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The epidermal growth factor receptor (EGFR) variant type III (variously called EGFRvlll, de2–7 EGFR or ΔGFR) has an in‐frame deletion of the extracellular domain and is found in numerous types of ... human tumors. Since EGFRvlll has been reported to be tumorspecific and has oncogenic potential, it is being investigated as a potential therapeutic target. Because the cell‐specific expression of EGFRvlll in lung has not been well documented, we examined the expression of EGFRvlll in 76 non‐small cell lung cancers (NSCLCs) and 10 non‐neoplastic lung tissues by immunohistochemistry using a new monoclonal antibody specific for this variant receptor. We found a higher incidence (30 of 76, 39%) of enhanced EGFRvlll expression in NSCLC than previously described. Interestingly, the presence of EGFRvlll was also observed in several normal tissue components of lung (e.g., normal bronchial epithelium). Given the high prevalence of EGFRvlll in NSCLC, a newly developed phospho‐specific (activated) EGFR antibody was employed for immunohistochemical analysis that permitted visualization of activated EGFR and/or EGFRvlll in tumors. This study presents evidence, for the first time, that EGFRvlll expressed in human tumors is phosphorylated and hence activated. Our results suggest that the sustained activation of EGFRvlll is implicated in the pathogenesis of NSCLC and thus EGFRvlll is a potential therapeutic target in this challenging disease. (Cancer Sci 2003; 94: 50–56) more

This study was designed to determine the recommended dose of carboplatin and pemetrexed for elderly (≥70-year-old) chemotherapy-naïve patients with advanced nonsquamous non-small-cell lung cancer ... (NSCLC) and to investigate the pharmacokinetics of pemetrexed. The patients were treated with 4-6 cycles of carboplatin plus a fixed dose of pemetrexed (500 mg/m(2)) every 3 weeks; the dose of carboplatin was escalated from area under the curve (AUC) 4 to AUC 6. To examine the pharmacokinetics of pemetrexed, blood samples were collected before and after pemetrexed infusion, and the blood levels of pemetrexed were measured by liquid chromatography-mass spectrometry. Grade 3 infection as a dose-limiting toxicity was observed at a carboplatin dose of AUC 6. We therefore determined a carboplatin dose of AUC 5 and a pemetrexed dose of 500 mg/m(2) as the recommended doses from this study. The pharmacokinetic study showed a significant inverse correlation between the AUC of pemetrexed and the creatinine clearance. For elderly chemotherapy-naïve patients with advanced nonsquamous NSCLC, the combination of carboplatin AUC 5 plus pemetrexed 500 mg/m(2) is recommended as a promising regimen; however, a reduction of the pemetrexed dose may be required for patients with renal dysfunction because of the high risk of hematotoxicities. more

Paragonimiasis is a parasitic pleuropulmonary infection caused by eating raw crustaceans and wild boar meat and this infection is endemic in Asia. We herein report two cases of pulmonary Paragonimus ... westermani infection associated with elevated levels of serum immunoglobulin (Ig) G4 and dense infiltration of IgG4‐positive plasma cells in the lung lesions. Treatment with praziquantel resolved the pulmonary lesions and decreased the serum levels of IgG4. IgG4‐related disease is a systemic disease occasionally involving the lungs and leads to increased serum levels of IgG4. Our findings suggest that P. westermani infection requires a differential diagnosis from IgG4‐related diseases and the serum IgG4 level may be a potentially useful marker of P. westermani infection. Paragonimiasis, a parasitic pleuropulmonary infection caused by eating raw crustaceans and wild boar meat, is endemic in Asia. We report two cases of pulmonary Paragonimus westermani infection with elevated levels of serum IgG4 and dense infiltration of IgG4‐positive plasma cells in lung lesions both resolved with praziquantel treatment. Our findings suggest that serum IgG4 level may be a useful marker of Paragonimus westermani infection. more

58歳男性．肺腺癌術後補助化学療法目的で入院中に左半側空間無視を発症し，同時に低酸素血症も出現した．MRIで右前頭葉皮質に脳梗塞，造影CTで肺塞栓症および下肢静脈血栓症を認めた．凝固異常もあり，がん関連血栓塞栓症と診断し，DOACで再発予防を行ったが，第24病日に再梗塞を認めた．ワルファリンに変更したが，第45病日に肺塞栓症再発を認めた．高次医療機関に転院し，未分画ヘパリン皮下注を開始，血栓症のコントロールが可能となった．術後補助療法中止後の肺癌再発症例であったが，抗血栓療法で再発なく，状態が改善したため，免疫チェックポイント阻害薬での癌治療を開始した結果，長期生存が可能となった．癌治療の進歩によって，進行期癌においても生命予後は改善しているが，本症例の如く，がん関連血栓塞栓症は増加していくと考えられ，未分画ヘパリン皮下注を含めた2次再発予防の重要性が示唆された．

