Published papers

Objectives: Lymphocele development is the most frequently reported postoperative complication of pelvic lymph node dissection (PLND) performed with laparoscopic radical prostatectomy (LRP). This study evaluated the efficacy of a vessel-sealing device (VSD) for the prevention of lymphocele development. Methods: A total of 120 patients who underwent LRP with PLND were prospectively enrolled. The patients were randomly assigned to one of the two groups: PLND using a conventional technique (group 1), and PLND performed with VSD (group 2). All patients underwent computed tomography (CT) scanning 1 month postoperatively to evaluate the maximum sectional area of the lymphoceles. Results: Lymphoceles developed in 63 cases (52.5%). One case (0.8%) was symptomatic with infection, and drainage tube placement was required. In the other 62 patients, the lymphoceles developed asymptomatically and were detected by CT scanning. There was no significant difference in the lymphocele development ratio between the two groups. However, when we defined a lymphocele over 1500 mm2 as being a significant size, lymphoceles were present in 16 of 60 patients in group 1 and 4 of 60 patients in group 2. The incidence of significant lymphoceles over 1500 mm2 in the group using VSD was much lower than that of the group without VSD (p<0.01). Multivariate analysis demonstrated that VSD was the only independent factor that had an effect on preventing the development of lymphoceles over 1500 mm2 (p<0.01, odds ratio=4.96). Conclusion: The results indicate that the development of large lymphoceles can be prevented by using VSD in LRP with PLND.

Germ cells are similar to pluripotent stem cells in terms of gene expression patterns and the capacity to convert to pluripotent stem cells in culture. The factors involved in germ cell development are also able to reprogram somatic cells. This suggests that germ cells are useful tools for investigating the mechanisms responsible for somatic cell reprograming. In this study, the expression of reprograming factors in primordial germ cells (PGCs) was analyzed. PGCs expressed Oct3/4, Sox2, and c-Myc but not Klf4. However, Klf2, Klf5, Essrb, or Essrg, which were expressed in PGCs, could compensate for Klf4 during somatic cell reprograming. Furthermore, PGCs could be converted to a pluripotent state by infection with any of the known reprogramming factors (Oct3/4, Sox2, Klf4, and c-Myc). These cells were designated as multipotent PGCs (mPGCs). Contrary to differences in the origins of somatic cells in somatic cell reprogramming, we hypothesized that the gene expression levels of the reprogramming factors would vary in mPGCs. Candidate genes involved in the regulation of tumorigenicity and/or reprogramming efficiency were identified by comparing the gene expression profiles of mPGCs generated by the exogenous expression of c-Myc or L-Myc.

Purpose To investigate the safety and efficacy of mirabegron for patients with overactive bladder (OAB) that is unresponsive to antimuscarinic agents or is related to benign prostatic hyperplasia (BPH). Methods Fifty-two newly diagnosed OAB patients (M group) and 45 patients with OAB that was unresponsive to antimuscarinics (S group) received mirabegron 50 mg once daily and were evaluated by OAB symptom score (OABSS), IPSS-QOL index, and IPSS at the time of baseline, 4 and 8 weeks. Newly diagnosed OAB patients treated with antimuscarinic agents were compared as controls. Results Mirabegron was effective for 85.2 % in M group. Significant improvements were seen in each domain of OABSS, and there was no significant difference with antimuscarinic therapy. Mirabegron was efficacious for 61.6 % of S group, and significant decreases of OABSS and IPSS-QOL index were observed. Significant improvements were also seen in voiding symptoms in men. Post-void residual urine volumes before and after treatment were 32.1 and 34.8 ml, and 26.2 and 31.3 ml in M and S group, respectively, and there was no significant difference. The incidence of adverse events was 8.4 %, although none were serious, and the patients recovered spontaneously after mirabegron was discontinued. Conclusion The present study suggests mirabegron is as effective as antimuscarinics for OAB. It improves OAB symptoms in patients with OAB for which antimuscarinic agents are insufficient. This study revealed that mirabegron improves not only OAB symptoms related to BPH, but also voiding symptoms in men. Low and mild incidences of side effects support the safe utility of mirabegron.

