廣島 健三

Introduction: Carbon ion radiotherapy (CIRT) is a promising modality with excellent localization and significant biologic effects on tumors. Nevertheless, success depends primarily on accurate staging before radiotherapy. Surgical interventions should be avoided in patients considered for CIRT because they usually have multiple comorbidities. The aim of this study was to evaluate the effectiveness of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) for lymph node staging in patients with non-small cell lung cancer before CIRT. Methods: From April 2005 to December 2007, 49 patients with non-small cell lung cancer considered for CIRT with abnormal positron emission tomography-computed tomography (PET-CT) accumulations in the mediastinum and/or hilum were evaluated by EBUS-TBNA. The convex probe EBUS was used for EBUS-TBNA. Results: There were 38 men and 11 women. Their mean age was 75.2 years (range: 55-87). Based on PET-CT, clinical staging was four with N1 disease, 42 with N2 disease, and three with N3 disease. By histology, 26 patients had adenocarcinoma, 19 had squamous cell carcinoma, and four had other histologies. All positive lymph nodes on PET-CT were aspirated (range: 1-5; average 2.55 lymph nodes/patient). EBUS-TBNA diagnosed 43 cases as N0 disease and as a result underwent CIRT. Forty of the 43 cases remained in stable condition without local recurrences (follow-up 6-46 months). The diagnostic accuracy of EBUS-TBNA for lymph node staging was 93.9%. Conclusions: EBUS-TBNA offers accurate minimally invasive lymph node staging in patients who are candidates for CIRT. EBUS-TBNA can be safely performed with a high diagnostic accuracy before CIRT.

A 46-year-old man was first diagnosed as Buerger's disease according to his clinical and radiological features because he had no evidence of parasitic, allergic and connective tissue disease. Soft subcutaneous nodules suspected of lymphadenopathy on the bilateral inguinal regions were recognized after admission. Positron emission tomography scan showed the increased uptake of 18F-fluoro-2-deoxyglucose in the bilateral inguinal regions. We finally diagnosed him as Kimura's disease based on pathologic findings and laboratory data, and started steroid therapy. The uptake of 18F-fluoro-2-deoxyglucose disappeared and his leg pain was improved after the treatment. This is the first case report presenting a patient of Kimura's disease with Buerger's disease-like vasculitis who was demonstrated by positron emission tomography. © 2008 Elsevier Ireland Ltd. All rights reserved.

The aim of this study was to evaluate the molecular influence of chronic obstructive pulmonary diseases (COPD) on the pathogenesis of non-small cell lung cancer (NSCLC). The methylation profiles of 12 genes, and the epidermal growth factor receptor (EGFR) and KRAS mutations were determined for samples from 229 NSCLC patients. In addition, protein expression of EGFR and HER2 in 116 NSCLCs was analyzed based on the presence or absence of COPD. IL-12R beta 2 and Wif-1 methylation and HER2 overexpression were more frequent events in the COPD group. Eighty nonmalignant lung tissues had no correlation with any molecular changes between the COPD and the non-COPD group. EGFR mutation was significantly higher in the non-COPD group, while EGFR expression was inversely correlated with %FEV1.0. In the COPD group, unmethylated SPARC and sFRP-2 genes or a negative CpG island methylator phenotype (CIMP) was a negative prognostic factor, while methylation of p16(INK4A) and WNT antagonist genes was a negative prognostic factor in the non-COPD group. Novel characteristics of COPD-related NSCLC were identified by examination of methylation profiles and alterations of EGFR signaling. In consideration of the high sensitivity to smoking in patients with COPD, NSCLC with COPD might be a distinct population of smoke-related NSCLC, the genetic profile of which is quite different from non-COPD NSCLC.

We report a case of choroidal metastasis from rectal cancer manifesting visual loss as the initial recurrence symptom. A 49-year-old man with progressive vision loss in the left eye referred 15 months after radical rectal cancer surgery was found in funduscopy to have a choroidal tumor with exudative detached retinas and in chest computed tomography (CT) to have small multiple tumors with central cavitations in both lungs. Trans-bronchial lung biopsy showed adenocarcinoma cells. We diagnosed left choroidal metastasis and multiple lung rectal cancer metastases. Systemic chemotherapy, improved exudative detached retinas and retinochoroidal effusion and the choroidal tumor became smaller and flatten, vision was permanently lost. Lung metastases gradually worsened and the cervical vertebra metastasis appeared. The man died 11 months after the first manifestation of recurrence. Nine cases of choroidal metastasis from colorectal cancer, including our case, have been reported. Because most had multiple organ metastases involving the liver and lung, choroidal metastasis is suspected to be derived secondarily from liver or lung metastases. ©2010 The Japanese Society of Gastroenterological Surgery.

