Nobuhiko Hyochi

Portless endoscopic radical nephrectomy via a single minimum incision in 80 patients

Abstract Aim: To assess the feasibility of our portless endoscopic radical nephrectomy via a single minimum incision, which narrowly permitted extraction of the specimen in the initial 80 patients.

Portless endoscopic adrenalectomy via a single minimal incision using a retroperitoneal approach: Experience with initial 30 cases

Abstract Aim: To assess the feasibility of portless endoscopic adrenalectomy via a single minimum incision that narrowly permits extraction of the specimen.

Endoscopic minilaparotomy radical nephrectomy for chronic dialysis patients

Abstract Background : To assess the feasibility of laparoscope‐guided minilaparotomy (endoscopic minilaparotomy) for renal cell carcinoma in patients on chronic dialysis.

The androgen receptor as putative therapeutic target in hormone-refractory prostate cancer.

The androgen receptor (AR) plays a central role in the initiation and growth of prostate cancer. Androgen deprivation therapy (ADT) has been a gold standard for advanced prostate cancer for decades. Unfortunately, suppressive effects of ADT do not last long and hormone-refractory prostate cancer develops within several years. In spite of extensive research on mechanisms of hormone-independent growth of prostate cancer, there are few effective treatment options for recurrent tumors and most patients die from the disease in a short period of time. Accumulating evidence suggests that the AR signaling system remains intact and activated despite low levels of androgens in hormone-resistant prostate cancer. Currently, modifications to the AR via mutations, amplification and phosphorylation have been proposed as underlying mechanisms of hormone-resistance of prostate cancer cells. In addition, changes in AR cofactors are implicated in ligand-independent activation of AR signaling. Thus, the development of novel and more effective treatment modalities targeting the AR and AR-related molecules may provide better management of androgen-independent prostate cancer. Although recent patents on the AR related to prostate cancer are focused on antiandrogens, future trend will be shifted to agents or methods suppressing molecules or pathways that activate AR signaling in low androgen environments.

Positive expression of HIF-2α/EPAS1 in invasive bladder cancer

Abstract Objectives. To investigate the expression of hypoxia-inducible factor (HIF)-2α/endothelial PAS domain protein 1 (EPAS1) in bladder cancer. Methods. Two bladder cancer cell lines (T24, EJ-1) were examined for the expression of HIF-2α/EPAS1 mRNA by reverse transcriptase-polymerase chain reaction and HIF-2α/EPAS1 protein by Western blot analysis, respectively. Expression of HIF-2α/EPAS1 protein was also investigated immunohistochemically on paraffin-embedded sections from 24 patients with bladder cancer. Results. HIF-2α/EPAS1 mRNA and protein could be detected in the two bladder cell lines under normoxia. The normal urothelium and all 7 superficial cases (pTis-pTa) were negative for HIF-2α/EPAS1. Five of the 8 pT1 cases (62.5%) and all 9 muscle-invasive cases were positive. The invasive compartment showed stronger HIF-2α/EPAS1 immunoreactivity compared with the superficial compartment. All the tumor clusters infiltrating to the interstitial tissue among muscle fibers showed moderate to strong positive staining. Conclusions. HIF-2α/EPAS1 is mostly expressed in invasive bladder cancer, which indicates a possible role for HIF-2α/EPAS1 in the invasion of bladder cancer.

Suppression of spermatogenesis in ipsilateral and contralateral testicular tissues in patients with seminoma by human chorionic gonadotropin beta subunit

OBJECTIVES The pathologic complexity of the testicular tumor makes it difficult to demonstrate exactly the relationship between the impaired spermatogenesis in patients with a testicular tumor and the serum level of the human chorionic gonadotropin beta subunit (beta-hCG). Therefore, we performed quantitative evaluation of spermatogenesis in ipsilateral and contralateral testicular tissues of seminoma to simplify the relation pathologically and endocrinologically and to demonstrate the exact correlation between spermatogenesis and serum beta-hCG levels. METHODS Fifty-three biopsy specimens from ipsilateral and contralateral testicular tissues of seminoma were analyzed histologically. The quantitative evaluation of spermatogenesis was performed by the mean Johnsens score count (MJSC). Beta-hCG expression in seminoma was examined immunohistochemically. Serum beta-hCG, testosterone, estradiol, luteinizing hormone, and follicle-stimulating hormone levels were analyzed before orchiectomy. RESULTS A significant linear relationship (r = -0.82; P <0.005) was found between the serum level of beta-hCG and the MJSC in contralateral testicular tissues but not in ipsilateral ones, although the suppression of spermatogenesis was observed in both sides without suppression of luteinizing hormone and/or follicle-stimulating hormone production. CONCLUSIONS A clearcut fall in the MJSC with an associated rise in the serum level of beta-hCG was demonstrated in the contralateral testicular tissues but not in the ipsilateral ones of seminoma. It seems most likely that serum beta-hCG suppresses spermatogenesis in both ipsilateral and contralateral testicular tissues without the suppression occurring through the hypothalamus-pituitary-gonadal system, and also that some less well recognized factors affect spermatogenesis, making the relation between serum beta-hCG and MJSC obscure in ipsilateral testicular tissues.

