[Thoracic surgery for patients with bronchial asthma].

Thoracic surgery poses a risk for complications in the respiratory system. In particular, for patients with bronchial asthma, we need to care for perioperative complications because it is well known that these patients frequently have respiratory complications after surgery, and they may have bronchial spasms during surgery. If we can get good control of their bronchial asthma, we can usually perform surgery for these patients without limitations. For safe postoperative care, it is desirable that these patients have stable asthma conditions that are well-controlled before surgery, as thoracic surgery requires intrabronchial intubation for anesthesia and sometimes bronchial resection. These stimulations to the bronchus do not provide for good conditions because of the risk of bronchial spasm. Therefore, we should use the same agents that are used to control bronchial asthma if it is already well controlled. If it is not, we have to administer a ß2 stimulator, aminophylline, or steroidal agents for good control. Isoflurane or sevoflurane are effective for the safe control of anesthesia during surgery, and we should use a ß2 stimulator, with or without inhalation, or steroidal agents after surgery. It is important to understand that we can perform thoracic surgery for asthma patients if we can provide perioperative control of bronchial asthma, although these patients still have severe risks.

Analysis of cell cycle-related proteins in mediastinal lymph nodes of patients with N2-NSCLC obtained by EBUS-TBNA: relevance to chemotherapy response.

BACKGROUND: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is an accurate tool for lymph node staging of non-small cell lung cancer (NSCLC). Most patients with NSCLC require systemic chemotherapy during their treatment, with relatively poor responses. If the response to chemotherapy could be predicted, ideally at the time of the initial bronchoscopic examination, the therapeutic benefit could be maximised while limiting toxicity. A study was therefore undertaken to investigate the feasibility of EBUS-TBNA for obtaining tissue samples from mediastinal lymph nodes that can be used for immunohistochemical analysis, and to stratify patients with molecular-based pN2-NSCLC into chemo-responsive and chemoresistant subgroups who might benefit from tailoring of chemotherapy. METHODS: The expression of six cell cycle-related proteins (pRb, cyclin D1, p16(INK4A), p53, p21(Waf1), Ki-67) in mediastinal lymph node specimens obtained by EBUS-TBNA was investigated by immunohistochemistry in 36 patients with pN2-NSCLC. Their predictive role(s) in the response to platinum-based chemotherapy was examined. RESULTS: Immunostaining was feasible in all studied specimens. Univariate analysis revealed that p53 and p21(Waf1) expressions were significantly related to the response to chemotherapy (p = 0.002 and p = 0.011, respectively). Multivariate logistic regression analysis revealed that only p53 overexpression was associated with a poor response to chemotherapy (p = 0.021). CONCLUSIONS: These results suggest that EBUS-TBNA is a feasible tool for obtaining mediastinal nodal tissue samples amenable for immunohistochemical analysis. Immunostaining of p53 in EBUS-TBNA-guided specimens may be useful in predicting the response to chemotherapy in patients with N2-NSCLC and helping in the selection of patients who might benefit from certain chemotherapeutic strategies.

Expression of vascular endothelial growth factor in thoracic sarcomas.

BACKGROUND: A body of data indicates that vascular endothelial growth factor (VEGF) expression by carcinomas is closely related to the prognosis of carcinomas. However, the relationship between VEGF expression and the prognosis of sarcomas is contradictory. METHODS: Tissue from 27 cases of thoracic sarcoma was analyzed immunohistochemically for VEGF expression while tumor vascularity was quantified using an antibody directed against endothelial CD34. The relationship between VEGF expression and the prognosis of patients with sarcomas was then evaluated semiquantitatively. RESULTS: The microvessel count in sarcomas with strong VEGF expression was significantly higher than that in sarcomas with absent or faint VEGF expression. The disease-free survival rates of sarcomas with strong VEGF expression were significantly lower than those of sarcomas with absent or faint VEGF expression. We found that strong VEGF expression impacted on the disease-free survival in multivariate analyses. CONCLUSIONS: VEGF expression of thoracic sarcomas is directly related to angiogenesis and tumor vascularity, and our findings suggest that strong VEGF expression is an independent prognostic factor in patients with thoracic sarcomas.

Microsatellite alterations in patients with thoracic sarcoma.

