Biomedical subjects
Publications and source records attributed to Hideyuki Akaza.
Splenogonadal fusion is a rare congenital anomaly. We report herein a case of splenogonadal fusion associated with contra lateral testicular aplasia, and review the etiology, pathogenesis and management of this rare disease. As far as we know, this is the first reported case of splenogonadal fusion associated with testicular aplasia.
AIM: A retrospective review of patients with localized and locally advanced prostate cancer was performed to evaluate the efficacy of primary hormonal therapy and predict long-term prognosis in these patients. METHODS: A total of 628 patients who were diagnosed with stage T1c to T3 prostate cancer were treated with primary hormonal therapy at participating institutions. The patients were classified based on pretreatment prostate-specific antigen (PSA) level, Gleason score, and time to nadir PSA level. Disease-specific and progression-free survival rates were investigated, and compared among the subgroups. RESULTS: The mean age of patients was 74.5 years, and median pretreatment PSA level was 14.0 ng/mL. A total of 399 patients (63.5%) were treated with combined androgen blockade (CAB), and 229 patients (36.5%) were treated with castration monotherapy. The disease-specific survival rate of all 628 patients was 89.1% at 8 years. The group that showed a good response to primary hormonal therapy (Group G, pretreatment PSA level < or =20 ng/mL, Gleason score < or =7, and time to nadir PSA < or =6 months) accounted for approximately one-third of the total number of T1c-T3 patients. Disease-specific and progression-free survival rates at 8 years in Group G were 98.9% and 82.0%, respectively. These rates increased to 100% and 87.3%, respectively, in patients receiving CAB treatment in Group G. CONCLUSIONS: The results indicate the usefulness of primary hormonal therapy, especially CAB treatment, for patients showing a good response to hormonal therapy in long-term control of localized and locally advanced prostate cancer.
BACKGROUND: Elastography is a diagnostic imaging technique that evaluates the hardness of a lesion. It is expected to become a new diagnostic modality for prostate cancer. The aim of this study was to examine the usefulness of elastography in the diagnosis of prostate cancer. METHODS: A total of 29 patients with untreated, histologically proven prostate cancer were examined using an elastographic imaging technique. The patient was scanned in the dorsosacral position and the prostate was manually compressed with a transrectal ultrasonic probe. The echo signals from inside the tissue were measured before and after the tissue compression and an elastogram was generated by spatially differentiation of the displacement distribution. RESULTS: Elastography depicted the cancer lesion as a harder tissue than the surrounding normal prostatic tissue. Elastography successfully detected 93% (27 patients) of the untreated prostate cancer lesions. Detection of cancer lesions using elastography was significantly higher than by digital rectal examination (59%; 17 patients) and transrectal ultrasonography (55%; 16 patients). CONCLUSION: Elastography has great potential as a useful modality for diagnosis of prostate cancer. Differentiation between cancerous and normal tissues can be expected to become more accurate as a result of technical advances in the quantification of tissue hardness.
OBJECTIVE: To investigate, in a human urinary tract cell line, the interaction of Toll-like receptor (TLR) signals with cytoplasmic adapter proteins MyD88 and bacillus Calmette-Guérin (BCG), and evaluate the epithelial cytokine response to BCG infection. Intravesical BCG therapy is effective against carcinoma in situ and as prophylaxis for recurrence, but although immunological mechanisms have been assumed, the mechanisms of the antitumour effects of BCG have not been completely elucidated. MATERIALS AND METHODS: The cell line was first screened for TLR expression by reverse transcription-polymerase chain reaction (RT-PCR). Total RNA was isolated from a human urinary cell line, Hu35E6E7, and cDNA synthesised. PCR was used to measure the gene expression of TLR-2, -3, -4, -5, -9, MyD88, MD-2, CD14 and interleukin-8 and -6. The Hu35E6E7 cell line was cultured in keratinocyte serum-free medium, and BCG was added to the cell culture. After Hu35E6E7 cells were stimulated by BCG for various periods, the total RNA of the cells was extracted. Quantitative real-time PCR was conducted for MyD88 using appropriate probes, and the expression of MyD88 analysed. The cell supernatant was collected, and the levels of interferon-gamma, tumour necrosis factor-alpha, interleukin-2, -12, -4, -6, -10, -8 and -1beta were assayed using an enzyme-linked immunosorbent assay. RESULTS: Uroepithelial cells expressed TLR-2, -3, -4 and -9, and MyD88, MD2, CD14, interleukin-6 and -8 were also detected. At 3, 6, 9 and 12 h after adding BCG, quantitative PCR assay showed that the expression of MyD88 was maximal at 6 h. The presence of BCG stimulated the release only of interleukin-6 and -8 from Hu35E6E7 cells after 6 h. By contrast, interferon-gamma, tumour necrosis factor-alpha, interleukin-2, -12, -4, -10 and -1beta were not detected in the culture supernatant. CONCLUSION: These results show that uroepithelial cells, but not immune cells, responded directly to BCG through TLR signalling. Further investigation is needed to determine the role of cytokines released from uroepithelial cells after BCG infection.
