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Biomedical subjects

Masato Fujisawa

Publications and source records attributed to Masato Fujisawa.

At least 73 records · Page 4Linked to original sources

Clinical results of combined treatment conformal high-dose-rate iridium-192 brachytherapy and external beam radiotherapy using staging lymphadenectomy for localized prostate cancer.

PURPOSE: To report the first long-term biochemical control rate of patients treated with two protocols using a combination of external beam radiotherapy (EBRT) and high-dose-rate (HDR) brachytherapy for localized prostate cancer in Japan. METHODS AND MATERIALS: Between October 1997 and July 2001, 71 patients with localized prostatic adenocarcinoma were treated with a combination of EBRT and HDR brachytherapy. Patient age ranged from 58 to 81 years (mean 70.5). Of the 71 patients, 12, 41, and 18 had Stage T1c, T2, and T3, respectively, according to the International Union Against Cancer classification system (1997). The mean initial prostate-specific antigen (PSA) level was 24.2 ng/mL (median, 11.9 ng/mL); 30% of the patients had an initial PSA level >20 ng/mL. Of the 71 patients, 31 had received neoadjuvant hormonal therapy. Hormonal therapy before treatment was stopped at the beginning of RT in all cases. Patients in this series were treated on two protocols. In the initial protocol, patients were treated with whole pelvis EBRT to 45.0 Gy in 25 fractions and three HDR fractions of 5.5 Gy each (35 patients). In the second protocol, patients were treated with prostatic EBRT to 41.8 Gy in 19 fractions, with an added staging lymphadenectomy to rule out lymph node metastasis for patients with high-risk factors, and four HDR fractions of 5.5 Gy each (36 patients). The American Society for Therapeutic Radiology and Oncology consensus definition for biochemical failure was used. Acute and chronic toxicities were scored using the Radiation Therapy Oncology Group guidelines. Follow-up ranged from 24 to 65 months (median, 44 months). RESULTS: Of the 71 patients, 69 were alive at the last follow-up. Two patients had died of hepatocellular carcinoma and gastric cancer at 3.5 and 4.0 years after treatment with no biochemical failure. Sixty-six patients (93%), including the two who had died of intercurrent disease, showed a tendency for a PSA decline after treatment and had no biochemical or clinical evidence of disease at the last follow-up visit. Sixty patients (85%) achieved PSA nadir levels of < or =1.0 ng/mL. The biochemical/clinical failure-free control rate at 3 and at 5 years was 93% and 93%, respectively. The bladder and rectal complications were minimal. CONCLUSION: Despite the high frequency of high-risk patients in the present patient population, the actuarial biochemical control rate was 93% at 5 years. Acute and chronic toxicity with this method was acceptable. Additional long-term follow-up is required to assess this treatment, because the median survival is not likely to be reached for several years.

Aged↗

Effect of erythropoietin on Leydig cell is associated with the activation of Stat5 pathway.

In order to elucidate whether erythropoietin (EPO) influences male reproduction, EPO activation via erythropoietin receptor (EPOR) of Stat5 was studied in Leydig cell cultures. RT-PCR analysis of mRNA that had been prepared from primary rat Leydig cell culture and the mouse Leydig tumor cell line (I-10 cells) each demonstrated amplification of the appropriate fragment for the respective genes. Both I-10 cells and primary rat Leydig cell cultures were treated with 1U/ml recombinant human erythropoietin (rHuEPO) for various time periods upto 60 min, and cytoplasmic proteins, total cellular proteins, and nuclear extracts were isolated. Expression of Stat5b protein and phosphorylated Stat5b protein were investigated by Western blotting using anti-Stat5b pAb and anti-phospho-Stat5a/b pAb. Stat5b protein exists at the cytoplasmic level irrespective of exposure to rHuEPO, while phosphorylated Stat5b protein increases upon rHuEPO stimulation. DNA binding of nuclear protein to synthetic double-stranded oligonucleotides containing a DNA response element derived from PRL-inducible element (PIE) was examined using a gel mobility shift assay. The oligonucleotide representing the PIE of the rat beta-casein promoter was demonstrated to bind to the nuclear extract of rHuEPO-treated cells, time dependently forming a single mobility shift complex X. These data suggest that EPO binds to a receptor expressed on the surface of Leydig cells. This EPOR regulates expression of specific gene, through a Jak-Stat pathway to influence male reproductive function.

