[Show abstract][Hide abstract] ABSTRACT: Primary intrapulmonary thymomas (PITs), which are intrapulmonary tumors without an associated mediastinal component, are very rare. The diagnosis of a PIT can be difficult. Here, we report two cases of resected PITs that were difficult to differentiate from other lung tumors. The patients, of a 62-year-old man and a 64-year-old woman, had no significant symptoms and were both referred to our hospital due to the presence of an abnormal shadow on chest computed tomography (CT). The patients underwent (18)F-fluorodeoxyglucose positron emission tomography-CT (FDG-PET/CT) and subsequently tumor excision. A PIT was confirmed histopathologically in the surgical specimens from both patients. In one case, the tumor consisted of a type A thymoma without abnormal FDG uptake. In the other case, the tumor consisted of a type B2 thymoma presenting with weak FDG uptake. This report thus documents two cases of PITs with different histopathologic and FDG-PET/CT findings. Thoracoscopic surgery is essential in the differential diagnosis between PITs and other lung tumors.
[Show abstract][Hide abstract] ABSTRACT: Pericardial mesothelioma is a very rare pericardial tumor. Diagnosing pericardial disease can be challenging , and obtaining an antemortem diagnosis of pericardial mesothelioma is particularly difficult. We herein report the case of a 60-year-old man with pericardial mesothelioma diagnosed on endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA). Chest computed tomography showed a mass surrounding the pericardium, and EBUS-TBNA of the right inferior paratracheal and subcarinal stations was consequently performed. No uptake was noted on 18 F-fluorodeoxy glucose positron emission tomography, other than in the pericardial mass. The results of histological and immunohistochemical examinations indicated the features of malignant mesothelioma. We therefore diagnosed the patient with pericardial mesothe-lioma, which was subsequently confirmed at autopsy.
Internal Medicine 03/2015; 54(1):43-48. DOI:10.2169/internalmedicine.54.3216) · 0.90 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Completion pneumonectomy (CP) for non-small cell lung cancer may be required for local recurrence or second primary lung cancer. We evaluated the CP indications, postoperative complications, and prognosis by retrospectively reviewing 7 men and 2 women, with a mean age of 66.1 (52-77) years, who underwent CP (Jan. 1994 to Dec. 2013). The first primary lung cancer histology included adenocarcinoma (5), squamous cell carcinoma (3), and basaloid carcinoma (1); p-stage IA for 2, p-stage IB for 2, p-stage IIA for 2, and p-stage IIB for 3. Initial surgeries were lobectomy with mediastinal lymph node dissection. CP was performed for second primary lung cancer in 3, and local recurrence in 6. Post-CP complications were cerebral infarction, wound dehiscence, and wound infection (1 patient each). After CP, survival ranged from 2 to 90 months; the actuarial 5-year survival rate was 14.8%. Three of 9 patients survived for>3 years. Generally, CP is difficult, with high postoperative morbidity and mortality rates; however, prolonged survival can result if complications are successfully managed perioperatively. CP is an effective therapeutic method for recurrent or second primary lung cancer.
The Journal of the Japanese Associtation for Chest Surgery 01/2015; 29(2):122-128. DOI:10.2995/jacsurg.29.122
[Show abstract][Hide abstract] ABSTRACT: Background
The brain is a frequent site of metastases from non-small-cell lung cancer (NSCLC). We analyzed the frequency of brain metastases (BMs) from NSCLC in the era of magnetic resonance images, and evaluated the correlation between epidermal growth factor receptor (EGFR) mutations and BMs among East Asian patients.
Frequency, number, and size of BMs, and survival of 1,127 NSCLC patients were retrospectively reviewed. Mutation status of EGFR was evaluated in all cases, and its association with BMs was statistically evaluated.
EGFR mutations were found for 331 cases (29.4 %). BM was the cause of primary symptoms for 52 patients (4.6 %), and found before initiation of treatment for 102 other patients (9.1 %); In addition to these 154 patients, 107 patients (9.5 %) developed BMs, giving a total of 261 patients (23.2 %) who developed BMs from 1,127 with NSCLC. BM frequency was higher among EGFR-mutated cases (31.4 %) than EGFR-wild cases (19.7 %; odds ratio: 1.86; 95 % confidence interval (CI) 1.39–2.49; P
International Journal of Clinical Oncology 10/2014; 20(4). DOI:10.1007/s10147-014-0760-9 · 2.13 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A precise preoperative diagnosis of 'very early' lung carcinoma may identify patients who can undergo curative surgery with limited resections.
