Published papers

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.

The KiSS-1 gene has been reported to be a metastasis suppressor gene in human melanoma. The gene product was isolated from human placenta as the ligand of GPR54, a G protein-coupled receptor, and the C-terminally amidated peptide of 54 amino acids is called metastin. The binding of metastin to GPR54 has been shown to inhibit tumor metastasis in some tumor cells; however, its function remains unclear in urothelial carcinoma. We first evaluated KiSS-1 expression and GPR54 expression in 151 patients with upper urinary tract urothelial carcinoma to determine their prognostic significance. Next, we examined the role of metastin in the invasiveness and lung metastasis of MBT-2 variant (MBT-2V), which is a highly metastatic murine bladder cancer cell. Multivariate analysis revealed that KiSS-1 expression was an independent predictor of metastasis and overall survival. However, GPR54 expression was not selected. Hematogeneous metastasis had a significantly lower level of KiSS-1 expression compared with lymph node metastasis. Metastin treatment significantly reduced the invasiveness of MBT-2V cells and inhibited the DNA-binding activity of NF-kappaB by blocking its nuclear translocation, leading to a reduction in the expression and activity of matrix metalloproteinase-9. Metastin treatment dramatically prevented the occurrence of lung metastatic nodules (6.3 +/- 2.3, n = 15) compared with controls (30.4 +/- 5.1, n = 15; P < 0.01), as well as had survival benefit. KiSS-1 plays an important role in the prognosis of upper tract urothelial carcinoma and metastin may be an effective inhibitor of metastasis in urothelial carcinoma through its blockade of NF-kappaB function.

OBJECTIVES: To report our initial experience with transumbilical laparo-endoscopic single-site adrenalectomy for adrenal tumors by using a single port with a multichannel cannula and bent laparoscopic instrumentation. METHODS: Between December 2009 and December 2010, 30 patients underwent transumbilical laparo-endoscopic single-site adrenalectomy at our hospital. The procedure was carried out for adrenal cortical adenoma in 17 patients, adrenal pheochromocytoma in seven patients and other types of tumors in six patients. A multichannel port, bent laparoscopic instruments and Opti4 laparoscopic electrodes were used in all patients. The intraperitoneal space was approached through the umbilicus. The multichannel port was placed through a 2-cm incision at the inner edge of the umbilicus. A 5-mm flexible laparoscope was introduced to maintain an adequate laparoscopic view, and surgical specimens were extracted using an Endocatch bag. RESULTS: All procedures were successfully completed, with only one incision through the umbilicus, and without conversion to a standard laparoscopic approach. Mean operative time was 120.1 +/- 34.7 min. Tumor laterality and patient body mass index did not affect surgical morbidity. The initial 15 patients had a significantly longer mean pneumoperitoneum time (95.8 +/- 37.5 min) than the last 15 patients (70.5 +/- 18.7 min). Only one postoperative complication was observed (postoperative hematoma). CONCLUSIONS: A transumbilical approach for laparo-endoscopic single-site adrenalectomy is safe and feasible, and it results in superior cosmesis. Improvements in surgical devices might facilitate further development of this approach.

Interleukin-15 (IL-15) is known to stimulate the proliferation of CD8(+) T-cells and natural killer cells, and also to help to maintain memory CD8(+) T cells, suggesting that it may be of value in cytokine treatment of bladder cancer. In this experiment, we tested the efficiency of intravesical liposomal IL-15 gene delivery and its antitumor effect in a mouse orthotopic bladder cancer model. We established an orthotopic bladder cancer model by implanting 5x10(5) MBT-2 cells into female C3H/HeN mice through the urethra. The mice received repeated intravesical gene delivery injected with liposome-mediated plasmids (5 mug) transurethrally. On day 23, the bladder weights in the group receiving medium alone, the beta-galactosidase gene delivery control group, and the IL-15 gene therapy group were 196+/-36 mg, 201+/-35 mg, and 96+/-29 mg, respectively (p<0.05), demonstrating the antitumor effect of intravesical IL-15 gene therapy in this model. In the bladders treated with IL-15 gene plasmid instillation, histological analysis revealed that many inflammatory cells were induced around the tumors. Immunohistochemical analysis confirmed that there was predominant infiltration of CD8(+) T cells around the tumor nest. After the intravesical IL-15 gene therapy, the growth of rechallenged subcutaneous MBT-2 cells in surviving mice was inhibited again via tumor-specific cytotoxic T lymphocytes, although newly implanted FM3A cells in the same mice were not rejected. The present findings indicate that IL-15 gene therapy may be a promising new adjuvant therapy for bladder cancer.