Few studies on sarcomas have examined the relationships between microsatellite alterations in particular loci, tumor prognosis and tumorigenesis, because sarcomas are uncommon and those prognoses can be confounded by coexisting factors, such as tumor site. We studied the relationship between microsatellite alterations and prognosis in 31 patients with thoracic sarcoma. The frequency of loss of heterozygosity (LOH) at 17p13 in stage IV sarcomas was significantly higher than that in stage I and III sarcomas (p<0.05). The 5-year survival for patients with LOH at 17p13 was significantly lower than that for patients without LOH (p<0.05). Six of 31 cases (19.4%) revealed replication error. These results suggest that p53 abnormality occurs during advanced stages of sarcoma and are related to patient prognosis, and it is possible that aberrations in mismatch repair activity are related to sarcoma tumorigenesis.

Cytomorphologic features characteristic of tumor stages of thymomas.

The cytologic findings of the tumor cells characteristic of the stages of thymomas were investigated to assess the invasiveness of the tumors. Forty-six patients with thymoma who underwent extensive thymectomy without pre-operative corticosteroid therapy were included in this study. The histologic subtypes included 18 round/oval, 20 mixed, and 8 spindle type. The stages of thymoma classified according to Masaoka's clinicopathological classification included 16 stage I, 20 stage II, 6 stage III, 2 stage IVa, and 2 stage IVb, and myasthenia gravis was recognized in 5 patients. Cytologic findings were retrospectively analyzed in the Papanicolaou-stained stamp smears obtained from the cut surfaces of thymoma specimens. Morphometry of the epithelial tumor cells using Cosmozone-1A was performed to evaluate the validity of our cytologic categories. Compared with the cytologic findings of stage I or II thymomas, those of epithelial tumor cells in stage III or IV more frequently showed necrotic background (50.0%-stage III or IV vs 11.1%-stage I or II, p=0.006), large clusters of epithelial tumor cells (70.0% vs 36.1%, p=0.055), marked nuclear enlargement (90.0% vs 52.7%, p=0.033), marked anisokaryosis (100% vs 52.7%, p=0.006), marked nuclear polymorphism (40.0% vs 5.5%, p=0.004), hyperchromasia (50.0% vs 11.4%, p=0.007) and prominent nucleoli (50.0% vs 16.6%, p=0.028) whereas no significant correlation was observed between cytologic findings and tumor volume. Morphometric studies of thymoma tumor cells revealed that the nuclear size (mean values, 78.8 microm(3)-stage III or IV vs 58.2 microm(3)-stage I or II), the coefficient of variation of the nuclear size (0.326 vs 0.282), and the nuclear rotundity (0.849 vs 0.858) differed significantly between the two categories (p<0.05). Our findings demonstrated that there were significant differences between the cytologic findings of epithelial tumor cells of stage I or II thymomas and those of stage III or IV thymomas, and that the cytologic findings of thymoma tumor cells appear to be useful for distinguishing between non-invasive and invasive thymomas.

Surgical resection combined with intrathoracic hyperthermic perfusion for thymic carcinoma with an intrathoracic disseminated lesion: a case report.

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.

The primary mediastinal growing teratoma syndrome.

We encountered a case of mediastinal immature teratoma which revealed the feature of the so-called growing teratoma syndrome. A 20-year-old male with a cough was discovered to have an abnormal shadow in the mediastinum. The serum AFP was elevated to 3600 ng/ml. The specimen with percutaneous needle biopsy revealed mature teratoma. The tumor was suspected to be mature teratoma with a malignant component because of the high level of serum AFP and he underwent chemotherapy. The serum AFP declined markedly but the tumor further enlarged. The resected tumor was diagnosed as immature teratoma, although most of the tumor tissue was mature component.

Genetics and lung carcinoma in Okinawa Prefecture, Japan.

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 mutation, 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.

[Diagnosis and surgical treatment for small-sized peripheral lung cancer].

Small-sized peripheral lung cancers have been detected more frequently as a result of recent developments in diagnostic imaging including high-resolution computed tomography (HRCT). Although the diagnosis of small-sized peripheral lung cancers is difficult, it makes an adequate diagnosis possible using transbronchial fine needle aspiration cytology or a new thin-type bronchoscope. Surgical treatment using mini-thoracotomy or video-assisted thoracic surgery is effective for early stage small-sized peripheral lung cancers. Lesser resection of lung cancer may provide many benefits to patients, such as preserving vital lung tissue and providing the chance for further resection if a second primary lung cancer develops, however, lobectomy with systematic hilar and mediastinal lymph node dissection should remain the standard surgical treatment, and an intentional limited resection should be adopted for very limited patients with a definitive early stage because of recurrence rates.

