Detection of Novel US Neisseria meningitidis Urethritis Clade Subtypes in Japan.

Neisseria meningitidis causes invasive meningococcal diseases and has also been identified as a causative agent of sexually transmitted infections, including urethritis. Unencapsulated sequence type 11 meningococci containing the gonococcal aniA-norB locus and belonging to the United States N. meningitidis urethritis clade (US_NmUC) are causative agents of urethral infections in the United States, predominantly among men who have sex with men. We identified 2 subtypes of unencapsulated sequence type 11 meningococci in Japan that were phylogenetically close to US_NmUC, designated as the Japan N. meningitidis urethritis clade (J_NmUC). The subtypes were characterized by PCR, serologic testing, and whole-genome sequencing. Our study suggests that an ancestor of US_NmUC and J_NmUS urethritis-associated meningococci is disseminated worldwide. Global monitoring of urethritis-associated N. meningitidis isolates should be performed to further characterize microbiologic and epidemiologic characteristics of urethritis clade meningococci.

Antimicrobial Susceptibility of Neisseria gonorrhoeae in Japan from 2000 to 2015.

BACKGROUND: Gonococcal infections are difficult to treat because of their multidrug antimicrobial resistance. The outbreak of antimicrobial-resistant Neisseria gonorrhoeae has begun in Asia and particularly in Japan. Therefore, it is very important that we understand the trend of antimicrobial resistance of N. gonorrhoeae in Asia including Japan. Our surveillance of the antimicrobial susceptibility of N. gonorrhoeae began in 2000 under the guidance of the Department of Urology, Gifu University. We report our surveillance data from 2000 to 2015. METHODS: We collected N. gonorrhoeae strains isolated from patients with gonococcal infections who visited our cooperating medical institutions in Japan from 2000 to 2015. MICs of penicillin G, cefixime, ceftriaxone, tetracycline, spectinomycin, azithromycin, and levofloxacin were determined by the agar dilution method approved by the Clinical and Laboratory Standards Institute. RESULTS: From 2000 to 2015, 2471 isolates of N. gonorrhoeae were collected in Japan. High rates of nonsusceptibility to penicillin, tetracycline, levofloxacin, cefixime, and azithromycin were shown. Around 5% to 10% of the strains isolated had a 0.25-mg/L MIC of ceftriaxone in each year, and 6 strains (0.24%) with a 0.5-mg/L MIC of ceftriaxone were isolated throughout the study period. Approximately 5% to 10% of the strains were resistant to each of ceftriaxone, azithromycin, and levofloxacin according to European Committee on Antimicrobial Susceptibility Testing breakpoints, and the rate has not increased significantly. CONCLUSIONS: From this study and previous pharmacodynamic analyses, a single 1-g dose of ceftriaxone is recommended to treat gonorrhea. As strains with high-level ceftriaxone resistance continue to spread, higher doses of ceftriaxone in monotherapy or multiple doses of ceftriaxone should be considered.

[Advancements in diagnosis of sexually transmitted diseases in urology].

Sexually transmitted diseases diagnosed and treated exclusively in urology clinics are male urethritis and epididymitis caused by Neisseria gonorrhoeae and Chlamydia trachomatis. Although recent developments in diagnostic tools have made it possible to detect these microorganisms with extremely high sensitivities, the screening of Neisseria gonorrhoeae using the microscopic observation of intraleucocyte diplococci stained by methylene blue or gram staining in the first voided urine sediment or urethral smears still the key point in the diagnosis and treatment of gonococcal urethritis. In recent years, mycoplasmas and ureaplasmas have been supposed to be possible pathogens of prostatitis as well as urethritis. The objective diagnosis of genital skin lesions caused by herpes simplex virus and human papillomavirus are remained to be developed.

Single-dose treatment of male patients with gonococcal urethritis using 2g spectinomycin: microbiological and clinical evaluations.