Background Pyothorax-associated lymphoma (PAL) is a comparatively rare tumor, tend it is difficult. to definitively diagnose it preoperatively, especially in patients with only pleural thickening without mass formation. Pleural effusion aspiration cytology is a useful and easy diagnostic method for a large number of chest diseases. However, the cytologic findings of PAL have been rarely described. Here we report. on the cytologic findings in a patient with PAL, manifested by pleural thickening without mass formation, which was diagnosed preoperatively by pleural effusion aspiration cytology. Case A 64-year-old man was admitted to our hospital because of pleural thickening involving an empyema sac located in the left. thorax and rapidly increasing pleural effusion. He bad a 30-year history of chronic empyema and a 10-year history of diabetes mellitus. Left. pleural effusion aspiration cytology showed malignant lymphoma. The patient was admitted to our hospital for PAL treatment. Because of poor respiratory function, be only underwent decortication with complete resection of the thickening pleural peel. However, he was well, without recurrence, 5 years after the operation. The histologic examination revealed that lymphoma cells were located only in the thickening pleural peel. Conclusion This is a very rare case of PAL diagnosed by preoperative aspiration cytology for an increasing pleural effusion. This report demonstrates that pleural effusion aspiration cytology can be valuable for the diagnosis of PAL. (Acta Cytol 2010;54:66-70)

Background: The diagnosis of sarcoidosis requires both compatible clinical features and pathologic findings as a means to exclude other differential diagnoses. The utility of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) for diagnosis of sarcoidosis has been reported, although its indication remains unclear for cases of suspicious sarcoidosis. To clarify the role of EBUS-TBNA for the diagnosis of sarcoidosis, we compared three diagnostic modalities: EBUS-TBNA, transbronchial lung biopsy (TBLB) and bronchoalveolar lavage fluid analysis (BAL). Methods: Thirty-eight patients with suspicious sarcoidosis who had enlarged hilar and/or mediastinal lymph nodes on chest CT were retrospectively reviewed. Patients with malignancies or prior established diagnosis of sarcoidosis were excluded. BAL was initially performed followed by TBLB and finally EBUS-TBNA at the same setting. Microbacterial examinations were also performed from all samples. Results: Pathological findings compatible with sarcoidosis were obtained in 32 patients. The remaining 6 patients were diagnosed as one case each of chronic eosinophilic pneumonia, atypical mycobacterial infection and tuberculosis, and the remaining three were pathologically indefinite cases. Clinically, 35 patients were diagnosed with sarcoidosis. The diagnostic accuracy of sarcoidosis was significantly better by EBUS-TBNA (91.4%, p &lt 0.001) compared to the other two modalities. According to chest roentgenogram classifications, there were 31 stage I patients and 4 stage II patients. For stage I patients, EBUS-TBNA was significantly better (90.3%, p &lt 0.001), but each modality showed 100% accuracy for stage II patients. Conclusion: It is recommended that EBUS-TBNA is added to the conventional diagnostic modalities for patients with suspicious stage I sarcoidosis on chest roentgenogram. © 2009 Elsevier Ltd. All rights reserved.

Malignant mesotheliomas develop commonly in the pleural cavity and rarely arise in the peritoneal cavity. It is well established that asbestos exposure is related to malignant pleural mesothelioma, but the asbestos burden in the abdominal cavity in patients with malignant peritoneal mesothelioma has not been well studied. The purpose of the present study was therefore to report on an autopsy case of malignant peritoneal mesothelioma with quantitative analysis of the asbestos burden in tissues from the pleura and organs in the abdominal cavity. The patient was a 67-year-old man with a history of asbestos exposure. The peritoneum was thickened with diffuse tumor proliferation. This patient was diagnosed as having malignant peritoneal epithelioid mesothelioma. The number of asbestos fibers was > 10 000/g dry tissue in all samples examined except in the small intestine. The number of asbestos fibers in the stomach was 53 000/g, which was higher than that in a control asbestosis subject. The existence of numerous asbestos fibers found in the abdominal cavity suggests that asbestos stimuli are related to the tumorigenesis of malignant peritoneal mesothelioma.

