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Sasebo, Japan

Igawa T.,Nagasaki University | Tsurusaki T.,Red Cross | Nomata K.,Nagasaki Municipal Hospital | Hayashi M.,Nagasaki Medical Center | And 2 more authors.
Anticancer Research

Aim: To determine the treatment outcome of combined androgen blockade (CAB) therapy using the nonsteroidal antiandrogen bicalutamide or the steroidal antiandrogen chlormadinone in patients with prostate cancer. Patients and Methods: In total, 124 patients with prostate cancer enrolled in the present study were randomized to receive CAB therapy using a gonadotropin-releasing hormone (GnRH) agonist, combined with bicalutamide or chlormadinone. The survival of patients was analyzed. Results: The 5-year cancer-specific survival for the bicalutamide- and chlormadinone-treated groups were 91.7% and 86.6%, respectively, with no significant difference (p=0.39). Five-year overall survival was significantly (p=0.029) better in the bicalutamide-treated group. Moreover, M1 patients in the chlormadinone group had significantly lower cancer-specific and overall survival compared to those in the bicalutamidetreated group. However, in the case of M0 patients, no significant difference in cancer-specific nor in overall survival was observed. Conclusion: CAB therapy using chlormadinone led to a significantly poorer survival outcome versus the use of bicalutamide. However, because this survival trend was not observed in M0 cases, chlormadinone may still be an option for CAB therapy, depending on clinical stage and the severity of adverse effects, such as hot flashes. Source

Miura T.,Nagasaki University | Eishi K.,Nagasaki University | Yamachika S.,Inoue Hospital | Hashizume K.,Nagasaki University | And 6 more authors.
General Thoracic and Cardiovascular Surgery

Purpose: The aim of this study was to determine the mechanism of systolic anterior motion (SAM) after mitral valve (MV) repair by analyzing the clinical data of patients with MV repair. Methods: A total of 104 MV repairs were performed for patients with isolated degenerative posterior leaflet prolapse. Eight patients (7.7%) developed SAM with severe mitral regurgitation. We compared the preoperative and intraoperative findings of the two groups (8 patients in the SAM group, 96 in the non-SAM group) and reported the clinical courses of the SAM patients. Results: Preoperative left ventricular end-diastolic and end-systolic diameters were significantly smaller and the preoperative left ventricular ejection fraction was significantly greater in the SAM group than in the non-SAM group. The number of patients with a sigmoid septum and the number with anterior leaflet-septal contact (LSC) during diastole were significantly larger in the SAM group. Incidence of billowing posterior leaflet, prolapsed segments, and operative techniques were comparable for the two groups. SAM improved with correction of hemodynamic status in four patients. In four other patients secondary cardiopulmonary bypass was required to resolve SAM. SAM resolved with additional repairs in two patients, whereas the other two required MV replacement. Of the six patients in whom conservative treatment or re-repair was successful, one had recurrent SAM 3 months after surgery. Conclusion: The sigmoid septum and LSC may predict SAM after MV repair. A strict follow-up is imperative for patients with persistent or recurrent SAM. © 2011 The Japanese Association for Thoracic Surgery. Source

Nakamura Y.,Nagasaki University | Sano K.,Meiji Pharmaceutical University | Soda H.,Sasebo General Hospital | Takatani H.,Red Cross | And 6 more authors.
Journal of Thoracic Oncology

Introduction: We assessed the relationship between the plasma concentration of gefitinib and its efficacy in Japanese patients with advanced non-small cell lung cancer (NSCLC). Methods: Plasma trough levels of gefitinib were measured on days 3 (D3) and 8 (D8) by high-performance liquid chromatography in 44 patients with advanced NSCLC treated with 250 mg gefitinib daily. Eligibility criteria included performance status ≤3, age ≤ 80 years, and stages IIIB-IV cancer. Epidermal growth factor receptor mutations in 23 patients were analyzed retrospectively. Results: The median plasma gefitinib values were 662 ng/ml on D3 and 1064 ng/ml on D8, and the D8/D3 ratio was 1.587. The median progression-free survival (PFS) was 71 days, and the median overall survival was 224 days. Adenocarcinoma, never smoking, and high D8/D3 ratio were associated with better PFS. Multivariate analysis showed that PFS was associated with never smoking and high D8/D3 ratio. Never-smokers with a high D8/D3 ratio showed the best PFS. Overall survival was not associated with the D8/D3 ratio. Epidermal growth factor receptor mutation analysis of 23 patients showed that 15 patients had exon 19 deletion and/or exon 21 point mutation. Median PFS was similar between mutation-positive and mutation-negative individuals in the high D8/D3 group, whereas mutation-negative individuals in the low D8/D3 group showed the worst median PFS. Conclusions: A high D8/D3 ratio was independently associated with better PFS in patients with NSCLC treated with gefitinib. Our findings suggest that the pharmacokinetics of gefitinib may be involved in its antitumor activity. © 2010 by the International Association for the Study of Lung Cancer. Source

