INITIAL EXPERIENCE OF THE ENZALUTAMIDE TREATMENT FOR CASTRATION-RESISTANT PROSTATE CANCER.

(Objective) Enzalutamide is an oral androgen-receptor inhibitor that prolongs survival in men with castration-resistant prostate cancer (CRPC). We retrospectively evaluated clinical efficacy and safety of enzalutamide in CRPC. (Patients and methods) We reviewed clinical records of 73 patients who had received enzalutamide for the CRPC at Showa University and affiliated 7 hospitals. Enzalutamide was given at a dose of 160 mg/day, but some patients were treated at lower dose because of there age or poor performance status. Prostrate-specific antigen (PSA) response, prior docetaxel use and the previously administered agents were evaluated retrospectively. (Results) The median patients age was 77 years, the median Gleason score was 9 and the median PSA level at baseline was 26.9 ng/ml. The patients who had prior docetaxel use were 29 (39.7%) and the median of total docetaxel dose was 460 mg/body. The median number of total prior treatments (anti-androgens, Estramustine and steroid) was 3. Twenty seven (61.4%) patients with docetaxel-naïve achieved over 50% reduction of PSA level from baseline, but only 7 (24.1%) in patients previously treated with docetaxel. The most common adverse events included fatigue (24.7%), anorexia (24.7%) and the nausea (16.4%). We found a small proportion of responders to enzalutamide experienced a PSA flare. (Conclusion) Our results of the use of Enzaltamide for CRPC were similar with previous reports. PSA flare was found in some patients with CRPC who responded to enzaltamide. It should be noted that this possible PSA flare phenomenon.

Cost-efficient multiplex PCR for routine genotyping of up to nine classical HLA loci in a single analytical run of multiple samples by next generation sequencing.

BACKGROUND: HLA genotyping by next generation sequencing (NGS) requires three basic steps, PCR, NGS, and allele assignment. Compared to the conventional methods, such as PCR-sequence specific oligonucleotide primers (SSOP) and -sequence based typing (SBT), PCR-NGS is extremely labor intensive and time consuming. In order to simplify and accelerate the NGS-based HLA genotyping method for multiple DNA samples, we developed and evaluated four multiplex PCR methods for genotyping up to nine classical HLA loci including HLA-A, HLA-B, HLA-C, HLA-DRB1/3/4/5, HLA-DQB1, and HLA-DPB1. RESULTS: We developed multiplex PCR methods using newly and previously designed middle ranged PCR primer sets for genotyping different combinations of HLA loci, (1) HLA-DRB1/3/4/5, (2) HLA-DQB1 (3.8 kb to 5.3 kb), (3) HLA-A, HLA-B, HLA-C, and (4) HLA-DPB1 (4.6 kb to 7.2 kb). The primer sets were designed to genotype polymorphic exons to the field 3 level or 6-digit typing. When we evaluated the PCR method for genotyping all nine HLA loci (9LOCI) using 46 Japanese reference subjects who represented a distribution of more than 99.5% of the HLA alleles at each of the nine HLA loci, all of the 276 alleles genotyped, except for HLA-DRB3/4/5 alleles, were consistent with known alleles assigned by the conventional methods together with relevant locus balance and no excessive allelic imbalance. One multiplex PCR method (9LOCI) was able to provide precise genotyping data even when only 1 ng of genomic DNA was used for the PCR as a sample template. CONCLUSIONS: In this study, we have demonstrated that the multiplex PCR approach for NGS-based HLA genotyping could serve as an alternative routine HLA genotyping method, possibly replacing the conventional methods by providing an accelerated yet robust amplification step. The method also could provide significant merits for clinical applications with its ability to amplify lower quantity of samples and the cost-saving factors.

[A Case of Urachal Carcinoma Treated by TS-1/CDDP as Adjuvant Chemotherapy].