Owner : NLM<br /> Status : MEDLINE<br /> PubModel : Print<br /> Language : eng<br /> Pagination : 720-8

Birt-Hogg-Dube (BHD) syndrome is a rare disorder inherited in an autosomal dominant manner. The affected patients are predisposed to cutaneous fibrofolliculomas, renal cell tumors and lung cysts with recurrent pneumothorax. Contrary to neoplastic events in the skin and the kidney, the lung cysts have frequently been confused with non-neoplastic changes such as blebs or bullae. Herein is reported a case of multiple lung cysts associated with BHD syndrome. Detailed histopathological characteristics of the lesion are also given. The lung cysts were closely associated with the peripheral interlobular septum, visceral pleura or septal-pleural junctional region. These cysts were partly abutting alveolar structures, and lined by a layer of alveolar epithelium. These unique microscopic features supported the notion that the BHD lung lesions are distinct from other types of bullous changes. Genomic DNA analysis indicated an aberrant sequence repeat that caused frameshift mutation. Immunohistochemistry showed the localization of folliculin, the BHD gene-encoding protein, in macrophages and epithelial cells in the patient&apos;s and normal control&apos;s lungs. Haploinsufficiency of folliculin may cause deranged alveolar development, leading to the aberrant cystic alveolar formation. The unique mutation patterns of abnormal sequence repeats in patients with BHD syndrome are also reviewed.

Stent thrombosis is defined as thrombotic occlusion of a stent resulting in acute coronary syndrome (ACS). However, all thrombotic occlusions of stents might not result in ACS. The present case report describes silent, very late thrombotic occlusion of a drug-eluting stent that was confirmed from specimens removed by directional coronary atherectomy.

Background. We report a case of thymoma with squamous differentiation associated with lung cancer. Case. An 81-year-old man consulted his family doctor with chief complaints of shortness of breath and chest pain. A nodular shadow was noted in the left middle lung field of his chest X-ray, and the patient was referred to our Department of Respiratory Medicine. Transbronchial aspiration cytology was performed in the left B8a, and the tumor was diagnosed as adenocarcinoma. He was then referred to our department for surgery. The preoperative diagnosis of the lung cancer was classified as cT1N0M0 and stage IA by preoperative evaluation. Another 5.0 x 3.5 cm tumor was detected in the anterior mediastinum in the preoperative chest CT, and a thymoma was suspected. Simultaneous left lower lobectomy with lymphadenectomy (ND2a) and surgical removal of the anterior mediastinal tumor were performed. The postoperative histological examination revealed the lung cancer to be adenocarcinoma, pT2N0M0 and stage IB. The anterior mediastinal tumor was type B1 thymoma, showing squamous differentiation with keratinization. Conclusion. Thymoma with squamous differentiation is a rare histopathological feature. This case was valuable in that it suggested a relationship between thymoma and thymic carcinoma. © 2009 The Japan Lung Cancer Society.

Objectives: The prognosis for patients with large-cell neuroendocrine carcinoma is generally very poor. In this study, we describe the clinical features of recurrent tumors of large-cell neuroendocrine carcinoma and discuss the role of adjuvant chemotherapy and management of recurrence in patients with large-cell neuroendocrine carcinoma. Methods: We retrospectively analyzed clinical data from 79 patients and evaluated the prognosis of patients with platinum-based adjuvant chemotherapy, recurrence patterns, patient response to chemotherapy or radiation therapy, and prognosis in patients who experienced relapse. Results: Of 72 patients, 36 had confirmed recurrent tumors upon follow-up examinations. Of those with recurrent tumors, 33 patients (91.7%) had their first recurrent tumors within 3 years. Patients who underwent platinum-based adjuvant chemotherapy had a significantly lower rate of tumor recurrence and a higher rate of disease-free survival than those who had non-platinum-based adjuvant chemotherapy or no adjuvant chemotherapy. Multivariate analyses revealed that platinum-based adjuvant chemotherapy, pathologic stage, and the presence of second cancer are independent prognostic factors. Three patients with limited resection of the primary tumor had poor prognosis with recurrence. Postoperatively, 11 of the 36 patients without recurrence (30.6%) had metachronous second primary cancers, of which 4 patients had more than 1 site. Conclusions: Patients with large-cell neuroendocrine carcinoma had frequent recurrence following resection of the primary tumor, and those without recurrence often developed metachronous second primary cancers. Platinum-based adjuvant chemotherapy after surgery may be useful for preventing recurrence in patients with large-cell neuroendocrine carcinoma. © 2009 The American Association for Thoracic Surgery.

