Noriyoshi Miura

Radiation Pneumonitis Caused by a Migrated Brachytherapy Seed Lodged in the Lung

We report a case of radiation pneumonitis caused by a migrated seed lodged in the lung after prostate brachytherapy. A 71-year-old man underwent transperineal interstitial permanent prostate brachytherapy for localized prostate cancer. On the day after brachytherapy, a routine postimplant chest X-ray revealed migration of one seed to the lower lobe of the left lung. After 1 month, pulmonary opacities were observed in the left lower lobe but not near the seed. He was diagnosed with bacterial pneumonia, and antibiotic therapy was commenced. Two months after brachytherapy, the patients symptoms, laboratory data and pulmonary opacities improved; however, an abnormal shadow (consolidation) developed around the migrated seed. Lung consolidation disappeared almost completely 12 months after brachytherapy without any medical treatment. The abnormal shadow probably represented radiation pneumonitis. To the best of our knowledge, this is the first report of radiation pneumonitis caused by a migrated brachytherapy seed in the lung.

Inhibition of bladder tumour growth by histone deacetylase inhibitor

To examine the expression profile of histone deacetylase (HDAC)‐1 and explore its potential role in the development of bladder cancer, using valproic acid (VPA), a HDAC inhibitor, which reduces tumour growth and metastasis formation in animal models.

Health-related Quality of Life using SF-8 and EPIC Questionnaires after Treatment with Radical Retropubic Prostatectomy and Permanent Prostate Brachytherapy

OBJECTIVE The health-related quality of life (HRQOL) after treatment of prostate cancer is examined using a new HRQOL tool. HRQOL, based on the expanded prostate cancer index composite (EPIC) and SF-8 questionnaires, was prospectively compared after either a radical retropubic prostatectomy (RRP) or a permanent prostate brachytherapy (PPB) at a single institute. METHODS Between October 2005 and June 2007, 96 patients were treated by an RRP and 88 patients were treated by a PPB. A HRQOL survey was completed at baseline, and at 1, 3, 6 and 12 months after treatment, prospectively. RESULTS The general HRQOL in the RRP and PPB groups was not different after 3 months. However, at baseline and 1 month after treatment, the mental component summary was significantly better in the PPB group than in the RRP group. Moreover, the disease-specific HRQOL was worse regarding urinary and sexual functions in the RRP group. Urinary irritative/obstructive was worse in the PPB group, but urinary incontinence was worse in the RRP group and had not recovered to baseline after 12 months. The bowel function and bother were worse in the PPB group than in the RRP group after 3 months. In the RRP group, the patients with nerve sparing demonstrated the same scores in sexual function as the PPB group. CONCLUSIONS This prospective study revealed the differences in the HRQOL after an RRP and PPB. Disease-specific HRQOL is clarified by using EPIC survey. These results will be helpful for making treatment decisions.

Docetaxel–Prednisolone Combination Therapy for Japanese Patients with Hormone-refractory Prostate Cancer: a Single Institution Experience

OBJECTIVE To evaluate the efficacy and toxicity of docetaxel plus prednisolone treatment in Japanese patients with hormone-refractory prostate cancer (HRPC). METHODS From April 2004 through August 2008, we used docetaxel plus prednisolone to treat 55 HRPC patients (median age, 72 years). Eighteen patients (32.7%) had measurable soft tissue lesions, whereas 52 patients (94.5%) had bone metastases. During the 21-day treatment cycle, docetaxel (70 mg/m(2)) was administered once every 21 days and oral prednisolone (5 mg), twice daily. Prostate-specific antigen (PSA) response, defined as a reduction of at least 50% in the baseline levels for 4 weeks, was evaluated. RESULTS The median follow-up period was 30.1 months; median overall survival, 15.3 months and median progression-free survival, 7.5 months. During follow-up, 37 patients (67.3%) achieved the PSA response, and 5 of 18 (27.8%) patients with measurable disease showed a partial response. Among the 27 patients who experienced cancer pain before treatment initiation, 15 (55.5%) reduced their analgesic drug intake. Multivariate analysis of the prognostic variables revealed a significant association between the overall survival and pain (P = 0.033). Hematological toxicity (grades 3-4) included neutropenia (87.3%), febrile neutropenia (25.5%) and thrombocytopenia (5.5%). Frequent non-hematological adverse events were general edema (52.7%), general fatigue (32.7%) and sensory neuropathy (30.9%). Three patients died of adult respiratory distress syndrome (ARDS). CONCLUSION Docetaxel plus prednisolone treatment is effective in Japanese HRPC patients. The main toxicity is neutropenia, which can be safely controlled by outpatient treatment with granulocyte-colony stimulating factor. However, the Japanese patients in our study developed ARDS more frequently than other patients in previous studies did.

