Yasuyuki Kobayashi

Okayama University, Okayama, Okayama, Japan

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Publications (16)26.12 Total impact

  • Hypertension Research 03/2014; · 2.79 Impact Factor
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    ABSTRACT: OBJECTIVES: To describe the frequency of and to determine predictive factors associated with Radiation Therapy Oncology Group urinary toxicity in prostate brachytherapy patients. METHODS: From January 2004 to April 2011, 466 consecutive Japanese patients underwent permanent iodine-125-seed brachytherapy (median follow up 48 months). International Prostate Symptom Score and Radiation Therapy Oncology Group toxicity data were prospectively collected. Prostate volume, International Prostate Symptom Score before and after brachytherapy, and postimplant analysis were examined for an association with urinary toxicity, defined as Radiation Therapy Oncology Group urinary toxicity of Grade 1 or higher. Logistic regression analysis was used to examine the factors associated with urinary toxicity. RESULTS: The rate of Radiation Therapy Oncology Group urinary toxicity grade 1 or higher at 1, 6, 12, 24, 36 and 48 months was 67%, 40%, 21%, 31%, 27% and 28%, respectively. Grade 2 or higher urinary toxicity was less than 1% at each time-point. International Prostate Symptom Score was highest at 3 months and returned to normal 12 months after brachytherapy. On univariate analysis, patients with a larger prostate size, greater baseline International Prostate Symptom Score, higher prostate V100, higher prostate V150, higher prostate D90 and a greater number of seeds had more acute urinary toxicities at 1 month and 12 months after brachytherapy. On multivariate analysis, significant predictors for urinary toxicity at 1 month and 12 months were a greater baseline International Prostate Symptom Score and prostate V100. CONCLUSIONS: Most urinary symptoms are tolerated and resolved within 12 months after prostate brachytherapy. Acute and late urinary toxicity after brachytherapy is strongly related to the baseline International Prostate Symptom Score and prostate V100.
    International Journal of Urology 01/2013; · 1.73 Impact Factor
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    ABSTRACT: Bladder cancer is one of the most common urogenital malignancies. The intravesical instillation of anticancer agents is an attractive strategy to treat a superficial lesion or floating/disseminated cancer cells after transurethral operation. An adenovirus carrying REIC/Dkk-3, a tumor suppressor gene (Ad-REIC), exhibits cancer-specific apoptotic effects in various types of cancer cells. The aim of the present study was to examine the potential of Ad-REIC as a therapeutic agent for bladder cancer. KK47 and RT4 human bladder cancer cells were sensitive to the Ad-REIC treatment for apoptosis induction, but some human bladder cancer cell lines (T24, J82 and TccSup) were resistant. Significant cell growth inhibition was observed when these resistant cancer cell lines were treated with Ad-REIC in a condition of floating cells, which is clinically observed after transurethral operation and becomes a cause of intravesical cancer dissemination. The therapeutic potential of Ad-REIC for the treatment of multidrug-resistant bladder cancer was investigated. The adriamycin-resistant KK47 bladder cancer cells (KK47/ADM), which also present multidrug resistance, showed induction of significant apoptosis following Ad-REIC treatment. The Ad-REIC treatment induced downregulation of P-glycoprotein in KK47/ADM cells and restored the sensitivity to doxorubicin (adriamycin). Ad-REIC suppressed P-glycoprotein expression in a c-Jun-NH2-kinase (JNK)-dependent manner. Therefore, the current study indicated two therapeutic aspects of the Ad-REIC agent against human bladder cancer cells, as an apoptosis inducer/cell growth inhibitor and as a sensitizer of chemotherapeutic agents in multidrug-resistant cancer cells. The intravesical instillation of Ad-REIC could be an attractive therapeutic method in human bladder cancer where the treatment of superficial lesions and floating/disseminated or multidrug-resistant cancer cells is necessary.
