廣島 健三

Bronchial dysplasiaを中心に蛍光気管支内視鏡による異常蛍光部位に対して拡大気管支ビデオスコープ(XBF-200HM2, オリンパス)を用いた気管支の微細観察を行った。喀痰細胞診要精査例を中心に31症例, 45部位に対して, 白色光気管支ビデオスコープによる検査の後, 蛍光気管支内視鏡を施行した。引き続き異常蛍光部位に対して拡大気管支ビデオスコープを用いた気管支の微細観察を行った後, 生検を施行し拡大気管支ビデオスコープ画像所見と病理組織学的所見とを比較検討した。更に拡大気管支ビデオスコープにて観察された気管支粘膜における血管所見に注目し, 画像解析装置を用いて描出された血管パターンの血管面積比の算出を行い比較検討した。異常蛍光部位の血管パターンは, type 1:微細な血管がわずかに認められる, type 2:血管網か血液のプーリングを認める, type 3:蛇行した血管網が錯綜している。以上3型に大別された。病理組織学的に, 正常もしくは気管支炎24部位では, 20部位がtype1かtype2であったが, dysplasia 21部位中15部位では, type 3が観察された。type 1:8部位, type 2:18部位, type 3:19部位の血管面積比の比較では, type 1は, 0.057±0.029, type 2は, 0.104±0.048, type 3は, 0.205±0.053であり, 各typeごとに推計学的有意差を認めた。正常もしくは気管支炎24部位とdysplasia 21部位の比較では, 0.108±0.071と0.173±0.067であり, dysplasiaグループは推計学的に有意に高値を呈した。以上より蛍光気管支内視鏡での異常蛍光部位には, 種々の程度の微細血管が観察されたが, 病理組織学的に, 正常または気管支炎に比べ, bronchial dysplasiaでは蛇行した血管網が錯綜, 増生しておりその血管面積比も高値を示し, bronchial dysplasiaと血管新生の関連が示唆された。

Bronchial dysplasiaを中心に蛍光気管支内視鏡による異常蛍光部位に対して拡大気管支ビデオスコープ(XBF-200HM2, オリンパス)を用いた気管支の微細観察を行った。喀痰細胞診要精査例を中心に31症例, 45部位に対して, 白色光気管支ビデオスコープによる検査の後, 蛍光気管支内視鏡を施行した。引き続き異常蛍光部位に対して拡大気管支ビデオスコープを用いた気管支の微細観察を行った後, 生検を施行し拡大気管支ビデオスコープ画像所見と病理組織学的所見とを比較検討した。更に拡大気管支ビデオスコープにて観察された気管支粘膜における血管所見に注目し, 画像解析装置を用いて描出された血管パターンの血管面積比の算出を行い比較検討した。異常蛍光部位の血管パターンは, type 1:微細な血管がわずかに認められる, type 2:血管網か血液のプーリングを認める, type 3:蛇行した血管網が錯綜している。以上3型に大別された。病理組織学的に, 正常もしくは気管支炎24部位では, 20部位がtype1かtype2であったが, dysplasia 21部位中15部位では, type 3が観察された。type 1:8部位, type 2:18部位, type 3:19部位の血管面積比の比較では, type 1は, 0.057±0.029, type 2は, 0.104±0.048, type 3は, 0.205±0.053であり, 各typeごとに推計学的有意差を認めた。正常もしくは気管支炎24部位とdysplasia 21部位の比較では, 0.108±0.071と0.173±0.067であり, dysplasiaグループは推計学的に有意に高値を呈した。以上より蛍光気管支内視鏡での異常蛍光部位には, 種々の程度の微細血管が観察されたが, 病理組織学的に, 正常または気管支炎に比べ, bronchial dysplasiaでは蛇行した血管網が錯綜, 増生しておりその血管面積比も高値を示し, bronchial dysplasiaと血管新生の関連が示唆された。

中葉症候群を伴った気管支結石症に対し中葉切除を施行した。症例は51歳女性。強い咳嗽発作を主訴とし, 前医にて中葉気管支の閉塞を指摘され, 加療目的に当科受診。胸部X線像にて中葉の無気肺を, 気管支鏡検査にて中葉支を閉塞する炎症性肉芽を認めた。中葉切除術を施行し, 術後症状の改善を見た。病理学的には結核を示唆する所見は見られなかったが, 画像所見, 手術所見より本症例は結核性と思われる石灰化したリンパ節の気管支内穿孔による気管支結石症であると考えられた。