The earliest pathological events in the development of malignant pleural mesothelioma (MPM) are not understood. The aim of the present study was to elucidate the early histopathological features of MPM. A total of 16 extrapleural MPM pneumonectomy patients were investigated. Early stage mesothelioma was arbitrarily defined as a tumor &lt; 5 mm in thickness regardless of the nodal status or other organ involvement. Eight of these patients (six with epithelioid, two with biphasic) had early stage mesothelioma by this definition. Macroscopically there was no visible tumor, but the parietal and visceral pleura were thickened and there was focal adhesion between them. Microscopically, the mesothelioma lesions were multifocal and discontinuous on the pleura. In extremely early cases of epithelioid mesothelioma, tumor cells were generally arrayed in a single layer, but papillary proliferation was observed elsewhere. In sarcomatoid mesothelioma, mesothelioma cells proliferated, forming multiple small polypoid nodules on the pleura. Epithelial membrane antigen was helpful to distinguish reactive from neoplastic mesothelium, but glucose transporter-1 was not. Mesothelioma cells disseminate diffusely throughout the parietal and visceral pleura and mediastinal fat tissue before becoming visible. Stage Ia mesothelioma (neoplasm limited to the parietal pleura) would not be observed in daily practice.

Somatic mutations in the epidermal growth factor receptor (EGFR) gene in non-small-cell lung cancers (NSCLC) are a well-established predictive factor for the response of tumors to EGFR tyrosine kinase inhibitors.In the present study,we developed a simple method for detecting somatic mutations in exons 19 and 21 of the EGFR gene,which covers approximately 90% of known mutations in Japanese patients suffering from NSCLC,and evaluated it.Our findings indicated that the presence of around 1% of genes harboring L858R mutation was sufficient for detecting mutation by our method,although a mutation rate of at least 20% appeared to be necessary for direct sequencing detection.Molecular diagnosis to detect target mutations was successful when various DNA samples taken from fresh or frozen biopsy specimens,or formalin-fixed paraffin-embedded (FFPE) blocks or slices for pathological examination,or tumor materials obtained from surgical resection were employed.These results show that our method is a simple,low cost means of achieving rapid,sensitive detection of the major EGFR mutations and that it would be a practical diagnosis procedure for hospitals.

Purpose: Malignant rhabdoid tumors (MRT) have poor prognoses. Breast MRT is extremely rare only three cases have been documented, with a mean prognosis of 7 months. Multi-agent chemotherapy with mastectomy and irradiation, as used in this case, may extend survival in breast MRT. Patient and methods: A 68-year-old woman who underwent a standard mastectomy was diagnosed with breast MRT. Postoperatively she received six cycles of cyclophosphamide/methotrexate/5- fluorouracil followed by oral administration of doxifluridine and anastrozole, after which no metastasis was detected. About 8 months postoperative, magnetic resonance imaging revealed cervical bone metastasis, and local irradiation and nine doses of "basic chemotherapy" consisting of biweekly paclitaxel and anastrozole were administered. About 4 months later, multiple lung metastases were revealed, and four doses of "basic chemotherapy" with added pirarubicin hydrochloride were administered. Four months after that, multiple large liver metastases were discovered, and five doses of "basic chemotherapy" with added carboplatin were administered. Results: The 19-month survival period of our case was almost three times that of reported breast MRT patients. Conclusion: Multi-agent chemotherapy combined with irradiation may be associated with the relatively long survival of the present case. © 2009 Springer-Verlag.

Objective. The aim of this study was to determine the significance of extrapleural pneumonectomy for malignant pleural mesothelioma. A retrospective study was performed on its surgical outcomes and prognostic factors. Subjects. The subjects were 32 patients in whom our research group performed extrapleural pneumonectomy. Results. The patients were 31 men and 1 woman. Their mean age was 55.4 years old. The incidence of postoperative complications was 56.3% which included empyema and detachment of a reconstruction patch for the diaphragm. There were 2 operative deaths (6.3%). Combination therapy was performed in 13 patients (40.6%) including intrathoracic perfusion chemohyperthermia and systemic chemotherapy. The postoperative 2- and 3-year cumulative survival rates among all patients were 40.1% and 16.0%, respectively. The median survival time was 16.2 months. The multivariate analysis on prognostic factors indicated that the following were 3 significant independent factors for good prognosis: an Eastern Cooperative Oncology Group Performance Status of 0, N0, and operative time &lt 600 minutes. The 2- and 3-year survival rates of patients satisfying all 3 factors were 64.8% and 51.9%, respectively. Conclusion. Extrapleural pneumonectomy for malignant pleural mesothelioma can be expected to have a relatively good prognosis by appropriate patient selection. © 2009 The Japan Lung Cancer Society.