A 49-year-old female presented complaining of gross hematuria. Cystoscopy and magnetic resonance imaging revealed a papillary tumor on the bladder dome. At biopsy pathology the tumor was diagnosed as adenocarcinoma. We diagnosed the tumor as urachal adenocarcinoma and performed partial cystectomy of bladder dome with en-bloc resection of the urachal ligament up to the umbilicus. In surgical pathology, the tumor had invaded to the fat tissue around the urachal ligament with metastasis to the lymph node. Therefore the tumor was diagnosed as a stage IVA (Sheldon's category) urachal adenocarcinoma. After surgery, 6 cycles of chemotherapy with TS-1 and cisplatin (CDDP) were performed. There has been no relapse 5 years after surgery. This is the first report of successful adjuvant chemotherapy with TS-1/CDDP for advanced urachal adenocarcinoma.

[A case of mucinous tubular and spindle cell carcinoma of the kidney].

Mucinous tubular and spindle cell carcinoma (MTSCC) is a distinct entity in the World Health Organization classification of kidney tumors since 2004. Herein, we report a case of a patient with MTSCC of the kidney. A 48-year-man visited our hospital with a chief complaint of occult blood in his urine, confirmed by urine occult blood reaction. Computed tomography revealed a solid tumor in the right kidney. The tumor was 40×38 mm in length and was slightly enhanced (cT1aN0M0). Therefore, we performed radical nephrectomy. On analysis of the resected specimen, we found that the number of comparatively small malignant cells had increased markedly, forming branched tubular cuboidal cells. Further more, positive results were obtained on staining the stroma with both PAS and alcian blue stains characteristic of papillary renal cell carcinoma ; however, extracellular mucinous material was found to be depleted. Therefore, we needed to differentiate between papillary renal cell carcinoma and MTSCC. Finally, on the basis of the immunohistochemical staining results-vimentin (＋), CK34ßE12 (-), and CD10 (-)-MTSCC was confirmed.

[A case of vesical endometriosis that worsened during the early pregnancy period].

We report a case of vesical endometriosis that worsened during the early pregnancy period. A 37-year old woman had been under treatment for endometriosis (including vesical endometriosis) by a gynecologist during the past 10 years. She was treated for sterility 1 year ago, and became pregnant through in vitro fertilization. In her 8th gestational week, she complained of gross hematuria at our hospital. Cystoscopic findings revealed some tumors that appeared worse than the last findings two years ago. In order to deny malignancy, transurethral resection of the bladder tumor was performed in her 12th gestational week. The pathologic diagnosis was endometriosis. She was able to stay pregnant, and delivered a girl. After delivery, cystoscopic findings revealed reduction of tumors. In most cases pregnancy cures endometriosis ; however, in this case symptoms became worse during the early stage of pregnancy. The reason for this contrary event is discussed.

[EFFICACY AND SAFETY OF 25 AND 50 µg DESMOPRESSIN ORALLY DISINTEGRATING TABLETS IN NOCTURIA DUE TO NOCTURNAL POLYURIA IN JAPANESE MALE PATIENTS].

(Purpose) To conduct a prospective study on the efficacy and safety of desmopressin for nocturnal polyuria. (Materials and methods) We selected 51 Japanese men, aged ≥50 years, with complaints of nocturia and a nocturnal polyuria index of ≥0.33. We administered 25 or 50 µg desmopressin (Minirinmelt Orally Disintegrating Tablet®), once daily at bedtime. We evaluated the nighttime urinary frequency and urine volume, nocturnal polyuria index, time to the first urination after falling asleep, and International Prostate Symptom Score (IPSS) at baseline and at 4, 8, and 12 weeks after administration. In addition, they underwent clinical examinations and blood tests at 1, 4, and 12 weeks to evaluate the safety of the drug. (Results) We observed a decrease in the nighttime urinary frequency and urine volume, and nocturnal polyuria index, increased prolonged time to the first urination after falling asleep, and improved IPSS at and after 4 weeks, compared to baseline data. Furthermore, the drug remained effective even at 12 weeks for all parameters. We observed adverse events in 31.3% of the patients. The incidence of hyponatraemia was particularly high in 15.7% of the patients. Those with a lower serum sodium level and lesser body weight at baseline were more likely to develop hyponatraemia. (Conclusion) Desmopressin was identified as a potential drug for the treatment of nocturnal polyuria. However, hyponatraemia, an important adverse event, resulted in treatment discontinuation in several patients. A sodium level lower than the normal level and low body weight at baseline were the risk factors for hyponatraemia.

High-resolution HLA typing by long reads from the R10.3 Oxford nanopore flow cells.

