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Biomedical subjects

Akihiko Tokue

Publications and source records attributed to Akihiko Tokue.

At least 19 recordsLinked to original sources

Discontinuation of tamsulosin treatment in men with lower urinary tract symptoms: a pilot study.

OBJECTIVES: Since little investigation has been undertaken to determine if alpha1-blockers should be given continuously to sustain their efficacy, we conducted a pilot study to determine symptom change following discontinuation of tamsulosin after an initial improvement in symptoms in men with lower urinary tract symptoms (LUTS). PATIENTS AND METHODS: Thirty-three of 78 patients with mild-to-moderate prostate hyperplasia, who had symptom improvement according to the International Prostate Symptom Score (IPSS) to <10 or the quality of life (QOL) index to < or =3 after initial treatment with tamsulosin, were enrolled in this study. Subjective parameters (IPSS and QOL index) and objective parameters (maximum and mean urinary flow rates) were evaluated at baseline and after initial treatment, and 4, 8, 12 and 24 weeks after discontinuing tamsulosin. RESULTS: The rates of successful discontinuation of tamsulosin were high throughout the follow-up period, i.e., 80.6% at 4 weeks, 80.6% at 8 weeks, 80.0% at 12 weeks, and 68.9% at 24 weeks. Temporary worsening in both subjective and objective parameters was observed only at 4 weeks; however, these parameters recovered to almost post-treatment levels at 24 weeks. CONCLUSION: The present study suggests that continuous treatment is not always needed to maintain urinary symptom relief in a specific subset of patients who felt symptom improvement after initial treatment with tamsulosin.

Adrenergic alpha-Antagonists↗

Vascular endothelial growth factor-C (VEGF-C) expression predicts lymph node metastasis of transitional cell carcinoma of the bladder.

PURPOSE: It has been found that expression of vascular endothelial growth factor-C (VEGF-C) in several carcinomas is significantly associated with angiogenesis, lymphangiogenesis and regional lymph node metastasis. However, VEGF-C expression in bladder transitional cell carcinoma (TCC) has not yet been reported. To elucidate the role of VEGF-C in bladder TCC, we examined VEGF-C expression in bladder TCC and pelvic lymph node metastasis specimens obtained from patients who underwent radical cystectomy. METHODS: Eighty-seven patients who underwent radical cystectomy for clinically organ-confined TCC of the bladder were enrolled in the present study. No neoadjuvant treatments, except transurethral resection of the tumor, were given to these patients. The VEGF-C expressions of 87 bladder tumors and 20 pelvic lymph node metastasis specimens were examined immunohistochemically and the association between VEGF-C expression and clinicopathological factors, including angiogenesis as evaluated by microvessel density (MVD), was also examined. RESULTS: Vascular endothelial growth factor-C expression was found in the cytoplasm of tumor cells, but not in the normal transitional epithelium. Vascular endothelial growth factor-C expression was significantly associated with the pathological T stage (P = 0.0289), pelvic lymph node metastasis (P < 0.0001), lymphatic involvement (P = 0.0008), venous involvement (P = 0.0002) and high MVD (P = 0.0043). The multivariate analysis demonstrated that VEGF-C expression and high MVD in bladder TCC were independent risk factors influencing the pelvic lymph node metastasis. Moreover, the patients with VEGF-C-positive tumors had significantly poorer prognoses than those with the VEGF-C-negative tumors (P = 0.0087) in the univariate analysis. The multivariate analysis based on Cox proportional hazard model showed that the independent prognostic factors were patient age (P = 0.0132) and pelvic lymph node metastasis (P = 0.0333). CONCLUSION: The present study suggests that VEGF-C expression is an important predictive factor of pelvic lymph node metastasis in bladder cancer patients.

Age Factors↗

Intraindividual variation in total and percent free prostate-specific antigen levels in prostate cancer suspects.