The microbiological and clinical efficacies of a single-dose treatment of 2g spectinomycin administered by intramuscular injection were studied in 365 male patients with gonococcal urethritis. A total of 210 patients (57.5%) could be evaluated, in 28 (13.3%) of whom Chlamydia trachomatis was detected in addition to Neisseria gonorrhoeae. A single dose of spectinomycin eradicated N. gonorrhoeae in 203 (96.7%) of the 210 patients. Among patients in whom N. gonorrhoeae was eradicated, pyuria and clinical symptoms, respectively, disappeared in 92.6% (162/175) and 98.9% (173/175) of patients without concomitant C. trachomatis and in 78.6% (22/28) and 71.4% (20/28) with C. trachomatis. Minimal inhibitory concentrations (MICs) were determined for four of seven N. gonorrhoeae strains isolated after spectinomycin treatment. MICs to spectinomycin for three of the four isolates were 16 microg/mL (defined as susceptible) and the MIC of the other isolate was 128 microg/mL, indicating resistance. The resistant isolate was a multidrug-resistant strain with resistance to ciprofloxacin, tetracycline, penicillin and cephalosporins, except for ceftriaxone. The results of this study indicate that a single-dose treatment using 2g spectinomycin is effective in treating patients with urethritis caused by N. gonorrhoeae, even in the era of multidrug-resistant N. gonorrhoeae.

Ultrasonic measurement of bladder weight as a possible predictor of acute urinary retention in men with lower urinary tract symptoms suggestive of benign prostatic hyperplasia.

Acute urinary retention (AUR) is one of the most undesirable events for elderly men with benign prostatic hyperplasia (BPH). This study was designed to test the clinical utility of ultrasonic measurement of bladder weight as a predictor of AUR. A total number of 160 men visited our clinic with lower urinary tract symptoms (LUTS) suggestive of BPH and underwent urodynamic studies, including transrectal ultrasonography of the prostate and the measurement of ultrasound (US) estimated bladder weight (UEBW). Among them, 31 (19.4%) presented to our clinic with AUR. From the thickness of the anterior bladder wall measured by transabdominal ultrasonography and the intravesical volume, UEBW was calculated, supposing the bladder to be a sphere. Between patients with and without AUR, there were significant differences for age (75.4 vs. 71.1 years, p < 0.005), prostatic volume (45.5 vs. 35.8 g, p < 0.05), transition zone (TZ) volume (29.4 vs. 20.2 g, p < 0.05), TZ index (0.606 vs. 0.493, p < 0.005) and UEBW (50.3 vs. 34.7 g, p < 0.0001). A receiver-operating characteristic curve analysis demonstrated UEBW to be superior to the other prostatic ultrasonic measures in identifying AUR. Patients with LUTS suggestive of BPH having UEBW greater than 35.0 g were 13.4 times as likely to suffer from AUR. The significant association of UEBW with an increased risk of AUR suggests that it would be promising as a noninvasive urodynamic parameter capable of identifying patients at increased risk of AUR.

Ultrasonic measurement of bladder weight as a novel urodynamic modality.

Although pressure-flow studies (PFS) are currently recognized as the gold standard for the diagnosis of infravesical obstruction, their clinical use is limited, due to the invasive nature of procedure. Recently, we developed a new urodynamic parameter, ultrasound estimated bladder weight (UEBW), which was calculated from the bladder wall thickness measured ultrasonically and intravesical volume. Our comparative study between UEBW and PFS showed that UEBW diagnosed infravesical obstruction with a diagnosis accuracy of 73% using a cut-off value of 35 gm. UEBW could also be used as a reliable tool in monitoring therapeutic effects on BPH patients in terms of the relief of obstruction. In addition, UEBW is of clinical use in the management of neurogenic bladder dysfunction, in which there was a significant negative correlation noted between UEBW and bladder compliance. Consequently, UEBW could be a reliable predictor for a low-compliant bladder. Since UEBW can be obtained non-invasively, it is readily applicable to pediatric urology. In healthy children, UEBW increased significantly with age. For the evaluation of UEBW in an individual child patient, the deviation from age-matched UEBW, obtained from the formula of the linear correlation between UEBW and age, was employed. In our recent studies, the deviation from age-matched UEBW is likely to be used as a predictor for bladder dysfunction in children, such as secondary vesicoureteral reflux and a low-compliant bladder. In conclusion, UEBW is promising as a non-invasive urodynamic modality capable of evaluating bladder hypertrophy with its functional abnormalities.

[Clinical study on prostatic cancer detected incidentally by transurethral resection of the prostate].

Transurethral resection of the prostate (TUR-P) was performed on 463 consecutive patients with clinically diagnosed benign prostatic hyperplasia (BPH) between April 1994 and June 2000. Pathological examinations of resected prostatic tissues revealed prostatic cancer in 15 (3.2%) of them. Eight (53.3%) of them were in stage A1, and 7 (46.7%) in stage A2. Between 15 cases with prostatic cancer and those with BPH, clinical features including age, serum prostate specific antigen (PSA) levels, prostatic volume, PSA density (PSAD), and resected prostatic tissue weight were compared. As a result, age was the only parameter related with prostatic cancer with a statistically significant difference. The higher the age, prostate cancer was found more frequently. Postoperatively, radical prostatectomy and antiandrogen therapy were performed in 1 and 9 cases, respectively. The remaining 5 cases are being followed with no treatment for prostatic cancer, and have shown no findings suggesting recurrence. These 15 cases are all living disease-free at present. It seems of importance to explain preoperatively the possible detection of prostatic cancer in association with TUR-P, particularly for elderly patients aged 80 years or older.