Nanopore sequencing has been investigated as a rapid and cost-efficient option for HLA typing in recent years. Despite the lower raw read accuracy, encouraging typing accuracy has been reported, and long reads from the platform offer additional benefits of the improved phasing of distant variants. The newly released R10.3 flow cells are expected to provide higher read-level accuracy than previous chemistries. We examined the performance of R10.3 flow cells on the MinION device in HLA typing after enrichment of target genes by multiplexed PCR. We also aimed to mimic a 1-day workflow with 8-24 samples per sequencing run. A diverse collection of 102 unique samples were typed for HLA-A, -B, -C, -DPA1, -DPB1, -DQA1, -DQB1, -DRB1, -DRB3/4/5 loci. The concordance rates at 2-field and 3-field resolutions were 99.5% (1836 alleles) and 99.3% (1710 alleles). We also report important quality metrics from these sequencing runs. Continued research and independent validations are warranted to increase the robustness of nanopore-based HLA typing for broad clinical application.

[INITIAL TREATMENT OF NOCTURIA CAUSED BY NOCTURNAL POLYURIA WITH LOW-DOSE DESMOPRESSIN].

(Objective) Nocturia, an important male lower urinary tract symptom (LUTS), is often difficult to treat. Herein, we report our experience of the initial treatment of nocturia with the novel drug desmopressin. (Subjects and methods) Subjects included 25 patients with LUTS treated with desmopressin who had the chief complaint of nocturia. Before treatment, the frequency of nocturnal urination (≥2) and nocturnal polyuria index (≥0.33) were confirmed based on the urination diary for ≥ 72 h. Before sleep, 25 or 50 mg desmopressin (Minirin® Melt OD tablets) was administered once daily. The frequency of nocturnal urination, volume of nocturnal urine, time from falling asleep to first urination, first urinary volume after falling asleep, nocturnal polyuria index, International Prostate Symptom Score (IPSS), quality of life index, Overactive Bladder Symptom Score, and residual urine volume were comparatively evaluated before and 4 weeks after treatment. Treatment effect was self-evaluated by patients 4 weeks after the treatment. Safety was evaluated by interview and blood testing 1 and 4 weeks after the treatment. (Results) Decrease in the frequency of nocturnal urination and improvement in IPSS were observed. According to self-evaluation of the treatment, 72.6% of the patients considered the treatment efficacious. Regarding safety, adverse events were observed in 28% of the patients, particularly hyponatremia (12% of the patients). (Conclusion) Desmopressin is a potential key drug for the treatment of nocturia caused by nocturnal polyuria.

Next-generation HLA typing of 382 International Histocompatibility Working Group reference B-lymphoblastoid cell lines: Report from the 17th International HLA and Immunogenetics Workshop.

Extended molecular characterization of HLA genes in the IHWG reference B-lymphoblastoid cell lines (B-LCLs) was one of the major goals for the 17th International HLA and Immunogenetics Workshop (IHIW). Although reference B-LCLs have been examined extensively in previous workshops complete high-resolution typing was not completed for all the classical class I and class II HLA genes. To address this, we conducted a single-blind study where select panels of B-LCL genomic DNA samples were distributed to multiple laboratories for HLA genotyping by next-generation sequencing methods. Identical cell panels comprised of 24 and 346 samples were distributed and typed by at least four laboratories in order to derive accurate consensus HLA genotypes. Overall concordance rates calculated at both 2- and 4-field allele-level resolutions ranged from 90.4% to 100%. Concordance for the class I genes ranged from 91.7 to 100%, whereas concordance for class II genes was variable; the lowest observed at HLA-DRB3 (84.2%). At the maximum allele-resolution 78 B-LCLs were defined as homozygous for all 11 loci. We identified 11 novel exon polymorphisms in the entire cell panel. A comparison of the B-LCLs NGS HLA genotypes with the HLA genotypes catalogued in the IPD-IMGT/HLA Database Cell Repository, revealed an overall allele match at 68.4%. Typing discrepancies between the two datasets were mostly due to the lower-resolution historical typing methods resulting in incomplete HLA genotypes for some samples listed in the IPD-IMGT/HLA Database Cell Repository. Our approach of multiple-laboratory NGS HLA typing of the B-LCLs has provided accurate genotyping data. The data generated by the tremendous collaborative efforts of the 17th IHIW participants is useful for updating the current cell and sequence databases and will be a valuable resource for future studies.