Although lung cancer is frequently accompanied by COPD and interstitial lung disease (ILD), the precise coincidence of these diseases with lung cancer is not well understood. The objectives of this study were to determine the prevalence of abnormal CT and spirometric findings suggestive of COPD or ILD in a population of patients with untreated lung cancer, and to estimate the lung cancer risk in this population. The study population consisted of 256 patients with untreated lung cancer and 947 subjects participating in a CT screening programme for lung cancer. Semi-quantitative analysis of low attenuation area (LAA), fibrosis and ground glass attenuation (GGA) on CT was performed by scoring. Gender- and age-matched subpopulations, with stratification by smoking status, were compared using the Mantel-Haenszel projection method. Inter-observer consistency was excellent for LAA, but not as good for fibrosis or GGA scores. Pooled odds ratios for lung cancer risk using LAA, fibrosis, GGA scores and reduced FEV(1)/FVC and %VC were 3.63, 5.10, 2.71, 7.17 and 4.73, respectively (P &lt; 0.0001 for all parameters). Multivariate regression analyses confirmed these results. Abnormal CT and spirometric parameters suggestive of COPD and ILD were strong risk factors for lung cancer, even after adjusting for gender, age and smoking status.

Several studies have described p16(INK4A) and prostaglandin E2 (PGE2) co-alterations in various solid tumors, including non-small cell lung cancer (NSCLC). In this study, we examined the correlation between PGE2 receptor 2 (EP2) expression and p16(INK4A) methylation in NSCLC, and the association with clinicopathological features and prognostic significance. We retrospectively reviewed 88 NSCLC patients who underwent resection from July 1993 to May 1997. The tumors included 43 adenocarcinomas, 39 squamous cell carcinomas, and 6 large cell carcinomas. EP2 expression was determined by immunostaining, and p16(INK4A) methylation was analyzed by methylation specific PCR. EP2 was overexpressed in 44% of NSCLC patients, 61% of adenocarcinoma cases, 28% of squamous cell carcinoma cases, and 33% of large cell carcinoma cases. EP2 expression positively correlated with lymph node metastasis (P=0.034), especially in patients with squamous cell carcinoma (P &lt; 0.009). Methylation of p16(INK4A) was detected in 34% of NSCLC patients, 23% of adenocarcinoma cases, 44% of squamous cell carcinoma cases, and 50%, of large cell carcinoma cases. In patients with squamous cell carcinoma, EP2 overexpression correlated with poor prognosis with a relative risk of 2.4 (confidence interval 2.1-51.8, P &lt; 0.003), and positively correlated with p16(INK4A) methylation (P &lt; 0.024). Adenocarcinoma patients with p16(INK4A) methylation had poor prognosis with a relative risk of 2.4 (confidence interval 1.8-69.7, P &lt; 0.009), but this was not. correlated with EP2 expression. In conclusion, EP2 overexpression was common in NSCLCs, especially in adenocarcinomas. Synchronous alteration of p16(INK4A) and EP2 may accelerate progression of squamous cell carcinomas. These two alterations may differentially affect pathogenesis among subtypes of NSCLC.

Background. Retained fiber levels of over 1,000 asbestos bodies per gram of dry lung tissue are recommended to identify persons with a high probability of exposure to asbestos dust at work. A 2-fold risk of lung cancer is related to retained fiber levels of 5,000 to 15,000 asbestos bodies per gram of dry lung tissue. Methods. We counted the asbestos bodies in paraffin-embedded sections of lung tissues stained for iron, and compared those numbers with the asbestos body counts determined by hypochlorite digestion of wet formalin-fixed lung tissue in cases with asbestos-related lung carcinoma, mesothelioma, usual interstitial pneumonia, and asbestosis. Results. There is a relationship of the numbers of asbestos bodies on tissue sections to the number measured by a tissue digestion technique. The patients are heavily exposed to asbestos if the number of asbestos bodies on tissue sections is equal to or more than 7. Conclusion. The presence of one or more than one asbestos body on tissue sections means the existence of higher levels of exposure to asbestos than average persons. The patients are con sidered to have been heavily exposed to asbestos if the number of asbestos bodies on tissue sections is equal to or more than 7. There are cases in which the number of asbestos bodies on tissue sections is zero, although they were exposed to asbestos. We must be cautious about evaluating the level of asbestos exposure, when the numbers of asbestos bodies on tissue are low. © 2009 The Japan Lung Cancer Society.