We report six cases of pulmonary dirofilariasis diagnosed at our laboratory with clinical and pathological features. The nodules of dirofilariasis were round in three cases as previously reported, however dumbbell-shaped in two eases. The nodule did not attach to the pleura in four cases. Microscopically, the nodules were granulomas composed of central coagulation necrosis and peripheral fibrosis with round cell infiltration, histiocytes, and multinucleated giant cells. Necrotic pulmonary artery with single or multiple sections of degenerated nematode was observed in the center of the nodule. Dilated bronchioles with inflammation were observed in the nodule in four cases. Collapse of the alveoli, organizing pneumonia, hemosiderin-laden macrophages were observed around the nodule. We suppose that the nodule is not an infarction but a granuloma caused by antigen released from the nematode. Because the pulmonary dirofilariasis is difficult to be differentiated from primary or metastatic lung carcinoma, and the inflammation exists around the nodule, the nodule should be removed surgically. (C) 1999 Tohoku University Medical Press.

Intranuclear inclusion bodies are sometimes observed in pulmonary adenocarcinoma by light microscopy. Electron microscopic characteristics of lung cancer cells with intranuclear inclusion bodies were studied. In addition, polymerase chain reaction (PCR) was performed using primers coding for human papillomavirus (HPV) types 16, 18, and 33. Eosinophilic intranuclear inclusion bodies were observed in 22 out of 285 cases by light microscopy. Immunohistochemically, cancer cell nuclei stained with PE-10. Three types of intranuclear inclusion bodies were classified electron microscopically. Type A showed aggregation of electron dense particles (30-40 nm) with an electron-dense core and was most frequently observed. Type B consisted of a mass of branching and whirling tubular structures. Type B intranuclear inclusions had a relationship with inner nuclear membrane. In type C, several spherical inclusions were observed in one nucleus. HPV DNA was detected using PCR and type-specific probes in a case with type A inclusion bodies. This study suggests that intranuclear inclusion bodies in pulmonary adenocarcinoma are formed by several different mechanisms.

Background: Although the incidence of all cancers in Okinawa is the lowest in Japan, that of lung cancer is high. This study was performed to clarify the underlying mechanism of this tendency. Materials and Methods: Family histories of the lung cancer patients in Okinawa, p53 nutation, microsatellite alterations and titers of serum anti-p53 antibodies were examined. Results: The number of patients who had relatives with some malignancies in relatives was low in Okinawa, but lung cancer was frequently observed in their relatives. Overexpression of p53 protein was frequently observed in squamous cell carcinoma (SCC) than in adenocarcinoma (AD), and in smokers than in non-smokers. Anti-p53 antibodies were detected in 17.4%. The incidence of loss of heterozygosity at D3S643 and at IFNA were higher in SCC than in AD. Conclusions: Lung cancer was frequently observed in relatives of lung cancer patients Pulmonary SCC had different genetic alterations compared with pulmonary AD in Okinawa.

第984回千葉医学会例会・第33回肺癌研究施設例会

Purpose: The majority of lung carcinoma patients requiring resection have smoking habits prior to surgical treatment, and the correlation of smoking with postoperative complications is well known, However, few studies have investigated the correlation between long-term survival and cigarette smoking in patients with primary, resected lung carcinoma. We analyzed the relationship between clinical factors, including cigarette smoking before surgery, and 10-year survival in stage I nan-small-cell lung carcinoma (NSCLC). Patients and Methods: Cigarette smoking habit and other factors influencing either the overall survival or the disease-specific survival rates of patients with stage I primary, resected NSCLC were evaluated according to the Cox proportional hazards model using a total of 369 patients with stage I-NSCLC, Results: Comparison of the cause of death in patients with 30 or more pack-years and patients with less than 30 pack-years showed significant differences in the prevalence of recurrent disease and onset of nonmalignant disease, Multivariate analysis demonstrated significant correlations between overall survival and age and pack-years. Disease-specific survival showed significant correlations with age, tumor classification, and visceral pleural invasion. Conclusion: Smoking pack-years is an important clinical prognostic factor in evaluating overall long-term survival in patients with stage I primary, resected NSCLC. (C) 1999 by American Society of Clinical Oncology.