Animals↗

Adenoviral-mediated HGF expression inhibits germ cell apoptosis in rats with cryptorchidism.

BACKGROUND: Prior studies have shown that the hepatocyte growth factor (HGF), as known for its multiple biological effects, possibly regulates spermatogenesis or tubulogenesis in the testis. To clarify the effect of HGF on restoration of spermatogenesis, or testicular weight, we transferred the HGF gene into the testis of the rat experimental cryptorchid model. METHODS: Replication-deficient recombinant adenoviral vectors containing the CAG promoter driving rat HGF (pAxCAHGF) and LacZ (pAxCALacZ) were constructed. Sprague-Dawley rats surgically induced with unilateral cryptorchidism and subsequent orchidopexy were divided into three groups: control (PBS), pAxCALacZ and pAxCAHGF by intratesticular injection. At 2 and 4 weeks after subsequent orchidopexy, testes were removed and weighed. These specimens were analyzed histopathologically, and examined for cell apoptosis. HGF expression in these specimens associated with c-Met receptor-mediated signal molecules was examined by reverse transcription-polymerase chain reaction (RT-PCR), Western blot or immunohistochemical study. RESULTS: Adenovirus-mediated HGF gene transfer induced overexpression of HGF in some seminiferous epithelial cells and interstitial cells, increased the phosphorylation of ERK and Akt, and decreased numbers of apoptotic cells of germ cells. HGF transduction also significantly increased the numbers of germ cells and testicular weight by 4 weeks compared with the other control groups. CONCLUSIONS: Adenoviral-mediated HGF gene transfer into the testis in the cryptorchidism rats inhibited germ cell apoptosis and restored spermatogenesis.

Adenoviridae↗

Assessment of availability of magnetic resonance angiography (MRA) in renal arteriovenous fistula.

We report two cases of cirsoid-type renal arteriovenous fistula (RAVF) which were difficult to differentiate from renal pelvic tumor by intravenous pyelogram (IVP) and computed tomography (CT) scan. Two women visited our department complaining of sudden asymptomatic macroscopic hematuria. CT scans showed an irregular mass in the right kidney. Magnetic resonance angiography (MRA) revealed a cirsoid-type RAVF. These patients were treated with transarterial embolization (TAE) using ethanol, geratin sponge, and a coil. It is suggested that MRA is useful for the diagnosis of renal arteriovenous fistula.

Aged↗

Serum testosterone levels in patients with nonmosaic Klinefelter syndrome after testicular sperm extraction for intracytoplasmic sperm injection.

We measured testosterone levels in 24 patients with nonmosaic Klinefelter syndrome before and at 6 and 12 months after conventional or microdissection testicular sperm extraction. Testosterone levels decreased after surgery by either technique, and they did not recover to baseline concentrations, even when using less invasive microdissection techniques.

Humans↗

Fertility after high-dose chemotherapy for testicular cancer.

