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Maeda H.,National Hospital Organization Toneyama Hospital | Matsumura A.,Kinki Chuo Chest Medical Center | Kawabata T.,NHO Okinawa Hospital | Suito T.,NHO Ibaraki Higashi Hospital | And 4 more authors.
European Journal of Cardio-thoracic Surgery | Year: 2012

OBJECTIVES: An adenosquamous carcinoma (ASC) of the lung is a relatively rare tumor. In this multi-institutional cohort study, we tested the hypothesis that an ASC exhibits more aggressive clinical behavior as compared to adenocarcinoma (AC) and squamous cell carcinoma (SC). METHODS: This retrospective cohort study used a prospective database produced by the Japan National Hospital Organization Study Group for Lung Cancer over a 7-year period (operations from 1997 to 2003, follow-up data until March 2010). During that period, 4668 cases underwent an operation for various types of primary malignant lung tumors. When a sample from a tumor comprised at least 20% each of SC and AC, the case was classified as ASC. Pathologic staging was done according to the seventh edition of the International Union against Cancer (UICC) Tumor Node Matastasis (TNM) classification of malignant tumors. RESULTS: We identified 114 patients with ASC (2.4%), 2993 withAC (64.2%), and 1369 with SC (29.3%). Kaplan-Meier survival curves for all stage cases, p-stage IA, IB, and IIIA tumors indicated that ASC cases had the least favorable survival. The 5-year survival rates for all stage cases were 23.3% for ASC, 58.0% for AC (p < 0.0001), and 40.8% for SC (p < 0.0001). The 5-year survival rates for p-stage IA were 42.0%for ASC, 81.8% for AC (p = 0.0005), and 63.4% for SC not significant (NS), while those for p-stage IB were 19.3%, 65.3% (p = 0.0024), and 46.8% (NS), respectively, and those for p-stage IIIA were 17.8%, 24.8% (p = 0.0154), and 18.8% (NS), respectively. There was a tendency for greater survival differences between ASC and AC in earlier tumor stages. A step-wise multivariable model demonstrated that sex, age, performance status, histology, tumor size, p-stage, operative method,and neoadjuvant/adjuvant therapy were independent prognostic factors. CONCLUSION: ASC of the lung is more aggressive than AC and SC. The decreased survival of patients with ASC as compared with either of those single histology tumors suggests the need for a clinical trial of adjuvant chemotherapy that includes early-stage patients. © The Author 2011. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.


Ose N.,Osaka University | Ose N.,National Hospital Organization Toneyama Hospital | Sawabata N.,Osaka University | Minami M.,Osaka University | And 4 more authors.
European Journal of Cardio-thoracic Surgery | Year: 2012

Objectives: Positron emission tomography with 2-[18F] fluoro-2-deoxy-. d-glucose as a tracer and computed tomography (FDG-PET/CT) are utilized for the diagnosis of lymph node (LN) metastasis from lung cancer. In this study, we analyzed the diagnostic ability of FDG-PET for N staging by focusing on the clinical features of false-positive (FP) and false-negative (FN) cases. Methods: From March 2006 to February 2010, 112 patients underwent preoperative examinations using FDG-PET/CT followed by radical resection with hilar and mediastinal dissection. We analyzed their clinicopathological characteristics based on preoperative FDG-PET/CT findings and post-operative histopathological diagnosis of resected LNs. Results: Based on the PET/CT results, 17 patients were misdiagnosed (9 FN and 8 FP). The sensitivity, specificity, accuracy and negative and positive predictive values for N1/N2 were 50.0, 94.5, 84.0, 93.0 and 58.3%, respectively, whereas those for N2 were 57.8, 90.3, 84.8, 90.3 and 61.1%, respectively. FP findings more frequently occurred in cases with elevated white blood cell (WBC) count (P = 0.015) and smokers (P = 0.04). In the FN group, the maximum standardized uptake value for the primary tumour was lower than that in the true-positive (TP) group (P = 0.01). The short-axis sizes of 71 LNs differently diagnosed by PET/CT and histopathology findings were significantly smaller in the FN group than the TP group (P < 0.001), whereas there was no difference between TP and FP. As for FN LNs in the TP group, there was no significant difference. Conclusions: PET/CT showed a good ability to detect metastatic LNs, especially for N2 diagnosis. However, there were some limitations, especially in cases with elevated peripheral WBC count and/or smoking history. © The Author 2012. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.