[A case report of idiopathic hypogonadotropic hypogonadism with particular reference to monitoring of prostate volume].

A 23-year-old man visited our hospital, complaining of a lack of secondary sexual characteristics. Based on both clinical and endocrinological examinations, he was diagnosed as suffering from idiopathic hypogonadotropic hypogonadism (IHH). With human chorionic gonadotropin (hCG)/human menopausal gonadotropin (hMG) replacement therapy, clinical symptoms and serum testosterone levels improved to normal ranges. Interestingly, prostate volume as measured by transrectal ultrasonography increased considerably from 3.6 ml before treatment to 20.2 ml after treatment. The monitoring of prostate volume might be a parameter useful for evaluating the treatment effect of hCG/hMG replacement therapy in IHH.

[Case of lower urinary tract symptoms caused by urothelial papilloma-inverted type as diagnosed by transrectal ultrasonography at voiding].

A 54-year-old male visited our hospital, complaining of lower urinary tract symptoms (LUTS) such as loss of urinary force following the unsuccessful treatment using an alpha1-blocker. Transabdominal ultrasonography performed for measuring postvoid residual urine volume incidentally detected a solid tumor at the bladder neck. In addition, transrectal ultrasonography at voiding confirmed the tumor to obstruct prostatic urethra during voiding. Pathological diagnosis of the tumor resected transurethrally was urothelial papilloma-inverted type. Following the operation, LUTS improved markedly. Voiding TRUS was of clinical use for the definitive diagnosis of the etiology of LUTS.

[A case of primary adenocarcinoma of the epididymis].

A 68-year-old man presented with right intrascrotal swelling. On palpation, a hard tumor without pain was recognized at the head of the right epididymis. Power Doppler ultrasonography revealed blood flow signals within the tumor. Surgical exploration was performed under the tentative diagnosis as possible malignant tumor of the epididymis. The right epididymis adhered to the testis so strongly, that the epididymis was resected with the testis. Pathological diagnosis was moderately differentiated adenocarcinoma of the epididymis. The results of general examinations on possible presence of primary lesions in other organs were all negative. Finally, the diagnosis of primary adenocarcinoma of the epididymis was obtained. He remains free of disease 17 months after surgery.

[The clinical evaluation of 414 cases of male urethritis].

PURPOSE: We reviewed the clinical data of male urethritis diagnosed as sexually transmitted disease with the aim of revealing its clinical features. PATIENTS AND METHODS: In a total number of 414 males diagnosed as having acute urethritis transmitted by sexual activities between January and December in 2000, clinical data were collected and analyzed. In addition, questionnaire concerning the awareness of pharyngeal infection was obtained. RESULTS: Their ages ranged from 16 to 60 years with a mean of 31 years. The source of infection was a commercial sexual worker (CSW) in 288 (69.6%) out of 414 cases. In 241 cases in whom an infection route was determined, 199 cases (82.6%) were considered to have an infection through oral sex. Microbiological examinations isolated Neisseria gonorrhea alone in 206 (49.8%), Chlamydia tracomatis alone in 47 (11.3%) and both in 46 (11.1%) cases. In our study, 57.5% and 20.8% of Neisseria gonorrhea strains were resistant to penicillin and new quinolones, respectively. Based on questionnaire, 174 (57.8%) out of 301 cases were not aware of possible infection from the pharynx through oral sex. CONCLUSION: The remarkable prevalence of gonococcal urethritis might be in part due to the lacking of awareness of infection through oral sex and sexual activities without a condom. Instruction on the prevention as well as the actual situation of urethritis is needed for general population with a broad age spectrum. The appropriate use of antimicrobial agents with sufficient susceptibility and less inductivity of drug-resistance is also of clinical importance.

[Systematic prostate biopsy before transurethral resection of the prostate].

