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Chronic obstructive pulmonary disease (COPD) is a risk factor for osteoporosis. Nevertheless, much remains unclear regarding the bone metabolism dynamics associated with COPD. The present study focuses on the associations between the COPD severity and serum bone metabolism biomarkers.

The post-surgical follow-up strategy in non-small cell lung cancer (NSCLC) is still controversial. Data on factors that affect the interval between surgery and recurrence or predict survival after recurrence in NSCLC patients are still limited.

The purpose of this study was to evaluate the efficacy and toxicity of the postoperative radiotherapy in patients with incompletely resected NSCLC, and to investigate whether the histological subtype is a prognostic factor. Forty-one incompletely resected NSCLC patients who underwent postoperative radiotherapy were retrospectively analyzed. The microscopic residual tumor (R1 group) was recognized in 23 patients, and the macroscopic residual tumor (R2 group) in 18. The postoperative pathological stages were I (n = 3), II (n = 8), IIIA (n = 17), and IIIB (n = 13). The histology included squamous cell carcinoma (n = 23), adenocarcinoma (n = 14) or other types (n = 4). The first site of disease progression was distant metastases alone for 3 (13%) of 23 with squamous cell carcinoma, and for 9 (64%) of 14 with adenocarcinoma (p < 0.01). The 5-year overall, local control, disease-free, and distant metastasis-free survival rates were 56%, 63%, 37% and 49%. Univariate analyses showed that squamous cell carcinoma histology, N0-1 stage and the R1 group were significant predictors for better disease-free and distant metastasis-free survival. Multivariate showed that squamous cell carcinoma and N0-1 stage were significant predictors for better distant metastasis-free survival. Toxicity was generally mild; Grade 3 toxicities occurred in 3 patients (neutropenia, radiation pneumonia and esophageal stenosis), and no acute and late toxicities of Grade 4 to 5 were observed. In conclusion, postoperative radiotherapy for incompletely resected NSCLC could achieve a relatively high local control rate without severe toxicity. However, different treatment strategies for non-squamous cell carcinoma should be considered, because of the higher risk for the distant metastases.

Endobronchial lipoma is a rare, benign disease. When it causes chronic cough and pneumonia due to obstruction of the central airway, appropriate treatment is required. We herein report 2 cases of endobronchial lipoma successfully treated with a high-frequency electric snare through a flexible bronchoscope. Case 1, an 83-year-old man, visited a nearby hospital because of dyspnea on exertion. Chest computerized tomography revealed a tumor in the right main bronchus. He was referred to our hospital for further examination and treatment. Bronchoscopy showed a polypoid lesion in the right main bronchus. The tumor was resected by high-frequency electric snare through a flexible bronchoscope. Case 2 was an 83-year-old man who was diagnosed with pneumonia by a primary care physician on the basis of findings on chest computerized tomography. Bronchoscopy showed a polypoid lesion at the orifice of the right B6 bronchus, which caused segmental obstructive pneumonia. The tumor was bronchoscopically resected using a high-frequency electric snare and an neodymium-yttrium-aluminum-garnet laser. In both cases, the pathologic diagnosis was endobronchial lipoma.

Aberrant methylation of the promoter CpG island (methylation) is known as a major inactivation mechanism of tumor suppressor and tumor‐related genes. In this study, the authors studied the presence of methylation by investigated the inactivation of genes and prognostic factors in patients with nonsmall cell lung carcinoma (NSCLC) by examining resection samples for the presence of methylation.Samples were obtained from 224 patients who underwent pulmonary resection for NSCLC. The authors used those samples to study methylation status with methylation‐specific polymerase chain reaction analysis and to study protein expression with immunohistochemistry for 3 different genes: CDH1, p16INK4A, and fragile histidine triad (FHIT).The frequency of methylation in NSCLC was determined as 58.0% for CDH1, 21.9% for p16INK4A, and 52.2% for FHIT. The methylation of p16INK4A was observed significantly in heavy smokers compared either with nonsmokers or with patients who had smoked for <20 pack‐years (P = .0420); it also was more significant in squamous cell carcinomas than in adenocarcinomas (P = .0343). FHIT methylation also was correlated significantly with lymph node metastasis (P = .0361). Patients who had tumors with both methylation and reduced expression of CDH1 had a significantly poorer prognosis compared with patients who had tumors both without methylation and with positive expression of CDH1 (P = .0259 and P = .0369, respectively; multivariate Cox analysis). For p16INK4A methylation, 63.3% of tumors showed reduced expression; whereas, in p16INK4A‐unmethylated tumors, 33.7% showed reduced expression (P = .0002). However, for CDH1 and FHIT, no significant correlation was found for either methylation or reduced expression.Although protein expression was not inactivated by methylation alone, p16 expression was inactivated strongly by methylation. In addition, the analysis of methylation and expression of CDH1 played a clinically important role in treatment strategies for patients with NSCLC. Cancer 2006. © 2006 American Cancer Society.