Adseverin: A novel cisplatin-resistant marker in the human bladder cancer cell line HT1376 identified by quantitative proteomic analysis

Cisplatin is currently the most effective antitumor agent available against bladder cancer. However, a majority of patients eventually relapse with cisplatin‐resistant disease. Chemoresistance thus remains a major obstacle in bladder cancer therapy. To clarify the molecular mechanisms underlying cisplatin resistance in bladder cancer, we established a cisplatin‐resistant subline from the human bladder cancer cell line HT1376 (HT1376‐CisR), and conducted large‐scale analyses of the expressed proteins using two‐dimensional (2D) gel electrophoresis coupled with mass spectrometry (MS). Comparative proteomic analysis of HT1376 and HT1376‐CisR cells revealed 36 differentially expressed proteins, wherein 21 proteins were upregulated and 15 were downregulated in HT1376‐CisR cells. Among the differentially regulated proteins, adseverin (SCIN), a calcium‐dependent actin‐binding protein, was overexpressed (4‐fold upregulation) in HT1376‐CisR, with the increase being more prominent in the mitochondrial fraction than in the cytosol fraction. SCIN mRNA knockdown significantly reduced cell proliferation with mitochondria‐mediated apoptosis in HT1376‐CisR cells. Immunoprecipitation analysis revealed voltage‐dependent anion channels (VDACs) to be bound to SCIN in the mitochondrial fraction. Our results suggest that the VDAC‐SCIN interaction may inhibit mitochondria‐mediated apoptosis in cisplatin‐resistant cells. Targeting the VDAC‐SCIN interaction may offer a new therapeutic strategy for cisplatin‐resistant bladder cancer.

Long‑term exposure to leptin enhances the growth of prostate cancer cells.

Obesity correlates with an increased risk of developing prostate cancer (PCa) and leptin plays an important role in PCa progression. Since leptin is produced by adipocytes, the serum leptin level is higher in obese than in non-obese individuals. However, the effects of leptin remain controversial and unclear. The aim of the present study was to investigate the effect of leptin on PCa cell aggressiveness. Three human PCa cell lines (LNCaP, DU145 and PC-3) were treated with recombinant leptin for 28 days. Cell proliferation, migration, and invasion were estimated using the WST assay, a wound-healing assay, and a BD Matrigel invasion assay, respectively. The mechanism underlying the proliferative effect of leptin was investigated by cell transfections with small interfering RNA (siRNA) against the leptin receptor (ObR) or forkhead box O1 (FOXO1), and by immunocytochemistry. Long-term exposure of PCa cells to leptin enhanced their proliferation, migration and invasion. Leptin increased ObR expression and enhanced Akt phosphorylation constitutively. Leptin also increased the phosphorylation of FOXO1 via PI3K signaling and FOXO1 gene silencing enhanced PCa cell proliferation. Leptin induced the translocation of FOXO1 from the nucleus to the cytoplasm. Furthermore, the PI3K inhibitor, LY294002 suppressed this translocation. These results suggested that leptin regulated the subcellular localization of FOXO1 and induced Akt phosphorylation. Additionally, we revealed that leptin increased the expression of cyclin D1 and decreased the expression of p21 protein. In conclusion, long-term exposure to leptin increased the cell proliferation, migration, and invasion of PCa cells through inactivation of FOXO1. This inactivation resulted from exclusion of FOXO1 from the nucleus and its restriction to the cytoplasm through PI3K/Akt signaling. Our findings contribute to an understanding of the association between obesity and PCa aggressiveness.

Bladder preservation therapy conducted by intra-arterial chemotherapy and radiotherapy for muscle invasive bladder cancer.