OBJECTIVES: To describe long-term gonadal function after high-dose chemotherapy (HDC). HDC for testicular cancer was recently developed. The evaluation of testicular function after chemotherapy for testicular cancer is an important part of overall care, especially in young patients. METHODS: Between 1994 and 2001, 27 patients underwent HDC (1250 mg/m2 carboplatin, 1500 mg/m2 etoposide, and 7.5 g/m2 ifosfamide) at Kobe University Hospital. Information on gonadal function during follow-up was available for 10 of these patients. The mean patient age +/- SD at treatment was 32.2 +/- 8.4 years. The relationships among age at treatment, semen analysis, serum hormone levels (follicle-stimulating hormone, luteinizing hormone, testosterone, prolactin, and estradiol), cumulative dose of cisplatin and carboplatin, and length of follow-up were determined. RESULTS: Spermatogenesis recovered after cessation of HDC in 5 of 10 patients. Semen analysis in these patients showed the mean sperm concentration and motility at 42.4 +/- 10.4 million/mL and 67.2% +/- 17.0%, respectively. The patients were divided into azoospermic and nonazoospermic groups. The age of the nonazoospermic and azoospermic patients was 28.2 +/- 8.7 and 36.2 +/- 6.5 years, respectively. Follicle-stimulating hormone levels in the nonazoospermic group (11.7 +/- 3.4 mIU/mL) were significantly lower than in the azoospermic group (32.8 +/- 14.4 mIU/mL; P = 0.0472). No other statistically significant difference was observed in the other hormone levels or the cumulative dose of cisplatin and carboplatin between the azoospermic and nonazoospermic groups. CONCLUSIONS: Spermatogenesis recovers after HDC in some patients. Patients should be informed that they may or may not be fertile after HDC.

Adult↗

High-dose-rate iridium-192 afterloading therapy combined with external beam radiotherapy for T1c-T3bN0M0 prostate cancer.

OBJECTIVES: To determine the efficacy of radiotherapy (RT) for T1c-T3bN0M0 prostate cancer in a prospective clinical trial of concurrent external beam RT and fractionated iridium-192 high-dose-rate brachytherapy. METHODS: Included in the study were 98 patients with T1c-T3bN0M0 prostate cancer who were diagnosed between October 1997 and September 2002 and underwent high-dose-rate brachytherapy with external beam RT. Treatment consisted of external beam RT (four ports) to the prostate of 16 fractions of 2.3 Gy to a total dose of 36.8 Gy and high-dose-rate brachytherapy of 4 fractions of 6.0 Gy within 30 hours to a total dose of 24.0 Gy. No patient received adjuvant hormonal therapy after RT. RESULTS: The most recent prostate-specific antigen level was 0.0 to 3.9 ng/mL (median 0.4). Seven patients (7.1%) developed recurrence and treatment was considered a failure (bone metastasis in two and biochemical failure in five). The overall biochemical disease-free survival (bDFS) rate was 95.9% at 2 years and 92.9% at 5 years. The bDFS rate by T stage was 98.6% at 2 years and 95.9% at 5 years for Stage T1c-T2b and 88.0% and 84.0% for Stage T3a-b, respectively (P = 0.047). The 2-year and 5-year bDFS rate was better in patients with an initial prostate-specific antigen level of less than 20 ng/mL compared with 20 ng/mL or greater (98.6% and 97.1% versus 93.1% and 82.8%, respectively, P = 0.0261). Acute toxicity was mild to moderate (Radiation Therapy Oncology Group grade 1-2) and consisted of cystourethritis or proctitis in 29 (29.6%) of 98 patients. CONCLUSIONS: With a low complication rate and satisfactory bDFS rates, this combination therapy can be considered an alternative method for clinical Stage T1c-T3b prostate cancer and is expected to improve patient quality of life. Additional long-term follow-up is needed to confirm this treatment.

Adenocarcinoma↗

Oncocytic adrenocortical carcinoma.

Oncocytic adrenocortical carcinoma is rare. To our knowledge, only 6 cases have been previously reported. We describe an additional case of oncocytic adrenocortical carcinoma. A 54-year-old man presented with a right subcostal mass. Computed tomography demonstrated a massive tumor in the right abdomen. Because renal or adrenal cancer was suspected, right adrenalectomy and nephrectomy were performed. Histologic examination revealed an oncocytic adrenocortical carcinoma. Five months postoperatively, multiple metastases had developed and were treated with surgical resection, chemotherapy, vascular embolization, and radiotherapy. At last follow-up, the patient was alive with pulmonary and adrenal metastases and undergoing treatment with mitotane.

