Search

Background Sclerosing hemangiomas of the lung are uncommon tumors and are thought to be benign. However, the histogenesis and clinicopathological features of these tumors have not been elucidated. Methods We analyzed the clinicopathological features of 26 sclerosing hemangiomas. The immunoreactivity for Ki-67 and p53 of sclerosing hemangiomas was determined and compared with that of pathological stage 1 pulmonary papillary adenocarcinomas. Results The patients of sclerosing hemangioma were predominantly female. Eighteen patients were detected as a result of routine medical examinations and 15 were nonsmokers. Seven patients underwent tumor enucleation, 10 underwent a wedge resection, and 9 underwent a lobectomy. The mean tumor size was 2.2 cm (range 1 to 5 cm). Pathological findings demonstrated a papillary pattern in 23 cases, sclerotic pattern in 26 cases, hemorrhagic pattern in 22 cases and a solid pattern in 25 cases. Twenty-five cases had an excellent prognosis with no evidence of recurrence following surgery. However, 1 patient who had undergone a wedge resection developed a local recurrence and required an additional wedge resection. The Ki-67 labeling index of sclerosing hemangiomas was significantly lower than that of adenocarcinomas, whereas the Ki-67 labeling index of the recurrent case was 0.4%. No significant immunohistochemical staining for p53 was observed in sclerosing hemangioma cases. Conclusions Sclerosing hemangioma exhibits various histologic findings. Although we experienced one case with a recurrent tumor, sclerosing hemangiomas did not exhibit malignant behavior.

Study objectives: Although various techniques are available for obtaining pathology specimens from the mediastinal lymph nodes, including conventional bronchoscopic transbronchial needle aspiration (TBNA), transesophageal ultrasonography-guided needle aspiration, and mediastinoscopy, there are limitations to these techniques, which include low yield, poor access, need for general anesthesia, or complications. To overcome these problems, we undertook the current study to evaluate the clinical utility of the newly developed ultrasound puncture bronchoscope to visualize and perform real-time TBNA of the mediastinal and hilar lymph nodes under direct endobronchial ultrasonography (EBUS) guidance. Design: Prospective patient enrollment. Setting: University teaching hospital. Patients: From March 2002 to September 2003, 70 patients were included in the study. Interventions: The new convex probe (CP) EBUS is integrated with a convex scanning probe on its tip with a separate working channel, thus permitting real-time EBUS-guided TBNA. The indications for CP-EBUS were the diagnosis of mediastinal and/or hilar lymphadenopathy for known or suspected malignancy. Lymph nodes and the surrounding vessels were first visualized with CP-EBUS using the Doppler mode. The dimensions of the lymph nodes were recorded, followed by real-time TBNA under direct EBUS guidance. Final diagnosis was based on cytology, surgical results, and/or clinical follow-up. Results: All lymph nodes that were detected on the chest CT scan could be visualized using CP-EBUS. In 70 patients, CP-EBUS-guided TBNA was performed to obtain samples from mediastinal lymph nodes (58 nodes) and hilar lymph nodes (12 nodes). The sensitivity, specificity, and accuracy of CP-EBUS-guided TBNA in distinguishing benign from malignant lymph nodes were 95.7%, 100%, and 97.1%, respectively. The procedure was uneventful, and there were no complications. Conclusions: Real-time CP-EBUS-guided TBNA of mediastinal and hilar lymph nodes is a novel approach that is safe and has a good diagnostic yield. This new ultrasound puncture bronchoscope has an excellent potential for assisting in safe and accurate diagnostic interventional bronchoscopy.

Background In 1999, the World Health Organization classified large cell neuroendocrine carcinoma as a variant of large cell carcinoma and this has been categorized as lying between atypical carcinoid and small cell lung carcinoma in terms of clinical aggressiveness. Methods We analyzed the proliferative activity of stage 1 large cell neuroendocrine carcinoma derived from patients with primary lung cancer who underwent surgical resection and compared the results with stage 1 classic large cell carcinoma cases. The mitotic rate was counted in ten high-power fields of light microscope. Immunohistochemical staining using anti-Ki-67 antibody was performed. The Ki-67 labeling index, expressed as a percentage of positive cells, was determined by light microscopy with random counting of at least 1,000 tumor nuclei. The expression of P53 and Bcl-2 was examined and compared. Results The mitotic rate of large cell neuroendocrine carcinoma cases was significantly higher than that of classic large cell carcinoma cases. The Ki-67 labeling index of stage 1 large cell neuroendocrine carcinoma cases was significantly higher than that of stage 1 classic large cell carcinoma cases. Immunohistochemical expression of P53 in large cell neuroendocrine carcinoma and classic large cell carcinoma was comparable. However, large cell neuroendocrine carcinoma exhibited a significantly higher expression of Bcl-2 than classic large cell carcinoma. The disease specific disease-free survival for patients with stage 1 large cell neuroendocrine carcinoma was significantly lower than that for patients with stage 1 classic large cell carcinoma. Conclusions Large cell neuroendocrine carcinoma appears to be more clinically aggressive than classic large cell carcinoma with these findings indicating that large cell neuroendocrine carcinoma has a higher level of proliferative activity than classic large cell carcinoma.

