Akitomi Shirato

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.

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.

Tertiary Gleason pattern 5 and oncological outcomes after radical prostatectomy.

OBJECTIVES This study examined the rate of Gleason pattern 5 and the influence of tertiary Gleason pattern 5 on oncological outcomes. METHODS Four hundred sixty-six patients underwent a radical prostatectomy between 1993 and 2008. Each surgical specimen was reviewed and assessed for the tumor diameter, Gleason score (which was based on the 2005 International Society of Urological Pathology Consensus Conference criteria) and the percentage of Gleason pattern 5. RESULTS The median patient age was 68.0 years old and the median prostate-specific antigen level was 9.28 ng/ml. A tertiary Gleason pattern 5 was present in 24.2% of patients with a Gleason score of <9; in 12.2% of patients with a Gleason score of 3 + 4 and in 45.9% of patients with a Gleason score of 4 + 3. A multivariate analysis showed that a tertiary Gleason pattern 5 was not independently associated with biochemical recurrence-free survival among patients in the Gleason score of 7 and 8 pN0 groups. One hundred eighty-seven patients had any rate of Gleason pattern 5 and significantly worse pathological factors, compared with patients who did not have this pattern. A multivariate analysis of all patients showed that the surgical margin, Gleason score, prostate-specific antigen level and pathological stage were all independent predictors of biochemical recurrence. However, the rate of Gleason pattern 5 was not an independent factor. CONCLUSIONS Tertiary Gleason pattern 5 was not a significant predictive factor for biochemical recurrence. The rate of Gleason pattern 5 was associated with adverse pathological factors.

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).

Phase I Clinical Study of the Dietary Supplement, Agaricus blazei Murill, in Cancer Patients in Remission

Although many cancer patients use complementary and alternative medicine, including Agaricus blazei Murill (ABM), safety is not yet well understood. Cancer survivors took 1.8, 3.6, or 5.4 g ABM granulated powder (Kyowa Wellness Co., Ltd., Tokyo, Japan) per day orally for 6 months. Adverse events were defined by subjective/objective symptoms and laboratory data according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 3.0 (NCI-CTCAE v3.0). Seventy-eight patients were assessed for safety of ABM (30/24/24 subjects at 1/2/3 packs per day, resp.). Adverse events were observed in 9 patients (12%). Most were digestive in nature such as nausea and diarrhea, and one patient developed a liver dysfunction-related food allergy, drug lymphocyte product. However, none of these adverse events occurred in a dose-dependent manner. This study shows that ABM does not cause problems in most patients within laboratory parameters at the dosages tested over 6 months. This trial supports previous evidence that the ABM product is generally safe, excluding possible allergic reaction.

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.

Cisplatin resistance by induction of aldo-keto reductase family 1 member C2 in human bladder cancer cells

Cisplatin is currently the most effective anti-tumor agent available against bladder cancer. To clarify the mechanism underlying cisplatin resistance in bladder cancer, the present study examined the role of the aldo-keto reductase family 1 member C2 (AKR1C2) protein on chemoresistance using a human bladder cancer cell line. The function of AKR1C2 in chemoresistance was studied using the human HT1376 bladder cancer cell line and the cisplatin-resistant HT1376-CisR subline. AKR1C2 was expressed in HT1376-CisR cells, but not in the parental cells. The effect of small interfering (si) RNAs and an inhibitor targeting AKR1C2 was examined to determine whether cisplatin sensitivity can be rescued by blocking AKR1C2 expression or function. Silencing of AKR1C2 mRNA or inhibition of AKR1C2 by 5β-cholanic acid resulted in a decrease in the survival of cells following cisplatin exposure. Intracellular accumulation of reactive oxygen species (ROS) was determined using a 2,7-dichlorodihydrofluorescein diacetate (H2DCFDA) fluorescent probe. Cisplatin exposure increased the level of intracellular ROS in HT1376 cells in a dose-dependent manner. The ROS levels in HT1376-CisR cells were significantly lower than those in HT1376 cells and knockdown of AKR1C2 mRNA significantly restored ROS levels. Cisplatin exposure did not increase intracellular ROS in HT1376-CisR cells, although the level of intracellular ROS increased in HT1376 cells following cisplatin exposure. Silencing of AKR1C2 mRNA restored the ROS increase response to cisplatin and menadione as an oxidative stressor in HT1376-CisR cells. Menadione has the function of an oxidative stressor. The silencing of AKR1C2 mRNA restored the increased ROS response to cisplatin and menadione in HT1376-CisR cells. These results indicate that induction of AKR1C2 in human bladder cancer cells aids in the development of cisplatin resistance through antioxidative effects. The results of this study indicate that AKR1C2 may be an effective molecular target for restoring cisplatin resistance.