[Supraannular implantation of bioprosthetic valve for severe tricuspid valve regurgitation associated with atrial septal defect in an adult patient].

With an adult atrial septal defect, there was often regurgitation of the mitral and tricuspid valve due to volume overload in a long term period. Especially concerning tricuspid regurgitation, what can be done surgically has not yet been decided. For severe tricuspid regurgitation, some cases where tricuspid valve annuloplasty were performed have had exacerbation of tricuspid regurgitation. We experienced a case where tricuspid valve supraanular implantation without excision of native tricuspid valve (TVSI) was performed for severe tricuspid regurgitation associated with atrial septal defect, and improved. A 53-year-old female complained of dyspnea on exertion. An atrial septal defect was revealed being 4 cm in size, complicated with severe tricuspid regurgitation (IV), and 62 mmHg difference of pressure from the right atrium to right ventricle shown by a ultrasonography. Pulmonary artery pressure was 66/16 mmHg by cardiac catheter. Patch closure for ASD and TVSI for TR was performed on her, and amelioration of cardiac function was recognized.

[Multiple systemic embolization from floating thrombus in left atrium].

A 66-year-old woman was referred to our hospital because of cerebral infarction, myocardial infarction and renal infarction. Further examination indicated that she was suffering from mitral valve stenosis with a floating thrombus in the left atrium. She underwent emergency mitral valve replacement and thrombectomy. The thrombus was attached to the left atrium by only four thin and weak strings and removed easily. We think that the thrombus was the precursor of a free-floating ball thrombus without stalk.

[Detection of emphysematous bullae in spontaneous pneumothorax by three-dimensional computed topography].

The patient was a 20-year-old woman with spontaneous pneumothorax, who had had pneumothorax twice on each side. Three-dimensional computed topographic (CT) images were made as follows. The range 12.5 cm caudad from the pulmonary apex was scanned by rapid helical CT, and three-dimensional images were obtained with the surface-rendering technique at a voxel extraction threshold ranging-850 HU to 1,600 HU. The three-dimensional CT images provided a stereotactic rendering of the lung surface. Irregular findings were observed at both pulmonary apices; they indicated the presence of one emphysematous bulla in the right lung and many emphysematous bullae of various sizes in the left lung. These findings were highly consistent with the sites and structures of the emphysematous bullae, as observed during thoracoscopy, which suggests that three-dimensional CT is a useful method for diagnosing and evaluating emphysematous bullae in patients with spontaneous pneumothorax.

Transbronchial fine needle aspiration cytological examination: a useful tool for diagnosing primary lung cancer.

BACKGROUND: Obtaining a definitive preoperative diagnosis plays a critical role in deciding upon the treatment approach for lung carcinoma. However, success in making definitive diagnoses of small primary lung cancers will require new approaches because these cancers are difficult to detect using standard biopsy procedures. METHODS: We evaluated the results of morphologic definitive diagnosis together with various clinical factors in 1003 primary lung cancers resected surgically. Patients underwent transbronchial brushing, fine needle aspiration cytology, forceps biopsy, and/or forceps biopsy-stamp cytology for preoperative diagnoses, in conjunction with the use of Diff-Quik to confirm that hits had been made on the radiographic shadows before terminating the examinations. RESULTS: Sensitivities of the diagnostic procedures for primary lung cancers were as follows: 64.8% for brushing, 56.1% for transbronchial forceps biopsy, 72.0% for transbronchial forceps biopsy-stamp cytology, and 86.4% for transbronchial fine needle aspiration. The four transbronchial biopsy procedures had a combined overall sensitivity of 92.7%. In patients with peripheral lung cancers of 2 cm or less in diameter, transbronchial fine needle aspiration had a sensitivity of 75.9%, which was the highest sensitivity for all transbronchial examinations. In the subset of 296 patients who underwent all four transbronchial biopsy examinations, transbronchial fine needle aspiration had the highest sensitivity of preoperative diagnosis of all the transbronchial examination methods. CONCLUSIONS: The sensitivity of preoperative cytological diagnosis for primary lung cancers, especially transbronchial aspiration cytology, is high. Transbronchial fine needle aspiration cytology is useful for the preoperative diagnosis of primary lung cancer.

Frequency of loss of heterozygosity at 3 p, 9 p, 13 q, and 17 p is related to proliferative activity in smokers with stage I non-small cell lung cancer.