OBJECTIVE: To examine the chemopreventive effects of a selective cyclooxygenase (COX)-2 inhibitor, meloxicam, and a selective epidermal growth factor (EGF)-receptor tyrosine kinase inhibitor, gefitinib (as a single agent) on a carcinogen-induced rodent bladder carcinogenesis model. MATERIALS AND METHODS: The study comprised 103 male Fisher-344 rats (8 weeks old); after initial carcinogen treatment for 8 weeks with 0.05%N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) in drinking water, the rats were divided into five groups, i.e. group 1, control (vehicle only); group 2, gefitinib high-dose (15 mg/kg by gavage once daily); group 3, gefitinib low-dose (5 mg/kg); group 4, meloxicam high-dose (1.8 mg/kg by gavage once daily); and group 5, meloxicam low-dose (0.6 mg/kg). Twelve weeks later the rats were killed; after fixing the bladder in 10% formalin, the number and size of hyperplasia and carcinoma foci were recorded microscopically in sections stained with haematoxylin and eosin, submitted entirely as multiple strips. RESULTS: The incidence of carcinoma, confirmed microscopically, was: control 14/20 (70%); high-dose gefitinib, 7/20 (35%); low-dose gefitinib, 7/20 (35%); high-dose meloxicam 7/21 (33%); and low-dose meloxicam, 12/20 (60%). The mean numbers of carcinomas per bladder in groups 1-5 were 1.2, 0.5, 0.4, 0.5 and 1.1, respectively. The incidence and the mean number of carcinomas per bladder were significantly lower in the treatment groups (P < 0.05) than in the control group, except in the low-dose meloxicam group. There were no significant adverse effects. CONCLUSION: Both meloxicam and gefitinib have inhibitory effects on rat bladder carcinogenesis with no significant adverse effects. A combination of these drugs would be worth studying for their synergistic effects.
OBJECTIVE: To evaluate the efficacy of primary hormone therapy for localized or locally advanced prostate cancer, by analysing the 10-year survival rates for men with localized or locally advanced prostate cancer treated with primary hormone therapy or prostatectomy. PATIENTS AND METHODS: Between February 1993 and March 1995, men with T1b, T1c or T2-3 N0M0 prostate cancer were enrolled. In all, 176 men who had a prostatectomy were assigned to Study 1 and were given adjuvant luteinizing hormone-releasing hormone (LHRH) agonist; 151 men who did not have a prostatectomy were assigned to Study 2 and had LHRH agonist monotherapy or combined androgen blockade. They were followed until death, loss to follow-up, or until the end of the observation period (31 March 2004). We analysed all cases in each study as a single population, and compared Study 1 with Study 2. RESULTS: The mean patient ages were 67.2 years in Study 1 and 75.7 years in Study 2. During a median of 10.4 years of follow-up, 20 men in Study 1 and 17 in Study 2 died from prostate cancer, and 21 men in Study 1 and 50 in Study 2 died from other causes. In Study 1, the 10-year overall survival rate was 73% and the 10-year cause-specific survival rate was 86%, vs 41% and 78% in Study 2. Overall survival curves were similar to expected survival curves in both studies. There was no significant difference between studies in cause-specific survival. CONCLUSIONS: The progression of prostate cancer was retarded by primary hormone therapy in men with localized or locally advanced prostate cancer. With primary hormone therapy or prostatectomy, the men had a life-expectancy similar to that of the normal population.