BACKGROUND Small cell lung carcinoma (SCLC) and pulmonary large cell neuroendocrine carcinoma (LCNEC) are high-grade malignant neuroendocrine tumors. Histologic differentiation between SCLC and LCNEC is difficult in some cases and to the authors' knowledge, genetic alterations associated with LCNEC have not been identified. Therefore, the authors studied genetic alterations found in LCNEC and compared them with those of SCLC and classic large cell carcinoma (CLCC). METHODS Twenty-two patients with UICC TNM Stage I LCNEC, 12 patients with Stage I CLCC, and 11 patients with SCLC with limited disease were studied. All tumors were resected completely. Loss of heterozygosity (LOH) of the tumor cells was detected using fluorescent primers. Methylation status of the p16 gene and expression of the p53 protein, retinoblastoma protein, and p16 protein were evaluated immunohistochemically. RESULTS LOH at TP53 and 13q14 was observed in most patients. The prevalence of LOH at D3S1295, D3S1234, and D5S407 was significantly higher in patients with LCNEC and SCLC than in patients with CLCC. The prevalence of LOH at D5S422 was higher in patients with CLCC and in patients with SCLC than in patients with LCNEC. Expression of the p16 protein was observed more frequently in SCLC than in CLCC or LCNEC. Hypermethylation of the p16 gene was observed more frequently in LCNEC than in SCLC. Patients with allelic losses at D3S1234 and D10S1686 had poorer prognoses compared with patients without allelic losses at these sites. CONCLUSIONS Genetic alterations of LCNEC were akin to those of SCLC. However, allelic losses at 5q and abnormalities in the p16 gene may differentiate LCNEC from SCLC. Cancer 2004. © 2004 American Cancer Society.

BACKGROUND Angiogenesis plays a crucial role in tumor growth and metastasis. Recently, some studies have focused on the angiogenesis inhibitor endostatin. However, the biologic role of the precursor of endostatin, collagen XVIII, in human malignancy is unknown. The purpose of the current study was to evaluate whether the expression of collagen XVIII has additional prognostic value for survival in patients with nonsmall cell lung carcinoma (NSCLC). METHODS The authors investigated the expression of collagen XVIII in 221 patients using immunohistochemical methods. To confirm the specificity of the collagen XVIII polyclonal antibody used in the current study and to test the expression of collagen XVIII in human lung carcinoma, Western blot analysis was performed on a panel of human lung carcinoma cell lines. RESULTS Collagen XVIII expression was detected in 162 of 221 patients with NSCLC (73%), primarily in the tumor cell cytoplasm. Low collagen XVIII expression levels were found in 75 tumor specimens, while high collagen XVIII expression levels were noted in 87 tumor specimens. The prevalence of positive collagen XVIII expression was greater in T2–4 tumors than in T1 tumors (P = 0.0235). The prognosis for patients with strongly collagen XVIII–positive NSCLC was significantly worse than the prognosis for patients with collagen XVIII–positive or collagen XVIII–negative NSCLC (P = 0.0010). Multivariate analysis indicated that T status, lymph node status, and the overexpression of collagen XVIII were independent prognostic factors. CONCLUSIONS The results of the current study indicated that the overexpression of collagen XVIII was associated with NSCLC progression and poor outcome. Thus, collagen XVIII expression may serve as a useful prognostic marker in patients with NSCLC. Cancer 2004. © 2004 American Cancer Society.

A 67-year-old man was admitted to our hospital because of an abnormal chest echoic lesion detected incidentally by echocardiography. A chest roentgenogram showed the presence of a giant mass, and computed tomography of the chest confirmed the presence of a mass with a nonhomogeneous density in the left mediastinum, just adjacent to the left ventricle of the heart. Percutaneous aspiration cytology of the mass showed benign fibrous cells and a small amount of lymphocytes. The preoperative diagnosis of the tumor suggested a thymoma, and the patient underwent a thoracotomy. A pedunculated tumor arose from the visceral pleura of the left upper lobe of the lung, and it was capsulated within the pleura. The tumor measured 15 x 12 x 8 cm in size and it was successfully resected. The pathological diagnosis of the tumor was benign localized fibrous tumor of the pleura.

Background: We investigated the use of high magnification bronchovideoscopy combined with narrow band imaging (NBI) for the detailed examination of angiogenic squamous dysplasia (ASD). This was carried out in relation to bronchial vascular patterns with abnormal mucosal fluorescence in heavy smokers at high risk for lung cancer. Methods: Forty eight patients with sputum cytology specimens suspicious or positive for malignancy were entered into the study. Conventional white light and fluorescence bronchoscopic examination was first performed. Observations by high magnification bronchovideoscopy with conventional white light were made primarily at sites of abnormal fluorescence, and then repeated with NBI light to examine microvascular networks in the bronchial mucosa. Spectral features on the RGB (Red/Green/Blue) sequential videoscope system were changed from the conventional RGB broadband filter to the new NBI filter. The wavelength ranges of the new NBI filter were B1: 400–430 nm, B2: 420–470 nm, and G: 560–590 nm. ASD tissues were also examined using a confocal laser scanning microscope equipped with argon-krypton (488 nm) and argon (514 nm) laser sources. Results: The microvessels, vascular networks of various grades, and dotted vessels in ASD tissues were clearly observed in NBI-B1 images. Diameters of the dotted vessels visible on NBI-B1 images agreed with the diameters of ASD capillary blood vessels diagnosed by pathological examination. Capillary blood vessels were also clearly visualised by green fluorescence by confocal laser scanning microscopy. There was a significant association between the frequency of dotted vessels by NBI-B1 imaging and tissues confirmed as ASD pathologically (p=0.002). Conclusions: High magnification bronchovideoscopy combined with NBI was useful in the detection of capillary blood vessels in ASD lesions at sites of abnormal fluorescence. This may enable the discrimination between ASD and another pre-invasive bronchial lesion.

