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Yasutomo Nasu

Publications and source records attributed to Yasutomo Nasu.

At least 19 recordsLinked to original sources

Time course of serum testosterone and luteinizing hormone levels after cessation of long-term luteinizing hormone-releasing hormone agonist treatment in patients with prostate cancer.

INTRODUCTION: In order to elucidate the influence of hormone-releasing hormone (LH-RH) agonist therapy cessation on pituitary/testicular function and its clinical implications, we investigated prospectively hormonal (luteinizing hormone: LH; testosterone: T) responses in patients with prostate cancer who received long-term LH-RH 10 agonist therapy. PATIENTS AND METHODS: A consecutive 32 patients who had received LH-RH agonist therapy over 24 months were enrolled. As a baseline, T and LH were measured at the time of LH-RH agonist therapy cessation, monthly for 3 months, and subsequently, every 3 months. RESULTS: The median duration of LH-RH agonist therapy was 30 months (24-87 months) with median follow-up duration of 24 months following cessation. All patients had castrated T levels and suppressed LH levels at baseline. Median duration of castrated T levels following cessation was 6 months. Median time to normalization of T levels was 24 months. LH levels returned to normal within 3 months in all cases. Patients who received androgen deprivation therapy for 30 months or longer required a longer time for recovery of T levels. Patients over 65 years of age showed a statistically significant longer time for recovery of T levels (P=0.0167). CONCLUSIONS: Long-term LH-RH agonist therapy has remarkable effects on serum T level that last for a significant time after cessation, a fact that should be applied to the interpretation of both PSA and serum T levels after cessation of androgen deprivation therapy.

Aged↗

Effects of radiofrequency ablation on individual renal function: assessment by technetium-99m mercaptoacetyltriglycine renal scintigraphy.

We quantitatively evaluated total and individual renal function by technetium-99m mercaptoacetyltriglycine (Tc-99m MAG3) renal scintigraphy before and after radiofrequency ablation (RFA) of renal tumors. Eleven patients who underwent Tc-99m MAG3 renal scintigraphy 1 week before and after RFA were evaluated (7 men and 4 women; age range: 23-83 years; mean age: 60.6 years). Five patients had solitary kidneys, and five had normally or minimally functioning contralateral kidneys. One patient had a renal cell carcinoma in the contralateral kidney. One patient with a solitary kidney underwent RFA a second time for a residual tumor. In patients with a solitary kidney, MAG3 clearance decreased after 5 of 6 RFAs, and in patients with a normally functioning contralateral kidney, MAG3 clearance decreased after 4 of 5 RFAs, but no significant differences were observed between before and after treatments. In addition to the total MAG3 clearance, the split MAG3 clearance was evaluated in patients with a normally functioning contralateral kidney. MAG3 clearance decreased in 4 of 5 treated kidneys, while it adversely increased in the contralateral kidneys after 4 of 5 RFAs. No significant differences, however, were observed between before and after treatments. The results of our study revealed no significant differences in sCr, BUN, CCr, or MAG3 clearance between pre- and post-RFA values. These results support data regarding the functional impact and safety of renal RFA in published reports. We evaluated total and individual renal function quantitatively using Tc-99m MAG3 renal scintigraphy before and after treatment. This scintigraphy was very useful in assessing the effects of RFA on renal function.

Adult↗

Combination chemotherapy with estramustine phosphate, ifosfamide and cisplatin for hormone-refractory prostate cancer.

We evaluated the efficiency and toxicity of estramustine phosphate (ECT), ifosfamide (IFM) and cisplatin (CDDP) combination chemotherapy in twenty-one patients with hormone-refractory prostate cancer (HRPC), for which there is currently no effective treatment. Patients received a daily dose of 560 mg ECT in combination with 1.2 g/m2 IFM on days 1 to 5 and 70 mg/m2 CDDP on day 1. This combination therapy was given every 3 to 4 weeks. An objective response of more than 50% reduction in prostate-specific antigen was observed in 9 of 18 patients (50%), and a more than 50% reduction in bi-dimensionally measurable soft-tissue lesions was observed in 2 of 7 patients (29%). The median duration of response among the cases showing partial response was 40 weeks, while the median duration of response of overall partial-response plus stable cases was 30 weeks. The median survival duration of all cases was 47 weeks. Toxicity was modest and acceptable. In conclusion, the ECT, IFM and CDDP combination chemotherapy regimen is a viable treatment option for HRPC. However, in comparison with our previous chemotherapy regimen of IFM and CDDP, no additional long-lasting effects resulting from the inclusion of ECT could be affirmed.