A 69-year-old man who had a complaint of melena and hematemesis was referred to our hospital for further evaluation and treatment of renal masses, bilateral adrenal swelling and a tumor in the small intestine. The abdominal CT scan demonstrated two tumors sized 45 mm and 15 mm in diameter, located in the center and lower pole of the left kidney. Bilateral adrenal swelling and a small intestinal tumor with invagination were also observed. We diagnosed left renal cell carcinomas with bilateral adrenal metastases or hyperplasia, and a primary or metastatic small intestinal tumor. He received left radical nephrectomy, right adrenalectomy, and small intestinal resection. Pathological diagnosis was renal cell carcinoma, granular cell carcinoma, G2>G3>G1, INFalpha, v (+), pT1a, pM1, Stage IV. Bilateral adrenal swelling and small intestinal tumor were metastases from the renal cell carcinoma After operation, we administered interferon-alpha and steroid replacement. He died after 27-month follow-up period because of renal cell carcinoma. Renal cell carcinoma with simultaneous metastases to bilateral adrenal glands and the small intestine is extremely rare.
A 37-year-old man underwent Miles' operation and adjuvant irradiation therapy for rectum cancer in 1999. The patient suffered from bilateral ureteral stricture after the previous therapies. Bilateral double-J ureteral stents were inserted and exchanged at regular intervals. Four years after the start of ureteral stenting, he complicated with gross hematuria and dysuria. When the right double-J stent was exchanged, massive bleeding from external opening of urethra was observed. Retrograde pyelography showed right uretero-iliac arterial fistula. Since endovascular treatment with covered stents had failed, we performed right common iliac artery embolization and femoral-femoral artery bypass. Two days after the operation, gross hematuria developed again. When the left ureteral stent was exchanged, active bleeding from the external meatus of urethra was revealed. Angiography showed extravasation from left common iliac artery. We diagnosed left uretero-iliac arterial fistula. Although we tried endovascular treatment with covered stent that was made of artificial vessel graft and metallic stent, thromboembolism was occurred in the covered stent. Finally, right axillo-femoral artery bypass was indicated. The last treatment achieved long-term good control of uretero-arterial fistula. The present case shows that uretero-arterial fistula is a serious complication of long-term ureteral stenting, especially in the case of post pelvic surgery and irradiation.
Interferon-alpha (IFN) is widely used for the treatment of progressive renal cell carcinoma (RCC), but its effective response rate is only about 15%. New biomarkers of RCC contributing to the effective IFN treatment are needed to establish a sensitivity test for evaluating if the IFN is effective or not against RCC. All the proteins expressed in the IFN-susceptible and -resistant RCC cell lysates were analyzed by surface enhanced laser desorption ionization (SELDI) mass spectrometry using ProteinChip technology and their different protein expression were detected by the comparison of the profiles between them. We detected the following candidate markers that exhibited peak shifts: a) in the IFN-susceptible cell lines, a candidate marker with a molecular weight of 5,688 Da was detected on a hydrophobic (H4) chip: b) in the IFN-resistant cell lines, candidate markers each with a molecular weight of 8,049, 3,157, 3,993, and 8,959 Da were detected on strong anion exchange (SAX2, pH 9.0, two types) chips, H4 chip, and weak cation exchange (WCX, pH 9.0) chips, respectively. IFN treatment produced no weight increase in these four proteins, and c) candidate marker with a molecular weight of 1,623 Da that was expressed in both cell lines after the IFN treatment was detected on the H4 chip. These data suggest that the ProteinChip system is very useful in identifying proteins showing unique peaks in the RCC cell lines with different IFN susceptibility, and the comparison of these proteins measured in RCC cell lysates may help to identify the IFN sensitivity. Furthermore, the discovery of a susceptibility and or a inhibitory factor may eventually lead to the development of a novel drug targeting the respective factor for the improvement of anticancer chemotherapy.
Renal cell carcinomas (RCCs) primarily express cadherin-6 and N-cadherin rather than E-cadherin, and the aberrant expression of cadherin-6 correlates with a poor prognosis in patients with E-cadherin-absent RCC. However, the role of N-cadherin in RCC has not yet been elucidated. In this study, we analyze the expression pattern of N-cadherin in surgical RCC specimens and discuss the function of N-cadherin in RCC together with a re-evaluation of our previous study. Forty-six surgically resected RCC specimens were used in this study. The expression and localization of E-cadherin and N-cadherin in surgical specimens were demonstrated by immunohistochemistry. Correlations between the expression pattern of each cadherin, pathological parameters and patient survival were analyzed. RCC specimens expressed N-cadherin as a normal pattern despite the elevation of tumor grade, and patients with N-cadherin-normal RCC had a poorer prognosis than those with N-cadherin-abnormal RCC. Since our previous study showed that N-cadherin only functioned in cell attachment when E-cadherin and cadherin-6 were impaired, N-cadherin plays a different role from E-cadherin or cadherin-6 in RCC and may be associated with the aggressiveness and malignant potential of RCC.