BACKGROUND: Multigene aberrant methylation profiling may predict response to chemotherapy in lung cancer. The purpose of this study was to analyze the feasibility of detecting aberrant methylation in biopsy samples obtained by endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA). METHODS: Lymph node samples from 30 patients with nonsmall cell lung cancer diagnosed as metastatic carcinoma by EBUS-TBNA were analyzed. Histologic cores obtained by EBUS-TBNA were separately stored at -80°C. DNA was extracted from EBUS-TBNA samples and bisulfate modification was performed. We evaluated the methylation status of a panel of 6 genes (FANCF, Reprimo, TMS1/ASC, activated protein-2α, CHFR, and ATM) using methylation-specific polymerase chain reaction. Twenty-four patients with adenocarcinoma or squamous cell carcinoma metastasis received platinum-based combination chemotherapy. We reviewed their response to chemotherapy in correlation to the methylation status. RESULTS: Bisulfate modification was successfully performed in all samples using DNA obtained from EBUS-TBNA samples by checking p16 unmethylation expression. Aberrant methylation was detected as follows: 9 cases of FANCF (30.0%), 14 cases of Reprimo (46.7%), 10 cases of TMS1/ASC (33.3%), and 19 cases of activated protein-2α (63.3%). In response to chemotherapy, there were 1 complete response, 6 partial response, 12 stable disease, and 5 progressive disease (PD) cases. The number of methylated genes was significantly smaller in the PD group than in the non-PD groups (P=0.0435). CONCLUSIONS: Aberrant methylation analysis can be performed in metastatic lymph nodes sampled by EBUS-TBNA. EBUS-TBNA allows for genetic evaluations of tumor cells and may help to guide the most effective treatment strategies in the near future. © 2009 Lippincott Williams &amp Wilkins, Inc.

Amyloidosis is an uncommon disease caused by the deposition of abnormal proteins within the soft tissues. Mediastinal lymph node involvement of the disease is rare. When mediastinal lymph nodes are affected, tissue sampling is required for obtaining a firm diagnosis. Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a minimally invasive method of sampling tissues from mediastinal and hilar lymph nodes. We report a case of primary amyloidosis involving mediastinal lymph nodes successfully diagnosed by EBUS-TBNA. © 2008 Elsevier Ltd. All rights reserved.

Patients with N2 nonsmall cell lung cancer (N2-NSCLC) represent heterogeneous groups. Survivin is a member of the inhibitor of apoptosis family. If N2-NSCLC patients could be stratified, based on survivin expression and/or its relation to cell cycle proteins, into homogeneous subgroups, certain therapies could be selected for those patients. Survivin expression in 78 surgically resected primary pathological N2-NSCLC tumours was evaluated using immunohistochemistry. Relationships of survivin expression to overall survival, clinical features and expression of six cell cycle-related proteins (pRb, cyclin D1, p16(INK4A), p53, p21(Waf1) and Ki-67) were analysed. Nuclear survivin and the number of mediastinal lymph node (LN) stations were independent prognostic factors. The patient group with combined negative survivin/single mediastinal LN station were the most favourable prognostic group, and was related to the clinical nodal factor. Indeed, patients with negative survivin/low Ki-67 labelling indices had the best survival, especially in nonsquamous histopathology. The current authors conclude that nuclear survivin is strongly related to lymph node metastasis and proliferative potentials in pathological N2 nonsmall cell lung cancer patients. Pre-operative N2 nonsmall cell lung cancer patients with combined negative nuclear survivin and a single mediastinal lymph node station, or low proliferative indices, particularly in clinical N0-1 disease and nonsquamous histopathology, respectively, are expected to have a favourable post-operative prognosis and may be candidates for primary resection.

Chronic active Epstein-Barr virus (CAEBV) infection is characterized by chronic or recurrent infectious mononucleosis-like symptoms and the prognosis of CAEBV infection is quite poor. The incidence of myocarditis as a complication of EBV infection is not so high and it is unusual that heart failure appears as the initial symptom. However, it is very important to detect and treat chronic active myocarditis in the early phase of CAEBV infection because chronic active myocarditis disorganizes and decreases cardiomyocytes, resulting in the progression to heart failure. We report a case of a 45-year-old man with CAEBV infection for 5 years. Echocardiography revealed moderate left ventricular systolic dysfunction with mild pericardial effusion. Endomyocardial biopsies demonstrated massive lymphocytic infiltration with adjacent myocytolysis and necrosis of cardiomyocytes suggesting active myocarditis. Immunohistological analysis of biopsies revealed that the infiltrating cells were mainly T lymphocytes. And some of the infiltrating cells showed a positive signal for the EBV-encoded small nuclear RNA by in situ hybridization. Positron emission tomography using 18F-fluoro-2-deoxyglucose (18F-FDG) performed revealed increased uptake of 18F-FDG of whole left ventricular wall with mild heterogeneity. © 2007 Elsevier Ireland Ltd. All rights reserved.