Adenocarcinoma↗

Possible mechanism responsible for the acquisition of resistance to cis-diamminedichloroplatinum (II) by cultured human testicular seminoma cells.

PURPOSE: We established a cis-diamminedichloroplatinum (II) (CDDP) resistant cell line and determined the mechanisms of CDDP resistance. MATERIALS AND METHODS: The CDDP resistant cell line JKT/DDP was established from the highly metastatic human testicular seminoma cell line JKT-HM by long-term intermittent administration of low dose CDDP. Growth curves, CDDP sensitivity and intracellular CDDP concentrations were compared in JKT/DDP, the seminoma cell line JKT-1 and JKT-HM cells. Expression of the mRNA of MDR1, MRP, LRP and GST-pi was also compared. RESULTS: The growth curve and doubling time of JKT/DDP were similar to those of JKT-1 and JKT-HM in culture without CDDP but different with CDDP added to the culture. Morphologically cytoplasm segmentation and chromatin aggregation in JKT-1 and JKT-HM were observed when CDDP was present, while JKT/DDP cells were spindle-shaped and showed cobblestone growth. The IC50 for CDDP determined by the collagen gel drop embedded drug sensitivity test showed that JKT/DDP was more resistant to CDDP than the other 2 cell lines. The expression of MDR1, MRP and GST-pi was higher than in JKT-1 or JKT-HM cells and the intracellular CDDP concentration was lower in JKT/DDP. CONCLUSIONS: The JKT/DDP cell line acquired CDDP resistance by increased cytoplasmic CDDP metabolism.

Antineoplastic Agents↗

Anatomical analysis of the neurovascular bundle supplying penile cavernous tissue to ensure a reliable nerve graft after radical prostatectomy.

PURPOSE: Urologists and anatomists have disagreed concerning pelvic neurovascular bundle (NVB) structure. Recently interposition nerve grafting has been performed to improve erectile function after radical prostatectomy. To refine this procedure we reviewed NVB structure from the surgical viewpoint. MATERIALS AND METHODS: Seven fresh cadavers and serial horizontal sections from 20 formalin fixed cadavers were used for gross dissection and histological examination. RESULTS: Fresh cadaver dissections demonstrated that the pelvic splanchnic nerve (PSN) joined the NVB at a point distal or inferior to the bladder-prostate (BP) junction. Histologically hypogastric nerve fibers were much more dominant than PSN fibers at the BP junction, and the NVB, covered by the lateral pelvic fascia, became evident at levels more than 20 to 30 mm below the BP junction. PSN components joined the NVB in a spray-like distribution at multiple levels more than 20 mm distal to the BP junction. At these low levels nerves tended to be located outside of the NVB at the dorsolateral margin of the prostate. The cranial end of the mimic interposition nerve graft was directed toward the hypogastric nerve rather than the PSN. CONCLUSIONS: In contrast to general clinical opinion, the NVB appears to supply few PSN components at the BP junction with caudal PSN branches reaching the dorsolateral prostate more than 20 mm below the BP junction. This anatomy has important implications for a reliable nerve graft.

Aged↗

Inflammatory pseudotumor of the kidney.

A 38-year-old man without prior contributory history presented complaining of a tumor in the left upper abdomen without tenderness. Suspecting renal cell carcinoma of the dark cell type, a nephrectomy was performed. Microscopic examination showed a proliferation of spindle cells containing numerous blood vessels. A diffuse infiltrate of lymphocytes and plasma cells was scattered throughout the lesion.

Adult↗

Long-term outcome of postoperative interferon-alpha adjuvant therapy for non-metastatic renal cell carcinoma.