Nojiri T.,National Hospital Organization Toneyama Hospital | Nojiri T.,Osaka University | Inoue M.,Osaka University | Maeda H.,National Hospital Organization Toneyama Hospital | And 5 more authors.
European Journal of Cardio-thoracic Surgery | Year: 2013

OBJECTIVES: Lung cancer patients with chronic obstructive pulmonary disease are at an increased risk of respiratory and cardiovascular complications after pulmonary resection. The objective of the present study was to evaluate the clinical effects of low-dose human atrial natriuretic peptide (hANP) on postoperative cardiopulmonary complications in untreated chronic obstructive pulmonary disease patients undergoing lung cancer surgery. METHODS: Of 824 patients who underwent an elective pulmonary resection procedure for lung cancer in two specialized thoracic centres between 2008 and 2011, 202 consecutive patients who had airflow limitation before surgery were included in this retrospective study. The results were compared between patients who did and those who did not receive hANP during the perioperative period. The primary endpoint was the incidence of postoperative cardiopulmonary complications. Postoperative haemodynamics, white blood cell (WBC) counts and C-reactive protein (CRP) levels were also examined. Furthermore, propensity score matching analysis was used to reduce treatment selection bias from patient characteristics. RESULTS: The incidence of postoperative cardiopulmonary complications was significantly lower in the hANP group than in the control group (14 vs 36%, P < 0.01). The propensity score matching analysis confirmed the significantly decreased frequency of postoperative cardiopulmonary complications in the hANP group. Patients in the hANP group showed significantly lower WBC counts and serum CRP levels postoperatively. CONCLUSIONS: Treatment with hANP during the perioperative period had a prophylactic effect against postoperative cardiopulmonary complications in chronic obstructive pulmonary disease patients undergoing lung cancer surgery. Trial registration number: JPRN-UMIN000003631. © The Author 2012. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery.


Maekura R.,National Hospital Organization Toneyama Hospital | Hiraga T.,National Hospital Organization Toneyama Hospital | Miki K.,National Hospital Organization Toneyama Hospital | Kitada S.,National Hospital Organization Toneyama Hospital | And 3 more authors.
Respiratory Care | Year: 2014

BACKGROUND: Patients with COPD have reduced exercise tolerance associated with dyspnea. This exercise intolerance is primarily due to impaired ventilatory mechanics, but it is also associated with a combination of factors, including inefficient gas exchange, lactic acidosis at a low work rate, and exercise-induced hypoxemia. The survival prognosis of COPD patients with severely reduced exercise capacity is extremely poor, but the pathophysiology of these patients during exercise remains to be accurately established. The present study aimed to characterize life-threatening factors such as hypoxemia, acidosis, and sympathetic activation during exercise in these patients. METHODS: We monitored changes in life-threatening factors and compared these factors among quartile groups, defined according to their peak oxygen uptake status. Ninety-one COPD subjects (82 males, 9 females, average age 69.7 ± 6.8 y) consecutively underwent incremental cardiopulmonary exercise testing using a cycle ergometer. Arterial blood gases, lactate, and catecholamines were measured during cardiopulmonary exercise testing. RESULTS: The pathophysiology of the COPD differed among the 4 subject groups. Subjects with the most severely reduced exercise capacity (peak oxygen uptake ≤ 623 mL/min) were characterized by exercise-induced steep decrease in PaO2 slope (-78 ± 70 mm Hg/L/min), rapid progression of respiratory acidosis, little change in lactic acidosis, and sympathetic activation at low-intensity work load (plasma norepinephrine 1.41 ± 0.94 ng/mL at 20 watts work load), in addition to the limitation of increase in ventilation and impaired gas exchange. CONCLUSIONS: The mechanisms of exercise intolerance in COPD patients significantly differed among subjects with different exercise capacities. Subjects with the most severely reduced exercise capacity had the characteristics of exercise-induced hypoxemia, sympathetic overactivity, and progressive respiratory acidosis at low-intensity exercise. These life-threatening pathophysiological conditions could be improved by medication and/or pulmonary rehabilitation. © 2014 Daedalus Enterprises.