Quality control project of NGS HLA genotyping for the 17th International HLA and Immunogenetics Workshop.

The 17th International HLA and Immunogenetics Workshop (IHIW) organizers conducted a Pilot Study (PS) in which 13 laboratories (15 groups) participated to assess the performance of the various sequencing library preparation protocols, NGS platforms and software in use prior to the workshop. The organizers sent 50 cell lines to each of the 15 groups, scored the 15 independently generated sets of NGS HLA genotyping data, and generated "consensus" HLA genotypes for each of the 50 cell lines. Proficiency Testing (PT) was subsequently organized using four sets of 24 cell lines, selected from 48 of 50 PS cell lines, to validate the quality of NGS HLA typing data from the 34 participating IHIW laboratories. Completion of the PT program with a minimum score of 95% concordance at the HLA-A, HLA-B, HLA-C, HLA-DRB1 and HLA-DQB1 loci satisfied the requirements to submit NGS HLA typing data for the 17th IHIW projects. Together, these PS and PT efforts constituted the 17th IHIW Quality Control project. Overall PT concordance rates for HLA-A, HLA-B, HLA-C, HLA-DPA1, HLA-DPB1, HLA-DQA1, HLA-DQB1, HLA-DRB1, HLA-DRB3, HLA-DRB4 and HLA-DRB5 were 98.1%, 97.0% and 98.1%, 99.0%, 98.6%, 98.8%, 97.6%, 96.0%, 99.1%, 90.0% and 91.7%, respectively. Across all loci, the majority of the discordance was due to allele dropout. The high cost of NGS HLA genotyping per experiment likely prevented the retyping of initially failed HLA loci. Despite the high HLA genotype concordance rates of the software, there remains room for improvement in the assembly of more accurate consensus DNA sequences by NGS HLA genotyping software.

[A CASE OF RENAL CELL CARCINOMA WITH INFERIOR VENA CAVAL TUMOR THROMBUS WHICH THE REDUCTION OF TUMOR IN SPITE OF DRUG DISCONTINUANCE AFTER THE FULMINANT HEPATITIS ONSET WITH THE SUNITNIB].

A 70-year-old man presented with right renal cell carcinoma with inferior vena caval tumor thrombus into the right atrium. CT Scan presented local invasion and lymph node metastasis. We estimated inoperative case, so he was started sunitinib. After 5 month he had general fatigue and admitted to our hospital. He diagnosed serious adverse events of fulminant hepatitis and left ventricular systolic dysfunction and discontinued sunitnib. After drug discontinuance reduction of tumor and tumor thrombus were detected. 7-months later, we showed the increase of tumor and the improvement of the left ventricular systolic dysfunction. We performed right renal nephrectomy and it passes now in 14 months after surgery, but doses not show a recurrence, metastasis.

Application of High-Throughput Next-Generation Sequencing for HLA Typing on Buccal Extracted DNA: Results from over 10,000 Donor Recruitment Samples.

BACKGROUND: Unambiguous HLA typing is important in hematopoietic stem cell transplantation (HSCT), HLA disease association studies, and solid organ transplantation. However, current molecular typing methods only interrogate the antigen recognition site (ARS) of HLA genes, resulting in many cis-trans ambiguities that require additional typing methods to resolve. Here we report high-resolution HLA typing of 10,063 National Marrow Donor Program (NMDP) registry donors using long-range PCR by next generation sequencing (NGS) approach on buccal swab DNA. METHODS: Multiplex long-range PCR primers amplified the full-length of HLA class I genes (A, B, C) from promotor to 3' UTR. Class II genes (DRB1, DQB1) were amplified from exon 2 through part of exon 4. PCR amplicons were pooled and sheared using Covaris fragmentation. Library preparation was performed using the Illumina TruSeq Nano kit on the Beckman FX automated platform. Each sample was tagged with a unique barcode, followed by 2×250 bp paired-end sequencing on the Illumina MiSeq. HLA typing was assigned using Omixon Twin software that combines two independent computational algorithms to ensure high confidence in allele calling. Consensus sequence and typing results were reported in Histoimmunogenetics Markup Language (HML) format. All homozygous alleles were confirmed by Luminex SSO typing and exon novelties were confirmed by Sanger sequencing. RESULTS: Using this automated workflow, over 10,063 NMDP registry donors were successfully typed under high-resolution by NGS. Despite known challenges of nucleic acid degradation and low DNA concentration commonly associated with buccal-based specimens, 97.8% of samples were successfully amplified using long-range PCR. Among these, 98.2% were successfully reported by NGS, with an accuracy rate of 99.84% in an independent blind Quality Control audit performed by the NDMP. In this study, NGS-HLA typing identified 23 null alleles (0.023%), 92 rare alleles (0.091%) and 42 exon novelties (0.042%). CONCLUSION: Long-range, unambiguous HLA genotyping is achievable on clinical buccal swab-extracted DNA. Importantly, full-length gene sequencing and the ability to curate full sequence data will permit future interrogation of the impact of introns, expanded exons, and other gene regulatory sequences on clinical outcomes in transplantation.