Lung carcinoma represents the most frequent cause of cancer death worldwide because of tumor metastases. The objective of the current study was to analyze the immunologic response during the progress of lung carcinoma metastasis.The authors established two tumor cell lines that were derived from primary and metastatic lesions in a patient with lung carcinoma (Patient G603). One cell line (G603L) was established from the primary lesion, and the other cell line (G603AD) was established from a metastatic lesion in the right adrenal gland 7 months after the patient underwent surgery for the primary lesion. Autologous regional lymph node lymphocytes were stimulated with CD80‐transfected G603L cells, then cytotoxic T lymphocytes (CTLs) were induced against both lung carcinoma cell lines.Both G603L cells and G603AD cells expressed Class I human leukocyte antigen, intracellular cell adhesion molecule 1, and lymphocyte‐associated antigen type 3 (LFA‐3), but not Fas or Fas ligand on their surfaces. By stimulation with CD80‐transfected G603L cells, 2 CTL clones (H2/17 and H2/36) were established from the bulk CTLs. CTL clone H2/17 lysed G603L cells but not G603AD cells, suggesting that the antigen recognized by CTL clone H2/17 was abrogated during the process of metastasis. In contrast, CTL clone H2/36 lysed both G603L cells and G603AD cells, indicating that the antigen recognized by CTL clone H2/36 was maintained in the tumor cells throughout tumor progression.The results demonstrated the possibility that some tumor‐associated antigens may be abrogated during the process of metastasis, although others are maintained. The identification of these antigens will lead to a better understanding of their immunologic role during disease progression in patients with lung carcinoma. Cancer 2005. © 2004 American Cancer Society.

Human lung adenocarcinoma‐specific cytotoxic T lymphocytes (CTL) were generated by multiple stimulations with autologous tumor cells (named A110L) from regional lymph node lymphocytes and tumor‐infiltrating lymphocytes expanded by solid‐phase anti‐CD3 monoclonal antibody (mAb) and recombinant interleukin‐2. The CTL lysed A110L but failed to kill either autologous B lymphocytes immortalized by the Epstein‐Barr virus or K562. The killing activity of the CTL against autologous A110L was inhibited by anti‐MHC class I mAb (W6/32), but not by anti‐MHC class II mAb. The CTL produced interferon‐γ and GM‐CSF in response to A110L and the production was completely blocked by the addition of anti‐MHC class I mAb. The HLA type of the CTL was HLA‐A2/A24, B52/B54, Cw1/‐. Allele‐specific deletion of HLA‐A2 molecules was observed in A110L by staining with anti‐HLA‐A2 mAb. A partial blocking effect on the cytokine production from the CTL was also obtained with anti‐CD8, and anti‐HLA‐A24 mAbs, but not with anti‐MHC class II, anti‐CD4 and anti‐HLA‐A2 mAbs. To analyze further the mechanism of antigen recognition by the CTL, the cross reactivity of the CTL against several HLA‐A locus‐matched (HLA‐A24+) and mismatched allogeneic tumor cells (HLA‐A24‐) was investigated. The A110L‐specific CTL showed a weak but significant cytotoxicity against some HLA‐A24 positive lung cancer cell lines, such as Sq‐1 (HLA‐A11/A24, squamous cell carcinoma) and PC‐9 (HLA‐A2/A24, adenocarcinoma), but failed to kill HLA‐A locus‐mismatched allogeneic tumors. This cross reactivity of the CTL against Sq‐1 and PC‐9 was blocked by anti‐MHC class I mAb. These results thus demonstrate that shared common tumor antigens might exist among lung cancer cells in the context of HLA‐A24.

To induce cytotoxic T lymphocytes (CTL) against non‐small cell lung cancer (NSCLC) efficiently, the induction of CTL was attempted using HLA‐A locus‐shared allogeneic NSCLC cells. T cells derived from either tumor tissue specimens or the regional lymph nodes of patients with NSCLC were stimulated twice or three times with an HLA‐A2/A24‐positive NSCLC cell line (PC‐9), and thereafter the cytotoxic activity was examined by 51Cr‐release assay. In patients with HLA‐A24/ adenocarcinoma, anti‐PC‐9 cytotoxicity was induced in all 6 patients tested. Anti‐PC‐9 cytotoxicity was induced in 2 out of 5patients with HLA‐A2 (A24−)/adenocarcinoma, in 2 out of 4 patients with HLA‐A24/squamous cell carcinoma, and 1 of 2 patients with HLA‐A2/squamous cell carcinoma. The cytotoxic activity was observed to kill PC‐9 selectively, not other NSCLC lines, and the activity was substantially blocked by anti‐MHC class I antibody, but not by anti‐MHC class II antibody. The PC‐9‐specific CTL produced γ‐interferon in response to autologous tumor cells. These results indicated that the anti‐PC‐9 cytotoxicity was mediated by cytotoxic T lymphocytes that may recognize the T cell epitope(s) shared and presented by HLA‐A2 and/or HLA‐A24‐positive NSCLC.

