Kikuo Nakano

Significance of pulmonary artery pressure in emphysema patients with mild-to-moderate hypoxemia

The guidelines of the Global Initiative for Chronic Obstructive Lung Disease (GOLD) do not recommend the measurement of pulmonary artery pressure in patients with chronic obstructive pulmonary disease (COPD). This is on the basis that the mean pulmonary artery pressure (mPAP) does not provide more clinical information than measurement of the oxygen tension in arterial blood (PaO2). The mPAP correlates well with PaO2 in emphysema patients with severe hypoxemia (PaO2 < or = 7.3 kPa (55 mmHg)). However, the occurrence and significance of mPAP is unclear in patients without severe hypoxemia (PaO2 > 7.3 kPa (55 mmHg)). In order to evaluate the usefulness of measurement of mPAP in emphysema patients without severe hypoxemia, we performed right heart catheterization and investigated the pulmonary hemodynamics of 53 patients without severe hypoxemia. In addition, we identified long-term prognostic factors with a mean follow-up term of 77 months after right heart catheterization. Seventeen of 27 patients with mild-to-moderate hypoxemia exhibited pulmonary hypertension (mPAP > or = 2.7 kPa (20 mmHg)) and the classification according to severity in GOLD exhibited a greater correlation to mPAP than PaO2. Moreover, only mPAP was found to be a significant prognostic factor according to multivariate proportional hazards analysis (P = 0.01). We conclude that mPAP is more informative about the severity of emphysema than PaO2 in patients with mild-to-moderate hypoxemia.

Methylation of breast cancer susceptibility gene 1 (BRCA1) predicts recurrence in patients with curatively resected stage I non–small cell lung cancer

Even after early detection and curative resection of early stage non–small cell lung cancer (NSCLC), a significant fraction of patients develop recurrent disease. Molecular biomarkers that can predict the risk of recurrence thus need to be identified to improve clinical outcomes.

Methylation of Breast Cancer Susceptibility Gene 1 (BRCA1) Predicts Recurrence in Patients With Curatively Resected Stage I Non-Small Cell Lung Cancer

BACKGROUND: Even after early detection and curative resection of early stage non–small cell lung cancer (NSCLC), a significant fraction of patients develop recurrent disease. Molecular biomarkers that can predict the risk of recurrence thus need to be identified to improve clinical outcomes. METHODS: Using the methylation-specific polymerase chain reaction assay, promoter methylation of the breast cancer susceptibility gene 1 (BRCA1) was assessed in cancer tissues from 70 patients with curatively resected stage I NSCLC. The clinical relevance of BRCA1 methylation status was evaluated in terms of outcome of the disease. RESULTS: Methylation of the BRCA1 promoter was detected in 13 of 70 patients (18.6%). Multiple logistic regression analysis revealed that BRCA1 methylation was an independent risk factor for recurrence (P ¼ .0197) and that patients with BRCA1 methylation demonstrated significantly poorer recurrence-free survival compared to those without (P ¼ .0139). Cox’s proportional hazard regression analysis revealed that BRCA1 methylation was an independent risk factor for recurrence-free survival (P ¼ .0155). CONCLUSIONS: Methylated BRCA1 can be a potential biomarker that predicts the prognosis after curative resection of stage I NSCLC. Considering that BRCA1 plays a role in chemotherapy-induced apoptosis, it is plausible that identification of methylated BRCA1 could provide information that is clinically relevant to tailored adjuvant therapy. Cancer 2013;119:792–8. V C 2013 American Cancer Society.

The Effective Treatment of Lung Infection Due to Scedosporium prolificans with Voriconazole and Surgery

Scedosporium prolificans is a fungus that has demonstrated resistance against most currently available antifungal agents and which causes a rapidly disseminating and potentially fatal infection. A 68-year-old woman presented with a fever and consolidation in the lung field. Her symptoms and inflammatory reaction did not improve despite treatment with tazobactam/piperacillin, meropenem, and micafungin. Scedosporium prolificans was detected from the patients bronchial lavage fluid, and we initiated treatment with voriconazole. Voriconazole was effective in shrinking the consolidation and suppressing the inflammatory reaction. The residual lesion was surgically resected because of the risk of systemic dissemination. The patient is currently alive without relapse or dissemination.

