Choichiro Ozu

Induction of Apoptosis of Cytokine-Producing Bladder Cancer Cells by Adenovirus-Mediated I kappa B alpha Overexpression

We investigated whether the cell growth and apoptosis of multiple cytokine-producing bladder cancer cells can be regulated by nuclear factor kappaB (NF-kappaB). The bladder cancer cell line KU-19-19, obtained from a 76-year-old man who demonstrated marked leukocytosis, produces multiple cytokines and demonstrates autocrine growth by granulocyte colony-stimulating factor (G-CSF). Electrophoretic mobility shift assay (EMSA) revealed that NF-kappaB was activated in KU-19-19 but not in other bladder cancer cell lines (KU-1, KU-7, or T-24, respectively). The inhibition of NF-kappaB DNA-binding activity with adenovirus vectors expressing the stable form of the NF-kappaB inhibitor IkappaBalpha (multiplicity of infection [MOI] of 10) inhibited growth and induced apoptosis of KU-19-19, but not KU-1, KU-7, or T-24. The production of several cytokines was suppressed significantly in KU-19-19 by this gene delivery. Although dexamethasone (10 microM) could also suppress cytokine production, it did not induce dramatic cell death in KU-19-19 because it could not inhibit NF-kappaB activation stably and strongly. These results suggest that NF-kappaB activation maintains the cell viability as well as regulates cytokine production in cytokine-producing cancer cells and therefore these in vitro experiments support a rationale for preclinical in vivo studies to demonstrate growth inhibition in established tumors.

Prediction of bone metastases by combination of tartrate‐resistant acid phosphatase, alkaline phosphatase and prostate specific antigen in patients with prostate cancer

Objective:  The clinical value of serum tartrate‐resistant acid phosphatase (TRACP), prostate specific antigen (PSA), alkaline phosphatase (ALP), and prostatic acid phosphatase (PACP) for the prediction of bone metastases in prostate cancer were investigated.

Robotic Versus Open Radical Cystectomy: Prospective Comparison of Perioperative and Pathologic Outcomes in Japan

OBJECTIVE In Japan, no study has compared the perioperative outcomes observed between robot-assisted radical cystectomy (RARC) and open radical cystectomy (ORC). This study aimed at a prospective comparison of the perioperative outcomes between RARC and ORC performed by a single surgeon. METHODS Between 2008 and 2011, 26 bladder cancer patients underwent radical cystectomy by one surgeon, 11 robotically and 15 by open procedure. We prospectively collected perioperative and pathological data for these 26 patients, and retrospectively compared these two different surgical procedures. RESULTS The RARC cohort had a significant decrease in both estimated blood loss (656.9 vs. 1788.7 ml, P=0.0015) and allogeneic transfusion requirement (0 vs. 40%, P=0.0237). The total operative time was almost the same (P=0.2306) but increased duration of bladder removal and lymphadenectomy was observed in the RARC cohort (P=0.0049). Surgery-related complication rates within 30 days were not significantly different (P=0.4185). Positive surgical margin was observed in three patients in the ORC cohort and in one patient in the RARC cohort (P=0.4664). The RARC cohort had a larger number of removed lymph nodes than the ORC cohort, and the difference was statistically significant (20.7 vs. 13.8, P=0.0421). CONCLUSIONS We confirmed that RARC is safe and yields acceptable outcomes in comparison with ORC for the treatment of bladder cancer if it is performed by a surgeon who has experience of over 60 cases of robot-assisted radical prostatectomy. It is hoped that RARC will gain acceptance in Japan as a minimally invasive surgery for muscle-invasive bladder cancer.

Learning Curve and Perioperative Outcomes of Robot-Assisted Radical Prostatectomy in 200 Initial Japanese Cases by a Single Surgeon

PURPOSE The aim of the present study was to investigate the learning curve and perioperative outcomes in 200 consecutive patients with prostate cancer who underwent robot-assisted radical prostatectomy (RARP). PATIENTS AND METHODS Between August 2006 and August 2011, 200 patients with prostate cancer underwent RARP and were enrolled in this study. We prospectively collected the demographic data and analyzed the pathologic and functional outcomes. The operative outcomes analyzed were total operative time, estimated blood loss (EBL), positive surgical margin (PSM), incontinence, and perioperative complications. We also evaluated the relationship between the surgeons experience and operative variables. RESULTS The sloping learning curve for this surgeon showed that total operative time was strongly correlated with the accumulation of experience for the initial 25 cases (|rs|=0.71, P<0.001). The average EBL was not strongly correlated with additional experience (|rs|<0.7). The PSM rate for the first 50 cases was significantly higher than that of the next 150 cases (34.8% vs 19.4%, P=0.035). The complication rate among the first 50 patients was significantly higher than that among the remaining 150 patients (32% vs 12.7%, P=0.002). The incontinence rate at 12 months was significantly higher for the first 100 cases compared with that for the next 100 cases (9.0% vs 1.0%, P=0.009). For the surgeon to optimize total operative time, PSM rate, complication rate, and incontinence rate, slope learning curves of 25, 50, 50, and 100 cases were needed. CONCLUSIONS The functional and pathologic results of this minimally invasive procedure seemed to be promising. Distinct learning curves were observed with respect to operative time, PSM, complication rate, and incontinence rate. Exposure to 100 surgeries would be necessary for a surgeon to adequately master the required skills.