Although mucosa-associated lymphoid tissue (MALT) lymphoma is classified as an indolent lymphoma, it frequently disseminates and recurs to make the disease difficult to cure. The present case had metachronous lesions in the skin, orbit and pleura, and all of them were diagnosed as derived from the same monoclonal tumor cell. A 65-year-old woman was admitted to our hospital because of a pleural tumor with pleural effusion. Two years before, she had undergone surgical resection for skin erythematous lesion and an ocular adnexa tumor, which were diagnosed as lymphoid hyperplasia by histological examination at that time. On admission, thoracoscopy-guided biopsy of the pleural tumor with local anesthesia established a diagnosis of MALT lymphoma. The rearranged immunoglobulin heavy chain of the skin tumor, ocular adnexa tumor, pleural tumor and lymphocytes in the pleural effusion were analyzed using a polymerase chain reaction (PCR)-based assay. This analysis revealed the metachronous MALT lymphoma originated from a distinct B-cell clone. After rituximub and CHOP therapy, complete remission was obtained. Although MALT lymphoma occurs in a wide variety of body sites, the pleural presentation of MALT lymphoma is very rare. Lifelong observation of all patients treated for MALT lymphoma is required because of the high frequency of dissemination and recurrence.

Background: The diagnosis of centrally located intrapulmonary tumors not visible on bronchoscopy may be a challenge. Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) has been shown to be useful for the evaluation of mediastinal lymph nodes. However, there have been no reports of the utility of EBUS-TBNA for the diagnosis of intrapulmonary tumors. Objectives: The purpose of this study was to evaluate the usefulness of EBUS-TBNA for the diagnosis of intrapulmonary tumors located adjacent to the central airway. Methods: From December 2002 to June 2007, 35 patients with pulmonary masses located close to the central airways were accessed by EBUS-TBNA. Conventional bronchoscopic biopsy before EBUS-TBNA was nondiagnostic in 25 of the 35 cases. Patients with endobronchial lesions were excluded from this study. Results: EBUS-TBNA was performed in 19 peritracheal and 16 peribronchial lesions. Cytologic and/or histologic samples were diagnostic in 33 of 35 patients. The final diagnoses of the pulmonary masses were lung cancer in 26 cases (1 small cell lung cancer, 25 non-small cell lung cancer), metastatic lung tumors in 5, and BALT lymphoma in one. The sensitivity and the diagnostic accuracy Of EBUS-TBNA for the diagnosis of unknown pulmonary masses was 94.1% and 94.3%, respectively. Conclusions: Intrapulmonary lesions not assessable by conventional bronchoscopic procedures can easily be assessed and diagnosed by EBUS-TBNA as long as it is within the reach of the EBUS-TBNA scope. EBUS-TBNA is a real-time procedure with a high yield which can be applied for the diagnosis Of lung tumors.

Acute respiratory distress syndrome after pulmonary resection for lung cancer frequently has a lethal outcome. Treatment with a combination therapy of neutrophil elastase inhibitor and steroid administration was used to achieve good control, without impairing lung function, in a patient with postoperative acute respiratory distress syndrome. A 74-year-old man was diagnosed with lung cancer and referred to the outpatient department of Chiba University Hospital with double primary lung cancers located in the right upper lobe that were staged at T2N0M0 (stage IB). He underwent right upper lobectomy with hilar and mediastinal lymph node dissection. After 10 postoperative days, he had acute respiratory distress syndrome. He was given a corticosteroid and a neutrophil elastase inhibitor, which resulted in rapid improvement without lung dysfunction. © 2008 The Japanese Association for Thoracic Surgery.

We report a case of α-fetoprotein (AFP)-producing pulmonary carcinoma with studies for messenger RNA (mRNA) expression of hepatocyte nuclear factor (HNF)-4α, which is a transcription factor that is highly expressed in the process of liver development. The patient was a 64-year-old man with a pulmonary tumor in his left lower lobe. Serum AFP was 673 ng/mL. The microscopic analysis of the surgical specimen revealed a large cell neuroendocrine carcinoma with occasional hepatoid foci. The competitive reverse transcriptase polymerase chain reaction analysis revealed that HNF-4α mRNA was expressed on the order of 102- to 103-fold more abundantly than control pulmonary carcinomas and normal lung tissues. In addition, AFP and HNF-4α expression was restricted in hepatoid foci. Two previously reported cases of AFP-producing pulmonary carcinoma were also positive, whereas all 18 control pulmonary carcinomas were negative for HNF-4α. These findings suggest that aberrant expression of HNF-4α is implicated in the emergence or maintenance of hepatoid foci in AFP-producing pulmonary carcinomas. © 2008 Elsevier Inc. All rights reserved.