    International Journal of Oncology 05/2012; 41(2):559-64. · 2.66 Impact Factor
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    ABSTRACT: Polypropylene mesh implants for the correction of pelvic organ prolapse (POP) are now available in Japan. We developed an innovative approach for correcting POP by placing polypropylene mesh transvaginally with laparoscopic assistance. From June 2007 through March 2010, sixteen consecutive patients with symptomatic stage 2 or 3 pelvic organ prolapse underwent the laparoscopic-assisted tension-free vaginal mesh procedure at Okayama University Hospital. All patients were evaluated before and at 1, 3, 6, and 12 months after surgery. Female sexual function was also evaluated with the Female Sexual Function Index (FSFI). The procedure was performed successfully without significant complications. Fifteen of 16 patients were considered anatomically cured (93.8%) at 12 months postoperatively. One patient with a recurrent stage 3 vaginal vault prolapse required sacral colpopexy six months postoperatively. Total FSFI scores improved significantly from 10.3 ± 1.3 at baseline to 18.0 ± 1.2 at 12 months after surgery. The laparoscopic-assisted trans-vaginal mesh is a safe, effective, and simple procedure for POP repairs. The procedure not only restores anatomic relationships but also improves sexual function.
    Acta medica Okayama 02/2012; 66(1):23-9. · 0.65 Impact Factor
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    ABSTRACT: OBJECTIVES: The traditional surgical approach for removing a urachal remnant is via a large transverse or midline infraumbilical incision. We review our experience with laparoscopic urachal cyst excision and report the efficacy and outcomes of this approach as a less morbid, minimally invasive alternative. METHODS: Between August 2005 and March 2009, eight patients with a mean age of 26 years who had symptomatic urachal cysts underwent laparoscopic radical excision of the urachal remnant. Using three ports, the urachal remnant was dissected from the umbilicus to the bladder dome and then removed intact via the umbilicus. Umbilicoplasty was performed by a plastic surgeon. We retrospectively reviewed the perioperative records to assess morbidity and outcomes. RESULTS: All eight operations were completed successfully. No intraoperative or postoperative complications were reported at a mean follow-up of 3.2 years. Mean operative time was 147.5 min including umbilicoplasty. Pathological evaluation confirmed a benign urachal remnant in each case. There have been no recurrences of symptoms nor postoperative complications during follow-up. Mean time to full recovery, defined as return to normal life without pain, was 16 days. The patients with bladder cuff resection had a delayed full convalescence (25 vs. 13 days) due to a minimum degree of dysuria. CONCLUSION: A laparoscopic approach with the removal of urachal remnants via the umbilicus appears to be a safe and effective alternative with better cosmesis when compared to an open approach.
    World Journal of Urology 01/2012; · 2.89 Impact Factor
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    ABSTRACT: BACKGROUND: The clinical impact of salvage surgery after chemotherapy on cancer survival of patients with metastatic urothelial carcinoma is controversial. We aimed to verify the clinical role of salvage surgery by analyzing the long-term outcome in patients with urothelial carcinoma treated by chemotherapy. METHODS: Between 2003 and 2010 at a single institution, 31 of 47 patients (66%) with metastatic urothelial carcinoma showed objective responses (CR in 4, PR in 27) after multiple courses of cisplatin/gemcitabine/paclitaxel-based chemotherapy, and a cohort of patients with partial response (PR) were retrospectively enrolled. Twelve (10 male and 2 female, median age 64.0 years) of 27 patients with PR underwent salvage surgeries after the chemotherapy: metastatectomy of residual lesions (10 retroperitoneal lymph nodes, 2 lung), and 6 radical surgeries for primary lesions as well. Progression-free survival and overall patient survival rates were analyzed retrospectively and compared with those of patients without salvage surgery. RESULTS: All 12 patients achieved surgical CR. Pathological findings of metastatic lesions showed viable cancer cells in 3 patients. In univariate analysis, sole salvage surgery affected overall survival in 27 patients with PR to the chemotherapy (P = 0.0037). Progression-free survival and overall survival rates in patients with salvage surgery were better than those in 15 PR patients without the surgery (39.8 vs. 0%, and 71.6 vs. 12.1% at 3 years, P = 0.01032 and 0.01048; log-rank test). CONCLUSIONS: Salvage surgery for patients with residual tumor who achieve partial response to chemotherapy could have a possible impact on cancer survival.