Background. To determine whether the administration of renin-angiotensin system (RAS) inhibitors, such as angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs), affect disease outcome in non-muscle-invasive bladder cancer (NMIBC). Methods. A total of 330 patients with initially diagnosed NMIBC were identified. We retrospectively investigated the clinical outcomes after transurethral resection of bladder tumor (TUR-BT) in patients who did or did not receive RAS inhibitors. The median follow-up period was 4.1 years. Results. A total of 128 patients (38.8 %) experienced subsequent tumor recurrence, and stage progression was observed in 17 patients (5.2 %) during follow-up. Fifty-one patients (15.5 %) had received ACEI or ARB administration at transurethral resection. Multivariate analysis demonstrated that tumor multiplicity, absence of bacillus Calmette-Guérin instillation, and no administration of ACEI or ARB (P = 0.010, hazard ratio 2.26) were independent risk factors for subsequent tumor recurrence. The 5-year recurrence-free survival rate was 78.4 % in patients administered ACEIs or ARBs, and 53.3 % in their counterparts (P = 0.011). Conclusions. The absence of RAS inhibitor administration was an independent risk factor for subsequent tumor recurrence in patients with initially diagnosed NMIBC. Our data support further investigation of the role of RAS inhibitors as a potential therapy to decrease tumor recurrence in NMIBC.

Purpose: To determine predictive factors for perioperative complications of laparoscopic adrenalectomy (LA) including single-site surgery performed or supervised by experienced laparoscopic surgeons. Patients and Methods: We retrospectively reviewed 265 consecutive unilateral LAs performed at a single institution from 2001 to 2011. All surgical procedures were performed or supervised by one of two experienced laparoscopic surgeons. The transabdominal approach was used in 248 patients, while a retroperitoneal approach was used in 17 patients. Laparoendoscopic single-site adrenalectomy was performed in 58 patients. Predictive factors for postoperative complications were analyzed. Results: There were no postoperative deaths. At least one postoperative complication occurred in 12 (4.6%) patients. No patient underwent reoperation for a complication. Only one (0.4%) patient's procedure was converted to open surgery, and only this patient needed a blood transfusion during the operation. One patient who underwent laparoendoscopic single-site adrenalectomy had the procedure converted to conventional laparoscopic adrenalectomy. Multivariable logistic regression analysis showed that an American Society of Anesthesiologists-physical status grade 3 or above was the only predictive factor for perioperative complications. Conclusion: American Society of Anesthesiologists-physical status grade 3 or above was a statistically significant factor for perioperative complications associated with laparoscopic adrenalectomy that involved laparoendoscopic single-site adrenalectomy, which was performed or supervised by an experienced laparoscopic surgeon. According to the findings of this retrospective study, single-site operation, obesity, adrenal tumor size, and tumor type may not be considered as risk factors for perioperative complications after LA performed or supervised by an experienced laparoscopic surgeon.

A 53-year-old man presented for further evaluation due to microscopic hematuria and left lumbar pain. Computed tomography revealed a large tumour in the left renal pelvis with multiple metastases. Despite effective systemic chemotherapy, he developed dyspnea, and was diagnosed with cardiac tamponade. Pericardial involvement in an advanced malignancy is common, but symptomatic cardiac metastasis from urothelial carcinoma is rare. Of the reports of symptomatic cardiac metastasis from urothelial carcinoma, only 3 cases presented as cardiac tamponade. We report here a rare case of cardiac tamponade caused by a renal pelvic carcinoma with positive cytodiagnosis of pericardial effusion. We also summarize and discuss the symptoms, treatment, and prognosis of the pathological condition, and present a brief review of previously published reports.

Somatic cell reprogramming is achieved by four reprogramming transcription factors (RTFs), Oct3/4, Sox2, Klf4, and c-Myc. However, in addition to the induction of pluripotent cells, these RTFs also generate pseudo-pluripotent cells, which do not show Nanog promoter activity. Therefore, it should be possible to fine-tune the RTFs to produce only fully pluripotent cells. For this study, a tagging system was developed to sort induced pluripotent stem (iPS) cells according to the expression levels of each of the four RTFs. Using this system, the most effective ratio (Oct3/4-high, Sox2-low, Klf4-high, c-Myc-high) of the RTFs was 88 times more efficient at producing iPS cells than the worst effective ratio (Oct3/4-low, Sox2-high, Klf4-low, c-Myclow). Among the various RTF combinations, Oct3/4-high and Sox2-low produced the most efficient results. To investigate the molecular basis, microarray analysis was performed on iPS cells generated under high (Oct3/4-high and Sox2-low) and low (Oct3/4-low and Sox2-high) efficiency reprogramming conditions. Pathway analysis revealed that the G protein-coupled receptor (GPCR) pathway was up-regulated significantly under the high efficiency condition and treatment with the chemokine, C-C motif ligand 2, a member of the GPCR family, enhanced somatic cell reprogramming 12.3 times. Furthermore, data from the analysis of the signature gene expression profiles of mouse embryonic fibroblasts at 2 days after RTF infection revealed that the genetic modifier, Whsc1l1 (variant 1), also improved the efficiency of somatic cell reprogramming. Finally, comparison of the overall gene expression profiles between the high and low efficiency conditions will provide novel insights into mechanisms underlying somatic cell reprogramming.