Adult↗

Hepsin shows inhibitory effects through apoptotic pathway on ovarian cancer cell lines.

In light of the poor prognosis for ovarian cancer patients, the research continues for innovative and efficacious treatment modalities. Along with surgical and chemotherapeutic regimens, gene therapy has emerged as one of the leading contenders in the treatment armamentarium. Hepsin is a type II transmembrane serine protease originally identified in the human liver as a cDNA clone. However, the biological function of Hepsin expression remains unclear. Apoptotic cell was increasingly common among higher proportions of Hepsin transfectants. We discovered that first-time stable transfectants of Hepsin significantly inhibited cell growth in the monolayer, anchorage-independent cell growth in the soft agar in vitro, and tumorigenicity in vivo in ovarian cancer cell lines. These results demonstrated that Hepsin has a potential therapeutic effect that inhibits through up-regulation of p53-dependent apoptosis and caspase-3, -6, and -7 activations. Our findings in this study identify Hepsin as a target for new approaches in ovarian cancer treatment.

Animals↗

Adenovirus-mediated overexpression of REIC/Dkk-3 selectively induces apoptosis in human prostate cancer cells through activation of c-Jun-NH2-kinase.

Alteration in genes which takes place during malignant conversion and progression could be potential targets for gene therapy. We previously identified REIC/Dkk-3 as a gene whose expression is reduced in many human cancers. Here, we showed that expression of REIC/Dkk-3 was consistently reduced in human prostate cancer tissues in a stage-dependent manner. Forced expression of REIC/Dkk-3 induced apoptosis in human prostate cancer cell lines lacking endogenous REIC/Dkk-3 expression but not in REIC/Dkk-3-proficient normal prostate epithelial and stromal cells. The apoptosis involved c-Jun-NH2-kinase activation, mitochondrial translocation of Bax, and reduction of Bcl-2. A single injection of an adenovirus vector carrying REIC/Dkk-3 showed a dramatic antitumor effect on a xenotransplanted human prostate cancer. Thus, REIC/Dkk-3 could be a novel target for gene-based therapy of prostate cancer.

Adaptor Proteins, Signal Transducing↗

Analysis of human ejaculation using color Doppler ultrasonography: a comparison between antegrade and retrograde ejaculation.

OBJECTIVES: To observe the phenomenon of human ejaculation dynamically using color Doppler ultrasonography. METHODS: Human ejaculation was observed using transrectal color Doppler ultrasonography in a healthy man and a patient with retrograde ejaculation. Ejaculation was induced manually with audiovisual sexual stimulation. The ejaculatory phenomenon was analyzed and compared with that of retrograde ejaculation. RESULTS: In the healthy man, the prostatic urethra flattened slightly and the bladder neck contracted just before expulsion. The ejaculatory stream spurted from the seminal vesicles to the bulbous urethra through the ejaculatory duct. In the patient with retrograde ejaculation, the ejaculatory stream from the seminal vesicles and inframontanal and distal prostatic urethras distended into a globular-shaped sac filled with semen. No seminal flow toward the bulbous urethra occurred. The semen remaining in the prostatic urethra began flowing slowly into the bladder. CONCLUSIONS: Differences between antegrade and retrograde ejaculation can be clearly detected by color Doppler ultrasonography, providing a noninvasive method to diagnose ejaculatory disorders.

Adult↗

Adeno-associated virus 2-mediated intratumoral prostate cancer gene therapy: long-term maspin expression efficiently suppresses tumor growth.

Maspin is a member of the serine protease inhibitors and the maspin gene, a tumor suppressor gene, is down-regulated in a large fraction of prostate cancers. We evaluated the use of adeno-associated virus (AAV, serotype 2) vector encoding maspin as a means for in vivo gene therapy for human prostate cancer. TUNEL assay of subcutaneously formed LNCaP or DU145 tumors in nude mice showed that intratumoral AAV-mediated maspin expression significantly upregulated the number of apoptotic cells compared with AAV-LacZ treatment. Immunofluorescence double staining for maspin protein and apoptosis in LNCaP tumors showed that the percentage of apoptotic cells in AAV-maspin-mediated maspin-expressing cells was significantly high compared with that in AAV-GFP-mediated GFP-expressing cells. Moreover, significantly fewer CD31-positive microvessels were observed in AAV-maspin-treated tumors compared with the control tumors. These therapeutic responses were highly correlated to persistent maspin expression in tumors, confirmed by Western blot analysis until at least day 56 after treatment. Finally, intratumoral delivery of AAV-maspin significantly suppressed growth of LNCaP and DU145 tumors and improved survival of mice. We conclude that AAV-mediated prolonged maspin expression efficiently suppresses human prostate tumor growth in vivo by apoptosis induction and inhibition of angiogenesis.