OBJECTIVES: To investigate intraindividual total and percent free serum prostate-specific antigen (PSA) in prostate cancer suspects and to understand the clinical implications. PATIENTS AND METHODS: Total and percent free PSA were measured using Tandem-R or chemiluminescent enzyme-linked immunoassay for a median of three times in 126 men. Prostate biopsies were performed in all patients; benign prostatic hyperplasia was diagnosed in 81 patients and prostate cancer in 45 patients. RESULTS: The overall mean coefficients of variation for total and percent free PSA were 16.10 +/- 11.94% and 15.45 +/- 15.91%, respectively. A significant correlation (p = 0.0056) was observed between the two variations. The variations in total and percent free PSA were related to none of such stratifications as baseline total PSA level, histology, age, or measurement interval, but for measurement interval on that for total PSA. CONCLUSION: Intraindividual variation in serum PSA should be considered in decision-making about performing prostate biopsies. Also, care should be taken in interpreting repeated percent free PSA measurements in order to enhance the specificity of total PSA, because it had a similar variation to total PSA variation.

Aged↗

Vesicoureteral reflux after intravesical instillation of bacillus Calmette-Guérin against carcinoma in situ of the bladder.

We report a case of vesicoureteral reflux (VUR) 3 years after intravesical instillation of bacillus Calmette-Guérin (BCG, Tokyo 172 strain) against carcinoma in situ of the bladder. The present case suggests that a long-term careful follow-up is needed to detect not only tumor recurrences but also VUR as a late complication after intravesical BCG instillation.

Administration, Intravesical↗

[A case of advanced rhabdomyosarcoma of the spermatic cord who occurred epilepsy-like symptoms, but was completely responded to chemotherapy].

A 19-year-old man presented with left aggressive painless scrotal swelling. On the diagnosis of left intrascrotal tumor, left high orchiectomy with partial scrotal skin resection was performed. Pathological examination of the specimen and systemic metastasis survey revealed embryonal rhabdomyosarcoma of left spermatic cord with multiple lung metastasis (Intergroup Rhabdomyosarcoma Study Group IV). Systemic chemotherapy with etoposide (VP-16), cisplatin (CDDP), and ifosfamide (IFO) (VIP therapy) was started. Although epilepsy-like symptoms occurred at the first course of VIP therapy, these symptoms immediately improved by diazepam administration. These symptoms were thought to be due to the adverse effects of IFO. To our knowledge, there were little reports on epilepsy-like symptoms caused by IFO in Japan. On the other hand, his multiple lung metastasis disappeared after the second course of VIP therapy. Although IFO may be effective in rhabdomyosarcoma, the toxicity of various nervous systems may be discovered.

Adult↗

Elevated serum progastrin-releasing peptide (31-98) level is a predictor of short response duration after hormonal therapy in metastatic prostate cancer.

BACKGROUND: The neuroendocrine (NE) pathway has been attracting attention as a mechanism for the androgen-independent progression because the neuropeptide provokes tumor growth and inhibits apoptosis under androgen-deprived milieu in prostate cancer cells. On the basis that serum progastrin-releasing peptide (ProGRP) is elevated in patients with advanced disease stage, we examined the prognostic value of the neuropeptide. METHODS: Serum ProGRP status was determined with an enzyme-linked immunosorbent assay (ELISA) in 460 men with benign and malignant prostatic diseases, chronic renal failure, and healthy controls. Seventy patients with metastatic prostate cancer including four patients (5.7%) with NE carcinoma who underwent hormonal therapy were enrolled in the prognostic analyses by Cox proportional hazards model. RESULTS: The serum status steadily shifted toward predominant expression of ProGRP with the progression of prostate cancer into metastatic and androgen-independent stages. Univariate analysis revealed that the deteriorated performance status (PS) and extent of bony disease (EOD), and high serum alkaline phosphatase (ALP), serum ProGRP, and nadir prostate-specific antigen (PSA) levels were associated with a lower progression-free survival (PFS) rate (P < 0.005). Multivariate analysis demonstrated that PS, serum ProGRP, and nadir PSA held an independent predictive value for PFS (P < 0.05), and all correlated with bone-related factors. Serum ProGRP was the most significant predictor among pre-treatment factors in this model (P = 0.0094). CONCLUSIONS: The neuropeptide precursor ProGRP is a distinct serum marker that is useful to know the NE milieu and provides prognostic information in patients with advanced prostate cancer. Standard therapy for metastatic prostate cancer may make progress when further studies will clarify the causative link between serum ProGRP level and androgen-independent disease progression.