Although serum NY-ESO-1 antibodies (s-NY-ESO-1-Abs) have been reported in patients with esophageal carcinoma, this assay system has not been used to study a large series of patients with various other cancers. Serum samples of 1969 cancer patients [esophageal cancer (n = 172), lung cancer (n = 269), hepatocellular carcinoma (n = 91), prostate cancer (n = 358), gastric cancer (n = 313), colorectal cancer (n = 262), breast cancer (n = 365)] and 74 healthy individuals were analyzed using an originally developed enzyme-linked immunosorbent assay system for s-NY-ESO-1-Abs. The optical density cut-off value, determined as the mean plus three standard deviations for serum samples from the healthy controls, was fixed at 0.165. Conventional tumor markers were also evaluated in patients with esophageal carcinoma. The positive rate of s-NY-ESO-1-Abs in patients with esophageal cancer (31 %) was significantly higher than that in the other groups: patients with lung cancer (13 %), patients with hepatocellular carcinoma (11 %), patients with prostate cancer (10 %), patients with gastric cancer (10 %), patients with colorectal cancer (8 %), patients with breast cancer (7 %), and healthy controls (0 %). The positive rate of s-NY-ESO-1-Abs was comparable to that of serum p53 antibodies (33 %), squamous cell carcinoma antigen (36 %), carcinoembryonic antigen (26 %), and CYFRA 21-1 (18 %) and gradually increased with the tumor stage. The positive rate of s-NY-ESO-1-Abs was significantly higher in patients with esophageal cancer than in patients with the other types of cancers. On the basis of its high specificity and sensitivity, even in patients with stage I tumors, s-NY-ESO-1-Abs may be one of the first choices for esophageal cancer.

Distant metastases from osteosarcoma most commonly occur in the lungs. Osteosarcoma can be cured by complete surgical resection of all metastatic lesions if the number is limited (oligo-recurrence: ≤5 metastatic or recurrent lesions with controlled primary lesions). This study aimed to clarify the prognostic factors for osteosarcoma patients with pulmonary metastasis and determine their oligo-recurrence status. Patients with conventional osteosarcoma who underwent definitive surgery for the primary lesion and at least one thoracotomy for pulmonary metastases were recruited to this retrospective study. Clinicopathological information was collected on each thoracotomy from 1976 to 2011, and was then analyzed statistically. We counted the number of resected nodules that were pathologically confirmed as metastatic lesions from osteosarcoma. In total, 151 thoracotomies in 71 patients were analyzed. Forty-seven patients (66 %) underwent up to two thoracotomies, and the maximum number of thoracotomies was six. The median number of resected nodules on each thoracotomy was two, and the median total size of metastatic lesions was 20 mm. Incomplete surgical remission [relative risk (RR) 3.42], a less than 1-year interval from a previous thoracotomy (RR 1.97), more than three resected nodules (RR 2.42); and total size of more than 30 mm for pulmonary metastases (RR 2.19) were independent predictors of increased risk of tumor death by multivariate analysis. We propose that factors contributing to oligo-recurrence of patients with pulmonary metastatic osteosarcoma include complete surgical remission, an interval from a previous thoracotomy, number of resected nodules, and total size of pulmonary metastases.

Human Vα24 NKT cells bearing an invariant Vα24JαQ antigen receptor, the counterpart of murine Vα14 NKT cells, are activated by a specific ligand, α-GalCer, in a CD1d-dependent manner. Here, we demonstrate decreased numbers of circulating Vα24 NKT cells in patients with primary lung cancer compared to healthy volunteers. However, Vα24 NKT cells and DCs from lung cancer patients were functionally normal, even in the presence of tumor. Furthermore, levels of Vα24 NKT cells in surgically resected lung tissue appeared to be equivalent to those of Vα14 NKT cells in the mouse lung. Levels of Vα24 NKT cells in the tumor tissue itself were increased about 2.5 times. Administration of α-GalCer-pulsed DCs expanded Vα14 NKT cells in the lung more than 10 times, and the increased levels were sustained for 1 week. This may explain the previous finding that α-GalCer-pulsed DCs exerted strong antitumor activity in mouse lung tumor metastatic models. The potential use of α-GalCer-pulsed DCs for immunotherapy aimed at activating endogenous Vα24 NKT cells in the lung of cancer patients is discussed. © 2002 Wiley-Liss, Inc.

To demonstrate the importance of preoperative diagnosis of pulmonary cancers presenting as peripheral small-sized solitary shadows we evaluated the results of morphologic definitive diagnosis together with various clinical factors in 91 tumors with less than 15-mm diameter resected surgically between 1983 and 1999. Histologically, these tumors consisted of 73 adenocarcinomas, nine squamous cell carcinomas, and nine other types. Regarding the pathologic stage, 57 tumors were classified in stage IA, three in IB, six in IIA, seven in IIIA, 14 in IIIB, and four in IV. Comparing various biopsy techniques, the sensitivity of preoperative cytodiagnosis was 43.7% for transbronchial brushing ( n =48), 52.9% for transbronchial forceps biopsy-stamp cytology ( n =51), 66.6% for transbronchial fine needle aspiration ( n =78), and 85.0% for percutaneous fine needle aspiration ( n =20). The overall sensitivity of preoperative cytodiagnosis was 79.0% for transbronchial biopsy ( n =81), and 87.3% for transbronchial and percutaneous biopsy ( n =87). Of 73 clinical N0 cases in which lobectomy was performed, 10 cases (13.6%) were diagnosed as between pathological degrees N1, N2 and N3. However, lung cancer cases with less than 10-mm diameter did not have lymph node metastasis. Our study of histologic differentiation showed that all cases of well-differentiated adenocarcinomas ( n =20) were pathological degree N0. The overall sensitivity of preoperative diagnosis increased to 89.1% in cases ( n =74) of tumors with 11–15-mm diameter. The sensitivity of cytodiagnosis for peripheral small-sized primary lung cancers is high, and we can estimate histological differentiation based on the cytological findings. Therefore, cytodiagnosis is an effective and indispensable diagnostic method for determination of the optimal treatment approach, including approaches such as intentionally limited resection.