Animals↗

Predicting postoperative renal insufficiency in patients undergoing nephrectomy for renal malignancy: assessment by renal scintigraphy using 99mtechnetium-mercaptoacetyltriglycine.

PURPOSE: We performed Tc-mercaptoacetyltriglycine (MAG3) renal scintigraphy in patients with renal malignancy to evaluate the function of each renal unit before and after nephrectomy to see if postoperative functional deterioration could be predicted based on scintigraphy results and creatinine clearance. MATERIALS AND METHODS: A total of 22 men and 13 women with renal malignancy, including 32 with renal cell carcinoma and 3 with urothelial cancer, were prospectively enrolled in this study. Average patient age was 64.3 years (median 65, range 43 to 88). All patients underwent MAG3 renal scintigraphy before and after unilateral nephrectomy. At the same time serum creatinine and endogenous creatinine clearance were determined. RESULTS: Mean serum creatinine was 0.93 mg/dl before and 1.31 after nephrectomy (p <0.0001). Preoperative endogenous creatinine clearance was 70.8 ml per minute per 1.73 m, which decreased to 49.0 ml per minute per 1.73 m after nephrectomy (p <0.0001). Mean MAG3 clearance of the remaining kidney increased 35.1% above baseline from 156.5 to 211.5 ml per minute per 1.73 m following nephrectomy. Spearman rank core analysis revealed that preoperative MAG3 clearance of the remaining kidney significantly correlated with postoperative creatinine clearance (r = 0.596, p = 0.0005). Preoperative MAG3 clearance of the remaining kidney more than 130 ml per minute per 1.73 m coincided with postoperative creatinine clearance above 40 ml per minute per 1.73 m. CONCLUSIONS: MAG3 renal scintigraphy may be useful for predicting renal insufficiency after nephrectomy. The findings in this study suggest that preoperative MAG3 clearance of the remaining kidney less than 130 ml per minute per 1.73 m is a risk factor for postoperative renal insufficiency.

Adult↗

XAGE-1 mRNA expression in prostate cancer and antibody response in patients.

To evaluate the feasibility of cancer vaccine targeting XAGE-1, we investigated the expression of 4 XAGE-1 transcript variants and the humoral immune response to XAGE-1 in prostate cancer patients. XAGE-1a, b, c, d mRNA expression was analyzed in 54 prostate cancer specimens and 8 specimens of benign prostate hypertrophy (BPH) by reverse transcription-polymerase chain reaction (RT-PCR). The humoral response to XAGE-1 was investigated in sera obtained from 278 patients with prostate cancer and 40 healthy volunteers by enzyme-linked immunosorbent assay (ELISA) using recombinant protein. XAGE-1b mRNA expression was observed in 14 of 54 (26%) prostate cancer specimens, while XAGE-1a, c, and d mRNA expressions were observed in 1, 1, and 3, respectively. None of the 4 XAGE-1 transcript variants was observed in the 8 BPH specimens. Antibody against XAGE-1 was detected in sera from 2 of 129 stage D2 patients, whereas none of sera from 149 patients with localized prostate cancer or lymph node metastasis had detectable XAGE-1 antibody. No reactivity to XAGE-1 was found in sera from the 40 healthy individuals.

Aged↗

Varicocele rupture due to sexual intercourse.

Varicocele rupture was diagnosed in a 23-year-old man who presented with swelling and pain in the left scrotum after sexual intercourse. Color Doppler ultrasonography revealed blood flowing into the space surrounding the left testis, a hematoma and reflux of blood in the left spermatic vein. Varicocele rupture is a very rare condition and there have been only five reported cases.

Adult↗

Minimal invasiveness and effectivity of subinguinal microscopic varicocelectomy: a comparative study with retroperitoneal high and laparoscopic approaches.