    International Journal of Clinical Oncology 11/2011; · 1.41 Impact Factor
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    ABSTRACT: To evaluate the impact of pathological review by pathologist with genitourinary expertise (PGU) on treatment modality of localized prostate cancer, we analyzed Gleason grade (GG) migration and the final treatment decision in a cohort of patients designated for permanent prostate brachytherapy (PPB). From February 2005 to July 2010, a total of 247 patients with localized prostate cancer diagnosed by local community hospitals were referred to our hospital for PPB monotheray. All pathologic slides of prostate biopsies were reviewed by a single PGU. Patients ultimately selected their treatment modality from our recommendations based on the review. Indication for PPB monotherapy was the NCCN classification of patients as good or intermediate risk. In addition, patient with Primary GG 4 was regarded as unadapted case. Six cases were reinterpreted as no cancer (2.4%). GG change occurred in 94 cases (38.1%) of which 77 (81.9%) were upgraded and 17 (18.1%) downgraded. Of the total 247 patients, 86 (34.8%) changed therapies and 30 (12.1%) did so based on the pathologic slide review. Pathological review of biopsy specimens is mandatory for the determination of treatment modality especially in candidates for monotherapy of permanent prostate brachytherapy.
    World Journal of Urology 08/2011; 30(3):375-8. · 2.89 Impact Factor
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    ABSTRACT: To determine the independent risk factors of bladder recurrence in patients with upper urinary tract urothelial carcinoma (UUT-UC). A total of 364 patients underwent nephroureterectomy (NUx) for UUT-UC between January 2005 and April 2009 in Okayama University and 17 affiliated hospitals. Patients with concomitant bladder cancer were excluded from the analysis. The clinicopathologic data for the remaining 288 patients with UUT-UC were retrospectively reviewed. Median follow-up after NUx was 20.2 months. The following variables were evaluated for any association with bladder recurrence: sex, age, tumor stage, tumor grade, venous invasion, lymphatic invasion, tumor location, multifocality, surgical modalities, time of ligation of the ureter, and preoperative urine cytology. The significance of each variable was tested univariately using the log-rank test. The simultaneous effects of multiple risk factors were estimated by multiple regression analysis using the Cox proportional hazards model. Bladder recurrence occurred in 103 patients (35.8%). Median time to first bladder recurrence was 6.9 months. Significant risk factors for bladder recurrences on univariate analysis were tumor location (P = 0.046) and preoperative positive urine cytology (P < 0.001). Multivariate analysis revealed that preoperative urine cytology positive was significant for bladder recurrence (HR: 1.977; 95% CI: 1.310-2.983, P = 0.001). Risk factor for subsequent development of bladder cancer after NUx was preoperative positive urine cytology.
    World Journal of Urology 07/2011; 30(2):271-5. · 2.89 Impact Factor
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    ABSTRACT: The two-step transcriptional amplification (TSTA) system was previously reported to enhance the tissue-specific gene expression driven by weak promoters, but the enhancement of the gene expression is limited to use in in vitro and in vivo experimental situations. To achieve robust tissue-specific gene expression using the TSTA system, we developed an advanced TSTA system which includes polyglutamines and rat glucocorticoid receptor sequences between the GAL4 and VP16 sequences in the region of the first step of transcription. We evaluated the advanced TSTA system as a method to enhance the human telomerase reverse transcriptase (hTERT) promoter-driving cancer-specific transcription in various cancer cell lines. As a result, the advanced TSTA enhanced cancer-specific luciferase gene expression in all of the examined cancer cell lines, when compared with both the one-step and conventional TSTA systems (an ~6- and ~17-fold enhancement, respectively). Notably, the enhancement of the hTERT driven expression by the conventional TSTA system was modest and even inferior to the one-step system in several cancer cell lines. We then constructed a luciferase gene encoding the adeno-associated virus vector in which the hTERT promoter-mediated expression was driven by the advanced TSTA or control systems. In an orthotopic liver tumor model, mice were treated with the vector via tail vein injection. An optical imaging device was used to visualize the in vivo luciferase expression in the orthotopic tumor. The advanced TSTA system significantly enhanced the luciferase expression compared with the one-step and conventional TSTA systems (18.0±1.0- and 15.9±0.85-fold gain, respectively). Therefore, the advanced TSTA system significantly improves hTERT-dependent cancer-specific gene expression both in vitro and in vivo when compared with the previous systems. Since the advanced TSTA method can also be applied to other site-specific gene expression systems using tissue-specific promoters, this approach is expected to become a valuable tool enabling in vivo site-specific targeting in the field of gene therapy and molecular imaging.