Background and Purpose: The roles and criteria for pelvic lymph node dissection (PLND) are not fully evaluated in patients with low-risk prostate cancer who are treated by laparoscopic radical prostatectomy (LRP). In this study, the outcome of PLND was assessed in terms of the biochemical relapse-free survival rates of low-risk prostate cancer patients who had undergone LRP. Patients and Methods: Included were 286 consecutive patients who were treated with LRP without previous endocrine therapy between 2002 and 2006 at our institution. Failure rates for LRP were compared in 139 patients with low-risk prostate cancer between those who underwent PLND (n=85) and those who did not (n=54). Biochemical relapse-free survival for each group was estimated by Kaplan-Meier analysis. Results: The mean number of retrieved lymph nodes was 5.4±0.4 (range 2-22). The 5- and 7-year biochemical relapse-free survival rates were 90.1% and 88.3% in patients with PLND, and 82.4% and 82.4% in those without PLND (P=0.278), respectively (median follow-up 69.4 mos). None of the 85 patients undergoing PLND had positive lymph nodes. Only one patient had symptomatic lymphocele, and he was treated as an inpatient. The average time needed for PLND was 16 minutes, which corresponded to 7% of the entire operative time. Conclusion: These results indicate that the dissection of pelvic lymph nodes is not related to biochemical relapse-free survival. The omission of PLND in patients with low-risk prostate cancer not only does not adversely affect biochemical relapse-free survival, but might decrease the incidence of complication and operative time of LRP.

A 60-year-old man undergoing hemodialysis for 13 years was referred to our department for evaluation of gross hematuria and a right renal mass. Voided urine cytology was negative. Computed tomography and magnetic resonance imaging demonstrated a right renal mass (32 × 22 × 20 mm in diameter). We clinically diagnosed the tumor as renal cell carcinoma staged T1aN0M0 arising from a horseshoe kidney, and performed right heminephrectomy. Pathological examination of the surgical specimen showed a grade 2, pT1a, clear cell carcinoma and negative surgical margin. To our knowledge, this is a rare case of a renal cell carcinoma arising from a horseshoe kidney in a chronic hemodialysis patient.

Purpose: Vasohibin-1 (VASH1) is a novel angiogenic molecule that is specifically expressed in activated vascular endothelial cells, and the status of VASH1 expression has been documented in cancer angiogenesis. The aim of this study was to address the prognostic value of VASH1 expression in upper urinary tract urothelial carcinomas (UTUC). Experimental Design: We retrospectively analyzed the clinical records of 171 patients with locally advanced UTUC (Ta-3N0M0). The median follow-up period was 3.8 years. We immunohistochemically examined the accomplished microvessels with anti-CD34 as microvessel density (MVD) and the microvessels with activated endothelial cells as VASH1 density. Then, we analyzed the association between immunohistochemical expression and clinical outcomes. Results: Forty-two patients experienced tumor recurrence and of these 34 died of the disease during follow-up. VASH1 density was significantly associated with tumor grade, pathologic T stage, and MVD. The 5-year recurrence-free and cancer-specific survival rates were 66.1% and 72.8% in patients with VASH1 density (≥ 40/mm2) and 81.0% and 86.5% in their counterparts, respectively (P < 0.05). MVD was not an independent predictor of tumor recurrence or cancer-specific survival. Multivariate analyses revealed that high VASH1 density was an independent prognostic indicator of both tumor recurrence (P = 0.024, HR = 2.10) and cancer-specific survival (P = 0.031, HR = 2.23) as well as other standard prognostic factors including high tumor grade and lymphovascular invasion. Conclusions: VASH1 density represents a clinically relevant predictor of patient prognosis in UTUC. The results suggest that VASH1 density could become a new biomarker and provide additional prognostic information in patients with UTUC.