BACKGROUND: We have started using laparo-endoscopic single-site surgery (LESS) in urologic surgery, although its use has not gained momentum due to its level of difficulty. We here report our initial experience with transumbilical LESS for adrenal cortical adenoma by using a single port with a multichannel cannula (SILS port) and bent laparoscopic instrumentation. FINDINGS: A multichannel port (SILS port), bent laparoscopic instrument (Roticulator Endo Mini-Shears) and Opti4 laparoscopic electrodes were used in all cases. The intraperitoneal space was approached through the umbilicus. The SILS port was placed through a 2 cm incision at the inner edge of the umbilicus. A 5 mm flexible laparoscope was introduced to keep the laparoscope outside, and surgical specimens were extracted using an Endocatch bag. In addition, as a case control study, we compared perioperative data of LESS adrenalectomy (LESS-A) with that of conventional laparoscopic adrenalectomy (LA). We performed transumbilical LESS-A for adrenal cortical adenoma in 12 cases, beginning in December, 2009. All procedures were successfully completed, with only one incision through the umbilicus, and without conversion to a standard laparoscopic approach. Mean operative time for LESS-A was 121.2 +/- 7.8 min, which was slightly longer than LA (110.2 +/- 7.3 min). For right adrenal tumors, we used a miniport (2 mm port) in addition to a SILS port, and were able to successfully perform adrenalectomy "with no visible scaring". Tumor laterality and patient BMI did not affect surgical morbidity in these procedures. Moreover, there was no significant difference between LESS-A and LA in blood loss, analgesic requirement, hospital stay, and scar satisfaction. CONCLUSIONS: The transumbilical approach in LESS for adrenalectomy is safe and feasible and also improves cosmetic outcome compared with standard laparoscopic procedures. Improvements in surgical devices may aid the further development of this approach.

OBJECTIVE: The effect of local immunotherapy with bacille Calmette-Guerin in elderly patients with non-muscle-invasive bladder cancer has not yet been fully evaluated. The aim of the present study was to evaluate whether patients' age influences the response to bacille Calmette-Guerin treatment for the prevention of tumor recurrence and whether the side effects were tolerable. METHODS: We reviewed 1252 cases with non-muscle-invasive bladder cancer treated with transurethral bladder tumor resection, and 447 cases who underwent bacille Calmette-Guerin immunotherapy were included. The associations between patient age or pathological findings and tumor recurrence were determined. Side effects were classified as minor or major and were analyzed on the basis of their incidences in each age group. RESULTS: The patients were divided into four age categories: younger than 55 (n= 86), 55-64 (n = 143), 65-74 (n = 132) and equal or older than 75 years (n = 86). The Kaplan-Meier curves of recurrence-free survival rates demonstrated that patients aged 55-64 had been continuously tumor-free than the equal or older than 75 group. The presence of previous bladder cancer and Grade 3 were independent predictors for tumor recurrence; however, patients' age was not selected. The incidence of fever was slightly higher and that of cystitis was lower in the younger group. CONCLUSIONS: Age does not certainly affect recurrence in patients with bladder cancer treated with bacille Calmette-Guerin therapy. The related side effects in the elderly patients were almost equal to those in the younger. With careful monitoring, bacille Calmette-Guerin therapy is safe even in elderly patients.