HLA-genotyping of clinical specimens using Ion Torrent-based NGS.

We have evaluated and validated the NXType™ workflow (One Lambda, Inc.) and the accompanying TypeStream™ software on the Ion Torrent Next Generation Sequencing (NGS) platform using a comprehensive testing panel. The panel consisted of 285 genomic DNA (gDNA) samples derived from four major ethnic populations and contained 59 PT samples and 226 clinical specimens. The total number of alleles from the six loci interrogated by NGS was 3420. This validation panel provided a wide range of HLA sequence variations including many rare alleles, new variants and homozygous alleles. The NXType™ system (reagents and software) was able to correctly genotype the vast majority of these specimens. The concordance rate between SBT-derived genotypes and those generated by TypeStream™ auto-analysis ranged from 99.5% to 99.8% for the HLA-A, B, C, DRB1 and DQB1 loci, and was 98.9% for HLA-DPB1. A strategy for data review was developed that would allow correction of most of the few remaining typing errors. The entire NGS workflow from gDNA amplification to genotype assignment could be completed within 3 working days. Through this validation study, the limitations and shortcomings of the platform, specific assay system, and software algorithm were also revealed for further evaluation and improvement.

[The evaluation of urination status and International Prostate Symptom Score following radical prostatectomy].

PURPOSE: We evaluated condition of urination and International Prostate Symptom Score (I-PSS) after radical prostatectomy. PATIENTS AND METHODS: Forty-three men with prostatic cancer underwent radical prostatectomy between October 1993 and October 2002. Mean patients age was 66 years (range 56 to 79) and clinical follow-up averaged 38.6 months (range 3 to 84). Urodynamics studies including uroflowmetry, cystometry and evaluation of I-PSS were performed before and 1, 3, 6, 12 months after the operation. After 12 months these studies were performed every year. The status of postoperative urinary incontinence was based on patients' report. RESULTS: First desire to void, maximum desire to void and maximal flow rate was decrease temporarily after radical prostatectomy. However most patients had normal uroflowmetorogram and normal cystometrogram at 6 months. I-PSS and QOL index was improved during postoperative 12 months. CONCLUSIONS: Postoperatively urodynamics studies was improved from 3 to 6 months, but evaluation of I-PSS and QOL index was improved from 6 to 12 months. The difference was formed to both.

Effects of varicocele repair in adults on ultrasonographically determined testicular volume and on semen profile.

OBJECTIVES: We determined the effect of varicocele repair on testicular volume according to scrotal ultrasonography, reported to provide the best approximation of actual testicular volume. METHODS: Forty-four men with left varicocele (mean age +/- standard deviation, 33.4 +/- 5.4 years) underwent varicocele repair. We performed both scrotal ultrasonography with color Doppler imaging and semen analysis before and after varicocele repair. Among these patients, 19 had a clinical left varicocele, 22 had clinical left and subclinical right varicoceles, and 3 had clinical left and right varicoceles. We calculated testicular volumes using the formula: Length x Width x Height x 0.71. RESULTS: For all 44 patients, mean left and total testicular volume improved significantly after varicocele repair (increases of 1.5 and 2.4 mL, respectively) as did semen profile data such as sperm per unit volume and percentage of motile sperm. In the 19 men with a clinical left varicocele, mean left testicular volume increased significantly (by 1.5 mL) after left varicocele repair, in association with increases in sperm per unit volume and motility percentage. In the 25 men with clinical left varicocele plus a subclinical or clinical right varicocele, mean left and total testicular volume improved significantly after repair of right and left varicoceles (increases of 1.5 and 2.7 mL, respectively). However, right testicular volume showed no significant increase in any patient group. CONCLUSIONS: Varicocele repair in adults with a clinical left varicocele increased left testicular volume and improved semen profiles.