Data from a multi-institutional project were collected on 1737 patients who had undergone limited resections (segmentectomy or wedge resection) for T1N0M0 non-small-cell carcinomas. As it was expected, this study was predominantly including ground glass nodules. Computed tomography was used to obtain the ratio of consolidation to the maximal tumour diameter to determine invasive potential of the tumours. Overall and disease-free survivals and recurrence-free proportions were analysed.
Median age was 64 years. Mean maximal diameter of the tumours was 1.4 ± 0.5 cm. Overall and recurrence-free survivals after limited lung resection were 94.0 and 91.1% at 5 years, respectively. Recurrence-free proportions were 93.7% at 5 years. Unfavourable prognostic factors in overall survival were lymph node metastasis, interstitial pneumonia, male gender, older age, comorbidities (cardiac disease, diabetes etc.) and consolidation/tumour ratio (C/T) ≤ 0.25. C/T ≤ 0.25 predicted good outcomes especially in cT1aN0M0 disease. In a subclass analysis of cT1N0M0 squamous cell carcinomas, wedge resection was the only unfavourable prognostic factor in both overall and disease-free survivals.
If the patient was 75 years old or younger and was judged fit for lobectomy, limited resection for cStage I non-small-cell lung cancer (NSCLC) showed excellent outcomes and was not inferior to the reported results of lobectomy for small-sized NSCLC. The carcinomas with C/T ≤ 0.25 rarely recur and are especially good candidates for limited resection.
European journal of cardio-thoracic surgery: official journal of the European Association for Cardio-thoracic Surgery 04/2014; 47(1). DOI:10.1093/ejcts/ezu138 · 3.30 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background:
Chemokines and chemokine receptors not only have significant roles in cancer metastasis and tumorigenesis but also act as antitumour agents. The interaction between the Crk-like adaptor protein (CrkL), which is encoded by the CRKL gene, and non-receptor tyrosine kinase c-ABL is reported to transform many cells into malignant cells. We examined the effects of CC chemokine receptor 7 (CCR7), CCR7 ligands and CrkL and c-ABL in lung adenocarcinoma.
One hundred and twenty patients with lung adenocarcinoma were included in this historical cohort analysis. We examined CCR7 and CCR7 ligands and CrkL and c-ABL mRNA expressions in surgically resected lung adenocarcinoma specimens and evaluated their contribution to prognosis, and the relationship with epidermal growth factor receptor (EGFR) and TP53 mutations.
High CCR7 mRNA expressions indicated better prognoses than those of the groups with low CCR7 mRNA expressions (P=0.007, HR=2.00, 95% CI of ratio: 1.22 –3.31). In lung adenocarcinoma, CrkL and c-ABL mRNAs were related to CCR7 mRNA expression (P<0.0001). CrkL and c-ABL mRNA expressions were influenced by EGFR mutations. A high expression of CCL19 was a good prognostic factor of lung adenocarcinoma.
We propose that CCR7 and CCL19 are clinically good prognostic factors and that CCR7 is strongly related to CrkL and c-ABL kinase mRNA expression in lung adenocarcinoma.
British Journal of Cancer 08/2013; 109(5). DOI:10.1038/bjc.2013.440 · 4.84 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Purpose:
The aim of this retrospective study was to evaluate the relevance of surgery in non-small cell lung cancer (NSCLC) patients with ipsilateral pulmonary metastases.
The clinical records of 1,623 consecutive NSCLC patients who underwent surgery between 1990 and 2007 were retrospectively reviewed. Overall, 161 (9.9%) and 21 (1.3%) patients had additional nodules in the same lobe as the primary lesion (PM1) and additional nodules in the ipsilateral different lobe (PM2), respectively.
The 5-year survival rate was 54.4 % in the PM1 patients and 19.3% in the PM2 patients (log-rank test: p = 0.001). Tumor size ≤3 cm, N0-1 status and surgical procedures less extensive than bilobectomy were identified as favorable prognostic factors in the PM1 patients. The 5-year survival rate in the PM1-N0-1 patients was 68.7%, while that in the PM1-N2-3 patients was 29.1% (p < 0.0001). Compared to the non-PM1 stage IIIA patients, the stage IIIA patients with PM1 disease (PM1-N1) tended to experience longer survival times (p = 0.06). Squamous cell types and bilobectomy or more extensive procedures were found to be unfavorable factors in the PM2 patients. The survival of the PM2 patients was significantly worse than that of the other T4 patients (p = 0.007).
PM1 patients with N0-1 disease are good candidates for surgery, whereas PM2 patients do not appear to benefit from surgery.