Deferred combined androgen blockade therapy using bicalutamide in patients with hormone-refractory prostate cancer during androgen deprivation monotherapy.

To assess the effect of adding bicalutamide on serum prostate‐specific antigen (PSA) levels in patients with hormone‐refractory prostate cancer (HRPC) during androgen deprivation monotherapy (ADMT).

Favorable outcome of preoperative low dose chemoradiotherapy against muscle-invasive bladder cancer.

To investigate the feasibility of preoperative low-dose chemoradiotherapy, 50 patients with localized muscle-invasive bladder cancer (T2–T4) were treated with concurrent cisplatin (100 mg/body × 2 courses) and pelvic irradiation (40 Gy). Among 20 patients (40%) who achieved clinical complete regression, 11 with solitary tumor underwent partial cystectomy because of advanced age, poor condition of the patients, or a reluctance to have radical surgery. Radical cystectomy was carried out in the remaining 39 cases (complete regression 9, partial regression 30). Pathologic T0 response (no residual tumor) was achieved in 18 (36%) of all the cases. Median follow-up was 19 months (range 2–59 months). Estimated 3-year disease-free survival was 75% for all patients and 100% for T0 responders. Local recurrence (2 patients) or distant metastasis (6 patients) developed in 8 of 32 patients with pathologic persistent tumor. All of the 11 patients (9 with T0 response and 2 with a small residual tumor nest) who underwent partial cystectomy were recurrence free for observation periods up to 59 months. Low-dose chemoradiotherapy is as effective as other neoadjuvant protocols and is applicable to high-risk patients. The bladder can be preserved by partial cystectomy in selected cases with clinical complete regression.

Reconstruction of the sympathetic pathway projecting to the prostate, by nerve grafting in the dog

To examine the possibility of nerve grafting to repair the sympathetic pathway projecting to the prostate, as contraction of the prostate is known to be controlled by the sympathetic pathway via the hypogastric nerve (HGN), and injuries to the pathway cause significant disturbances in prostatic secretion.

A 2-week Maintenance Regimen of Intravesical Instillation of Bacillus Calmette–Guérin is Safe, Adherent and Effective in Patients with Non-Muscle-Invasive Bladder Cancer: A Prospective, Multicenter Phase II Clinical Trial

OBJECTIVE To investigate the safety and efficacy of a maintenance regimen of bacillus Calmette-Guérin therapy including 6-week induction and 2-week maintenance instillation for patients with recurrent or multiple Ta, T1 tumors or carcinoma in situ of the urinary bladder. METHODS This study was performed as single-arm multi-institutional study. The enrolled patients had been diagnosed with urothelial carcinoma of the bladder, including the presence of at least two bladder tumors, single tumors recurring within 12 months of follow-up, any Grade 3 Stage Ta or T1 tumor, and primary or recurrent biopsy proven carcinoma in situ. Patients received 81 mg intravesical bacillus Calmette-Guérin (Connaught strain). The instillation was repeated once a week for another 5 weeks, followed by once a week for 2 weeks at months 3, 6, 12, 18, 24, 30 and 36, for a total of 20 instillations in 3 years. RESULTS From 28 hospitals, 202 patients were registered. A total of 186 patients matched the inclusion criteria: 139 patients in the Ta/T1group and 47 patients in the carcinoma in situ group. At the 4-year median point of follow-up, recurrence-free survival rates in the Ta/T1 group and the carcinoma in situ group were 76.7 and 77.7%, respectively. Completion rates for maintenance therapy in both groups at months 3, 6, 12, 24 and 36 were 81.7, 68.9, 58.1, 42.5 and 35.0%, respectively. Common toxicities were pain on urination, urinary frequency and gross hematuria. There was no treatment-related death. CONCLUSIONS This regimen may be feasible in patients with Ta/T1 tumor or carcinoma in situ; however, future Phase III randomized study is needed to determine whether this regimen would be truly safe and effective compared with 3-week maintenance regimen.