BACKGROUND: Tumor cells of lung cancer exhibit genetic abnormalities as well as high proliferative activity. The purpose of this study was to evaluate the relationship of genetic abnormalities and smoking status, histological type, and tumor proliferative activity in resected samples of stage I non-small cell lung cancer (NSCLC). METHODS: We evaluated 126 samples of stage I NSCLC from patients who underwent complete resection between 1988 and 1993. Loss of heterozygosity (LOH) was assessed using primers that amplified polymorphic microsatellite markers at D3S1300, D3S643, D3S1317, D9S171, IFNA, D13S153, and TP53. Expression of Ki-67 nuclear antigen was examined using immunohistochemical methods to assess tumor proliferative activity. RESULTS: The Fractional Regional Loss index (FRL) was significantly higher in squamous cell carcinoma samples than in adenocarcinoma samples (p < 0.0001). In smokers, Ki-67 labeling index (LI) in high-FRL cases was significantly higher than in low-FRL cases (p < 0.0001). CONCLUSION: The frequency of LOH at 3 p, 9 p, 13 q, and 17 p was related to proliferative activity in smokers with stage I non-small cell lung cancer.

[A resected case of diffuse malignant pleural mesothelioma diagnosed by thoracoscopic biopsy].

A 53-year-old male was admitted with cough and chest pain. A chest X-ray film showed left pleural effusion and a chest CT revealed irregular thickening of the pleura. Pleural fluid cytology and percutaneous needle biopsy were negative for malignancy. Thoracoscopic findings revealed fibrin network with pleural effusions and yellow-white pleural thickening, but neither nodules nor masses were found. The thoracoscopic biopsy specimen from the pleural thickening resulted in the diagnosis of malignant pleural mesothelioma. Left pleuropneumonectomy with mediastinal lymph node dissection was performed. Since detailed inspection of the pleural cavity and taking large biopsy samples under thoracoscopic examination are possible, we consider thoracoscopic biopsy to be a useful method for obtaining diagnosis of malignant pleural mesothelioma. Pleuropneumonectomy and systematic lymph node dissection of the pulmonary hilum and mediastinum were believed to be necessary for the surgical treatments.

Clear cell adenocarcinoma with endobronchial polypoid growth.

Clear cell adenocarcinoma of the lung is extremely rare. On radiography, a 45-year-old female with fever was found to have an abnormal shadow in the left lower lung field. Bronchoscopy revealed a polypoid tumor in the left bronchus. On biopsy, the tumor was determined to be adenocarcinoma. Preoperative examination found no tumors outside of the lung. The patient underwent left lower lobectomy with bronchial wedge resection. The tumor had completely obstructed and dilated the left lower bronchus, but had not invaded the tissue outside the bronchial wall. Microscopically, the cytoplasm of the tumor cells contained abundant glycogen, and the tumor had solid and glandular structures. The tumor was diagnosed as clear cell adenocarcinoma of the lung.

Apoptosis and proliferative activity in mature and immature teratomas of the mediastinum.

BACKGROUND: Mediastinal teratomas are the most frequent mediastinal germ cell tumor. Whereas mature teratomas are benign tumors, immature teratomas are malignant. The purpose of this study was to find characteristics that could be used to distinguish between the growth and prognosis of the two teratoma types. METHODS: Twenty-four mediastinal teratomas (18 mature and 6 immature) were examined for apoptosis by 3'-end labeling of DNA and stained immunohistochemically for proliferating cell nuclear antigen, Bcl-2, Bax, p53 protein, and alpha-fetoprotein (AFP) expression in formalin fixed, paraffin embedded specimens. RESULTS: AFP was expressed in both immature teratomas and mature teratomas. Whereas p53 protein was expressed by most teratomas, p53 gene mutation was observed in only one patient with an immature teratoma in which the same mutation occurred in all tumor tissue components tested. Bax protein expression was relatively diffuse in mature teratomas but was focally expressed in immature teratomas. Bcl-2 protein was expressed focally in both mature and immature teratomas. Although the proliferative index was significantly higher in immature teratomas compared with mature teratomas (P < 0.001), the apoptotic index (AI) was significantly higher in mature teratomas compared with immature teratomas (P < 0.05). All patients except one in this study remain alive and disease free after undergoing tumor resection. CONCLUSIONS: The relatively high AI in mature teratomas may be due to the overexpression of the p53 protein. In contrast, immature teratomas exhibited higher proliferative activity and lower rates of apoptosis, which may explain the more aggressive behavior of these tumors. However, patients with immature mediastinal teratomas have a good prognosis if the tumor is resected completely after chemotherapy.