5-FU is a major anti-tumor agent, and many clinical trials have been conducted to determine the efficacy of 5-FU and fluoropyrimidine derivatives for the treatment of urological cancers. S-1 is an oral fluoropyrimidine derivative that should be tested to demonstrate clinical efficacy for the treatment of urological cancers. Two phase II trials are being conducted to evaluate the efficacy and safety of S-1 as a single agent therapy for patients with hormone-refractory prostate cancer (HRPC) and renal cell carcinoma (RCC).
We report a case of Kallmann syndrome in which the aging male's symptoms rating scale (AMS) was useful for assessment of subjective symptoms. A 30-year-old male was admitted to Tsukuba University Hospital with a complaint of delayed puberty in May 2003. He presented with hypogonadism, gynecomastia and anosmia. The plasma levels of luteinizing hormone (LH), follicle stimulating hormone (FSH) and testosterone were very low. However, the LH-releasing hormone test and human chorionic gonadotropin (hCG) loading test identified normal function of pituitary and Leydig cell. After 12 months of treatment with hCG and human menopausal gonadotropin (hMG), the amount of pubic hair and the volume of testes had increased as well as the level of serum testosterone. The total score of AMS after treatment has been improved from 39 to 20 as compared with that before treatment.
BACKGROUND: Genetic polymorphisms may affect the development of prostate cancer (Pca). HER-2 is a proto-oncogene that has an important role in many human cancers, including Pca. To determine the association of the HER-2 gene with Japanese sporadic Pca, we analyzed the frequency of codon 655 (A/G, isoleucine, or valine) in case and control group. METHODS: We genotyped Ile 655 Val in Pca patients (n = 285) and in matched controls (n = 233). Statistical analyses were performed by Fisher's exact test and logistic regression analysis. RESULTS: We observed a significantly lower frequency of the Val655 allele in the Pca patients (14.7%) compared to the control group (26.2%) (P = 0.0025, odds ratio (OR) = 0.476, 95% CI = 0.306-0.740). This SNP was not found to be correlated with clinical stage, PSA level, Gleason score of biopsies or age at diagnosis. CONCLUSIONS: Our results indicate that the frequency of Val655 in HER-2 was significantly lower in Japanese Pca patients, however, it was recently reported that Val655 was significant higher in breast cancer patients. This contradictory observation in prostate and breast cancer patients is interesting considering the opposite hormonal sensitivity of these two cancers.
This article discusses the development of international guidelines for the diagnosis, treatment, follow-up, and prevention of low-grade Ta urothelial carcinoma of the bladder. The authors, who are experts in this field from 3 continents and 7 countries, reviewed the English language literature through September 2004. The results of the authors' deliberations are presented here as a consensus document. The objective of this study was to determine the optimal diagnostic workup, treatment, follow-up, and prevention of low-grade, Ta urothelial carcinoma of the bladder. A consensus conference convened by the World Health Organization (WHO) and the Société Internationale d'Urologie (SIU) met to critically review the literature on the diagnosis and treatment of low-grade Ta urothelial carcinoma of the bladder. Research was conducted using Medline; this search engine also was used to identify additional works not detected at the initial search. Evidence-based recommendations for diagnosis and management of the disease were made with reference to a 4-point scale. Low-grade Ta urothelial carcinoma of the bladder is a well-studied subject with many level 1 and 2 evidence references that support clinical practice. Findings from 135 reviewed citations are summarized. Many grade A and B recommendations on the diagnostic workup and management of this disease can be given with level 1 and 2 evidence based on prospective randomized clinical trials of sufficient statistical power. This should improve the quality of the treatment of this disease.
PURPOSE: We report the potential of basic fibroblast growth factor (bFGF) incorporating gelatin microspheres to preserve erectile function in a diabetic rat model. MATERIALS AND METHODS: A total of 48 adult male rats were divided into 3 groups, namely control (nondiabetic rats), diabetes mellitus (DM) (diabetic rats that received gelatin microspheres with saline) and bFGF (diabetic rats that received gelatin microspheres with bFGF). After 4 and 8 weeks we examined intracavernous pressure responses with electrical stimulation to the cavernous nerve. For histological examination of the penis we performed Azan-Mallory staining for smooth muscle and collagen, and immunohistochemistry for endothelial nitric oxide synthase (NOS) in endothelium and neuronal NOS in cavernous nerve fiber. RESULTS: Although the intracavernous pressure response was significantly lower in the DM group than in the control group, pressure in the bFGF group was maintained at the normal level found in controls. Azan-Mallory staining showed a mass decrease in smooth muscle in cavernous tissue in the DM group. However, that in the bFGF group was maintained. There was no significant difference in endothelial NOS positive areas and the distribution of the diameter of neuronal NOS positive nerve fibers in cavernous tissue among the 3 groups. CONCLUSIONS: We report the maintenance of erectile function with bFGF incorporating gelatin microspheres in diabetic rats. The rationale of this maneuver is smooth muscle preservation by the long-term release of bFGF. This is a novel therapeutic option that is clinically applicable for diabetes induced erectile dysfunction.