AIM: To investigate the long-term efficacy of postoperative interferon-alpha (IFN-alpha) adjuvant therapy in preventing recurrence in non-metastatic renal cell carcinoma treated with radical nephrectomy and to identify related prognostic markers. METHODS: Long-term follow-up was conducted to study rates of survival and non-recurrence in 88 subjects following radical nephrectomy for non-metastatic disease. RESULTS: The overall survival rate was 90% at 5 years and 88% at 10, with corresponding non-recurrence rates of 81% and 74%. Survival rates reviewed by preadministration pT stage showed a falling tendency from T1 through to T3 in line with pathological progression; when cases at stage pT1b or below were compared with those at stage pT2 or above, the latter showed a tendency to lower survival rates (P = 0.0966, Breslow-Gehan-Wilcoxon). Similarly, non-recurrence rates tended to fall in line with pathological progression, with a significant difference found in the comparison of cases at stage pT1b or below with those at stage pT2 or above (P = 0.0265, log-rank, Mantel-Cox). Duration of IFN-alpha administration showed a tendency to positive correlation with long-term survival (P = 0.3765, Breslow-Gehan-Wilcoxon). Non-recurrence rate was not found to differ according to duration of administration. Comparison of groups with normal and abnormal preadministration immunosuppressive acidic protein values showed that the normal group tended to have higher rates of survival and non-recurrence (P = 0.3371, Breslow-Gehan-Wilcoxon). CONCLUSIONS: Immunosuppressive acidic protein values appear to be a useful predictive marker for recurrence. A randomized trial, examining long-term outcome according to tumor stage and variables such as duration of administration, dose, administration time, and dosing schedule is required.

Adult↗

Cut-to-the-light technique and potassium titanyl phosphate laser ureterotomy for complete ureteral obstruction.

We describe a case of complete ureteral obstruction managed by endoscopic recanalization using a 'cut-to-the-light' technique followed by potassium titanyl phosphate (KTP) laser ureterotomy. A 53-year-old man developed a ureteral obstruction following the transurethral resection of a bladder tumor (TUR-Bt) at the left ureteral orifice. The length of the obstructed segment was estimated at 1 cm based on combined antegrade and retrograde contrast studies. Histopathological analysis indicated that the obstruction was caused by fibrosis. The 'cut-to-the-light' technique was used for recanalization, and KTP laser ureterotomy was performed to obtain an adequate ureteral lumen. A 14 F/7 F endoureterotomy stent was removed 6 weeks after the operation. No significant complications and no signs of stenosis were observed 24 months after endoscopic repair. Endoscopic recanalization is a safe, effective technique for the management of a completely obliterated ureteral segment, especially in combination with subsequent KTP laser ureterotomy.

Endoscopy↗

Clinical and hormonal findings in testicular maturation arrest.

OBJECTIVE: To clarify the pathophysiology of maturation arrest (MA), one of the most important causes of male infertility, by examining testicular morphology and biophysical and endocrine profiles of azoospermic patients with MA. PATIENTS AND METHODS: Thirty azoospermic men were assessed; 10 were found to have Sertoli-cell only syndrome or chromosomal abnormalities, and 20 to have MA on biopsy. The second group had their clinical variables and findings analysed retrospectively after the diagnosis of MA (mean age 32.1 years, sd 5.2). Johnsen's score, serum hormone levels (follicle stimulating hormone, FSH, luteinizing hormone, LH, testosterone, prolactin and oestradiol), testicular volume, and the diameter of the seminiferous tubules, were evaluated. Patients were categorized into groups according to Johnsen score, i.e. group 1 (<4), group 2 (> or =4 and <6) or group 3 (> or =6). The clinical variables were compared in each group. RESULTS: Hormone levels in almost all patients were in the normal range. FSH was related to the stage of MA; the difference in FSH between groups 1 and 3 was significant (P = 0.006). Serum levels of LH, testosterone, prolactin or oestradiol were similar in all groups. The diameter of the seminiferous tubules was less in group 1 than in group 3 (r = 0.881, P < 0.001) and there was an inverse and linear correlation between the FSH concentration and the diameter of the seminiferous tubules (r = -0.661, P = 0.0028). CONCLUSIONS: FSH is the most useful variable for evaluating the severity of MA, even when it is within the normal range. The finding that gonadal hormone concentrations are normal in patients with MA suggests that an abnormality other than a disturbance in the hypothalamo-pituitary-testicular axis is responsible for MA.