AIM: The standard management of varicocele repair is the subject of ongoing controversy. We retrospectively evaluated three surgical methods of varicocele treatment to determine the minimally invasive and most effective procedure. METHODS: We performed 144 varicocelectomies on infertile patients with left clinical varicocele. Of the patients, 50 were treated with retroperitoneal high ligation under lumbar anesthesia, 33 with laparoscopic ligation under general anesthesia, and 61 with subinguinal microscopic ligation under local anesthesia. Operative time, hospital days, and clinical outcomes were compared between these techniques. RESULTS: The operating time and hospitalization period required for subinguinal microscopic ligation was signi fi cantly shorter compared to those for the other procedures. All patients treated with subinguinal microscopic ligation could achieve normal activity as soon as they returned to their rooms. Postoperative complications were observed in fi ve (10.0%) cases treated with high ligation and three (9.1%) laparoscopic cases, but were not observed after the subinguinal procedure. There were six cases (12.0%) of recurrence in the high ligation group and six (6.1%) in the laparoscopic group, but none in the subinguinal group. Sperm density was signi fi cantly improved in all procedures postoperatively, but sperm motility was not improved. The two-year pregnancy rate calculated by the Kaplan-Meier method was 35.8% for high ligation, 40.4% for laparoscopic ligation and 50.9% for subinguinal microscopic ligation, although there were no statistical differences between the three groups. CONCLUSION: We concluded that subinguinal microscopic varicocelectomy could be a minimally invasive procedure compared to the other two techniques and a worthy method for treating male infertility due to clinical varicocele.

Adult↗

Intracavernous injection of prostaglandin E1 is effective in patients with erectile dysfunction not responding to phosphodiseterase 5 inhibitors.

We report on 64 patients who did not achieve erections adequate for satisfactory sexual intercourse from among a total of 243 patients who were prescribed PDE5 inhibitors for erectile dysfunction (ED). Intracavernous injection (ICI) of PGE was performed in this non-responder group. An ICI of 20 or 40 mcg of PGE1 in 1 ml saline was performed and the responses evaluated. Forty-nine out of 64 (77 percent ) cases responded to 20 mcg of PGE1. Forty mcg of PGE was injected into the 15 non-responding cases, and 9 patients responded favorably. The overall effective rate was 58/64 (91 percent ). No major adverse effects were observed.

Adult↗

Clinical results of one-stage urethroplasty with parameatal foreskin flap for hypospadias.

We investigated the usefulness of one-stage urethroplasty by the parameatal foreskin flap method (OUPF procedure), which is useful for repairing all types of hypospadias. Between June 1992 and March 2001, the OUPF procedure was performed on 18 patients with hypospadias: 10 patients with distal and 8 with proximal hypospadias. The follow-up periods ranged from 33-75 months, with an average of 52 months. The duration of surgery, the catheter indwelling period, and the postoperative complications of each patient were analyzed. The median age of the patients at the time of surgery was 3 years and 8 months. The length of surgery for OUPF II ranged from 150-230 min (average 186 min), and from 190-365 min (average 267 min) for OUPF IV. Postoperative complications were confirmed in 3 of the 18 patients (16.6%). Two patients had fistulas, and one had a meatal regression. The fistulas were successfully closed by the simple multilayered closure method. After adopting DuoDerm dressings instead of elastic bandages for protection of the wound, no fistulization occurred. DuoDerm dressings are useful in the healing of wounds without complications. To date, the longest follow-up period has been 75 months, and during that time there have been no late complications such as urethral stenosis or penile curvature. OUPF is a useful method in the treatment of hypospadias with a low incidence of early and late complications.

Adolescent↗

Long-term clinical outcomes of 420 consecutive prostate cancer patients in a single institute.

This study was undertaken to reveal the trends of prostate cancer and the outcome of treatment modalities for each disease stage in patients in a single institute over a 10-year period. From January 1994 through December 2003, 420 consecutive patients with previously untreated and histologically confirmed prostate cancer were analyzed for annual distributions of disease stages and treatment modalities and for long-term clinical progression-free survival, prostate cancer-specific survival, and prostate-specific antigen (PSA) failure-free survival rates for each stage and treatment modality. Annual trends showed that the number of patients, especially those with clinically localized cancer, increased dramatically. The 5-year disease-specific survival rates for patients with clinically localized disease were 100 percent for all treatment modalities, including hormonal therapy alone. Patients with PSA levels less than 10 ng/ml showed an 81 percent 5-year PSA failure-free survival rate with radical prostatectomy. Stage C patients treated by surgery or radiation-based therapy with concomitant hormonal therapy obtained 93 percent and 100 percent cause-specific survival rates, respectively, and those treated by hormonal therapy alone showed a 79 percent rate. The number of patients with localized prostate cancer was increasing in this decade. While long-term hormonal therapy alone was highly efficient in controlling localized prostate cancer, radical therapies in conjunction with neo-adjuvant hormonal therapy produced better survival rates in cases of locally advanced disease.