Although characteristics of intraepithelial lymphocytes (IELs) in mucosal immunity have been well defined in the intestine, bronchial IELs have been little investigated. Recently, we showed that ... bronchial IELs have a distinct function that partly resembles that of intestinal IELs; however, surface antigen expression of bronchial IELs and the relationship of that expression to airway disease have not been studied. We analyzed phenotypic profiles of human bronchial IELs and lamina propria lymphocytes (LPLs) by double-staining immunohistochemistry using full-thickness bronchial specimens (10 nonasthmatic controls and 7 asthmatics) from lung resections. In controls, the percentage of CD4+ cells was lower, and the percentage of CD8+ cells was higher in IELs compared to LPLs (CD4: median 50.0% in IELs vs. 65.9% in LPLs, p = 0.01; CD8: 50.9% in IELs vs. 34.4% in LPLs, p = 0.007). The percentage of cells positive for CD103 (αE-integrin) was higher in IELs than that in LPLs (median 60.1% in IELs vs. 16.9% in LPLs; p < 0.001). In IELs from asthmatics, these characteristics were particularly significant (CD4: median 26.2%, p = 0.008; CD8: 79.8%, p = 0.007; CD103: 76.2%, p = 0.019; all compared with IELs from nonasthmatics). These results suggest that human bronchial IELs have roles distinct from subsets of other lymphocytes, and that CD8+ cells and CD103+ cells have potentially important functions in the bronchial epithelium. more

Paragonimiasis is a parasitic pleuropulmonary infection caused by eating raw crustaceans and wild boar meat and this infection is endemic in Asia. We herein report two cases of pulmonary Paragonimus ... westermani infection associated with elevated levels of serum immunoglobulin (Ig) G4 and dense infiltration of IgG4‐positive plasma cells in the lung lesions. Treatment with praziquantel resolved the pulmonary lesions and decreased the serum levels of IgG4. IgG4‐related disease is a systemic disease occasionally involving the lungs and leads to increased serum levels of IgG4. Our findings suggest that P. westermani infection requires a differential diagnosis from IgG4‐related diseases and the serum IgG4 level may be a potentially useful marker of P. westermani infection. more

Background. Extranodal natural killer (NK)/T-cell lymphoma, nasal type (ENKL) is a rare disease. In particular, primary pulmonary ENKL (primary pulmonary NK/T-cell lymphoma) is more rare. Case. A ... 71-year-old woman who had treated for interstitial pneumonia with systemic sclerosis presented new consolidations in both upper lobes and multiple nodules. Atypical cells were shown by repeated bronchoalveolar lavage and immunostaining and EBV-associated examination suggested NK/T-cell lymphoma. The patient was treated with chemotherapy, but she died on the 8th day after the chemotherapy because of progressive of respiratory failure. The autopsy showed NK/T-cell lymphoma in the lung and no lesion other than the lung including nasal cavity. Conclusion. We report a very rare case of primary pulmonary ENKL diagnosed by bronchoalveolar lavage. more

Case. A 28-year-old man was referred to our hospital because of fever for 2 months, obstruction of the truncus intermedius, obstructive pneumonia in the right middle and lower lobes, and hilar and ... mediastinal lymphadenopathies. Three bronchofiberscopy procedures showed a polyp in the truncus intermedius and histopathology of the lesion showed non-specific inflammation. Because hilar and mediastinal lymphadenopathies were so large as to suggest malignancy, we performed bronchofiberscopy to resect the polyp by a high frequency snare under general anesthesia. At resection, we found a plastic foreign body at the peripheral site, and we removed it. The patient remembered that he aspirated it when he was drunk 3 years previously. Obstructive pneumonia was improved by additional treatment of an antibacterial agent and the hilar and mediastinal lymphadenopathies gradually reduced. Histological analysis of the polyp was inflammation. We concluded that recurrent obstructive pneumonia with hilar and mediastinal lymphadenopathy was induced by the inflammatory polyp which was caused by the plastic foreign body aspirated 3 years previously. Conclusion. Plastic as a bronchial foreign body is hard to recognize because it is not radio-opaque. Therefore, this case suggests considering a diagnosis of foreign body in a case of inflammatory polyp in the bronchus and hilar and mediastinal lymphadenopathies. more