Yasuhiko Hirose

Novel effect of the inhibitor of mitochondrial cyclophilin D activation, N-methyl-4-isoleucine cyclosporin, on renal calcium crystallization

To experimentally evaluate the clinical application of N‐methyl‐4‐isoleucine cyclosporin, a novel selective inhibitor of cyclophilin D activation.

Novel Closing Method Using Subcutaneous Continuous Drain for Preventing Surgical Site Infections in Radical Cystectomy

To reduce the incidence of surgical site infection (SSI) after radical cystectomy, a new closing method using subcutaneous continuous aspiration drain was developed and compared to the conventional closing method. The new method involved (a) closed aspiration with an indwelling aspiration drain without suture of the subcutaneous fat and (b) covering with hydrocolloid wound dressing after suture of the dermis with 4-0 absorbable thread and reinforcement using strips. The incidence of SSI was significantly improved by using the new method. Furthermore, univariate and multivariate analysis associated with SSI revealed that the new closing method was statistically correlated with 85% reduction of SSI (odds ratio: 0.15, 95% confidence interval: 0.03–0.69).Our new method using continuous aspiration with subcutaneous drain is useful for preventing SSI through removal of effusions and reduction of dead space by apposition of the subcutaneous fat.

Seminomatous extragonadal germ cell tumor with complete obstruction of the superior vena cava responding to intensive chemotherapy.

A 20-year-old man was admitted to our hospital with persistent cough and dyspnea. He had bilateral distention of the jugular veins, and swollen lymph nodes were palpable in the right subclavicular region. Plain X-ray and computed tomography (CT) of the chest showed a solid soft tissue mass in the upper mediastinum, with leftward displacement of the trachea and complete obstruction of the superior vena cava. Mediastinal radiotherapy (1.8 Gy/day) and methylprednisolone (100 mg/day) were started immediately. Biopsy of the right subclavicular lymph nodes revealed metastatic seminoma. The patient was referred for chemotherapy, which was performed with a combination of cisplatin, bleomycin and etoposide (BEP). A partial response was observed after completion of 3 cycles of chemotherapy, but there was no further tumor shrinkage after additional salvage chemotherapy. The patient is being followed up on an outpatient basis and has been free of recurrence for 32 months after intensive treatment.

Therapeutic results in elderly patients with prostate cancer: chronological comparison in a single community hospital

Objective: There are few reports of the long-term outcomes of elderly patients with prostate cancer. We analyzed data from our institution from the past 12 years, including the patient history, treatment methods, and prognosis of patients with prostate cancer aged 80 years or more. Patients and Methods: A total of 179 cases of prostate cancer in patients aged 80 years or more were retrospectively evaluated. We divided them chronologically into groups A, B, C, and D: Group A included 40 cases from 2002–2004; Group B, 48 cases from 2005–2007; Group C, 46 cases from 2008–2010; and Group D, 45 cases from 2011–2013. Results: Sixty-one (30%) patients changed treatment course. Interestingly, no cancer deaths occurred in the patients who changed treatment course. Although 14 (7.8%) cancer deaths occurred (A: B: C: D = 4: 4: 6: 0, respectively), all occurred in 2011 or later. Conclusion: In our study, over 50 patients who underwent treatment survived for 5 years or more. By treating prostate cancer in elderly patients when appropriate, we can lower the mortality rate due to prostate cancer. Our results support the active treatment of prostate cancer in elderly patients.

MP33-15 MITOCHONDRIAL COLLAPSE DEPENDS ON CYCLOPHILIN D IN RENAL TUBULAR CELLS PROMOTES KIDNEY STONE FORMATION

INTRODUCTION AND OBJECTIVES: We recently reported that renal tubular cell injury induced by oxidative stress and subsequent mitochondrial collapse is the initial step in the process of kidney stone formation. Recently, it was shown that the mitochondrial permeability transition (MPT) is involved in mitochondrial collapse. Cyclophilin D (CypD) is a mitochondrial matrix protein involved in MPT. Thus, we hypothesized that CypD-dependent MPT causes mitochondrial collapse and is a trigger of kidney stone formation. In this study, we investigated whether mitochondrial collapse depends on CypD and determined its relationship to kidney stone formation using CypD-deficient mice. METHODS: We administered 80 mg

MP25-07 DEVELOPMENT OF A NEW BIOMARKER AND TREATMENT STRATEGY FOR KIDNEY STONE DISEASE TARGETING MITOCHONDRIAL CYCLOPHILIN D ACTIVITY