Acute aortic dissection in a patient with metastatic renal cell carcinoma treated with axitinib

axitinib is a potent, selective, second-generation inhibitor of vascular endothelial growth factor receptor (VEgFr) 1, 2, and 3, and has been approved for the treatment of advanced renal cell carcinoma after failure of one prior systemic therapy. Compared with first-generation tyrosine kinase inhibitors (TKis), such as sorafenib, axitinib is a more specific VEgFr inhibitor. The toxicity profile of axitinib is tolerable. Common adverse events of axitinib include diarrhea, hypertension, and fatigue, and they have also been reported after using other TKis. Other adverse events, such as palmar-plantar erythrodysesthesia, cutaneous toxicity, and myelosuppression, are less commonly reported after using axitinib than after using other TKis [1]. a 51-year-old man with a renal tumor, but without any other comorbidities including hypertension, underwent left radical nephrectomy. Pathological examination revealed the tumor as a pT3aN0M0 clear cell renal cell carcinoma. six months after surgery, multiple lung metastases were detected via thoracic computed tomography (CT), after which sunitinib was administered as a four-weeks-on and two-weeks-off schedule. sunitinib was discontinued owing to grade 3 palmar-plantar erythrodysesthesia after two cycles of treatment, and the patient was switched to axitinib. Ten days after receiving axitinib, he presented to the urology outpatient department with sudden midsternal pain. He looked well, and his blood pressure was 127/66 mmHg. an electrocardiogram showed sT-segment elevation in all leads. Contrast-enhanced thoracoabdominal CT revealed acute aortic dissection (stanford type a) from the ascending aorta to the left external iliac artery (Figure 1). The patient underwent emergency reconstruction of the ascending aorta. acute aortic dissection is a life-threatening entity. The most common predisposing factor is hypertension, followed by atherosclerosis, history of cardiac surgery, Marfan syndrome, and iatrogenic causes [2]. Hypertension is a frequent adverse event with axitinib and other small-molecule TKis. Other cardiovascular toxicities including heart failure, left ventricular systolic dysfunction, and QT prolongation have also been reported. The mechanism of TKiassociated cardiotoxicity remains poorly understood. Possible mechanisms include the loss of vascular stability because of endothelial cell damage or decreased production of nitric oxide through inhibition of VEgF pathways [3]. To our knowledge, this is the first case of acute aortic dissection in a patient treated with axitinib. Only two cases of aortic dissection during treatment with small-molecule multitargeted TKis (1 with sorafenib [4] and 1 with sunitinib [5]) were

The Initial Case Report: Salvage Robotic Assisted Radical Prostatectomy After Heavy Ion Radiotherapy

Salvage radical prostatectomy is one of treatments after radiation therapy to patients with prostate cancer. To date, no case of the salvage robotic assisted radical prostatectomy (RARP) following heavy ion radiotherapy (HIRT) has been published. We report on a 70-year-old man with a history of HIRT for prostate cancer in 2011. For 3 years after. HIRT, his serum PSA levels were permissible range. However, his PSA levels were increased. We had diagnosis localized prostate cancer after HIRT. We had carried out salvage RARP. Until 10 months after salvage RARP, his PSA level was not detectable.

Schmorl Nodes Mimicking Osteolytic Bone Metastases.

Bone is the third most common site of metastasis from upper tract urothelial carcinoma after radical nephroureterectomy. Although bone biopsy is the gold standard for the diagnosis of bone metastases, they can usually be diagnosed on the basis of imaging tests. We describe a case of upper tract urothelial carcinoma after radical nephroureterectomy presenting with a Schmorl node in the third lumbar vertebra, mimicking lytic bone metastasis. Differentiation of bone metastases from Schmorl nodes is essential for the appropriate management of patients with malignancy.