Academies and Institutes↗

Sex reassignment surgery for male to female transsexuals: initial experience in Okayama university hospital.

The first case of sex reassignment surgery (SRS) in our hospital was performed in January 2001; as of February, 2005, 4 cases of MTF-SRS had been performed. In the 2 most recent cases, we used penile and scrotal skin flaps to avoid complications. The depth and width of the new vagina was made to be adequate for sexual intercourse. Future attention should be focused on devising a surgical technique that will help prevent the complications of partial necrosis of the epidermal skin and wound dehiscence. Although ours is only an initial experience, we describe our surgical technique herein.

Female↗

[Prostate cancer gene therapy].

With the advance in genetic engineering, tumor biology and immunology, gene therapy has been recognized as a promising new treatment option for cancer including prostate cancer. Several clinical trials of prostate cancer gene therapy are currently underway, using therapeutic genes which include suicide genes, immunomodulatory genes, tumor suppressor genes and anti-oncogenes. Although the gene therapy for prostate cancer as a clinical alternative is still early stage which requires several technological breakthrough, some information obtained from clinical trial indicates full potential of prostate cancer gene therapy. Concordant progress both in the basic research and gene therapy technology will make prostate cancer gene therapy ready for wide-scale of practice in the future. In this report, general concept and current progress in prostate cancer gene therapy are summarized.

Adenoviridae↗

[Prostate cancer gene therapy].

With the advance in genetic engineering, tumor biology and immunology, gene therapy has been recognized as a promising new treatment option for cancer including prostate cancer. Several clinical trials of prostate cancer gene therapy are currently underway, using therapeutic genes which include suicide genes, immunomodulatory genes, tumor suppressor genes and anti-oncogenes. Although the gene therapy for prostate cancer as a clinical alternative is still early stage which requires several technological breakthrough, some information obtained from clinical trial indicates full potential of prostate cancer gene therapy. Concordant progress both in the basic research and gene therapy technology will make prostate cancer gene therapy ready for wide scale of practice in the future. In this report, general concept and current progress in prostate cancer gene therapy are summarized.

Genetic Therapy↗

Transrectal high-intensity focused ultrasound in the treatment of localized prostate cancer: a multicenter study.

We report a multicenter trial with transrectal high-intensity focused ultrasound (HIFU) in the treatment of localized prostate cancer. A total of 72 consecutive patients with stage T1c-2NOM0 prostate cancer were treated using the Sonablate 500TM HIFU device (Focus Surgery, Indianapolis, USA). Biochemical recurrence was defined according to the criteria recommended by the American Society for Therapeutic Radiology and Oncology Consensus Panel. The median age and prostate specific antigen (PSA) level were 72 years and 8.10 ng/ml, respectively. The median follow-up period for all patients was 14.0 months. Biochemical disease-free survival rates in all patients at 1 and 2 years were 78% and 76%, respectively. Biochemical disease-free survival rates in patients with stage T1c, T2a and T2b groups at 2 years were 89, 67% and 40% (p = 0.0817). Biochemical disease-free survival rates in patients with Gleason scores of 2-4, 5-7 and 8-10 at 2 years were 88, 72% and 80% (p = 0.6539). Biochemical disease-free survival rates in patients with serum PSA of less than 10 ng/ml and 10-20 ng/ml were 75% and 78% (p = 0.6152). No viable tumor cells were noted in 68% of patients by postoperative prostate needle biopsy. Prostatic volume was decreased from 24.2 ml to 14.0 ml at 6 months after HIFU (p < 0.01). No statistically significant differences were noted in International Prostate Symptom Score, maximum urinary flow rate and quality of life analysis with Functional Assessment of Cancer Therapy. HIFU therapy appears to be minimally invasive, efficacious and safe for patients with localized prostate cancer with pretreatment PSA levels less than 20 ng/ml.

Adult↗