Yoshimura K.,National Hospital Organization Toneyama Hospital | Maekura R.,National Hospital Organization Toneyama Hospital | Hiraga T.,National Hospital Organization Toneyama Hospital | Miki K.,National Hospital Organization Toneyama Hospital | And 4 more authors.
COPD: Journal of Chronic Obstructive Pulmonary Disease | Year: 2014

The survival rate of chronic obstructive pulmonary disease (COPD) patients with severely reduced exercise capacity is extremely low. We recently identified three life-threatening pathophysiological conditions during cardiopulmonary exercise testing (CPET): (1) exercise-induced hypoxemia, (2) sympathetic overactivity, and (3) progressive respiratory acidosis at low-intensity exercise. The present prospective observation study aimed to determine whether these parameters constitute risk factors of mortality in moderate-to-very severe COPD. Ninety-six COPD patients were followed-up, monthly, for >3 years. Subsequently, spirometry and CPET were performed to examine parameters of exercise-induced hypoxemia ([PaO2 slope, mmHg/L·min-1] = Decrease in PaO2/ΔVO2 (Difference in ΔVO2 between at rest and at peak exercise)), progression of acidosis ([ΔpH/ΔVO2,/L·min-1] = Decrease in pH/ΔVO2), and sympathetic overactivity ([Δnorepinephrine (NE)/ΔVO2, ng/mL/L·min-1] = Increase in NE/ΔVO2). Univariate analysis revealed a significant association between the three conditions with increased mortality. Kaplan-Meier analysis showed that the quartile combining the steepest PaO2 slope (≤-55 mmHg/ ΔVO2 [L/min]), steepest decrease in arterial blood pH (≤ -1.72/ΔVO2 [L/min]), and most rapid increase in plasma NE level (≥ 5.2 ng/VO2 [L/min]) during incremental exercise was associated with higher all-cause mortality. These conditions showed cumulative effects on COPD patients' survival. Multivariate analyses revealed that these three life-threatening factors are also independent predictors of mortality based on age, heart rate and PaO2 at rest, body mass index, and forced expiratory volume in 1 s. Thus, these new exercise-induced mortality risk factors may lead to more efficient pulmonary rehabilitation programs for COPD patients based on patient-specific exercise-induced pathophysiological profiles. Copyright © Informa Healthcare USA, Inc.


Funakoshi Y.,National Hospital Organization Toneyama Hospital | Takeuchi Y.,National Hospital Organization Toneyama Hospital | Kusumoto H.,National Hospital Organization Toneyama Hospital | Kimura T.,National Hospital Organization Toneyama Hospital | Maeda H.,National Hospital Organization Toneyama Hospital
Journal of Cancer Research and Clinical Oncology | Year: 2012

Objective Patients with pathologic N2 non-small cell lung cancer comprise a heterogeneous group. The objective of this study was to evaluate which subgroup of patients with pathologic N2 benefit from surgery in terms of survival probability. Methods This retrospective study included 141 patients who had undergone major resection with pathologically proven N2 from 1990 to 2006 (103 with adenocarcinoma, 38 with squamous cell carcinoma). Patients undergoing preoperative induction therapy were excluded. Records were examined for age, gender, tumor size, surgical procedure, surgical side, clinical N status, primary tumor lobe, curative resection, and metastatic N2 stations. Results In patients with adenocarcinoma, surgical procedure, clinical N status, curative resection, and metastatic N2 stations were significant prognostic factors in univariate analysis. Age and curative resection were significant factors in patients with squamous cell carcinoma. In multivariate analysis, clinical N2 (P = 0.003), incomplete resection (P = 0.04), and multi-station N2 (P = 0.004) were significant adverse prognostic factors in patients with adenocarcinoma, whereas only incomplete resection (P = 0.002) was significant in patients with squamous cell carcinoma. For adenocarcinoma patients with pathologic N2, the 5-year survival rates were 58.8% for clinical N0-1 and single-station N2, 50% for clinical N2 and singlestation N2, 23.9% for clinical N0-1 and multi-station N2, and 0% for clinical N2 and multi-station N2. Conclusions Prognosis of patients with pathologic N2 can be grouped according to clinical N status and metastatic N2 stations in adenocarcinoma, but not in squamous cell carcinoma. Only adenocarcinoma patients with pathologic N2 appear to have heterogeneous subgroups with different prognoses. © Springer-Verlag 2012.