Cytochrome P-450 (CYP) enzymes have been shown to play important roles in chemical carcinogenesis. Reports have indicated that polymorphism in CYP1A1, CYP1A2, CYP2A6, CYP2E1, and CYP2D6 are associated with an altered risk of developing cancers of the lung, bladder, liver, and colon. CYP2E1 plays an important role in alcohol metabolism and participates in the metabolic activation of various carcinogens, such as N-nitrosodimethylamine. Recently, we found repeated sequences that consist of four alleles (A1, A2, A3, and A4) and six genotypes (A1/A2, A2/A2, A2/A3, A2/A4, A3/A4 and A4/A4) of the CYP2E1 gene. In the present study, we investigated whether these polymorphisms are associated with lung cancer and esophageal cancer.DNA was isolated from blood samples of 192 healthy control subjects, 85 patients with lung cancer, and 82 patients with esophageal cancer in Japanese males. DNA samples were amplified by polymerase chain reaction in the 5'-flanking region of the CYP2E1 gene and in exon 12 in the ALDH2 gene. The tandem repeat polymorphisms were examined using DNA fragment analysis. Missense mutations in exon 12 of the ALDH2 gene were examined using fluorescence-based single strand conformational change polymorphism analysis. Written informed consent was obtained from all the subjects.In the CYP2E1 gene 5'-flanking region polymorphism, patients with esophageal cancer showed significantly higher frequency of the A4/A4 genotype compared with the control subjects (p = 0.02), but no difference was found in patients with lung cancer. The frequencies of the mutant ALDH2*2 allele were significantly higher in patients with esophageal cancer (27.7%) than in healthy control subjects (7.3%; p0.0001; habitual alcohol drinkers).The distribution of genotypes and allele frequencies of the tandem repeats of the 5'-flanking region of the CYP2E1 gene was significantly different in patients with esophageal cancer.

We investigated DNA copy-number aberrations in 22 cell lines derived from small cell lung cancers (SCLCs) using comparative genomic hybridization. A minimal common region at 5p13, within the 5p11-p13 amplicon that was most frequently involved, harbored the CDH6, PC4, and SKP2 genes. These three genes showed amplification and consequent overexpression in the SCLC cell lines. SKP2 positively regulates progression of cell cycle by targeting several regulators, such as the cell-cycle inhibitor p27(KIP1), for ubiquitin-mediated degradation. SKP2 was amplified in 7 (44%) of 16 primary SCLC tumors, and consequently overexpressed in 10 (83%) of the 12 of those tumors we examined. Expression levels of SKP2 protein were cell cycle-dependent in SCLC cells as well as in normal cells, and were correlated with the DNA copy-number of the gene. There was an inverse correlation between the expression of SKP2 and p27(KIP1) proteins. Down-regulation of SKP2 using an anti-sense oligonucleotide remarkably suppressed the growth of SCLC cells. Our results indicate that SKP2 is likely to be a target of the 5p13 amplification and to play an important role in the growth of SCLC cells.

原発性肺癌切除例における咽喉頭食道領域の重複癌について臨床的検討を加え，他臓器発生重複癌症例ならびに非重複例との比較した。1985∼1999年に切除した原発性肺癌1,279例のうち他臓器重複癌128例(10.0%)を対象とした。重複臓器は，3重複以上を含め咽喉頭14例，食道12例，胃十二指腸24例，結腸直腸33例，肝胆膵17例，甲状腺3例，子宮卵巣10例，腎尿路12例，乳腺6例，前立腺5例，リンパ節その他3例であった。重複部位別に，咽喉頭食道領域群26例，非咽喉頭食道領域群102例ならびに非重複群1,151例に分類した。各群の平均喫煙指数は，それぞれ1,031, 693, 714で，咽喉頭食道領域群は他の2群に比べ有意に平均喫煙指数が高かった(p=0.0174, p=0.0192)。肺癌の組織型は，咽喉頭食道領域群，非咽喉頭食道領域ならびに非重複群における扁平上皮癌：腺癌はそれぞれ18:5例，32:61例ならびに394:648例と咽喉頭食道領域群は有意に扁平上皮癌が腺癌に比べ多かった（いずれもp

The aim of this study was to examine the ability of endobronchial ultrasonography (EBUS) to image the bronchial wall structure in order to assess the depth of bronchial tumor invasion. Sixty-one patients who underwent lobectomy, pneumonectomy or forceps biopsy were included in this study. In 21 patients with bronchoscopically visible bronchial malignant tumors, EBUS was performed during bronchoscopy. In the remaining 40 patients, ultrasonography was performed on the resected specimens. The EBUS findings obtained using thin ultrasonic probes (20 MHz radial scanner) were compared with the macroscopic and histologic findings of the corresponding areas in the resected specimens. When the bronchial walls were imaged while immersed in normal saline, six ultrasonically distinct layers were detected in the cartilaginous and membranous portions. A similar wall structure was imaged when EBUS was performed during bronchoscopy using a latex balloon sheath. The image of the lamina propria and submucosa was occasionally compressed and mixed with a balloon echo due to the latex balloon sheath, whereas the cartilage layer was always distinctly imaged. A good correlation was observed between the EBUS-determined cartilage thickness and the actual histologic measurement, as measured with vernier calipers. Malignant tissues were imaged as hypoechoic areas, and tumor invasion of the cartilage layer was clearly detected. In conclusion, using high-resolution (20 MHz) ultrasonic probes, the bronchial wall structure could be imaged as six distinct layers. The cartilage layer was easily identified and could be used as a reference to evaluate the rest of the bronchial wall structure.

A 33 year-old man was referred to our center with swelling of the left scrotum. He underwent resection of the left testis,and pathological diagnosis indicated a germ cell tumor of that testis. His past history included lung cancer resection 5 yearsbefore the testicular surgery. Precise pathological reevaluation of the lung cancer using immunohistochemical methodsindicated that the tumor originally diagnosed as lung cancer was a metastasis of the germ cell tumor of the left testis.