We report herein a rare case of a 53 year old man with a benign lymphangioma of the small intestine. He presented with a complete obstruction of the small intestine and radiological examination revealed a small intestinal tumor. A long intestinal tube was passed, the intestinograms from which detected a submucosal tumor of the small intestine. Partial resection of the small intestine was thus performed and the tumor was found to be located mainly in the submucosa. The final pathological diagnosis was made as cavernous lymphangioma. This case is presented with a description of the roentgen appearance, followed by a review of the Japanese literature.

Aspergillosis was diagnosed in a 69-year-old man presenting with blood-stained sputum, and was treated with an antifungal agent. As radiographic lesions persisted after 3 months, left upper lobectomy was performed. The surgical specimen revealed pulmonary carcinoma associated with an intracavitary aspergillar infection.

Lung cancer‐specific cytotoxic T lymphocytes (CTL) were induced by repeated stimulations of regional lymph node lymphocytes (RLNL) in lung cancer patients with either autologous or HLA‐A‐locus‐matched tumor cells. To investigate the effect of interleukin‐12 (IL‐12), IL‐12 was added during the stimulation of RLNL from HLA A24 / adenocarcinoma patients with either autologous tumor cells or HLA A24‐positive adenocarcinoma cells (PC‐9) in combination with, or instead of interleukin‐2 (IL‐2), and then the cytotoxic activity, cytokine production and populations of the lymphocyte subsets were examined. The addition of IL‐12, or the substitution of IL‐2 by IL‐12 was found to enhance the cytotoxic activity and the cytokine production (IFN‐γ, GM‐CSF) of the CTL as compared with IL‐2 alone. The cytotoxic activity and cytokine production were both partially inhibited by anti‐MHC‐class I monoclonal antibody. The CTL thus induced by IL‐12 had a higher proportion of CD3+/CD56+cells than the CTL induced with IL‐2 alone. The positively selected CD8+/CD56–lymphocytes showed PC‐9‐specific cytotoxic activity, because the population did not show any cytotoxicity to K562 or A549 (HLA‐A26/A30). However, the CD3+/CD56+lymphocytes were cytotoxic to both PC‐9 and K562. In conclusion, IL‐12 is considered to be a useful cytokine for both the induction of lung‐cancer specific CTL and the augmentation of non‐MHC‐restricted cytotoxicity against tumor cells, and may be applicable for adoptive immunotherapy using CTL.

A rare case in tracheal invasion by a papillary carcinoma in an intrathoracic goiter is reported. Subtotal thyroidectomy and tracheoplasty were performed. Surgery should be considered as first-line treatment of intrathoracic goiter in order to avoid future compression of the respiratory tract and to remove possible concomitant malignant lesion.

Murine monoclonal antibodies were raised against 14-3-3 proteins, the antigen of human monoclonal antibody AE6F4 which had been shown potentially useful for the immunochemical diagnosis of lung cancer via sputum cytology. Enzyme-linked immunosorbent assays of the murine anti-14-3-3 monoclonal antibodies with isolated bovine brain 14-3-3 isoforms showed that the antibodies were classified into four different profiles of isoform reactivity. The comparison of 14-3-3 isoform and lung cancer tissue on the reactivity with murine monoclonal antibodies indicated that β isoform can be responsible for cancer recognition, whereas human monoclonal antibody AE6F4 showed preferential binding to ζ isoform. No murine monoclonal antibody of the same isoform specificity as human monoclonal antibody AE6F4 was obtained. Since murine monoclonal antibodies with different isoform specificities could immunostain lung cancer cells in sputum successfully, the combination use of murine monoclonal anti-14-3-3 antibodies with human monoclonal antibody AE6F4 is potentially usefol for facilitating the sputum cytodiagnosis of lung cancer.