PURPOSE: With the aim of evaluating the clinical significance of systematic prostate biopsy before transurethral resection of the prostate (TUR-P), clinical data were reviewed retrospectively in patients who had underwent prostate biopsy prior to scheduled TUR-P. PATIENTS AND METHODS: Between July, 1994 and June, 2000, TUR-P was scheduled in a total number of 456 patients with clinically diagnosed benign prostatic hyperplasia (BPH). RESULTS: In 218 (47.8%) out of 456 cases, prostatic biopsy was conducted prior to TUR-P due to abnormally elevated serum prostate specific antigen (PSA) levels of 4.0 ng/ml or more, revealing only 22 (10.1%) cases of prostatic cancer. Between these 22 cases with biopsy proven prostatic cancer and 189 cases with BPH confirmed both by biopsy and following TUR-P, statistically significant differences were noted in age (p < 0.05), prostate volume (p < 0.0001) and PSA density (p < 0.01). CONCLUSION: Considering the low positive rate of preoperative prostatic biopsy, it might be suggested that a considerable number of biopsy could be avoided in patients with clinically diagnosed BPH. Based on the results obtained from this study, prostatic biopsy might be unnecessary before TUR-P for those with prostate volume greater than 60 ml or PSA density less than 0.15.

[Primary symptoms of 301 patients with prostate cancer: Nagoya Urology Hospital experience].

PURPOSE: Primary symptoms were reviewed retrospectively in patients with prostate cancer diagnosed in our hospital with the aim of promoting early detection. MATERIALS AND METHODS: The subjects included 301 cases with prostate cancer diagnosed histologically in Nagoya Urology Hospital from August, 1988 to December, 2001. The mean age was 72.7 years, and the median PSA was 20.0 ng/ml. Primary symptoms were classified according to the General Rule for Clinical and Pathological Studies on Prostate Cancer (The 3rd Edition). RESULTS: Out of 301 cases, 274 (91%) visited our hospital with clinical symptoms. Of them, 272 had primary urological symptoms. In these 272 cases, 250 (92%) and 19 (7%) had lower urinary tract symptoms (LUTS) and macroscopic or microscopic hematuria, respectively. The majority of patients (82%) referred from other urologists had already undergone PSA measurement, compared to 50% in those referred from physicians other than urologists (p < 0.0005). CONCLUSION: The present data revealed that LUTS were important primary symptoms for the detection of prostate cancer, particularly in an area like Nagoya where the mass screening for prostate cancer is still unavailable. In terms of the early detection of prostate cancer, PSA has to be measured in patients with LUTS even when they visit physicians who are not urologists.

Significant relationship of time-dependent uroflowmetric parameters to lower urinary tract symptoms as measured by the International Prostate Symptom Score.

AIMS: The aim of the present paper is to elucidate the possible involvement of time-dependent parameters as obtained by uroflowmetry in the manifestation of lower urinary tract symptoms (LUTS) in elderly patients. METHODS: Using simple and multiple regression analyses, the correlation of the International Prostate Symptom Score (IPSS) with objective parameters including age, postvoid residual, uroflowmetry and transrectal ultrasonic measurements of the prostate was analyzed in 206 male patients (average age of 68.0 +/- 7.4 years) who visited our outpatient clinic complaining of LUTS. RESULTS: In the 206 patients, the mean maximum flow rate was 12.2 mL/s (13.7 mL/s in mild, 11.9 mL/s in moderate, and 11.2 mL/s in severe IPSS total score) and average flow rate was 4.4 mL/s (5.4 mL/s in mild, 4.3 mL/s in moderate, and 3.5 mL/s in severe IPSS total score). Simple regression analyses demonstrated that age, voiding time, and average and maximum flow rates correlate significantly with symptom scores. In particular, relatively strong relationships were found between average flow rate and scores of intermittency, weak stream and total and voiding symptoms scores. Serum prostate specific antigen level, postvoid residual and prostatic ultrasonic measurements did not show a significant correlation with symptom scores. Multiple regression analyses revealed age and average flow rate to be independent determinants for symptom scores. These results suggest that the time-dependent function in micturition interferes in the manifestation of LUTS in elderly men who have borderline or pathologic maximum flow rate. When evaluating uro flowmetry in elderly male patients with LUTS, attention should be paid to time-dependent parameters such as voiding time and average flow rate.

Complexed PSA improves prostate cancer detection: results from a multicenter Japanese clinical trial.