Adult↗

Inhibition mechanism of Gosha-jinki-gan on the micturition reflex in rats.

We investigated the actions of Gosha-jinki-gan, a traditional Japanese medicine containing processed Aconiti tubers, on urinary bladder function in anesthetized rats. In cystometrical investigations, Gosha-jinki-gan (1.0 g/kg, i.d.) increased bladder capacity as well as micturition threshold pressure. In addition, it decreased the frequency of distension-induced rhythmic bladder contractions. However, it did not influence the amplitude of bladder contractions induced by electrical stimulation of the pontine micturition center. The inhibitory effect of Gosha-jinki-gan on bladder motility was abolished by pretreatment with nor-binaltorphimine (10 mg/kg, s.c.), and was diminished by the concomitant use of anti-dynorphin A antiserum (10 microg, i.t.), yohimbine (10 microg, i.t.), or methysergide (20 microg, i.t.). Processed Aconiti tuber extract (27 mg/kg, i.d.) also suppressed bladder motility, and the effect was abolished by nor-binaltorphimine. These results suggest that Gosha-jinki-gan attenuates bladder sensation via the kappa-opioid receptor-stimulating action of processed Aconiti tuber. Gosha-jinki-gan may be a useful anti-pollakiuria agent that does not influence bladder contractility at micturition.

Aconitum↗

Solitary fibrous tumor in the pelvic space.

A case of a solitary fibrous tumor (SFT) of the pelvic space in a 64-year-old man is reported herein. Computed tomography (CT) of the pelvis showed a large mass enhanced heterogeneously left paracentral and posterior to the bladder and intimately associated with prostate. The site of origin of the mass could not be defined on CT because margins blended with the bladder, prostate, and rectum. A tumorectomy was performed and has remained well with no evidence of recurrence during the last 3 months. The tumor was 12.5 x 9.5 x 8.3 cm in size, solid with a fibromuscular capsule, and gray-tan in color. Histologically, the neoplasms were well circumscribed and composed of short spindle cells arranged without an obvious pattern. Immunohistochemically, these cells were strongly positive for CD 34 and negative for S-100, alpha SMA, and AE1/AE3.

Antigens, CD34↗

The efficacy of bilateral varicocelectomy in patients with palpable bilateral varicoceles: comparative study with unilateral varicocele.

To determine whether the beneficial effect of bilateral varicocelectomy for bilateral varicoceles is similar to that of unilateral varicocelectomy for unilateral varicoceles, we compared the effect of varicocelectomy in men with unilateral and bilateral palpable varicoceles. Seventy-five men with unilateral varicocele and 34 with bilateral varicoceles were included in this study. Serum concentrations of follicle-stimulating hormone (FSH), luteinizing hormone (LH), testosterone, prolactin, and estradiol were measured in morning blood specimens. Unilateral varicocelectomy was performed for unilateral and bilateral varicocelectomy for bilateral varicoceles using a microsurgical technique. The seminogram was determined every 3 months for up to 18 months. There were no significant differences in the change in the sperm concentration between the unilateral and bilateral groups. Sperm concentration before surgery in unilateral and bilateral group was 8.0+/-5.0x10(6)/ml and 8.1+/-4.9x10(6)/ml, respectively. Eighteen months after surgery, the sperm concentration significantly increased to 23.4+/-15.8x10(6)/ml and 26.9+/-24.6x10(6)/ml in unilateral and bilateral group, respectively. Preoperative motility in the unilateral and bilateral group was 38.9+/-15.2% and 39.6+/-15.7%, respectively. Eighteen months after operation, sperm motility had increased and was similar in the two groups, 43.1+/-19.2% and 45.4+/-17.6%. Sperm morphology was unaffected by surgery in either group. Improvement in the seminogram of patients following bilateral varicocelectomy was comparable to that in patients with unilateral varicocelectomy. Bilateral repair for bilateral varicocelectomies is justified for patients who desire improved spermatogenesis.

Adult↗