Clinical characterization of pulmonary large cell neuroendocrine carcinoma and large cell carcinoma with neuroendocrine morphology.

BACKGROUND: Large cell carcinoma has been classified as four potential types based on its neuroendocrine morphology and evidence of neuroendocrine differentiation discernible by immunohistochemistry or electron microscopy. However, the clinical relation among these four categories has not been clearly defined. In 1999, the World Health Organization (WHO) categorized large cell neuroendocrine carcinoma as a variant of large cell carcinoma. MATERIAL AND METHODS The authors analyzed 119 cases of large cell carcinoma from a total of 2070 primary lung carcinoma cases resected surgically between 1969-1999. Using light microscopy, electron microscopy, and immunohistochemical staining, the authors reclassified these cases into large cell neuroendocrine carcinoma (LCNEC), large cell carcinoma with neuroendocrine differentiation (LCCND), large cell carcinoma with neuroendocrine morphology (LCCNM), and classic large cell carcinoma (CLCC). RESULTS: In multivariate analyses, the authors found that large cell carcinoma with neuroendocrine features, which combined LCNEC, LCCND, and LCCNM, impacted both the overall survival and disease-free survival of patients. The clinical behavior of LCCNM was similar to that of LCNEC. CONCLUSIONS: Large cell carcinomas with neuroendocrine features appear to be more clinically aggressive than CLCCs. The authors' findings suggest that the histologic identification of neuroendocrine features in tumor tissue from patients diagnosed with large cell carcinoma of the lung may have clinical relevance.

Undifferentiated spindle-cell sarcoma of the chest wall with vascular endothelial growth factor expression: report of a case.

The expressions of some growth factors have been immunohistochemically confirmed in several kinds of tumors, and in particular the expression of vascular endothelial growth factor (VEGF) has been reported to be closely related to tumor cell proliferation. We report herein a case of undifferentiated spindle-cell sarcoma arising in the chest wall with VEGF expression. A 67-year-old man, who presented with coughing, was found to have an abnormal shadow on his right chest wall. He was admitted to Chiba Rosai Hospital and preoperative diagnosis of the tumor was sarcoma. The tumor was thus resected along with the right chest wall and right lower lobe of the lung. Histopathologically, the tumor cells were spindle-shaped and showed severe atypism. The tumor cells were positive for vimentin and VEGF antibody with immunohistochemical staining, but they did not show differentiation to any special type of sarcoma. The tumor was diagnosed to be undifferentiated spindle-cell sarcoma. The microvessel density of the tumor was measured using CD34 and it was found to be higher than the average density of usual sarcomas. The prognosis of this case was poor. The patient died of tumor metastasis to the lung and bone 1 year later in spite of the fact that the tumor was resected.

Adjuvant chemotherapy for large cell carcinoma with neuroendocrine features.

BACKGROUND: In 1999, the World Health Organization categorized large cell neuroendocrine carcinoma, large cell carcinoma with neuroendocrine differentiation, and large cell carcinoma with neuroendocrine morphology as a variant of large cell carcinoma. Patients with large cell carcinoma with neuroendocrine features have poor prognoses, comparable to those for small cell lung carcinoma. Small cell lung carcinoma is sensitive to chemotherapy; however, it is still unclear whether large cell carcinoma with neuroendocrine features is responsive to adjuvant chemotherapy. METHODS: The authors analyzed 73 patients with large cell carcinoma with neuroendocrine features who underwent resection of the tumor and studied the effect of adjuvant chemotherapy for large cell carcinoma with neuroendocrine features. RESULTS: In patients with Stage I disease, the overall survival for patients with adjuvant chemotherapy based on cisplatin, carboplatin, or cyclophosphamide, which were used as standard chemotherapy for small cell lung carcinoma, were significantly higher than the overall survival for patients without adjuvant chemotherapy. In patients with Stage II, III, and IV disease, there was no significant difference between patients with adjuvant chemotherapy and without adjuvant chemotherapy. CONCLUSIONS: Adjuvant chemotherapy based on cisplatin, carboplatin, or cyclophosphamide prolongs survival of patients with large cell carcinoma with neuroendocrine features in early stage.