BACKGROUND: Laparoscopic single-site surgery has recently emerged in the field of urology and this minimally-invasive surgery has resulted in a further reduction in morbidity compared with traditional laparoscopy. We present our initial experience with laparoendoscopic single-site surgery of partial adrenalectomy (LESS-PA) to treat aldosterone-producing adenomas. CASE PRESENTATION: A 60-year-old woman was diagnosed with aldosterone-producing macroadenomas in the left adrenal and aldosterone-producing microadenomas in the right adrenal. A two-step operation was planned. The first step involved transumbilical LESS-PA for the left adrenal tumors. A multichannel port was inserted through the center of the umbilicus and the left adrenal gland was approached using bent instruments according to standard traditional laparoscopic procedures. The tumors were resected using an ultrasonic scalpel, and the resected site was coagulated using a vessel sealing instrument and then sealed with fibrin glue. Operative time was 123 minutes and blood loss was minimal. The patient was discharged from hospital within 72 hours. Her right adrenal microadenomas will be treated in the next several months. CONCLUSIONS: Although our experience is limited, LESS-PA appears to be safe and feasible for treating aldosterone-producing adenomas. More cases and comparisons with the multiport technique are needed before drawing any definite conclusions concerning the technique.

OBJECTIVES: To investigate whether a training system using a dry box is feasible for training young urologists. Despite laparoscopic surgery being widely indicated for several urological diseases, a laparoscopic training system for young urologists has not been fully established yet. However, the learning curve for laparoscopic surgery has not yet been ascertained. METHODS: We continued to test 11 sixth-year residents (postgraduate year: PGY6) and third-year residents (PGY3) in our department in terms of surgical skills using a dry box. We gave them several tasks (cutting and suturing) and let them practice until task completion. We continued to test all participants by these tasks for 16 weeks. RESULTS: At the beginning of the present study, the PGY6 residents achieved significantly better scores than the PGY3 residents. However, the difference between the 2 groups became insignificant over time. Furthermore, statistical analysis revealed that a practice time of 100 minutes per week was the only significant factor affecting the last test score. For the final test, the mean practice time for all participants was 79.1 minutes per week. CONCLUSIONS: These results suggest that laparoscopic surgical skills can definitely be polished by adequate voluntary practice.

OBJECTIVES: To investigate whether the occurrence of side effects or discontinuance of bacille Calmette-Guerin (BCG) therapy because of side effects is associated with its therapeutic efficacy. METHODS: We analyzed the data from 145 patients who had had nonmuscle-invasive bladder cancer (Stage pTa, pT1, or pTis) and had undergone an initial course of adjuvant BCG therapy after transurethral resection of bladder tumor from 1996 and 2006 at Keio University Hospital. Side effects were classified as minor and major, and the association between the occurrence of side effects or discontinuance of BCG therapy because of side effects and tumor recurrence or progression was analyzed. RESULTS: Side effects occurred in 106 patients (73.1%) during BCG instillation. Of these 106 patients, 38 had major side effects and 95 had minor; 27 patients had both. BCG therapy was discontinued in 19 patients (13.1%) because of severe hematuria in 2, high fever in 8, and severe lower urinary tract symptoms in 9. Multivariate analyses demonstrated that discontinuance of BCG therapy (P = .018) was an independent predictor for tumor recurrence, in addition to multiplicity (P = .043). However, the occurrence of side effects was not an independent predictor for tumor recurrence (P = .935). Multivariate analyses also demonstrated that neither discontinuance of BCG therapy (P = .308) nor the occurrence of side effects (P = .333) was an independent predictor for tumor progression. CONCLUSIONS: Discontinuation of BCG therapy has a significantly deleterious effect on reducing the incidence of tumor recurrence. When major side effects occur, it might be preferable to attempt to mitigate the major side effects to maintain the BCG therapy on schedule.

Papillary renal cell carcinomas (PRCCs) tend to metastasize to lymph nodes, while metastasis to the brain is extremely rare. We report the case of a man who had a brain metastasis of PRCC type 2. He was brought to our hospital due to the sudden onset of convulsions. Diagnostic imaging studies showed a metastatic brain tumor in the left parietal lobe, and a primary renal tumor in the right kidney, with paraaortal lymph node metastases. An excision of brain tumor was performed. The brain tumor had a papillary structure with eosinophilic cytoplasm. Five weeks later nephrectomy was carried out. Histological analysis of the nephrectomy specimen revealed the same papillary structure, which was compatible with PRCC type 2.