Adult↗

Giant stercoral stone and catheterization difficulty.

An unusual case of giant calcification in the midline of the pelvis is reported herein. An 84-year-old male, whose urination was managed by clean intermittent self-catheterization (CIC), presented with catheter insertion difficulty. The patient had a history of transurethral operations for benign prostatic hyperplasia and small bladder stones. Kidney, ureter and bladder (KUB) X-ray of post-enhanced computed tomography (CT) suggested a giant ball-shaped calcification in the bladder. A recurrent bladder stone was suspected. However, pelvic CT scan revealed that the giant calcification was, in fact, situated in the rectum. Thus, a diagnosis of giant stercoral stone was made. After the stone was removed manually, the patient had no difficulty in inserting the catheter. His prior complaint may have been caused by urethral bladder neck obstruction due to the giant stercoral stone.

Aged↗

Quantitative analysis of thymidine phosphorylase and dihydropyrimidine dehydrogenase in renal cell carcinoma.

OBJECTIVE: The purpose of the present study was to clarify the clinicopathological significance of both thymidine phosphorylase (TP) and dihydropyrimidine dehydrogenase (DPD) in renal cell carcinoma (RCC) based on a quantitative analysis of RCC patients. METHODS: Levels of TP and DPD in RCC and/or uninvolved renal tissues from 65 RCC patients were measured by enzyme-linked immunosorbent assay. RESULTS: The TP level and TP/DPD ratio were significantly higher in RCC than in adjacent uninvolved renal tissues (p < 0.0001). There was no significant difference in DPD levels between RCC and uninvolved renal tissues. The ratio of the highest to the lowest level was 623 in TP level, 28.9 in DPD level, and 985 in TP/DPD ratio. In the univariate analysis, patient's age (p = 0.04), tumor stage (p < 0.0001), tumor size (p = 0.007), TP expression (p = 0.03), and DPD expression (p = 0.04) were significantly associated with increased risk of death. Multivariate analysis showed that patient's age, tumor stage, and TP expression were independent prognostic factors. CONCLUSIONS: TP and DPD in RCC provide prognostic information although DPD was not an independent prognostic factor. The present finding of a wide range in these enzyme expressions in RCC suggests that a certain subpopulation with a high TP/DPD ratio has potential responsiveness to fluoropyrimidines, especially 5'-deoxy-5-fluorouridine and capecitabine.

Aged↗

Forced expression of cytidine deaminase confers sensitivity to capecitabine.

OBJECTIVE: Cytidine deaminase (CDD) is involved in the metabolism of new pyrimidine analogues, capecitabine (N(4)-pentyloxycarbonyl-5'-deoxy-5-fluorocytidine) and gemcitabine (2',2'-difluorodeoxycytidine). The purpose of the present study was to directly examine the role of CDD in tumor cells themselves in mediating the sensitivity to capecitabine compared with gemcitabine. METHODS: The human bladder cancer cell line T24 was transfected with human CDD2 cDNA by the lipofectin method. RESULTS: Transfection of CDD2 cDNA did not change the levels of thymidine phosphorylase, dihydropyrimidine dehydrogenase and thymidylate synthase (TS) but increased the CDD activity significantly (p < 0.01). Forced expression of CDD made T24 sensitive to 5'-deoxy-5-fluorocytidine (5'DFCR) in vitro and capecitabine in vivo, but resistant to gemcitabine both in vitro and in vivo. Tetrahydrouridine, a specific CDD inhibitor, abrogated the changes in the in vitro sensitivity to 5'DFCR and gemcitabine by transfection of CDD2 cDNA. Transfection of CDD2 cDNA resulted in a significant increase in cellular 5-fluorouracil level (p < 0.01) and inhibition of TS activity (p < 0.01) after treatment with 5'DFCR in vitro. CONCLUSIONS: The present study clearly showed direct evidence for the contribution of CDD in tumor cells themselves to the sensitivities to capecitabine and gemcitabine.