Surgery Today 12/2012; 43(10). DOI:10.1007/s00595-012-0452-x · 1.53 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Objectives: We retrospectively investigated whether histological cell type could affect patient prognosis for each stage according to the seventh edition of the TNM classification.
Patients and methods: Clinical records of 1623 consecutive non-small cell lung cancer patients who underwent surgery between 1990 and 2007 were retrospectively reviewed. Over 92% of these patients had either adenocarcinoma (Ad; n = 1043, 64.3%) or squamous cell carcinoma (Sq; n = 452, 27.9%).
Results: The overall 5-year survival rates for patients of all stages with Ad, Sq, large cell carcinoma (La), and adenosquamous cell carcinoma (As) were 67%, 56%, 58%, and 41%, respectively. Ad patients experienced better survival than Sq, As, or La patients (HR: 0.66, P < 0.0001; HR: 0.38, P = 0.011; HR: 0.69, P = 0.057, respectively). Stage IA Ad patients experienced better survival than stage IA Sq patients (5-year survival; Ad/Sq = 91%/78%, log-rank test, P = 0.001). Such a difference was also observed among seventh-edition TNM stage IB patients (5-year survival; Ad/Sq = 78%/64%, log-rank test, P = 0.048), but not for sixth-edition stage IB patients. Multivariate analysis demonstrated that histological cell type is a significant prognostic factor among stage I ≥ T1b Ad and Sq patients.
Conclusions: Survival after complete resection of new stage I ≥ T1b Sq patients is significantly worse than that of Ad patients, which could be partially attributed to stage migration effect in stage IB disease between the sixth and seventh editions of the TNM staging system.
Thoracic Cancer 08/2012; 3(3):249-254. DOI:10.1111/j.1759-7714.2012.00118.x · 0.90 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The intravenous administration of α-Galactosylceramide (α-GalCer)-pulsed antigen presenting cells (APCs) is well tolerated and the increased IFN-γ producing cells in the peripheral blood after the treatment appeared to be associated with prolonged survival. An exploratory study protocol was designed with the preoperative administration of α-GalCer-pulsed APCs to clarify the mechanisms of these findings, while especially focusing on the precise tumor site.
Patients with operable advanced lung cancer received an intravenous injection of α-GalCer-pulsed APCs before surgery. The resected lung and tumor infiltrating lymphocytes (TILs) as well as peripheral blood mononuclear cells were collected and the invariant NKT (iNKT) cell-specific immune responses were analyzed.
Four patients completed the study protocol. We observed a significant increase in iNKT cell numbers in the TILs and augmented IFN-γ production by the α-GalCer-stimulated TILs.
The administration of α-GalCer-pulsed APCs successfully induced the dramatic infiltration and activation of iNKT cells in the tumor microenvironment.
[Show abstract][Hide abstract] ABSTRACT: A 32-year-old woman with ocular-typed myasthenia gravis (MG) without thymoma was admitted to the hospital to undergo surgical treatment. Video-assisted thoracoscopic surgery (VATS) extended thymectomy was successfully performed with three small ports using manual manipulators, the Radius Surgical System (RSS). The device may facilitate many degrees of freedom to general thoracic surgery.
The Annals of thoracic surgery 12/2011; 92(6):2246-8. DOI:10.1016/j.athoracsur.2011.05.031 · 3.85 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Analysis of the microRNA (miRNA) expression signature of lung squamous cell carcinoma (lung-SCC) revealed that the expression levels of miR-133a were significantly reduced in cancer tissues compared with normal tissues. In this study, we focused on the functional significance of miR-133a in cancer cell lines derived from lung-SCC and the identification of miR-133a-regulated novel cancer networks in lung-SCC. Restoration of miR-133a expression in PC10 and H157 cell lines resulted in significant inhibition of cell proliferation, suggesting that miR-133a functions as a tumor suppressor. We used genome-wide gene expression analysis to identify the molecular targets of miR-133a regulation. Gene expression data and web-based searching revealed several candidate genes, including transgelin 2 (TAGLN2), actin-related protein2/3 complex, subunit 5, 16kDa (ARPC5), LAG1 homolog, ceramide synthase 2 (LASS2) and glutathione S-transferase pi 1 (GSTP1). ARPC5 and GSTP1 likely represent bona fide targets as their expression is elevated in lung-SCC clinical specimens. Furthermore, transient transfection of miR-133a, repressed ARPC5 and GSTP1 mRNA and protein levels. As cell proliferation was significantly inhibited in lung-SCC cells following RNAi knock down of either gene, ARPC5 and GSTP1 may function as oncogenes in the development of lung-SCC. The identification of a tumor suppressive miRNA and the novel cancer pathways it regulates could provide new insights into potential molecular mechanisms of lung-SCC carcinogenesis.