Background: a new strategy in the treatment of squamous cell carcinoma of the tracheobronchial tree is the detection and eradication of preinvasive bronchial lesions before they become invasive cancers. It is, however, difficult to detect preinvasive lesions by conventional white-light bronchoscopy alone. Purpose: we conducted a detailed investigation on the use of fluorescence bronchoscopy in the detection of preinvasive bronchial lesions in patients with sputum cytology suspicious or positive for malignancy. Methods: 64 participants with sputum cytology suspicious or positive for malignancy were examined with both white light and fluorescence bronchoscopy (LIFE group). Earlier to this study, before fluorescence bronchoscopy became available in our institute, 48 participants having sputum cytology suspicious or positive for malignancy were examined with white light bronchoscopy alone (control group). Biopsy specimens for pathological examinations were taken of all abnormal areas discovered by white light or fluorescence bronchoscopy examination. Results: in sputum cytology suspicious or positive for malignancy, the diagnosis of preinvasive bronchial lesions was greatly enhanced in the LIFE group as compared with the control group (45 vs. 7 lesions). The percentage of participants with preinvasive bronchial lesions was also significantly higher in the LIFE group than in the control group (40.6 vs. 12.5%, P =0.00087, respectively). Conclusions: our study suggests that the use of fluorescence bronchoscopy in addition to conventional white-light examination could greatly enhance the detection and localization of preinvasive bronchial lesions in patients with sputum cytology suspicious or positive for malignancy.

Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) has been developed as a useful tool for the diagnosis of diseases adjacent to the airway to be used in place of open surgery or mediastinoscopy. In this report, we present a 46-year-old man with a solid tumor in the mediastinum. Since no other pathological sites were identified, EBUS-TBNA was employed for tumor sampling. Sufficient tissue specimens were collected and the diagnosis of follicular lymphoma was established based on the combination of immunohistochemistry, flow cytometry and FISH analysis. This report demonstrates the advantage of EBUS-TBNA even for the diagnosis of hematological disease.

A 60-year-old woman was diagnosed with pulmonary metastasis with endobronchial spread of sinonasal melanoma 9 years after the initial treatment. She had originally been diagnosed with sinonasal malignant melanoma and received chemotherapy combined with carbon ion radiotherapy. During routine follow-up, chest CT showed a nodular lesion on the left upper lung lobe. Bronchoscopic examination showed diffuse melanosis without intrinsic masses from the left main bronchus to the peripheral bronchial mucosa. Transbronchial biopsy was performed for both the pulmonary lesion and endobronchial melanosis lesions. Melanoma cells were histologically detected in both the mucosal and submucosal layers.

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, chi2-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, chi2-test). Serum titers of anti-p53 autoantibodies 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.

Expression of matrix metalloproteinase (MMP)-2, MMP-9, tissue inhibitor of metalloproteinases (TIMP)-1, and TIMP-2 was studied in non-small-cell lung cancer (NSCLC). Activity of MMP-2 and MMP-9 by gelatin zymography and expression of MMP-2, MMP-9, TIMP-1, and TIMP-2 mRNAs were examined in 11 lung cancer cell lines which included six small-cell lung cancer (SCLC) cell lines. Localization of MMP-2, MMP-9, TIMP-1, and TIMP-2 was examined by immunohistochemistry in 43 resected NSCLC (22 adenocarcinomas, 17 squamous cell carcinomas, 4 large cell carcinomas) using specific anti-human monoclonal antibodies. Expression of MMP-2 mRNA was detected in 5 (100%), MMP-9 in 1 (20%), TIMP-1 in 4 (80%), and TIMP-2 in 5 (100%) of 5 NSCLC cell lines examined. MMP-2 gelatinolytic activity also was detected in all five NSCLC cell lines, whereas MMP-9 activity was detected in only one cell line. In 43 patients, MMP-2, MMP-9, TIMP-1, and TIMP-2 immunoreactivity was demonstrated in 19 (44%), 9 (21%), 15 (35%), and 29 (67%) excised tumors, respectively. All stromal fibroblasts in tumor samples stained positive for MMP-2. There was a correlation between TIMP-2 immunoreactivity and disease stage (42% stage I versus 88% stages II, III, and IV) (p = 0.0024). Both cancer cell lines and NSCLC tumor samples frequently expressed MMP-2, MMP-9, TIMP-1, and TIMP-2; MMP-2 in particular was highly expressed in malignant cells and surrounding fibroblasts. These findings suggest that MMP-2 plays a more important role in invasion of NSCLC than MMP-9 and that TIMP-2 may have clinical relevance in NSCLC.

The clinical characteristics and results of surgical treatment in patients with double carcinomas of the lung and other organs were evaluated using 73 patients with pathologically confirmed double carcinomas out of a total of 1279 lung carcinoma patients resected from 1980 to 1996. The double carcinomas were divided into three groups according to anatomical conditions and environmental factors including smoking habits; Group A; laryngopharynx and esophagus; Group B: gastroduodenum, hepatopancreas, kidney and urinary bladder; Group C : colorectum, breast, uterus and other organs. Clinical features revealedsignificant differences in the gender distribution and smoking indices of Groups A, B and C. The re-occurrence interval also demonstrated a significant difference between Groups A and C. However, no significant differences were observed in age distribution, the histologic types of the lung carcinoma, or the pathological stages of the lung carcinoma. The overall 5-year survival rates from lung resection inGroups A, B and C were 61.5%, 46.6% and 68.7%, respectively. There was a significant difference between Groups B and C (p

We report a case of giant mediastinal neurinoma with expansion into the intraspinal canal. We resected the tumor safely with the two-stage operation. The patient was a 52-year-old male. An abnormal shadow in the left lung field was pointed out at a mass survey. The tumor shadow was 15 cm in size, and extended into the intraspinal canal on chest X-ray, CT, and MRI. It was diagnosed as neurinoma by percutaneous fine needle biopsy (PCNB). First we resected the intraspinal portion of the tumor by the posterior route.Subsequently, the remaining intrathoracic portion of the tumor was resected and reconstruction of the spinal column was performed via the postero-lateral route six weeks later.Pathological diagnosis was benign neurinoma. The patient improved neurologically, discharged on his foot and had been well after two years.