OBJECTIVES: To compare the distribution of total and complexed prostate-specific antigen (cPSA) in men with and without prostate cancer with another studied population and to ascertain whether cPSA could enhance the detection of prostate cancer in Japanese men. METHODS: A total of 760 men whose serum total PSA (tPSA) values ranged from 1.0 to 100 ng/mL were enrolled. Serum samples for tPSA and cPSA (ADVIA Centaur) were obtained in all cases. The area under the curve was calculated for comparison of the tPSA and cPSA values. We calculated the number of cancers missed and false-positive results at various cutoff values of cPSA compared with the conventional tPSA threshold of 4.0 ng/mL. RESULTS: Prostate cancer was detected in 268 (35.3%) of 760 patients. cPSA was greater than 8.3 ng/mL (equivalent to 10.0 ng/mL tPSA) in 46.6% of the men with cancer. The area under the curve for cPSA (0.741) was significantly better than that for tPSA (0.721, P <0.001). At a sensitivity of 85% to 95%, significant differences were found in the corresponding specificity between tPSA and cPSA. cPSA at a 3.0-ng/mL threshold detected an identical number of cancers as a tPSA cutoff of 4.0 ng/mL; however, it decreased the false-positive results by 28 cases. CONCLUSIONS: To our knowledge, this is the first report of the distribution of cPSA in Japanese men using a urologic referral population. cPSA can be an alternative to tPSA as the first screening test. A substantial number of men in Japan with prostate cancer are currently diagnosed with a tPSA value greater than 10.0 ng/mL.

Alterations in nuclear structure and expression of proPSA predict differences between native Japanese and Japanese-American prostate cancer.

OBJECTIVES: To differentiate the benign and/or malignant epithelial cells in prostate cancer (PCa) glands of native Japanese (NJ) and Japanese-American (JA) men using biomarkers. METHODS: Tissue microarrays from radical prostatectomy specimens of cancerous and adjacent benign areas from 25 NJ and 25 JA prostate glands were studied. Image analysis was used to quantify total prostate-specific antigen (PSA) and proPSA immunohistochemical staining, as well as the variance of several morphometric features from Feulgen-stained epithelial cell nuclei. Logistic regression analysis was applied to determine whether quantitative nuclear grade (QNG) calculations and PSA immunohistochemical staining could differentiate the two test groups. RESULTS: The QNG model differentiated changes in the benign epithelium of the two Japanese groups with an area under the receiver operating characteristic curve of 84% and accuracy of 82% (P = 0.0001). A second QNG model differentiated changes in the malignant epithelium of the two groups with an area under the receiver operating characteristic curve of 84% and accuracy of 76% (P = 0.0023). Logistic regression models combining proPSA immunohistochemical data and QNG from either benign or malignant tissue components yielded areas under the receiver operating characteristic curve of 96% and 91% (P <0.0001) for differentiation of the JA and NJ groups, respectively. CONCLUSIONS: Unique nuclear morphometric alterations demonstrated by QNG combined with proPSA immunohistologic localization independently predicted for significant differences between NJ and JA men with PCa. These preliminary observations indicate a basis for biologic and molecular alterations in the benign adjacent and malignant epithelium between these two groups.

Preoperative administration of chlormadinone acetate reduces blood loss associated with transurethral resection of the prostate: a prospective randomized study.

OBJECTIVES: To assess the effects of giving chlormadinone acetate (CMA) before surgery on blood loss associated with transurethral resection of the prostate (TURP), in a prospective randomized controlled study. PATIENTS AND METHODS: Candidates for TURP among patients with benign prostatic hyperplasia were randomized to either treatment with CMA (CMA+) or not (CMA-). In principle, CMA was started at least 28 days before TURP and continued until just before surgery. RESULTS: In all, 33 patients in the CMA+ (median duration of treatment 34.5 days) and 38 in the CMA- group were evaluable. The mean blood loss during TURP was less in the CMA+ (237.3 mL) than in the CMA- group (263.1 mL), but the difference was not significant. There was significantly less blood loss per gram of resected prostate tissue in the CMA+ (9.6 mL/g) than in the CMA- group (13.3 mL/g) (P < 0.05). Haematuria on the day of and the day after TURP was also significantly less severe in the CMA+ than in the CMA- group (P < 0.001 and P < 0.05, respectively). The mean microvessel density of resected prostate tissue was significantly less after CMA treatment (P < 0.001). CONCLUSIONS: CMA given for 1 month before TURP could reduce blood loss to some extent during and after TURP, and this may be related to a decrease in microvessel density.

Effects of acupuncture for chronic pelvic pain syndrome with intrapelvic venous congestion: preliminary results.