Testicular volume measurements using Prader orchidometer versus ultrasonography in patients with infertility.

OBJECTIVES: To compare the accuracy of testicular volume measurements with the Prader orchidometer versus ultrasonography. METHODS: The volume of 938 testes in 469 men with infertility (mean age 35.8 years) was measured using a Prader orchidometer and by ultrasonography. The ultrasound testicular volumes were calculated using the formula length x width x height x 0.71. To compare any differences between the methods according to testicular size, the patients were divided into six groups according to the ultrasound-determined volume: less than 5, 5 to 10, 10 to 15, 15 to 20, 20 to 25, and 25 cm3 or more. RESULTS: The mean volume by orchidometry and ultrasonography was 18.7 and 13.7 cm3 for the right testis and 18.0 and 12.5 cm3 for the left, respectively, and was significantly overestimated by orchidometry (P <0.0001; by 5.1 cm3 on the right and 5.5 cm3 on the left). The largest differences between methods were observed for volumes of 10 to 15 cm3 on the right and 5 to 10 cm3 on the left. The difference between the methods decreased as the ultrasound-determined volume increased (r = 0.636 on the right; r = 0.598 on the left testis). Nonetheless, the Prader orchidometric measurements showed a strong correlation with the ultrasound measurements (r = 0.707 on the right; r = 0.746 on the left). CONCLUSIONS: The testicular volume estimated by Prader orchidometry correlated closely with the measurements by ultrasonography. However, the orchidometer overestimated the testicular volume, especially in small testes.

Testicular volume measurement: comparison of ultrasonography, orchidometry, and water displacement.

OBJECTIVES: To determine the accuracy of orchidometry and ultrasonography for measuring the testicular volume by comparing the resultant measurements with the actual testicular volume in humans. METHODS: The testicular volume of 40 testes from 20 patients with prostate cancer (mean age +/- SD 74.5 +/- 7.5 years) was measured using the Prader orchidometer and ultrasonography before therapeutic bilateral orchiectomy. The ultrasound measurements of testicular volume were calculated using three formulas: length (L) x width (W) x height (H) x 0.52, L x W2 x 0.52, and L x W x H x 0.71. The actual testicular volumes were determined by water displacement of the surgical specimen. RESULTS: The mean actual testicular volume of the 40 testes was 9.3 cm3 (range 2.5 to 23.0). A strong correlation was found between the testicular volume calculated by the three ultrasound formulas and the actual volume (r = 0.910 to 0.965, P <0.0001) and was stronger than the correlation with the Prader orchidometer (r = 0.818, P <0.0001). The smallest mean difference from the actual testicular volume was observed with the formula L x W x H x 0.71, which overestimated the actual volume by 0.80 cm3 (7.42%). The measurements using the Prader orchidometer correlated with the actual testicular volume and with the testicular volume calculated using the three ultrasound formulas (r = 0.801 to 0.816, P <0.0001). However, the orchidometer measurements had the largest mean difference from the actual testicular volume (6.68 cm3, 81.7%). CONCLUSIONS: The results of this study have shown that measuring the testicular volume by ultrasonography is more accurate than by the Prader orchidometer, and the formula L x W x H x 0.71 was the most accurate for calculating the testicular volume.

Color Doppler ultrasonography as a routine clinical examination in male infertility.