Animals↗

[Clinical evaluation of hot flushes developing during endocrine therapy for prostate carcinoma].

OBJECTIVE: There are few clinical investigations on the hot flushes that develop during endocrine therapy for prostate cancer in Japan, although there are many reports in the Western countries. Therefore, we evaluated the incidence of hot flushes and the association between hot flushes and clinical characteristics of prostate cancer patients receiving endocrine therapy. PATIENTS AND METHODS: Sixty-eight prostate cancer patients receiving endocrine therapy (LH-RH analog (group LH-RHA); 22 patients, LH-RHA + non-steroidal antiandrogen (group LH-RHA + NSAA); 20 patients, LH-RHA + steroidal antiandrogen (group LH-RHA + SAA); 8 patients, LH-RHA + estramustine phosphate (group LH-RHA + EP); 1 patient, bilateral orchiectomy (group O); 5 patients, O + non-steroidal antiandrogen (group O + NSAA); 11 patients, and O + steroidal antiandrogen (group O + SAA); 1 patient) were evaluated by a fixed questionnaire. The incidence of the hot flush, the association between hot flushes and the clinical factors, as well as the therapy of hot flushes including SAA and Kampo therapy were analyzed. RESULTS: The overall incidence of hot flushes was 37% (36% in group LH-RHA, 45% in group LH-RHA + NSAA, 13% in group LH-RHA + SAA, 0% in group LH-RHA + EP, 20% in group O, 45% in group O + NSAA, 100% in group O + SAA). No significant association between the hot flushes and the clinical factors of the patients was observed. On the other hand, in 3 of 4 patients treated by SAA, hot flushes improved after 4 weeks. In 2 of 3 patients treated by Kampo, hot flushes improved after 4 weeks. CONCLUSION: Hot flushes are the major side effect of endocrine therapy for Japanese prostate cancer patients. SAA and Kampo are thought to be effective for treatment of hot flushes.

Aged↗

Isoliquiritigenin suppresses pulmonary metastasis of mouse renal cell carcinoma.

Isoliquiritigenin is a chalcone isolated from licorice and shallots. The ability of isoliquiritigenin to suppress metastasis was examined in a pulmonary metastasis model of mouse renal cell carcinoma. Isoliquiritigenin significantly reduced pulmonary metastasis, without any weight loss or leukocytopenia. Isoliquiritigenin suppressed in vitro proliferation of carcinoma cells, potentiated nitric oxide production by lipopolysaccharide-stimulated macrophages, and facilitated cytotoxicity of splenic lymphocytes in vitro. These findings suggest activation of macrophages, activation of cytotoxicity of lymphocytes, and direct cytotoxicity as possible mechanisms of metastasis suppression by isoliquiritigenin. In addition, isoliquiritigenin prevented severe leukocytopenia caused by administration of 5-fluorouracil.

Animals↗

Elevated serum progastrin-releasing peptide (31-98) in metastatic and androgen-independent prostate cancer patients.