Funakoshi Y.,National Hospital Organization Toneyama Hospital | Maeda H.,National Hospital Organization Toneyama Hospital | Takeda S.-I.,National Hospital Organization Toneyama Hospital | Nojiri T.,National Hospital Organization Toneyama Hospital | Kawamura T.,National Hospital Organization Toneyama Hospital
Lung Cancer | Year: 2010

Objective: Pathological examination of lung cancer often reveals a more advanced stage than clinical stage. The objective of this study was to evaluate whether the association between clinical and pathologic stages depends on tumor histology. Methods: This retrospective study enrolled patients who had undergone major lung resections and systemic lymph node dissections (1990-2004). In total, 483 patients had adenocarcinoma and 225 had squamous cell carcinoma. Results: Clinical and pathologic N-status were significantly different in patients with adenocarcinoma (p<0.0001) but not in those with squamous cell carcinoma. Patients with adenocarcinoma were more likely to be upstaged from clinical N0 disease to pathologic N2 disease than those with squamous cell carcinoma (p=0.04). Of those patients with adenocarcinoma, surgical procedure, clinical N-status, metastatic pathologic N2 stations and curability were significant prognostic factors. It is of interest, however, that a similar statistically significant difference could not be shown in patients with squamous cell carcinoma. Furthermore, multivariate analysis demonstrated that clinically detectable N2 disease and multiple pathologic N2 stations significantly affected the poorer prognosis in adenocarcinoma. Adenocarcinoma patients with clinically undetectable N2 disease had significantly better 5-year survival than those with clinically detectable N2 disease (p<0.0001), although this was not the case for patients with squamous cell carcinoma (p=0.81). Conclusion: In adenocarcinoma patients with pathologic N2 disease, clinical N-status and metastatic pathologic N2 stations were significant prognostic factors. A similar difference was not found in patients with squamous cell carcinoma. Adenocarcinoma and squamous cell carcinoma appear to have different tendencies for lymph node metastasis. © 2010 Elsevier Ireland Ltd.


Funakoshi Y.,National Hospital Organization Toneyama Hospital | Takeuchi Y.,National Hospital Organization Toneyama Hospital | Maeda H.,National Hospital Organization Toneyama Hospital
Asian Cardiovascular and Thoracic Annals | Year: 2013

A 69-year-old Japanese woman who had never smoked had lung adenocarcinoma harboring epidermal growth factor receptor mutation. After 8 months of gefitinib treatment, salvage pneumonectomy was performed. Microscopic examination showed that non-responsive adenocarcinoma remained although necrosis was prominent. Postoperatively, the patient developed empyema that was successfully managed. The postoperative empyema after treatment with gefitinib should be noted, as well as the finding that residual viable tumor cells remained even after the dramatic radiographic response. © 2012 The Author(s).


Izawa K.,National Hospital Organization Toneyama Hospital
Nihon rinsho. Japanese journal of clinical medicine | Year: 2011

As the incidence of tuberculosis in Japan decreases, osteoarticular tuberculosis becomes relatively rare. Therefore, it is often overlooked or misdiagnosed that leads to cryptic aggravation of the disease. On the other hand, because of population aging in Japan, degenerative conditions such as compression vertebral fracture or osteoarthritis should be considered as differential diagnoses of osteoarticular tuberculosis. In addition, we should beware of extra-pulmonary tuberculosis in the patients who undergo biological agent therapy for rheumatoid arthritis that has been advanced drastically in recent years. Surgical treatment for osteoarticular tuberculosis is still an essential part of its treatment in order to achieve early rehabilitation and rapid healing of the lesion.


Nojiri T.,National Hospital Organization Toneyama Hospital
General thoracic and cardiovascular surgery | Year: 2011

Postoperative atrial fibrillation is the most common complication encountered during the early postoperative period following a pulmonary resection procedure. Landiolol is a newly developed, ultrashortacting, β-adrenoceptor antagonist. The objective of the present study was to evaluate the efficacy and safety of low-dose landiolol for postoperative atrial fibrillation in patients undergoing pulmonary resection for lung cancer. Of 553 patients who underwent an elective pulmonary resection procedure for lung cancer at National Toneyama Hospital from January 2005 to December 2009, this analysis involved 30 consecutive patients who developed atrial fibrillation after surgery and needed treatment. These patients were divided into two groups: the landiolol group (n = 15) and the historical control group (treated with a combination of verapamil and digoxin, n = 15). Hemodynamic changes before and 30 min, 2 h, and 12 h after medication, the time required to restore sinus rhythm, and adverse events were evaluated. There were no significant differences between the two groups regarding blood pressure before and after medication. Heart rate was reduced immediately in both groups after medication and was significantly lower in the landiolol group than in the control group. The time to restore sinus rhythm was significantly shorter in the landiolol group than in the control group (8.1 ± 11.0 h vs. 23.0 ± 26.0 h, P < 0.05). In none of the subjects with the landiolol infusion was it discontinued because of side effects. Low-dose landiolol can be effective quickly and used safely in patients who develop atrial fibrillation after pulmonary resection for lung cancer.

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