Human monoclonal antibody (hMAb) AE6F4 has been shown to be potentially useful for immunocytological detection of lung cancer cells in sputum. By recombinant DNA technology, IgM type hMAb AE6F4 was switched to IgG. The IgG mimic recombinant AE6F4 antibody expression plasmid was assembled using the antibody heavy chain gene, which ligated the gene encoding VHand CH1 (μ) domains of hMAb AE6F4 heavy chain to the gene encoding CH2(γ 1) and CH3(γ1) domains of human IgG heavy chain, and the antibody light chain gene of hMAb AE6F4. The recombinant antibody expressed by baby hamster kidney (BHK) – 21 cells showed molecular size equivalence to IgG, and consisted of human μ–γ hybrid heavy and κ light chains. The immunological specificity of the recombinant antibody was the same as that of hMAb AE6F4 by immunoblotting analysis to the 14–3–3 protein, the putative antigen of hMAb AE6F4, and by immunohistochemical and immunocytological analyses using tissue sections and sputa of lung cancer patients. The transfected BHK-21 cells produced the recombinant antibody persistently and the productivity was greater than 20 times that by human-human hybridoma producing hMAb AE6F4.

Lactate dehydrogenase (LDH) and aspartate aminotransferase (AST) activities and total protein concentrations were examined in the postrinsing solutions from rat lungs preserved in phosphate-buffered saline (PBS), Euro-Collins (E-C) solution, or low-potassium E-C solution for 8 h at 4°C, 10°C, or 20°C. The LDH and AST activities were higher when the organs were preserved in PBS for 8 h at 20°C than at 4°C or 10°C, while the total protein concentration did not differ according to the temperature or solution. The activities were also higher when the lungs were preserved in Euro-Collins (E-C) solution than in PBS or the low-potassium E-C solution. On examining pulmonary functions utilizing an ex vivo reperfusion model, the lungs preserved at 20°C showed poorer gas exchange than those preserved at 4°C or 10°C. Moreover, the organs preserved in E-C solution showed poorer function than those preserved in any other solution. These findings suggest that some enzymatic activities in the postrinsing solution could be indicators of lung viability after preservation.

We describe herein a new experimental model in which an isolated rat lung was ventilated with a mixture of 95% nitrogen and 5% carbon dioxide to decrease the oxygen and increase the carbon dioxide in the perfused blood to create and maintain a gas composition similar to that of venous blood. By utilizing this system as a “deoxygenator,” pulmonary functions, including gas exchange, could be measured for at least 60 min in isolated and preserved lungs on reperfusion. When the effects of glucose in the flushing and storage solution were examined, 5 mM glucose in the solution resulted in better preservation of the lung, as shown by a higher uptake of oxygen and a lower intratracheal pressure, than when no glucose was given. However, the presence of 50 mM glucose was not beneficial, but rather increased the wet/dry weight ratio of the tissue.

Abstract: We report herein a rare case of primary lung cancer that occurred concomitantly with the calcified ova of a parasite. A 58-year-old man was referred to our department after a pulmonary abnormal shadow had been seen on a chest X-ray done at mass screening. A transbronchial lung biopsy (TBLB) revealed the calcified ova of a parasite. Because the possibility of concomitant lung cancer could not be ruled out, a lung biopsy was taken via video-assisted thoracic surgery (VATS). The pathological diagnosis was squamous cell carcinoma, and a left upper lobectomy was serially performed through a posterolateral thoracotomy. The patient recovered uneventfully and has remained in good health without any sign of recurrence for over 9 months. Following this case report, we review three other cases of this unusual disease combination documented in the literature.

We herein report the successful surgical treatment of 2 cases of chronic expanding hematoma in the chest. The first patient, who had undergone thoracoplasty 42 years earlier due to tuberculosis, became aware of a slowly growing mass protruding in the lateral thoracic wall. The second patient, who had tuberculous pleurisy 36 years earlier, was referred to our department because of a slowly expanding intrathoracic mass revealed by a roentgenogram. The tumors, which were encapsulated chronic hematomas, were both surgically resected. These cases are rare because of the development of a very large mass after undergoing treatment for tuberculosis more than 30 years previously.

AbstractWe here report a case presenting with the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) after having been treated for pleurodesis with OK-432, which is a lyophilized preparation of an attenuated strain of Streptococcus pyogenes. The patient, who had undergone a subtotal esophagectomy 4 years previously, was referred to our department after the diagnosis of a metastatic lung tumor. A right lower lobectomy of the lung was performed, and prolonged air leakage from a pulmonary fistula thereafter developed because of the dissection of severe pleural adhesion. OK-432 (5 klinische einheiten) was administered to the pleural cavity 3 times. On the 13th postoperative day, the patient began to complain of general fatigue and nausea. SIADH was diagnosed based on laboratory findings such as hyponatremia, serum hypo-osmolality and a high excretion of sodium in the urine. A restriction of the fluid intake with a sodium supplement resulted in the return to a normal serum level within 2 weeks. We therefore concluded that the intrapleural instillation of OK-432 had apparently caused SIADH in this case, because no other causes could be found.