BACKGROUND: Increases in neuroendocrine phenotype and secretory products are closely correlated with tumor progression and androgen independence in prostate cancer. In this study, we explored this correlation using serum progastrin-releasing peptide (ProGRP), a carboxy-terminal region common to three subtypes of precursors for gastrin-releasing peptide (GRP), which is released from the neuroendocrine phenotype to act as a growth factor. METHODS: In 60 patients with benign prostatic hyperplasia (BPH) and 200 with prostate cancer, serum ProGRP levels were determined with an enzyme-linked immunosorbent assay (ELISA) kit and evaluated in relation to clinical stage, hormonal treatment, and prostate-specific antigen (PSA) values. Fourteen randomly selected patients were entered in the follow-up study. Additionally, expression of ProGRP as determined by immunohistochemical analysis was compared to that of chromogranin-A (CgA) in tissue samples from several subjects. RESULTS: We found a positive correlation between PSA and ProGRP in patients with untreated prostate cancer; no correlation was found in the treated groups. The increases in the ProGRP value and in the percentage of patients with higher than normal values were significant (P < 0.0001), especially in the androgen-independent group (P < 0.0001). A longitudinal study showed that, in a subset of patients, the ProGRP values tended to increase transiently when the cancer became androgen independent, but remained unchanged or decreased at the androgen-dependent stage. Positive staining for ProGRP occurred in a different distribution in neuroendocrine tissues than that of staining for CgA. CONCLUSIONS: The clinical results demonstrated the existence of a regulatory mechanism for GRP, which to date had only been observed in cell lines. These findings suggest that GRP is a growth factor potentially upregulated by androgen but that does not rely principally on androgen modulation. The large overlap in levels of ProGRP among the groups limits the use of this value as a monitoring tool. Measurement of ProGRP, however, does have potential as an independent parameter to evaluate androgen-independent progression and to facilitate a new therapeutic strategy that may compensate for current limitations of diagnosis based on PSA alone.

Adult↗

A deserosalized muscle layer covering method for antireflux ureteroileostomy: a preliminary clinical trial.

PURPOSE: To achieve complete protection of the upper urinary tract in patients with a neobladder we designed and clinically applied the deserosalized muscle layer covering method, a new antireflux ureteroileal reimplantation technique in which the terminal ureter is implanted in the muscle layer of the ileum. We present the operative procedure and preliminary results. MATERIALS AND METHODS: We created an orthotopic ileal neobladder after radical cystectomy in 5 patients with invasive bladder cancer. The ureters were reimplanted into the reservoir using the deserosalized muscle layer covering method. The functional outcome of this procedure was evaluated by radiological studies. RESULTS: No patients died during the perioperative period and no reimplanted ureters showed ureteral reflux or ureteral stricture during the observation period. Video cystometrograms demonstrated the complete prevention of reflux during the voiding and storage phases. CONCLUSIONS: The deserosalized muscle layer covering method provided a nonobstructed unidirectional flow of urine in all renal units examined in this study. The efficacy of this method was proved during short-term followup.

Cystectomy↗

Giant bladder diverticulum due to previous bullet injury: findings of gadolinium-enhanced magnetic resonance imaging.

Non-obstructive acquired giant bladder diverticulum is rare. An 84-year-old man presented with difficulty in urination. Radiological examinations including pelvic magnetic resonance imaging, urethrocystography and urethrocystoscopy demonstrated a giant bladder diverticulum with normal infravesical urinary tract. The patient had a past history of gunshot bladder injury and underwent surgical removal of the bullet. The giant bladder diverticulum was thought to be associated with the injury or the operation.

Aged↗

Immunohistochemical study of bcl-2, p53 and Ki-67 expressions in collecting duct carcinoma of the kidney. Five cases and review of the literature on bcl-2, p53 and Ki-67 expressions in renal cell carcinoma and transitional cell carcinoma.

OBJECTIVES: This study was designed to examine the expressions of bcl-2, p53 and Ki-67 antigen in collecting duct carcinoma (CDC) of the kidney by an immunohistochemical method. METHODS: The diagnosis of CDC was based on the criteria proposed by Srigley and Eble. The clinical courses of 5 CDC cases examined in this study suggested that 3 cases were low grade and 2 cases high grade. The expressions of bcl-2, p53 and Ki-67 antigen were evaluated in paraffin-embedded surgical specimens using anti-bcl-2 and anti-p53 antibodies and Ki-67 antigen, respectively. RESULTS: The expression of bcl-2 was recognized in 3 of 5 cases (60%), p53 expression also in 3 of 5 cases (60%). The Ki-67 labeling index was 7.46 +/- 7.40 (mean +/- SD). CONCLUSIONS: It was suggested that there were two clinical types in CDC; the expression of bcl-2 did not correlate with the CDC patients' clinical courses and the cellular proliferation, and p53 expression was recognized in the CDC patients with highly cellular proliferation.

Aged↗