A case of familial hot tub lung.

Hot tub lung is a lung disease caused by Mycobacterium avium complex. We report the first case of familial hot tub lung appearing simultaneously in a husband and wife. Our case supports the consideration that hot tub lung is a hypersensitivity pneumonitis rather than an infectious lung disease. It also suggests that the state of hot tub lung changes seasonally depending on temperature variations, in a manner similar to summer-type hypersensitivity pneumonitis. This case demonstrates similarities between hot tub lung and summer-type hypersensitivity pneumonitis in regards to familial occurrence and seasonal changes in the disease state.

Implication of DNA Methylation Profiling in Oral Epithelium for Lung Cancer Screening

In lung cancer, the roles of molecular alterations in blood, sputum, bronchial brushing, and exhaled gas samples, which are relatively easy to obtain, have been evaluated for clinical availability. This study was based on the hypothesis that similar molecular alterations occur in the lung and oral cavity because both are exposed to the same environmental or tobacco-derived carcinogens. Because epigenetic alterations due to exposure to carcinogens are thought to play a major role in the development of lung cancer, the DNA methylation status of 11 genes in the oral epithelium was analyzed in lung cancer patients () and control individuals without lung cancer (). DNA methylation profiling revealed that GDNF, RARB, and HS3ST2 were methylated more frequently in cancer patients than in the control participants (, 0.0062, and 0.0193, resp.). Combined analysesindicatedthat 6 of 16 cancer patients (37.5%), but only 1 of 32 control individuals (3.1%) showed DNA methylation in 2-3 of these 3 genes (). These combined analyses showed the high specificity and positive predictive value in total and subgroup analyses. Our data suggest that DNA methylation profiling using oral epithelium may help in the identification of individuals with a high risk of lung cancer.

Two Cases of Malignant Pleural Mesothelioma Treated With Chemotherapy Plus Concurrent High-dose Hemithoracic Radiation After Extrapleural Pneumonectomy

背景.悪性胸膜中皮腫の根治治療として局所制御を狙った集学的治療が試みられているが, 依然として局所再発による腫瘍死が多い. 著者らは悪性胸膜中皮腫2例に対し胸膜肺全摘出術後に同時放射線化学療法を追加する集学的治療を行ったので報告する. 症例. 50歳と60歳の男性で, いずれも悪性胸膜中皮腫の上皮型で臨床病期Stage Iであった. 胸膜肺全摘術を行い2カ月後に, 片側胸郭に50Gyの放射線照射とシスプラチン6mg/m2 (連日) +ビンデシン3mg/m2 (週1回) との同時併用を追加した. Grade 3以上の毒性は2例とも好中球減少だけであり, 治療は遅延なく完遂できた. 2例とも切除断端の一部に腫瘍細胞を認めたが, 照射野内には再発しなかった. いずれも照射野外に再発したが1例は術後22カ月間生存中であり, 他方1例は術後10カ月で細菌性肺炎のため死亡した. 結論. 悪性胸膜中皮腫に対する胸膜肺全摘出術と同時放射線化学療法は, 耐用可能で局所制御を改善できる集学的治療と考える.

A Case of Malignant Fibrous Histiocytoma of the Lung.