Journal of Human Genetics 11/2011; 57(1):38-45. DOI:10.1038/jhg.2011.126 · 2.46 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We herein report a case of acute respiratory distress syndrome (ARDS) that appeared to be related to a granulocyte colony-stimulating factor (G-CSF)-producing lung cancer. A 77-year-old man with arterial sclerotic obstruction (ASO) underwent reconstructive surgery of the left femoral artery. He developed ARDS on the 5th postoperative day, which resolved following mechanical ventilation with steroid pulse treatment. Four months later, he was admitted with a fever and right arm pain. Chest computed tomography showed a malignant lesion in the right apical lung, and percutaneous needle biopsy demonstrated adenocarcinoma. Laboratory data revealed neutrophilia with elevated serum G-CSF levels. He underwent a right upper lobectomy with chest wall resection, and administration of sivelestat sodium to treat his postoperative pre-acute lung injury state. Pathology revealed a G-CSF-producing pleomorphic carcinoma. Retrospectively, a tumor shadow was noted on chest X-ray at the time of ARDS just after ASO surgery. The relationship between an abnormal G-CSF level and ARDS was considered, and the implications are herein discussed.
Surgery Today 08/2011; 41(8):1161-5. DOI:10.1007/s00595-010-4426-6 · 1.53 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: N-methyl-D-aspartate receptors (NMDAR) act as tumor suppressors of digestive malignancies. The expression and genetic methylation patterns of NMDAR2B in non-small cell lung cancer (NSCLC) are unknown.
The relationship between gene methylation and expression of NMDAR2B was analyzed in NSCLC cell lines (N = 9) and clinical tissues (N = 216). The cell lines were studied using RT-PCR and 5-aza-2'-deoxycytidine treatment, while the clinical tissues were examined by methylation specific real-time quantitative PCR and immunohistochemistry. Retrospective investigation of patient records was used to determine the clinical significance of NMDAR2B methylation.
NMDAR2B was silenced in five of the nine cell lines; 5-aza-2'-deoxycytidine treatment restored expression, and was inversely correlated with methylation. Aberrant methylation of NMDAR2B, detected in 61% (131/216) of clinical NSCLC tissues, was inversely correlated with the status of protein expression in 20 randomly examined tumors. Aberrant methylation was not associated with clinical factors such as gender, age, histological type, or TNM stage. However, aberrant methylation was an independent prognostic factor in squamous cell carcinoma cases.
Aberrant methylation of the NMDAR2B gene is a common event in NSCLC. The prognosis was significantly better for cases of squamous cell carcinoma in which NMDAR2B was methylated. It may have different roles in different histological types.
BMC Cancer 06/2011; 11(1):220. DOI:10.1186/1471-2407-11-220 · 3.36 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The prognosis of non-small-cell lung cancer (NSCLC) patients with malignant pleural disease (MPD), characterized by malignant pleural effusion and/or malignant pleural nodules, is reported to be poor, and patients with MPD are generally not subjected to surgery. However, whether or not the primary tumor should be resected, when MPD is first detected at thoracotomy, is controversial.
The clinical records of 1623 consecutive NSCLC patients, who underwent surgery between 1990 and 2007, were retrospectively reviewed. A hundred patients (6.2%) were classified with pathological stage IV disease according to the seventh edition of the Union for International Cancer Control (UICC) staging system. There were 73 patients with MPD, which included 32 with effusion without nodules (MPE) and 41 with nodules with or without effusion (MPN). Intra- or postoperative pleural chemotherapy was administered to 37 MPD patients.
The median survival time, the 3-year survival rate and the 5-year survival rate for MPD patients were 25.9 months, 41.4%, and 23.7%, respectively, which are better outcomes than those for M1b patients (8.7 months, 18% and 18%, respectively) (log-lank test: p=0.014). Among MPD patients, N0-1 disease was determined to be a favorable prognostic factor (p=0.01). MPD status (MPE or MPN) was not prognostically significant (p=0.40). MPE patients with N0-1 disease had a significantly better prognosis with a 5-year survival rate of 63.6% compared to MPE patients with N2-3 disease (p=0.003). Twenty-seven percent of MPN patients with N0-1 disease achieved 5-year survival, whereas none of the MPD patients with N2-3 disease survived longer than 5 years after surgery.