kg 1 glyoxylic acid, a precursor of oxalic acid, intraperitoneally for 6 consecutive days to 8week-old male CypD-deficient mice (CypD-/-, n 1⁄4 6) and wild-type mice (CypDþ/þ, n 1⁄4 6). We removed the kidneys of the mice in each group 6 days after glyoxylic acid administration. Stone formation and morphology were evaluated using a polarization microscope and Pizzolato staining, and the stone formation rate was estimated using image analysis software. The form of mitochondria was observed using a transmission electron microscope (TEM). Superoxide dismutase (SOD) and malondialdehyde (MDA), markers of oxidative stress, osteopontin (OPN), a stone matrix protein, and caspase 3, a marker of apoptosis, were evaluated by immunohistochemical staining and western blotting. RESULTS: The stone formation rate of CypD-/mice (0.05%) was significantly lower than that of CypDþ/þ mice (0.22%). Expression of MDA, OPN, and caspase 3 was lower in CypD-/mice than in CypDþ/þ mice. Expression of SOD was higher in CypD-/than in CypDþ/þ mice. Based on TEM observations, CypDþ/þ mice had a disorganized internal structure and rupture of the double membrane of the mitochondria suggesting mitochondrial collapse, but such morphological changes were rare in CypD-/mice. CONCLUSIONS: According to the results of this study, during kidney stone formation, CypD influences MPT by generating mitochondrial collapse via oxidative stress, leading to renal tubular cell injury and kidney stone formation. We elucidated the mechanism of CypDdependent MPT in promoting kidney stone formation.

2303 BISPHOSPHONATE PREVENTS UROLITHIASIS IN MEN WITH OSTEOPOROSIS BY REDUCING THE URINARY ION ACTIVITY PRODUCT OF CALCIUM STONE

the kidneys were harvested and examined calcium oxalate stones/crystals were suspected. Histopathological analysis on H&E stainings, fluorescent microscopy and stone analysis by infrared spectrum analysis confirmed calcium oxalate stones/crystal formation within the renal cortex and medulla. No crystal deposition was observed in the control group. CONCLUSIONS: Pigs fed ethylene glycol in combination with vitamin D, ammonium chloride, gentamycin, or Lasix formed calcium oxalate stones/crystals. The use of the above feeding substrate is inexpensive and effective at producing a novel porcine calcium oxalate stone forming model.

Beneficial Effect of Increasing the Dose of Tamsulosin to 0.4 mg in Japanese Patients with Benign Prostatic Hyperplasia

treated mice had stones. The number of stones ranged from 16-45 (25.86 / 10.96, n 181). All stones were in the small group, except one 3mm stone. Mean stone weight was 29.2 / 14.8mg (range 14.2-52.3mg). Mean bladder weight in mice with stones was 65.4 / 18.6mg (range 42.2-101.1) and without stones it was 18.6 / 5.2mg (range 10.2-25.2mg). Stone number, stone weight, and bladder weight were significantly different between the two groups (two-tailed t-test, p 0.05) and the difference in stone burden between the groups was clearly evident by micro CT. There was no significant difference in cystine concentration (nmol/mg creatinine) between the two groups (5,410 / 2,124 versus 4,343 / 1,577), suggesting that urine was saturated with cystine in both groups. CDME treatment had no side effects. A dose of 5 mg/ml administered in the water supply also had beneficial effects and no side effects. CONCLUSIONS: CDME-treated mice had a significantly smaller stone mass and stone size, strongly suggesting that CDME is inhibiting, but not preventing, the growth of cystine crystals into stones. While current treatments for cystinuria in humans have poor compliance and multiple side effects, CDME in mice had therapeutic potential and was without adverse effects. Further research is warranted to determine if CDME may provide a new treatment approach for cystinuria, which is clinically invaluable, since cystinuria patients are at risk for multiple surgeries and renal insufficiency.

Giant PSA-Positive Ectopic Prostatic Tissue outside of the Urinary Tract Originally Diagnosed as Benign Prostatic Hyperplasia

Objective: Tamsulosin is often administered at a dose of 0.2 mg in Japan, Korea, and elsewhere in Asia, while a dose of 0.4 mg is more common in the West. In order to determine the higher dose might also be appropriate in the North-East Asian setting, we studied whether the effect of increasing the dose to 0.4 mg in Japanese patients who had dysuria associated with benign prostatic hyperplasia. Patients and Methods: Twenty-two cases with a voiding volume ≥ 100 ml assessed by uroflowmetry out of 31 patients with benign prostatic hyperplasia and an IPSS (International Prostate Symptom Score) ≥ 8 whose symptoms were controlled with 0.2 mg of tamsulosin were entered into this study. We evaluated IPSS and QOL (quality of life) score, urinary flow parameters and residual urine volume before and 4 weeks after increasing the dose of tamsulosin. Results: Statistical analyses performed using the Wilcoxon test showed no significant alteration in IPSS total score or QOL score with the increased dose, but Qmax (maximum urinary flow rate) improved from 10.1 ± 5.5 ml/s to 12.1 ± 6.5 ml/s (p = 0.013), and residual urine volume improved from 37.6 ± 26.4 ml to 22.2 ± 24.3 ml (p = 0.012). Two of the 31 patients complained of new symptoms; 1 complained of breast pain and the other complained of dizziness. Conclusions: From the lack of side effects of more than moderate grade in the present study, increasing the dose of tamsulosin might be recommended before switching patients to other drugs.

A Paracrine Mechanism Involving Renal Tubular Cells, Adipocytes and Macrophages Promotes Kidney Stone Formation in a Simulated Metabolic Syndrome Environment

A 63-year-old man with a history of difficulty in defecating was diagnosed with a retroperitoneal tumor fully occupying the pelvic space. However, extensive histological examination of the resected material revealed only benign prostatic tissue. This is the ninth reported case of ectopic tissue found outside the urinary tract and at a gross weight of 398 g, the largest so far described. The lesion was also of interest because of its strong positive prostate specific antigen.