-Background. Malignant fibrous histiocytoma (MFH) originating in the lung is a rare tumor. We report a surgically resected case. Case. A 76-year-old man had a complaint of cough for six months. A chest X-ray revealed an abnormal shadow in the left lung. A computed tomography of the lung showed a tumor 6cm in diameter in the superior segment of his left lower lobe. At first, preoperative cytological examination of the curetted specimen through fiberoptic bronchoscope revealed squamous cell carcinoma. Left lower lobectomy with systematic lymph node dissection was performed. The tumor was 10•~6.5•~5.5cm in size. Postoperative histopathological findings revealed MFH of the lung. Lymph node metastasis was not recognized. Adjunctive chemotherapy was intended but so far not done because of prolonged postoperative elevation of fever and his age. Six months after the operation, right adrenal metastasis was pointed out, so right adrenectomy was done. He is doing well without any sign of recurrence one year since then. Conclusion. We found only 54 cases of MFH originating in the lung in the Japanese literature, but recently the number of reported cases has been increasing. The prognosis of MFH of the lung is said to be poor. Effectiveness of chemotherapy or radiation therapy has not been established, so only curative surgical resection is effective. (JJLC. 2002; 42: 631-635) KEY WORDS-Malignant fibrous histiocytoma, Lung tumor, Adrenal metastasis 国立病 院呉 医療セ ンター1呼 吸 器外 科,2呼 吸器科,3検 査 科;4現 大阪大学大学 院医学系研究科臓器制御外科学;5現 国 立療養所愛媛病院呼吸器外科;6現 大阪府立羽曳野病院外科. 別刷請求先:遠 藤俊治,大 阪大学大学院医学系研究科臓器制御 外科学,〒565-0871大 阪府吹田市 山田丘2-2 E1. Department of 1 General Thoracic Surgery, 2 Pulmonology, 3Pathology, National Hospital Kure Medical Center, Japan; 4 Dr Endo is now with Department of Surgery, Osaka University Graduate School of Medicine, Japan; 5 Dr Nakamura is now with Department of Chest Surgery, Ehime National Hospital for Chest Disease, Japan; 6 Dr Sakaguchi is now with Department of Surgery, Osaka Prefectural Habikino Hospital, Japan. Reprints: Shunji Endo, Department of Surgery, Osaka University Graduate School of Medicine, E1, 2-2, Yamadaoka, Suita-shi, Osaka 565-0871, Japan. Received December 10, 2001; accepted August 26, 2002

Concurrent high-dose thoracic irradiation plus daily low-dose cisplatin and vindesine in locally advanced unresectable stage III non-small cell lung cancer.

Patients with unresectable non small-cell lung cancer were treated to evaluate the toxicity and efficacy of high-dose thoracic irradiation (RT) combined with concurrent daily cisplatin plus vindesine. Fourteen evaluable patients with unresectable stage III non small-cell lung cancer treated with continuous-course RT (70 Gy in 35 fractions of 2 Gy once daily) and concurrent daily intravenous cisplatin (6 mg/m2) plus vindesine (3 mg/m2 on day 1 and day 8). The objective response rate was 86%, and two patients achieved a radiographic complete response. Leukocytopenia was the severe toxicity, but there were no episodes of discontinuation of treatment. Only one patient had grade 3 acute radiation esophagitis. Ten patients experienced late radiation pneumonitis and nine of those had grade 1 or grade 2. There was only one life-threatening case of toxicity (grade 5 pneumonitis). We concluded that the regimen of high-dose thoracic RT combined with concurrent daily cisplatin plus vindesine obtained a high response rate. Further testing on late toxicities and survival time is required.

A Case of Primary B Cell Lymphoma of the Lung.

症例は50歳の男性.検診にて右下肺野のair bronchogramを伴う腫瘤状陰影を指摘された.気管支鏡下肺生検標本の組織像にて異型性の少ない小型リンパ球の密な増殖を認め, 悪性リンパ腫が否定できないことから右下葉切除術を施行された.切除標本の免疫染色像ではIgMλのみが陽性となり, また, flow cytometoryでは表面マーカーのCD19と20が著増しており, 表面免疫グロブリンのlgMλが著増していた.この結果, 肺原発の非ポジキンリンパ腫 (diffuse, small cell type) と診断した.Southern blot法による切除標本の遺伝子解析では免疫グロブリンのみに明らかな遺伝子再構成が認められ, 免疫染色の診断を裏付ける結果を得た.術後は後療法を行わず経過観察中であるが, 3年を経過した現在, 再発は認めていない.本疾患の診断には免疫組織染色に加え, 遺伝子再構成の確認が重要であると考えられる.