PURPOSE: We developed and validated nomograms that accurately predict disease recurrence and progression in patients with Ta, T1, or CIS transitional cell carcinoma (TCC) of the bladder using a large international cohort. METHODS: Univariate and multivariate logistic regression models targeted histologically confirmed disease recurrence, and focused on 2,542 patients with bladder TCC from 10 participating centers. Variables consisted of pre-cystoscopy voided urine Nuclear Matrix Protein 22 (NMP22) assay, urine cytology, age and gender. Resulting nomograms were internally validated with bootstrapping. Nomogram performance was explored graphically with Loess smoothing plots. RESULTS: Overall 957 patients had recurrent TCC. Tumor grade and stage was available for 898 patients, including 24% grade I, 43% grade II, and 33% grade III; 45% stage Ta, 32% T1 and/or CIS, and 23% T2 or greater. Bootstrap corrected predictive accuracy for any TCC recurrence was 0.842; grade III Ta/T1 or CIS was 0.869; and T2 or higher stage TCC of any grade was 0.858. Virtually perfect performance characteristics were observed for the nomograms predicting any TCC recurrence or grade III Ta/T1 or CIS. The nomogram predicting T2 or higher stage TCC overestimated the observed probability for predicted values greater than 45%. CONCLUSIONS: We developed and internally validated nomograms that incorporate urinary NMP22, cytology, age and gender to predict with high accuracy the probability of disease recurrence and progression in patients with Ta, T1, and/or CIS bladder TCC. These nomograms could provide a means for individualizing followup in patients with Ta, T1, CIS bladder TCC.
AIM: In the present study, an audio-visual sexual stimulation (AVSS) test was used to evaluate the effectiveness of sildenafil, and the AVSS test was coevaluated with the international index of erectile function (IIEF) questionnaire. METHODS: Forty-two patients with erectile dysfunction (ED) were examined (age range, 28-73 years; mean, 51.9 +/- 11.4 years). Each patient answered the IIEF questionnaire and underwent laboratory tests and the AVSS test before administration of sildenafil. The IIEF questionnaire and AVSS test (1 h after administration of 25 mg or 50 mg sildenafil) were re-evaluated in the outpatient clinic 4 weeks later. Questions 3 and 4 of the IIEF test were used to evaluate the effectiveness of sildenafil. Sildenafil was determined to be effective if each score totalled four or five after administration. RESULTS: The rate of effectiveness of sildenafil was 52.4%, and the mean score of the IIEF 5 improved from 7.2 to 15.4 following treatment with sildenafil. The maximum and mean rigidity of the penile tip improved after the sildenafil treatment (36.1%vs 57.7% and 14.2%vs 35.8%, respectively). The maximum and mean rigidity of the penile base rose (42.4%vs 57.7% and 17.9%vs 36.8, respectively). Similarly, following treatment with sildenafil, the penile tumescence increased from 6.6 cm to 7.6 cm at the penile tip and from 7.5 cm to 8.5 cm at the penile base. CONCLUSIONS: In some ED patients the results of the IIEF questionnaire are not always consistent with those of objective evaluation, including AVSS. In these patients, combined assessment using the IIEF and AVSS might be more useful to evaluate the precise effectiveness of sildenafil, rather than relying on the IIEF results alone.
We report a case of a 60-year-old man with necrotizing fasciitis complicated by streptococcal toxic shock syndrome. The patient had received high-dose chemotherapy and radiotherapy to the pelvis for relapsed seminoma 7 years previously. He had been in long-term remission. He was admitted to the Tsukuba University Hospital, Tsukuba-City, Ibaraki, Japan, with complaints of fever and localized erythema over the foreskin. The patient suffered from septic shock and multiple organ failure. Despite intensive care, he died 18 h after admission. Streptococcus pyogenes was isolated from both the wound and blood culture. To our knowledge, this is the first description of necrotizing fasciitis primarily affecting the penile skin.