    Oncology Reports 07/2011; 26(4):769-75. · 2.30 Impact Factor
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    ABSTRACT: The tumor suppressor REIC/Dkk-3 is a secretory protein which was originally identified to be downregulated in human immortalized cells. In the present study, we investigated the expression pattern of REIC/Dkk-3 in various cell types to characterize its physiological functions. We first examined the expression level of REIC/Dkk-3 in a broad range of cancer cell types and confirmed that it was significantly downregulated in all of the cell types. We also examined the tissue distribution pattern in a variety of normal mouse organs. Ubiquitous REIC/Dkk-3 protein expression was observed in the organs. The expression was abundant in the liver, heart and brain tissue, but was absent in the spleen and peripheral blood mononuclear cells. The immunohistochemical analyses revealed that the subcellular localization of REIC/Dkk-3 had a punctate pattern around the nucleus, indicating its association with secretory vesicles. In cancer cells stably transfected with REIC/Dkk-3, the protein was predominantly localized to the endoplasmic reticulum (ER) under observation with confocal microscopy. Because REIC/Dkk-3 was found to be abundantly expressed in the acinar epithelial cells of the mouse prostate, we analyzed the effects of recombinant REIC/Dkk-3 protein on the acinar morphogenesis of RWPE-1 cells, which are derived from human normal prostate epithelium. Statistically significant acinar growth was observed in the culture condition with 10 µg/ml REIC/Dkk-3 protein, implicating the soluble form in prostatic acinar development. Current results suggest that REIC/Dkk-3 may play a role in regulating the morphological process of normal tissue architecture through an autocrine and/or paracrine manner.
    International Journal of Oncology 12/2010; 37(6):1495-501. · 2.66 Impact Factor
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    ABSTRACT: We analyzed the prognostic factors influencing survival after surgeries for upper urinary tract urothelial carcinoma (UUT-UC) with longer follow-up periods than in previous studies. Between January 2000 and December 2004, 386 patients underwent nephroureterectomy for UUT-UC. The data for the 221 patients with UUT-UC were retrospectively reviewed. Nine variables were evaluated for association with the survival outcomes of cause-specific survival. The prognostic significance was tested univariately with the log-rank test. The simultaneous effects of multiple prognostic factors were estimated by multiple regression analysis using the Cox proportional hazards model. The median follow-up was 38.4 months. The 5-year over all survival was 62.3%. Significant prognostic factors for disease-specific survival rate on univariate analysis were pathological stage (p < 0.0001), tumor grade (p = 0.0324), and venous invasion (p < 0.0001). Multivariate analysis revealed that only venous invasion was significant for disease-specific survival rate (p = 0.0205). Venous invasion was the only independent prognostic factor in pathologically localized UUT-UC.
    Acta medica Okayama 02/2010; 64(1):27-31. · 0.65 Impact Factor
  • Journal of Urology - J UROL. 01/2010; 183(4).
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    ABSTRACT: To evaluate morbidity in Hybrid Radical Prostatectomy (HRP, hybridized laparoscopic and open retropubic radical prostatectomy). The operative and pathological outcomes obtained in 25 consecutive patients who underwent HRP were reviewed. The median operating time was 220 min, median blood loss was 550 ml, and no patient required an allogenic blood transfusion. No severe postoperative complications were observed. The surgical margin was positive in 12% of all patients, and in 1 patient with pT2 or less (4.5%). These results indicate that HRP is safe and may be able to combine the benefits of both laparoscopic and open procedures.