OBJECTIVE A previous paper reported favorable results of intra-arterial chemotherapy in combination with radiotherapy for muscle-invasive bladder cancer. The current study will update those results. METHODS Between January 1992 and December 2006, 94 patients with confirmed muscle invasion were treated with intra-arterial chemotherapy and concurrent radiotherapy after an initial complete transurethral resection. Intra-arterial chemotherapy consisted of cisplatin (Days 1-3) and pirarubicin (Days 8-10), and radiation was administered with the chemotherapy (2 Gy/session) with a total dosage of 44 Gy. The median age was 67.0 years. There were 60 patients in T2, 19 patients in T3 and 15 patients in T4. The median follow-up period was 72.9 months in the survivors. RESULTS Among these patients, 84 patients (89.4%) obtained a complete response (CR) and 10 patients did not achieve a CR. Between the CR and non-CR patients, the clinical stage and the existence of hydronephrosis were significantly different. The cause-specific survival rates at 5 and 10 years were 76.2% and 67.5%, respectively. The overall survival rates at 5 and 10 years were 66.6% and 47.4%, respectively. A Cox proportional hazard model showed that only the cause-specific survival rate was associated with a CR after treatment. The bladder preservation rates were 89.7% at 5 years and 87.6% at 10 years. Myelosuppression was the major adverse event but it was manageable. Non-hematological sever adverse events were rare. CONCLUSIONS Bladder preservation therapy shows good survival and good bladder preservation rates. Clinical stage T2 and the absence of hydronephrosis are favorable factors.

A Prospective Longitudinal Study Comparing a Radical Retropubic Prostatectomy and Permanent Prostate Brachytherapy Regarding the Health-related Quality of Life for Localized Prostate Cancer

OBJECTIVE The health-related quality of life (HRQOL) after a radical retropubic prostatectomy (RRP) or a permanent prostate brachytherapy (PPB) was prospectively compared at a single institute. METHODS Between 2003 and 2005, 122 patients were treated by RRP and 82 patients were treated by PPB. A QOL survey was completed at baseline, and 1, 3, 6 and 12 months after treatment, prospectively. RESULTS The general HRQOL was not different between the RRP and PPB groups after 3 months. However, at 1 month after treatment, the general HRQOL scores, except for general health, were significantly better in the PPB group than that in the RRP group. Moreover, the disease-specific QOL was worse in urinary and sexual functions in the RRP group. Urinary function in the RRP group had not recovered to baseline after 12 months. Although the urinary function in the PPB group was better than that of the RRP group, urinary bother continued to worsen until 6 months and thereafter it recovered gradually. The bowel function was not worse in the PPB group but bowel bother was worse at 6 months in the PPB group. In the RRP group, the patients with nerve sparing demonstrated better in sexual function than those without nerve sparing, but the recovery did not reach the level of the PPB group. CONCLUSIONS This prospective study revealed the differences in the QOL after RRP and PPB. These results will be helpful for making treatment decisions.

Health-related quality of life after bladder preservation therapy for muscle invasive bladder cancer

Objective:  To assess health‐related quality of life (QOL) of bladder cancer patients following bladder preservation therapy (BPT).

Modified FOLFOX6 Chemotherapy in Patients with Metastatic Urachal Cancer

Background: To improve the prognosis of patients with urachal cancer and establish an effective chemotherapeutic regimen for distant metastases. Methods: We conducted a retrospective study to evaluate the efficacy and safety of a modified combination of 5-fluorouracil, leucovorin and oxaliplatin (mFOLFOX6) therapy in patients with metastatic urachal cancer. Results: Five patients were treated with mFOLFOX6. Their median age was 65 years (range 41-80). The median follow-up time was 42 months (range 18-46). Two of the 5 patients (40%) showed an objective response: 1 achieved a clinically complete response and 1 a partial response. The grade 3/4 toxicity associated with this regimen was primarily neutropenia, but febrile neutropenia was not observed. Oxaliplatin treatment was discontinued because of a grade 2 allergic reaction in 1 patient. Grade 2 peripheral sensory neuropathy caused by oxaliplatin was observed in 2 patients, and the OPTIMOX (stop and go) approach had to be adopted. Conclusions: mFOLFOX6 appears to be effective for the treatment of metastatic urachal cancer.