A 56-year-old woman was referred to our hospital for airway compromise. Relapsing polychondritis was diagnosed by bronchial cartilage biopsy. Bronchoscopy showed tracheobronchial malacia due to the disappearance of bronchial cartilage as a result of chondritis. Stent insertion using a Dynamic stent (Rüsch; Kernen, Germany), Ultraflex stent (Boston Scientific International, Colombes, France) and TM stent (Fuji Systems Corp, Tokyo, Japan) was repeated for more than 7 years. Dramatic improvement of dyspnea was obtained each time. The patient survived during this period without oxygen inhalation or mechanical ventilation before she suddenly died due to suffocation caused by difficulty of sputum discharge.

Primary leiomyosarcoma of the pulmonary artery is extremely uncommon and its cause remains unclear. We document a case of pulmonary artery leiomyosarcoma expressing Epstein-Barr virus DNA sequences in an immunocompetent patient 4 years after symptomatic Epstein-Barr virus infection.

非小細胞肺癌切除例66例 (腺癌37例, 扁平上皮癌20例, 大細胞癌7例, 腺扁平上皮癌2例) および良性疾患5例における, 所属リンパ節リンパ球および末梢血リンパ球のサブセットの変化を, フローサイトメトリーにて解析し, 組織型, 転移の有無との関連性につき検討した. 非小細胞肺癌の所属リンパ節では, 良性疾患と比較し, T細胞マーカーのCD3+, CD4+およびCD8+細胞数比が低く, CD8+細胞数比では有意差を認め, B細胞マーカーのCD20+細胞数比は高かった. 組織型別検討では, 腺癌に比較し, 扁平上皮癌の所属リンパ節では, CD3+, CD4+細胞数比およびCD4+細胞のCD28発現率は有意に低く, CD20+細胞数比は有意に高かった. 転移の有無による有意差はみられなかった. 所属リンパ節リンパ球サブセットの変化は, 腫瘍に関連して産生される液性因子を介した変化と考えられ, 組織型により免疫応答は異なる可能性が示唆された.

縦隔気管支嚢胞と併存し, さらにそれとの交通を認めた限局性蜂窩肺の一手術例を経験したので報告する.症例は14歳女性, 感冒様症状を主訴に近医を受診し, 胸部異常陰影を指摘された.胸部CTにて, 右上葉S3に蜂窩状陰影および気管右側にそれと併存する径3cm大の嚢胞状陰影を認めたため, 縦隔気管支嚢胞およびそれと交通する右上葉限局性蜂窩肺と診断し, 嚢胞および右上葉合併切除を施行した.嚢胞は縦隔内に存在するものの, 奇静脈弓下より右主気管支と併走する異常気管支を通じ蜂窩肺と交通しており, 病理組織学的には, 蜂窩肺は強い炎症像を示したが, 縦隔嚢胞には炎症性変化をほとんど認めず気管支嚢胞と診断された.本例は末梢気管支に発生した気管支嚢胞が, 奇静脈により肺内と縦隔に分離された発生異常の可能性が高いものと考えられた.

術前よりプレドニゾロン (PSL) 隔日大量療法を行うことにより重症筋無力症 (MG) に対する胸腺摘除術の安全性は向上したが, 依然として術後呼吸管理は重要な問題である.1979年より1996年3月までにPSL隔日大量併用胸腺摘除術を施行した全身型MG100例を対象とし, 周術期に関わる23の臨床的項目について検討した (Studentのt検定, χ2検定, Mann-Whitney のU検定).また検定結果よりロジスティック回帰分析を用いて術後呼吸不全発生の予測モデルを作成した.術後呼吸不全の発生に関連する重要な因子は術直前重症度 (p

We herein report a resection of a superior sulcus tumor in a patient with idiopathic thrombocytopenic purpura. A resection of the left upper lobe of the lung, left subclavian artery, and left first to third ribs, as well as a reconstruction of the left subclavian artery, were performed. Postoperative hemorrhaging was controlled due to preoperative high-dose intravenous immunoglobulin therapy and a platelet transfusion both during and following surgery. The resected tumor was diagnosed to be a pulmonary pleomorphic carcinoma, which was pathologically determined to be T3N0M0-Stage 2B. The patient remained in good condition for 20 months following the surgery; however, he eventually died due to bone metastases.

Background: Chemokines and chemokine receptors not only have significant roles in cancer metastasis and tumorigenesis but also act as antitumour agents. The interaction between the Crk-like adaptor protein (CrkL), which is encoded by the CRKL gene, and non-receptor tyrosine kinase c-ABL is reported to transform many cells into malignant cells. We examined the effects of CC chemokine receptor 7 (CCR7), CCR7 ligands and CrkL and c-ABL in lung adenocarcinoma. Methods: One hundred and twenty patients with lung adenocarcinoma were included in this historical cohort analysis. We examined CCR7 and CCR7 ligands and CrkL and c-ABL mRNA expressions in surgically resected lung adenocarcinoma specimens and evaluated their contribution to prognosis, and the relationship with epidermal growth factor receptor (EGFR) and TP53 mutations. Results: High CCR7 mRNA expressions indicated better prognoses than those of the groups with low CCR7 mRNA expressions (P=0.007, HR=2.00, 95% CI of ratio: 1.22 –3.31). In lung adenocarcinoma, CrkL and c-ABL mRNAs were related to CCR7 mRNA expression (P

The results of pulmonary resection and clinical factors relating to long-term survival were evaluated in 29 patients with histologically proven pulmonary metastasis from colorectal carcinoma. The patients were followed up from 4 months to 120 months, with an average of 43.7 months. Overall 5- and 10-year survival rates were 41% and 34% respectively. The 5- and 10-year survival rates in patients with metastatic nodules 30 cm or less in diameter were 77% and 58%, respectively, a significantly better result than in those with metastatic nodules over 30 mm in diameter. Survival in patients without nodal involvement was significantly better than that in patients with lymph node metastases. Multivariate analysis according to Cox proportional hazards model demonstrated that the size of the metastasis was an independent prognostic factor.

