whom died of cancer progression. Nausea and vomiting and anorexia occurred in most patients during the administration of cisplatin. Mild to moderate myelosuppression developed in patients who received CAF or CVA combination chemotherapy. Although adjuvant chemotherapy combined with radical surgery seemed to be effective in cases with a pathological stage of pT3a or less, more intensive pre- or postoperative chemotherapy is needed to improve the poor prognosis of patients with deeply invasive uroepithelial cancer.

[True hermaphrodite with ipsilateral vas deferens and intrascrotal ovary].

A 15-year-old, legally male patient came to our department with chief complaint of gynecomastia. Serum testosterone was at a low level of 1.6 ng/ml, and prolactin a high level of 23 ng/ml. Blood type was a mixed type of both type A and type B, and a chromosomal analysis with peripheral blood lymphocytes demonstrated a mosaic of 46, XX/46, XY. During the follow-up, he complained a painful swelling in his right scrotum, and received an emergent surgery. A large amount of blood was noted in the right scrotum. Unicorn uterus, Fallopian tube and finbriae were observed, and a thumb-sized gonad with hemorrhage and fissure was also seen in the upper part of the scrotum. The right gonad was an ovary and no testicular tissue was confirmed in the right scrotum, whereas the right vas deferens was noted. The left testis was accompanied by an induration on its upper pole which was histologically found to be ovarian tissue. The patient was diagnosed as a true hermaphroditism with 46, XX/46, XY chimera that had an ovary with inguinal uterus hernia and an unusual vas deferens in the right scrotum and an ovotestis in the left. It was considered that an adequate amount of testosterone secreted from the left testis during the early embryonal period might have affected the descent of the right ovary into the scrotum and on the development of the right vas deferens.

Clinical study on urothelial tumors of dye workers in Wakayama City.

Between January 1951 and December 31, 1990 urothelial tumors were detected in 112 of 1,085 male dye workers (10.3%) in Wakayama City who were formerly engaged in manufacturing of benzidine and/or beta-naphthylamine. The period from exposure to the chemicals to development of the tumor was a mean of 24.1 +/- 9.4 years. A peak incidence of urothelial tumors was observed also approximately 25 years after the peak period of manufacturing these intermediate products of dyes. The mean period from exposure to such carcinogenic chemicals to the onset of the disease was estimated to be 25 years. Of the 78 patients with primary bladder cancer diagnosed since 1969, 43 (55.1%) had tumors diagnosed mostly as a result of a positive urinary cytology test obtained as part of a screening program and 35 (44.9%) had tumors diagnosed as the result of symptoms. Ten patients (24.4%) in the screened group had been treated with total cystectomy by the last followup examination compared with 17 (50.0%) in the symptomatic group. The 10-year cumulative survival rates were significantly (p less than 0.05) higher in the screened patients (75.1%) than in the symptomatic patients (55.1%). Our results indicate that screening of high risk populations with urinary cytology tests is effective for early diagnosis and treatment of urothelial tumors, and it improves patient prognosis. Furthermore, the biological behavior of occupational urothelial tumors may be different from that of urothelial tumors in the general population.