BACKGROUND: The present study was designed to reveal the usefulness of acupuncture for chronic pelvic pain syndrome with intrapelvic venous congestion as evaluated by symptom scores, transrectal ultrasonography (TRUS) and magnetic resonance (MR) venography. METHODS: Ten male patients suffering from non-inflammatory chronic pelvic pain syndrome (NIH category IIIB) with intrapelvic venous congestion were treated using acupuncture. Eight patients had previously received pharmacotherapy, which was unsuccessful. Acupuncture was performed using disposable stainless steel needles, which were inserted into the bilateral BL-33 points and rotated manually for 10 min. The treatment was repeated every week for 5 weeks without other therapeutic maneuvers. Results from TRUS and MR venography, as well as clinical symptoms based on the NIH chronic prostatitis symptom index (NIH-CPSI) and the international prostate symptom score (IPSS), were compared before and after the treatment. RESULTS: No side-effects were recognized throughout the treatment period. The average pain and QOL scores of the NIH-CPSI 1 week after the 5th acupuncture treatment decreased significantly (P < 0.05 and P < 0.01, respectively) compared with the baseline. The maximum width of the sonolucent zone 1 week after the 5th treatment also decreased significantly (P < 0.01, compared with the baseline). Intrapelvic venous congestion demonstrated by MR venography was significantly improved in four patients. CONCLUSION: This study provided novel information concerning the therapeutic effects of acupuncture on non-inflammatory chronic pelvic pain syndrome.

Acute urethritis caused by Neisseria meningitidis.

A 48-year-old heterosexual Japanese man visited the outpatient clinic of Nagoya Urology Hospital, complaining of burning pain at voiding and pus discharge from the urethral orifice. These symptoms appeared the day following oral-genital contact (fellatio) with a commercial sex worker. On the basis of the presumptive clinical diagnosis of gonorrhea because of the microscopic detection of diplococci in the urethral discharge, he was treated with levofloxacin (300 mg per day) for 7 days. His symptoms responded quickly and urinalysis taken 7 days later was normal. Microbiological examinations isolated Neisseria meningitidis in the urethral discharge by culture with the use of enzymatic profiles. Further prevalence of sexually transmitted diseases (STD) through oral-genital contact would lead to an increase in meningococcal urethritis.

Prostate cancer in native Japanese and Japanese-American men: effects of dietary differences on prostatic tissue.

OBJECTIVES: To investigate the relationship between diet and prostate cancer (CaP) among native Japanese (NJ) and second-generation or third-generation Japanese-American (J-A) men--focusing on the effects of animal fat and soy on prostatic tissues. METHODS: The subjects were 50 Japanese men undergoing radical prostatectomy, 25 NJ living in Nagoya, Japan and 25 U.S.-born J-A men, living in Los Angeles, California. A priori, the NJ men were believed to be a low-fat, high-soy group and the J-A men, a high-fat, low-soy group. The studies included postoperative measurements of diet (Block questionnaire), body fat (bioimpedance), blood, urine, and prostatic biomarkers in malignant and adjacent normal tissue, using a tissue microarray made from the original paraffin blocks. RESULTS: The NJ and J-A men were similar in age (65 to 70 years old; P <0.05), prostate-specific antigen level (7.1 to 8.6 ng/mL), prostate volume (35 to 38 cm3), and Gleason score (5.6 to 6.6), but their body composition differed. J-A men had more body fat (24% versus 19%), higher serum triglyceride levels (245 versus 106 mg/dL), lower estradiol levels (27 versus 31 ng/mL), and much lower urinary soy-metabolite levels (1:3) than NJ men (P <0.02). In both NJ and J-A groups, expression of numerous tissue biomarkers separated normal from CaP tissue, including markers for apoptosis (Bcl-2, caspase-3), growth factor receptors (epidermal growth factor receptor), racemase, 5-lipoxygenase, kinase inhibition (p27), and cell proliferation (Ki-67; all P <0.02). Furthermore, within both normal and CaP tissues, caspase-3 and 5-lipoxygenase were expressed more in NJ than in J-A men (P <0.01). Nuclear morphometry showed that the chromatin in each of the four groups (normal versus CaP, NJ versus J-A) was different (area under the curve 85% to 94%, P <0.01), despite fundamental genetic homogeneity. CONCLUSIONS: NJ and J-A men, products of similar genetics but differing environments, were shown to have differences in body composition that could influence CaP evolution. The CaP specimens from the NJ and J-A men were histologically similar, but tissue biomarker expression, especially of lipoxygenase and the caspase family, suggested differing mechanisms of carcinogenesis. Differences in nuclear morphometry suggested the additional possibility of gene-nutrient interactions.