BACKGROUND. An accumulation of mutations can result in carcinogenesis. Comparing genetic alterations in preneoplastic lesions with those seen in cancer in the same patient may be helpful in the early diagnosis of lung carcinoma or preneoplastic lesions. METHODS. To identify genetic alterations that may play a role in the development of nonsmall cell lung carcinoma (NSCLC), the authors examined the p53 gene and microsatellite markers on chromosome 3p (D3S643, D3S1317), 9p (D9S171, IFNA) in 35 bronchial metaplastic lesions and 28 alveolar hyperplastic lesions from 61 patients. RESULTS. A total of 8 metaplastic lesions (I squamous metaplasia and 7 dysplasias) and 3 alveolar hyperplastic lesions (with atypia) showed genetic alterations, including loss of heterozygosity (LOH) of 3p, 9p and mutations of the p53 gene. In an analysis of microsatellite markers, 5 of 35 cases of squamous cell carcinoma (SCC) and 3 of 26 cases of adenocarcinoma (Ad) showed LOH in both preneoplastic lesions and synchronous cancers. Nine patients (25.7%) with SCC and 6 patients (23.1%) with Ad were shown to have mutations of the p53 gene by single-strand conformation polymorphism. In 2 of these 9 patients with SCC, the same mutation was observed in both dysplasia and SCC. CONCLUSIONS. These findings suggest that several genetic alterations may occur in preneoplastic lesions or the early stage of SCC of the lung, whereas the genetic alterations examined appeared to occur relatively late in the pathogenesis of pulmonary adenocarcinoma. (C) 1999 American Cancer Society.

A 47-year-old man was admitted to our hospital for treatment of an odontogenic infection, He presented with a fever, signs of sepsis, and neck swelling, and was initially diagnosed as having a neck abscess. After cervical drainage, he showed no improvement, and mediastinitis was detected by chest X-ray and computed tomography. A thoracotomy and mediastinal drainage was subsequently performed for descending necrotizing mediastinitis, which resulted in marked improvement. To date, only 83 cases of descending necrotizing mediastinitis have been reported in Japan, We present herein an additional case, followed by a review of the Japanese literature.

A 30-year-old woman was admitted to our hospital for investigation of an abnormal shadow in the right pulmonary hilus on a chest X-ray film, A percutaneous needle biopsy was performed, which revealed pulmonary blastoma. A right upper lobectomy was performed and the pathological stage was confirmed to be IIIa (T3N0M0). An analysis of preoperative cytological specimens showed that epithelial tumor cells,vith thin cytoplasm were either tubular or papillary, while some mesenchymal tumor cells with elliptic and spindle-shaped nuclei were also found in the necrotic background. Thus, pulmonary blastoma should be considered when a two-cell pattern consisting of both epithelial and mesenchymal components is observed. DNA analysis was performed on previously identified areas of the epithelial or sarcomatous components, using a microdissection method. An analysis of the p53 gene by the single-strand conformation polymorphysm method showed an abnormal band with shifted mobility of exon 8 in only the sarcomatous component.

Thymic undifferentiated carcinoma has a poor prognosis. We encountered a patient with thymic carcinoma associated with an intrathoracic disseminated lesion, who underwent surgery combined with intrathoracic hyperthermic perfusion after systemic chemotherapy and showed good,results. The 45-year-old mart was diagnosed as having a thymoma with an intrathoracic disseminated lesion. After he underwent three courses of systemic chemotherapy he was admitted to our hospital. An anterior mediastinal tumor and an intrathoracic disseminated lesion remained, and were treated by surgical resection combined with intrathoracic hyperthermic perfusion. The tumors were histopathologically! diagnosed as thymic undifferentiated carcinomas with pleural dissemination. At present, approximately 16 months after surgery the patient is alive without recurrence.

症例は53歳,男性.血疾を主訴とし,1998年3月近医を経て当科紹介受診.気管支鏡検査で有主気管支に結節状腫瘤を認め,生検で腺癌を示唆する悪性細胞を得た.右上幹,中間幹の粘膜は正常であり,気管支壁外浸潤はないことから縮小手術の適応と考え,右主気管支膜状切除。リンパ節郭清を施行した.組織学的には,多形性を示す唾液腺型腫瘍である粘表皮癌と診断された.リンパ節転移はなく,pT1N0M0,stage IAであった.本症例は病理組織学的診断に難渋した点,主気管支発生の粘表皮癌に対する術式の点で興味ある症例と考え報告した.

Thymic undifferentiated carcinoma has a poor prognosis. We encountered a patient with thymic carcinoma associated with an intrathoracic disseminated lesion, who underwent surgery combined with intrathoracic hyperthermic perfusion after systemic chemotherapy and showed good results. The 45-year-old man was diagnosed as having a thymoma with an intrathoracic disseminated lesion. After he underwent three courses of systemic chemotherapy, he was admitted to our hospital. An anterior mediastinal tumor and an intrathoracic disseminated lesion remained, and were treated by surgical resection combined with intrathoracic hyperthermic perfusion. The tumors were histopathologically diagnosed as thymic undifferentiated carcinomas with pleural dissemination. At present, approximately 16 months after surgery, the patient is alive without recurrence.