AIM: We assessed the value of scrotal color Doppler ultrasonography as a routine examination in infertile men. METHODS: Color Doppler ultrasonography was performed in 545 infertile men with a mean age of 35.8 years to detect intrascrotal abnormalities. Findings were compared with those of physical examination. RESULTS: Intrascrotal abnormalities were detected by ultrasonography in 65.3% of patients. Of 374 abnormalities, 58.3% were undetected by physical examination. Left varicocele was found in 313 patients (57.4%); testicular microlithiasis in 30 (5.5%); epididymal cyst in 21 (3.9%); right varicocele in 4 (0.8%); and testicular cysts in 3 (0.6%). One occurrence each (0.2%) was found for testicular tumor, intrascrotal hemangioma, and hydrocele of the spermatic cord. Compared to ultrasonography, sensitivity in detecting left varicocele by physical examination was 58.4%; specificity, 79.3%; accuracy, 67.3%; and positive predictive value, 79.3%. Venous diameters in the pampiniform plexus were 3 mm or more in 61.5% of 130 subclinical left varicoceles. Of 30 patients with testicular microlithiasis, 14 had varicocele, 2 had epididymal cyst,s 3 had a history of mumps orchitis, 1 had retractile testis, and 1 had a history of orchiectomy for contralateral testicular tumor. CONCLUSIONS: The routine Color Doppler ultrasonography is valuable for diagnosing scrotal abnormalities in infertile men, frequently detecting non-palpable lesions.

Testicular microlithiasis identified ultrasonographically in Japanese adult patients: prevalence and associated conditions.

OBJECTIVES: To determine the prevalence of testicular microlithiasis (TM) seen by testicular ultrasonography (US) in Japanese adult men referred for andrologic symptoms and evaluate associations of TM with pathologic conditions. METHODS: For 7 years, US was performed in 969 patients (mean age 40.9 years) at one institution. The patients were divided into groups with infertility (n = 550), unilateral testicular tumor (n = 46), or other andrologic conditions (n = 373). TM was identified as multiple small hyperechogenic foci. In the tumor group, only images of the tumor-free testis were reviewed. Patients with TM accompanying tumor or infertility completed follow-up questionnaires and US examinations. RESULTS: TM was diagnosed in 46 patients (mean age 38.5 years, range 23 to 75). The prevalence of TM was 17.4% in the tumor group, 5.6% in the infertility group, and 1.9% in the other-conditions group. TM was associated with testicular tumor and infertility, but not with other conditions. In patients with unilateral testicular germ cell tumor, the prevalence of carcinoma in situ in the contralateral testis was greater when TM was present in that testis (2 of 8 patients) than when TM was absent (0 of 32, P = 0.0037). No new testicular tumor developed subsequently. In the infertility group, the 31 patients with TM showed no subsequent testicular tumor development, and neither patient undergoing testicular biopsy had carcinoma in situ. CONCLUSIONS: TM, as demonstrated by US, was associated with infertility, as well as testicular tumor. TM in a testis contralateral to a unilateral testicular germ cell tumor may increase the risk of carcinoma in situ.

Anatomic variations of cavernous arteries and their effect on measurement of hemodynamic parameters: a power Doppler study.

OBJECTIVES: To assess the cavernous arterial (CA) anatomy with power Doppler imaging and evaluate the effects of any anatomic variations on the measurement of hemodynamic parameters. METHODS: Thirty-three patients with and 26 without a vascular component to their erectile dysfunction were examined. The CA anatomy was evaluated, and hemodynamic variables were measured at multiple sites, including sites in each artery, if multiple CAs were present. RESULTS: The frequency of anatomic variation was similar between the two groups. A single CA, considered normal, was observed in 57.7% of 52 corpora in the nonvasculogenic group and in 63.6% of 66 corpora in the vasculogenic group. Seven patients (26.9%) in the nonvasculogenic group and 11 (33.3%) in the vasculogenic group had CA anatomy that was different between the right and left corpora. In both groups, a single CA ordinarily showed at least a 35.0% decrement in the mean peak systolic velocity (PSV) between the crura and the proximal shaft; double, triple, and bifurcated CAs also had distally decreased PSV. However, two corpora with a single CA showed an increased PSV distally; in 1 patient, arterial communication between the corpora was responsible. In 86.7% of corpora with double CAs in the vasculogenic group and in 52.6% in the nonvasculogenic group, the CA distant from the crura showed a greater PSV than that near the crura. CONCLUSIONS: CA anatomy is variable, and the PSV differs between sites, irrespective of the presence of a vascular component to erectile dysfunction. Thus, anatomic variations should be considered when interpreting Doppler sonography.