Background: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is an accurate tool for lymph node staging of non-small cell lung cancer (NSCLC). Most patients with NSCLC require systemic chemotherapy during their treatment, with relatively poor responses. If the response to chemotherapy could be predicted, ideally at the time of the initial bronchoscopic examination, the therapeutic benefit could be maximised while limiting toxicity. A study was therefore undertaken to investigate the feasibility of EBUS-TBNA for obtaining tissue samples from mediastinal lymph nodes that can be used for immunohistochemical analysis, and to stratify patients with molecular-based pN2-NSCLC into chemoresponsive and chemoresistant subgroups who might benefit from tailoring of chemotherapy. Methods: The expression of six cell cycle-related proteins (pRb, cyclin D1, p16(INK4A), p53, p21(Waf1), Ki-67) in mediastinal lymph node specimens obtained by EBUS-TBNA was investigated by immunohistochemistry in 36 patients with pN2-NSCLC. Their predictive role(s) in the response to platinum-based chemotherapy was examined. Results: Immunostaining was feasible in all studied specimens. Univariate analysis revealed that p53 and p21(Waf1) expressions were significantly related to the response to chemotherapy (p=0.002 and p=0.011, respectively). Multivariate logistic regression analysis revealed that only p53 overexpression was associated with a poor response to chemotherapy (p=0.021). Conclusions: These results suggest that EBUS-TBNA is a feasible tool for obtaining mediastinal nodal tissue samples amenable for immunohistochemical analysis. Immunostaining of p53 in EBUS-TBNA-guided specimens may be useful in predicting the response to chemotherapy in patients with N2-NSCLC and helping in the selection of patients who might benefit from certain chemotherapeutic strategies.

Chemokines play an important role in the pathogenesis of non-small cell lung cancer (NSCLC). However, aberrant methylation of CXCL12 has not been examined in NSCLC. CXCL12 mRNA expression and methylation were examined in 17 NSCLC cell lines by RT-PCR and methylation-specific PCR (MSP). MSP was performed on 236 tumor specimens from NSCLC patients who received curative intent surgery. CXCL12 and CXCR4 protein expression was examined in 90 of the 236 NSCLC specimens by immunohistochernistry. Down-regulation of CXCL12 expression was found in 10 of 17 (59%) NSCLC cell lines compared with normal bronchial cells. Treatment of 8 expression-negative cell lines with a demethylating agent restored expression in all cases. Twelve cell lines (71%) showed aberrant methylation, and good concordance between methylation and expression was present. Aberrant methylation occurred in 85 out of 236 (36%) primary NSCLCs in a tumor-specific manner. In multivariate analysis, CXCL12 methylation correlated strongly and independently with prognosis both in all patients with NSCLCs and in those with stage I NSCLCs (hazard ratio=1.68, P=0.015 and hazard ratio=3.58, P=0.017). Secreted protein CXCL12 and its receptor CXCR4 were abundant in NSCLC cells (72 out of 90, 80%; 57 out of 90, 63%) and correlated with the progression of NSCLCs. In conclusion, epigenetic silencing of CXCL12 is a frequent event in NSCLCs, and could be an independent and powerful prognostic marker in patients with NSCLCs and those with stage I disease. Analysis for CXCL12 may provide novel opportunities for prognosis and therapy of resected NSCLCs.

During a recent investigation of LKB1 gene abnormality in lung lesions, strong expression of LKB1 protein in normal neuroendocrine (NE) cells of the bronchial epithelium was found. Because LKB1 functions as a tumor suppressor gene, the question of whether alteration of LKB1 expression is related to the development of pulmonary NE tumors of various grades was investigated. LKB1 immunohistochemistry was examined in a total of 68 primary pulmonary NE tumors consisting of 30 specimens of small cell lung carcinoma (SCLC), 23 large cell neuroendocrine carcinomas (LCNEC), two atypical carcinoids, and 13 typical carcinoids. Loss or low expression (&lt; 20% immunoreactive cells) of LKB1 protein expression was more frequently observed in high-grade NE tumors (SCLC and LCNEC; 45/53, 84.9%) than in typical and atypical carcinoids (3/15; 20%). The difference in LKB1 immunoreactivity between the high-grade NE tumors and the carcinoid group was statistically significant (P &lt; 0.0001). In conclusion, marked reduction of LKB1 expression in high-grade NE tumors of the lung suggests a possible role of LKB1 inactivation in its tumorigenesis. Although a few previous studies indicated rare genetic alterations of LKB1 in SCLC, further studies including analysis of other NE tumors and focusing on epigenetic abnormalities of LKB1 gene are warranted.