Pulmonary zygomycosis rarely occurs without pre-existing immunocompromised disease. A 72-year-old male was found to have a nodular shadow (3 cm x 4 cm) in the right S8 and S9 on a chest X-ray. Right lower lobectomy was performed and histological examination of the resected material demonstrated pulmonary zygomycosis. Hyphae stained positively not only with Grocott-Gomori methenamine silver staining, but also with an anti-Rhizopus oryzae polyclonal antibody.

A search for serum factors that modulate the mutability of human cells has been attempted in the peripheral blood of lung cancer patients. Factors were separated by dye-ligand chromatography and first identified as those exhibiting the ability to enhance the frequency of drug-resistance mutations in human RSa cells. The frequency was assessed by estimation of the cloning efficiency of mutant cells resistant to ouabain-mediated cell killing (Oua(R)) after irradiation with far-ultraviolet light (UV, mainly 254-nm wavelength), Pre-culture of cells with medium containing the factors prior to UV irradiation led to about a 19- to 37-fold increase in the OuaR mutation frequency compared with that of cells irradiated but not treated with the factors, The enhancing activity was detected in the serum of all 7 lung cancer patients, although the serum itself, which had not been treated with chromatography, had little or no enhancing activity in all patients. No enhancing activity was detected in serum preparations from healthy donors. The enhancing activity of lung cancer serum factors on UV-induced mutagenicity was next confirmed by detecting an enhancement of K-ras codon 12 base substitution mutations in human RSb cells, as analyzed by polymerase chain reaction (PCR) and differential dot-blot hybridization. Our results, together with previous findings; on suppression of mutagen-induced mutagenicity by human interferons, suggest the existence of extracellular factors that modulate the mutability of human cells. (C) 1998 Wiley-Liss, Inc.

The present study is aimed to evaluate the genetic evidence for multicentricity of synchronous and metachronous multiple lung carcinomas. Nineteen cases of synchronous multiple lung carcinomas and 11 cases of metachronous multiple lung carcinomas were analyzed for p53 protein overexpression by immunohistochemistry (DO-7) and for genetic abnormality of the p53 gene by loss of heterozygosity (LOH) at chromosome 17p and by polymerase chain reaction (PCR)-single-strand conformation polymorphism (SSCP) analysis. They were also analyzed for K-ras mutation. DNA from three patients was also sequenced by the dideoxy sequencing method to confirm the presence of mutations and determine the base substitutions. Different spectrums of genetic changes, which were evaluated by a combination of p53 mutation, LOH at chromosome 17p and p53 overexpression, were observed in 11 of 19 cases of synchronous multiple lung carcinomas (57.9%) in the present study. Similarly, five of 11 cases of metachronous multiple lung carcinomas (45.4%) showed a different pattern of genetic changes. The present data suggest that some of the multiple carcinomas have different clonal origins, although their histological types are identical, and support the use of genetic markers in the differential diagnosis between metastasis and second primary carcinoma of the lung.

Mutated p53 proteins accumulate in the nuclei of tumor cells, and anti-p53 autoantibodies are found in the sera of patients with non-small-cell lung carcinoma (NSCLC), We analyzed the correlation among serum anti-p53 autoantibodies, immunohistochemical staining for p53, and clinical features (age, gender, smoking history, histological type, differentiation, stage, T factor, tumor size, and N factor) in resected non-small-cell lung carcinomas. A total of 62 cases of resected NSCLC were studied (43 men and 19 women; 33 adenocarcinomas, 21 squamous cell carcinomas, 8 large-cell carcinomas). Preoperative serum titers of anti-p53 autoantibodies were detected in 13/62 cases (21.0%). A correlation between histological type and positive titers of serum p53 autoantibodies was seen (large-cell carcinoma versus squamous cell carcinoma and adenocarcinoma, P = 0.031, chi(2)-test). Out of 25 cases, 10 (40%) with positive immunohistochemical staining for p53 had positive titers, whereas 3 positive titers were found in 37 patients with negative immunohistochemical staining for p53 (P = 0.0025, chi(2)-test). Serum titers of anti-p53 autoanti bodies were present in approximately 20% of the cases of NSCLC, and overexpression of p53 protein in tumor cells was detectable in approximately 40%. Serum anti-p53 autoantibodies may be a clinical parameter for the presence of p53 mutations and p53 overexpression in NSCLC patients.