The prognosis of patients with surgically detected MPD, who underwent resection, was better than that of M1b patients. MPE patients with N0-1 disease may be candidates for resection.
European journal of cardio-thoracic surgery: official journal of the European Association for Cardio-thoracic Surgery 05/2011; 41(1):25-30. DOI:10.1016/j.ejcts.2011.04.010 · 3.30 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: In the seventh edition of TNM Classification of Malignant Tumours (TNM) staging, the stage-IIB category for lung cancer is comprised of four factors: lymph-node metastasis, chest-wall invasion, large tumor size (> 7 cm), and same-lobe nodules. Tumors are further classified into eight sub-categories based on each TN factor or factor combinations. This study evaluated the prognostic value of each TN factor or combinations for resected stage-IIB non-small-cell lung cancer (NSCLC).
We retrospectively studied 186 consecutive patients who had resections for NSCLC at Chiba University Hospital and were diagnosed as stage IIB according to the seventh edition of TNM staging.
Five-year survivals for each stage IIB were: T2bN1M0 = 47 ± 12% (± standard error); T3 (chest-wall invasion; N0M0) = 59 ± 7%; T3 (large tumor> 7 cm)=72 ± 11%; T3 (same-lobe nodules) = 78 ± 5%; T3 (invasion + > 7 cm)=44 ± 16%; T3 (invasion+same-lobe nodules) = 25 ± 22%; T3 (>7cm+same-lobe nodules) = 0%; and T3 (invasion + > 7 cm +same-lobe nodules)=0%. Among the four single factors, same-lobe nodules had the best prognoses, whereas T2bN1M0 had the worst prognoses. Comparing cases with single factors and multiple factors that decided stage IIB, cases with multiple factors had poorer prognoses (P=0.02).
The stage-IIB category is comprised of eight sub-categories, with either single factors or factor combinations; these sub-categories have different prognoses. The worst survivals were for cases with T2bN1M0 as a single factor or for cases with multiple factors, although these represented a small proportion of resected stage-IIB NSCLC cases.
European journal of cardio-thoracic surgery: official journal of the European Association for Cardio-thoracic Surgery 05/2011; 39(5):745-8. DOI:10.1016/j.ejcts.2010.08.014 · 3.30 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The prognosis for non-small cell lung cancer (NSCLC) with chest wall invasion can vary due to the heterogeneous nature of the cell population. Because NSCLC with large tumors (>7 cm) have been reclassified as T3, the applicability of the new designation must be evaluated. We reviewed 140 patients with chest wall T3 and 28 patients with T3 NSCLC with large tumors, but no chest wall invasion who underwent resection at our institution. Among chest wall T3 patients, elderly T3 patients (≥80 years old) who died within 42 months, patients with either lymph node or pulmonary metastasis, or patients with a large tumor (>7 cm) had poorer prognoses than those who had not. The survival rates for cases with chest wall T3 and cases with a large tumor without chest wall invasion were not significantly different. NSCLC patients with chest wall T3 with lymph node, or pulmonary metastasis, or with a large tumor should be considered for further multimodal treatment with or without resection to enhance their survival time. Elderly patients with chest wall invasion may not be good candidates for resection. A large tumor is so aggressive that re-classification of large tumor cases as T3 is suitable.
Interactive Cardiovascular and Thoracic Surgery 10/2010; 11(4):420-4. DOI:10.1510/icvts.2010.242743 · 1.16 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A surgical resection for locally advanced non-small cell lung carcinoma (NSCLC) remains controversial. This study analyzed the clinicopathological profile and surgical outcome of patients with locally advanced NSCLC to identify the predictors of survival.
This study retrospectively analyzed clinical data from 86 patients with pathological T3 or T4 primary NSCLC treated at Chiba University Hospital, and evaluated prognostic factors.
Sixty-eight of 86 cases were treated with a complete resection, and 18 were evaluated as an incomplete resection. The 5-year overall survival rate of all cases was 45.7%. Univariate analyses of survival were performed to determine the predictors of overall survival in patients with pathological T3 or T4 NSCLC. Age of 70 years or more, tumor length more than 5 cm, lymph node metastases, incomplete resection, and histology of non-adenocarcinoma were significantly associated with an unfavorable prognosis. Multivariate analyses revealed that older age, incomplete resection, and lymph node metastases were independent predictors of shorter survival.
A complete resection for selected cases is acceptable in the management of T3 or T4 NSCLC.
Surgery Today 08/2010; 40(8):725-8. DOI:10.1007/s00595-009-4127-1 · 1.53 Impact Factor