1965年から1984年までに切除した原発性肺癌症例のうち, 10年以上経過し, 病理組織学的に確定診断の得られた640例につき, 10年以上生存と関連する諸因子について検討した.切除例のうち10年以上生存例は134例 (20.9%), 10年生存率22.0%であった.組織型では, 最も多数を占める腺癌と扁平上皮癌の10年以上生存例を占める割合は21.0%, 19.2%で有意差を認めなかった.また前期 (1965～1974年) ならびに後期 (1975～1984年) における10年以上生存例の占める割合は, それぞれ16.5%, 24.2%と, 有意な増加を認めた.病期別10年以上生存例の占める割合は, IIIA期とIIIB期を除き, 病期の進行とともに悪化した.III期切除例における10年以上生存と関連する有意な因子は明確でないが, 1期症例では65歳未満の症例はそれ以上の症例に比べ, 女性は男性に比べて, また腺癌症例は扁平上皮癌症例に対し, 有意に長期生存が期待できるものと考えられた.

肺癌の臨床像より, その浸潤, 転移とマトリックスメタロプロテイナーゼ (MMPs) およびメタロプロテイナーゼインヒビター (TIMPs) との関連について検討するため, 原発性肺癌35例 (腺癌19例, 扁平上皮癌13例, 大細胞癌3例) の切除組織を免疫組織化学的に検討した.腫瘍組織における発現陽性率はMMP-2: 18例 (51%), MMP-9: 9例 (26%), TIMP-1: 15例 (43%), TIMP-2: 24例 (69%) であった.病期別にみると, MMP-2は1期14例中9例 (64%), III期以上20例中8例 (40%) で病期進行に伴い陽性率が低下する傾向がみられた.一方, 周囲間質におけるMMP-2は全例で陽性であった.TIMP-2では1期14例中7例 (50%), III期以上20例中16例 (80%) と, III期以上で陽性率が高くなる傾向が認められた (p=0.071).肺癌組織におけるMMP-2の発現は, 必ずしも病期進行と相関せず, 腫瘍の浸潤には周囲間質のMMP-2も利用しているものと考えられた.TIMP-2はMMPsを抑制的に調節するとともに, 腫瘍増殖を促進する作用も有するものと考えられた.

細胞外基質をコーティングしたポリスチレンディヅシュ上で, 無血清培地を用いたヒト気管支片のexplant cultureを行い, NHBECのoutgrowthの面積を測定して細胞外基質の効果を比較検討した.実験1 : type I, type II, type III, type IVの4種類のコラーゲンを比較した.Outgrowthの面積 (cm2) は, type I, type II, type III, type IVの順に, Donor 1では24, 17, 25, 28で, type IV>type II (P type I・type II (P type II・type III (P type I・type II・type III (P C (P F・C (P C (P L・F・C (P F・C (P

最近24年間にわれわれの施設において経験した腺様嚢胞癌切除11例の診断, 外科治療成績につき検討した. 内視鏡所見は本腫瘍に特徴的で内視鏡下生検により全例で術前診断が得られた. また内視鏡所見は腫瘍の浸潤様式を推定するのに有効であった. 気管発生の腺様嚢胞癌4例では術前に内視鏡下レーザー照射による気道開大術が臨床症状の改善および手術術式の決定に有効であった. 気管および主気管支発生例では, 手術術式は気道形成術が施行されたが, 切除断端陽性例が多数を占めた.断端陽性例にたいしては60Gy程度の術後放射線照射により良好な局所コントロールが得られた. 手術予後はおおむね良好で, 気管分岐部切除後に縫合不全を来した1例を除く5年生存率は100%, 平均生存期間は89.8月であった.

肺癌の外科治療に際して, 術前の画像解析では診断できず, 開胸時に発見された少量の胸水に対して術中迅速細胞診を施行した. 対象は最近10年間の開胸手術例321例で, 組織型の内訳は腺癌179例, 扁平上皮癌109例, 大細胞癌11例, 小細胞癌6例, その他16例である. その結果細胞診陽性と判定された症例は49例 (15.3%) で, 組織型は腺癌が46例 (94%) と大多数を占めた. 胸水とともに肉眼所見で胸膜播種巣が発見された症例は31例で, 残る18例 (37%) は細胞診のみで癌性胸膜炎が証明された. 切除標本による検討では細胞診陽性症例ではP1-2症例が84%, N2-3症例が65%と多数を占めた. 悪性胸水症例では標準的な肺葉切除術に加えてリンパ節郭清, 可及的胸膜播種巣切除, および閉胸時に抗癌剤による胸腔内洗浄を施行した. 胸水細胞診施行例の術後5年生存率は, 陽1生例20%, 陰性例60%で, 陽性例は陰性例に比較して有意に術後生存率が低下していた (p

Systemic arterial supply from the descending thoracic aorta to the basal segment of the left lower lobe without a pulmonary artery supply is a rare congenital anomaly within the spectrum of pulmonary sequestration cases. We encountered four consecutive cases, which were treated successfully by three basalectomies and one lower lobectomy to preserve lung function. q 2003 Elsevier Science B.V. All rights reserved.