    Acta medica Okayama 01/2009; 62(6):379-84. · 0.65 Impact Factor
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    ABSTRACT: The purpose of this study is to compare the performance of laparoscopic partial nephrectomy (LPN) with and without clamping of the renal artery and to evaluate the impact of clamping on postoperative renal function. A total of 20 patients underwent LPN, 13 without and 7 with clamping of the renal artery. The 2 groups were compared with respect to complications, blood loss, operative time, mean tumor size, and incidence of positive margins. Renal function was evaluated by pre- and postoperative renal scintigraphy using 99m Technetium-mercaptoacetyltriglycine (99mTc-MAG3). Intraoperative blood loss was significantly higher in the group without clamping than in the group with clamping (p0.04). In the group with clamping, the median warm ischemic time was 35 min (range 25-40 min). The serum creatinine values and the renal scintigraphy showed no influence on postoperative renal function with or without clamping. In the group without clamping, 2 cases were showed positive surgical margins. The procedure performed with clamping of the renal artery is superior to the procedure performed without clamping as it provides the advantages of controlling hemorrhaging without injury to renal function and prolonging the surgical time and allowing for more accurate resection of renal tumors.
    Acta medica Okayama 09/2008; 62(4):269-73. · 0.65 Impact Factor
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    ABSTRACT: From January 2004 to March 2007, 308 patients with clinically localized prostate cancer were treated using iodine-125 (125I) seed implantation (permanent brachytherapy) at Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences. We evaluated the treatments efficacy and morbidity in 300 prostate cancer patients who were followed up for more than 1 month after brachytherapy. Based on the National Comprehensive Cancer Network (NCCN) guidelines, patients with a prostate volume of less than 40 ml in transrectal ultrasound imaging were classified as low or intermediate risk. The median patient age was 67 years (range 50 to 79 years), the median prostate-specific antigen (PSA) value before biopsy was 6.95 ng/ml (range 1.13 to 24.7 ng/ml), and the median prostate volume was 24.33 ml (range 9.3 to 41.76 ml). The median follow-up was 18 months (range 1 to 36 months) and the PSA levels decreased in almost all patients after brachytherapy. Although 194 of 300 patients (64.7%) complained of difficulty in urination, pollakisuria/urgency, miction pain, and/or urinary incontinence, all of which might be associated with radiation prostatitis during the first month after brachytherapy, these symptoms gradually improved. 125I seed implantation brachytherapy is safe and effective for localized prostate cancer within short-term follow up.
    Acta medica Okayama 03/2008; 62(1):9-13. · 0.65 Impact Factor
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    ABSTRACT: From September 2003 to December 2005, 188 patients who visited our hospital and allied institutions for the purpose of prostate brachytherapy were administrated hormonal therapy for volume reductions before brachytherapy. The pretreatment and posttreatment of prostate volume using a transrectal ultrasound volumetric study and the types and duration of hormonal therapy were analyzed. We administered 91 patients with Luteinizing hormone-releasing hormone (LH-RH) agonist, 49 patients with anti-androgen (bicaltamide/flutamide), and 48 patients with maximum androgen blockade (MAB). The duration of the hormonal therapy was 1-3 months for 49 patients, 4-6 months for 59 patients, 7-9 months for 40 patients, 10-12 months for 32 patients, and over 13 months for 8 patients. Before the initiation of hormonal therapy, the mean prostate volume was 35.12 ml (11.04-78.71 ml), and the average of prostate volume before and after hormonal therapy was 36.79 ml and 24.79 ml, respectively (a 32.4% reduction). The prostate volume reduction rate was 32.0% for the LH-RH agonist only, 18.1% for the anti-androgen only and 41.2% for the MAB. No statistically significant difference was observed for the duration of hormonal therapy between 3 groups. A three-month course of the neoadjuvant LH-RH agonist indicated a sufficient volume reduction effectiveness for a large prostate volume.
    Acta medica Okayama 01/2008; 61(6):335-40. · 0.65 Impact Factor