Yamaguchi H.,Nagasaki University | Soda H.,Sasebo General Hospital | Nakamura Y.,Nagasaki University | Takasu M.,Nagasaki University | And 10 more authors.
Cancer Chemotherapy and Pharmacology

Purpose: Gefitinib is an epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) that has dramatic effects in selective patients with non-small cell lung cancer (NSCLC). A simple non-invasive method for predicting the efficacy of gefitinib is preferable in clinical settings. In this study, we evaluated prospectively whether surfactant protein-A (SP-A) and-D (SP-D) may be new conventional predictors of the efficacy of gefitinib treatment. Methods: We measured serum SP-A and SP-D levels on days 0 and 29 in 40 patients with advanced NSCLC treated with 250 mg gefitinib daily. Eligibility criteria included performance status ≤3, age ≤80 years, and stage IIIB-IV disease. In addition, EGFR mutations were analyzed in 24 patients. Results: Multivariate analysis showed that favorable progression-free survival (PFS) after gefitinib treatment was associated with adenocarcinoma and high serum SP-D levels before treatment. EGFR mutation analysis of 24 patients showed that 16 patients had exon 19 deletion and/or exon 21 point mutations. EGFR mutations were significantly correlated with response to gefitinib and serum SP-D levels before treatment was significantly high in patients with the EGFR mutations. Serum SP-A levels were not associated with PFS. Conclusions: The present study showed that measurement of serum SP-D levels before treatment in patients with NSCLC may be a new surrogate marker for predicting the response to gefitinib. © Springer-Verlag 2010. Source

Fukuda Mi.,Red Cross | Nakamura Y.,Nagasaki University | Kinoshita A.,Nagasaki Prefecture Shimabara Hospital | Soejima Y.,Ureshino Medical Center | And 10 more authors.
Cancer Chemotherapy and Pharmacology

Background Irinotecan and cisplatin are one of active regimens for patients with extensive-stage small cell lung cancer (SCLC). To determine the efficacy and toxicity of irinotecan and cisplatin with concurrent split-course thoracic radiotherapy in limited-disease (LD) SCLC, we conducted a phase II study. Patients and methods Thirty-four patients fulfilling the following eligibility criteria were enrolled: chemotherapynai ̈ve, good performance status (PS 0-1), age ≤75, LDSCLC, and adequate organ function. The patients received irinotecan 40 mg/m2 i.v. on days 1, 8, and 15, and cisplatin 60 mg/m2 i.v. on day 1. Four cycles of chemotherapy were repeated every 4 weeks. Split-course thoracic radiotherapy of once-daily 2 Gy/day commenced on day 2 of each chemotherapy cycle, with 26 and 24 Gy administered in the first and second cycles, respectively. Results Thirty-four patients were eligible and assessable for response, toxicity, and survival. Patients' characteristics were as follows: male/female = 29/5; PS 0/1 = 18/16; median age (range) = 67 (50-73); and stage IB/IIA/IIB/ IIIA/IIIB = 2/2/3/16/11. The overall response was 100 % (CR 8, PR 26). Grade 4 leukopenia, neutropenia, grade 3-5 pneumonitis, diarrhea, and esophagitis occurred in 24, 38, 6, 3, and 0 %, respectively. There were 2 treatment-related deaths from pneumonitis. The median time to tumor progression was 14.3 months. The median overall survival time and the 2- and 5-year survival rates were 44.5 months, 66.7 and 46.1 %, respectively. No tumor progression was observed in patients with CR. Conclusion Irinotecan plus cisplatin with concurrent split-course thoracic radiotherapy was effective and tolerable in untreated LD-SCLC. © Springer-Verlag 2012. Source

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