Background. The aims of the study were to identify the significance of interleukin (IL)-6 production and to determine whether IL-6 production influences long-term survival in patients with non-small-cell lung cancer (NSCLC). Method. A series of 90 patients with NSCLC who underwent surgery between 2005 and 2007 was analyzed. Preoperative serum IL-6 was measured, and tumor samples were immunohistochemically stained for IL-6. Results. Serum IL-6 levels were elevated in 43 of 90 cases (47.7%), and 23 (25.5%) of 90 cases stained positively for IL-6 ( P = .00265). The prognosis of patients with NSCLC who had positive immunohistochemical staining was significantly worse than that for those who had negative staining, by univariate analysis ( P = .0027). Multivariate analysis indicated that tumor size, postoperative stage, and overexpression of IL-6 were independent prognostic factors. Conclusions. The expression of IL-6 in tumor correlated with the concentration of serum IL-6, tumor progression, and overall survival in patients with NSCLC.

We report a surgical case involving localized honeycomb lung with mucus, caused by colonization of a Schizophyllum commune, which displayed a tumorous shadow in the right upper mediastinum. A 74-year-old male with a history of tuberculosis in the 1970s was referred to Chiba University Hospital (Chiba, Japan) with an abnormal shadow evident in the chest roentgenogram. A transbronchial biopsy failed to yield a definite diagnosis. We resected the right upper lobe, which was found to contain a consolidative lesion filled with viscous mucus in the right upper lobe adjacent to the right upper mediastinum. Microscopic examination revealed a honeycomb lung formation with mucus in the destroyed space. Culture of the mucus yielded a whitish filamentous fungus, positively identified as S. commune. This is the first report of S. commune leading to a deposit of mucus and the formation of a consolidative lesion in the destroyed lung.

Purpose: Anaplastic lymphoma kinase (ALK) fusion genes represent novel oncogenes for non–small cell lung cancers (NSCLC). Several ALK inhibitors have been developed, and are now being evaluated in ALK-positive NSCLC. The feasibility of detecting ALK fusion genes in samples obtained by endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) was determined. The clinicopathologic characteristics of ALK-positive lung cancer were also analyzed. Experimental Design: From April 2008 to July 2009, NSCLC cases with hilar/mediastinal lymph node metastases detected by EBUS-TBNA were enrolled. Positive expression of ALK fusion protein was determined using immunohistochemistry, and ALK gene rearrangements were further examined to verify the translocation between ALK and partner genes using fluorescent in situ hybridization and reverse transcription-PCR. Direct sequencing of PCR products was performed to identify ALK fusion variants. Results: One hundred and nine cases were eligible for the analysis using re-sliced samples. Screening of these specimens with immunohistochemistry revealed ALK positivity in seven cases (6.4%), all of which possessed echinoderm microtubule–associated protein-like 4–ALK fusion genes as detected by fluorescent in situ hybridization and reverse transcription-PCR. All ALK-positive cases had an adenocarcinoma histology and possessed no EGFR mutations. Compared with ALK-negative cases, ALK-positive cases were more likely to have smaller primary tumors (P < 0.05), to occur at a younger age ( Conclusions: EBUS-TBNA is a practical and feasible method for obtaining tissue from mediastinal and hilar lymph nodes that can be subjected to multimodal analysis of ALK fusion genes in NSCLC. Clin Cancer Res; 16(20); 4938–45. ©2010 AACR.

Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) has typically been performed using the 22 gauge (G) dedicated TBNA needle. Recently a new 21G TBNA needle has been introduced. The efficacy of using a larger gauge biopsy needle during EBUS-TBNA has not been reported. The purpose of this study was to compare the diagnostic yield and utility of 21G and 22G needles during EBUS-TBNA.EBUS-TBNA was performed using both 21G and 22G needles. Cytological and histological findings were recorded for each samples obtained by an independent cytologist and pathologist. The cellularity and blood contamination were evaluated in the cytological samples. The quality of the histological core was evaluated by the amount of blood clots versus the actual tissue. Each factor was compared within two slides from the two different size needles. The diagnostic yield and the differences of the cytology and histology were analysed.The evaluation of 45 lesions by EBUS-TBNA revealed that tumour cells were equally detected by both 21G and 22G needles. Two patients of adenocarcinoma were histologically diagnosed only by the 21G needle. Although histological structure was better preserved in five lesions collected by the 21G needle, there was more blood contamination with the 21G needle (P 0.0001).There were no differences in the diagnostic yield between the 21G and 22G needles during EBUS-TBNA. The preserved histological structure of the samples obtained by the 21G needle may be useful for the diagnosis of mediastinal and hilar adenopathy of unknown aetiology which may be a challenge with the 22G needle.

We present two cases of inoperable advanced lung cancer in which the main lesions were mediastinal lymph nodes detected with positive positron emission tomography (PET). Drug therapy was very effective, and post-treatment PET results were negative. Restaging by endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) was performed on the mediastinal lymph nodes with a short axisor = 10 mm measured by computed tomography (CT). Cancer cells were detected, which helped determine the therapeutic strategy. Re-evaluation of mediastinal lymph nodes using EBUS-TBNA appears to be useful, even among patients with inoperable advanced lung cancer.

A newly developed endobronchial ultrasound processor system (EU-ME1; Olympus Ltd., Tokyo, Japan) improves the quality of ultrasound image by elevating cycles per minute. We report identification of mediastinal lymph node metastasis in a patient with small cell lung cancer. The new endobronchial ultrasound system images enabled visualization of metastatic site within the subcarinal lymph node by the combination of ultrasound image and Doppler mode.

The usefulness of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) for lymph node staging of lung cancer is well known; however, its utility for the diagnosis of postoperative recurrence remains unclear. Establishing a pathological diagnosis of postoperative intrathoracic recurrence of lung cancer is very difficult because of the anatomical changes that occur after resection. Computed tomography (CT) and/or positron emission tomography (PET) have limitations, as they provide nonpathological information. We report a case of postoperative lymph node recurrence successfully diagnosed using EBUS-TBNA. Repeated EBUS-TBNA also allowed us to evaluate the effectiveness of chemotherapy and radiotherapy, and to follow the patient’s clinical course. We report this case to show the usefulness of EBUS-TBNA for making clinical decisions in the management of patients with postoperative recurrence of lung cancer.