Unique minithoracotomy assisted by videothoracoscopy facilitates a maximal view even with a minimal wound for resection of primary lung cancer.

Resection for primary lung cancer with an unique minithoracotomy and use of videothoracoscopy is described. Through an incision of approximately 10 cm at an ausculatory triangle, the 5th intercostal thoracotomy is done following dissection of muscles. At the anterior and posterior portion of the 6th rib, the 6th intercostal vessels and nerve were dissected and the rib was resected. This approach makes feasible opening of a thoracic window without injury to the nerve and removal of the rib. Thoracoscopy is introduced through a midaxillary wound of 2 cm. We report nine patients in whom we achieved resection for primary lung cancer by using this approach. This technique facilitates a standard operation for lung cancer and an almost painless postoperative state.

Survival of non-small cell lung cancer patients with postoperative recurrence at distant organs.

BACKGROUND: Recurrence after complete resection of non-small cell lung cancer (NSCLC) is often observed. However, its influence on the prognosis of patients with recurrence is still unclear. PATIENTS AND METHODS: Of 468 consecutive patients with NSCLC undergoing complete resection during 10 years, 118 experienced recurrence at distant organs. In such patients, the influence of the following variables on post-recurrent survival was analyzed; sex, age at recurrence, disease-free interval, cell type, pathological (p-) stage at operation, adjuvant therapy (thoracic radiation and/or chemotherapy), site of recurrence, and treatment against recurrence. To identify independent factors, multivariate analysis was performed for variables which were considered to be influential in univariate analysis. RESULTS: Mean post-recurrent survival time was 418 days, and survival rate at 2-years was 15.7%. Multivariate analysis revealed that female, early p-stage, younger age at recurrence, metastasectomy and intra-pulmonary metastasis were the significant favorable factors in patients with distant metastases. Adjuvant therapy and bone metastasis were marginally significant unfavorable factors. Chemotherapy for recurrence tended to prolong survival. Length of disease-free survival and post-recurrent survival exhibited a positive relationship with p-stage. Seven out of 16 patients who underwent metastasectomy survived more than 1000 days after recurrence. CONCLUSIONS: Patients even with recurrence in distant organs could expect for long survival if they are in the early p-stage of primary cancer or a resectable recurrent disease.

High vascularity in the peripheral region of non-small cell lung cancer tissue is associated with tumor progression.

OBJECTIVES: We attempted to determine if the degree of angiogenesis can serve as a prognostic factor in the case of completely resected non-small cell lung cancer patients, with special reference to the center and the periphery of the tumor tissue. METHOD: For 255 Japanese patients who underwent completely resected non-small cell lung cancer (NSCLC), micro vessel density (MVD) was assessed by visual quantification of microvessels immunostained with anti-CD34 monoclonal antibody in 5 m section. Vascular endothelial growth factor (VEGF) was also immunostained on the same paraffin block specimen. RESULTS: MVD at the center (MVD-c) and that at the periphery (MVD-p) were frequently different in each individual although a weak positive correlation was observed (r=0.499, P<0.0001). One hundred and one patients with high MVD-p, but not the 107 patients with high MVD-c, showed a significantly higher proportion of advanced stage, larger tumor size and nodal metastasis as compared with MVD. The 5 year survival rate and median survival time for the high MVD-p group were significantly lower than that of low the MVD-p group (43.0%/31 months vs 48.6%/54 months, P=0.0256). As to the relationship among vascular endothelial growth factor (VEGF) and MVD, expression of VEGF was not associated with the degree of MVD. However, patients with high grade MVD-p showed an unfavorable prognosis in cases of high expression of VEGF. CONCLUSION: High MVD-p is associated with advancement of NSCLC, and it was particularly apparent in conjunction with high VEGF expression.

Reduced expression of cell-cycle regulator p27(Kip1) correlates with a shortened survival in non-small cell lung cancer.

BACKGROUND: The cell cycle progression is governed by a family of cyclin-dependent kinases, which are regulated by associated cyclins and by phosphorylation. p27, a cyclin-dependent kinase inhibitor, regulates the progression from G1 into the S phase by binding and inhibiting cyclin/cdks. Although p27 mutations in human tumors are extremely rare, a reduced expression of p27 might to lead to a progression of cancer cells. METHODS: We examined tissues that had been surgically excised from 161 unselected Japanese patients with non-small cell lung cancer, and investigated the p27 protein expression by immunohistochemistry. RESULTS: A reduced expression of the p27 protein was found in 63 cases (39.0%). Statistical correlation was found between the reduced p27 expression and advanced stage, although no correlation was found between the level of p27 expression and the gender, T factor, N factor or histological differentiation. The 5-year survival rate in the reduced group was 35.4%, which was statistically poorer than the 63.2% rate in the normal group (P=0.0016), in patients with complete resection. In a multivariate analysis, the level of p27 expression was found to be an independent prognostic indicator. CONCLUSIONS: We demonstrated the expression of p27 protein to be a biological prognostic indicator which can indicate the subsets of patients with either a good or poor prognosis, in patients who underwent surgical resection.

Clinical significance of the Rb expression in adenocarcinoma of the lung.

BACKGROUND: Altered retinoblastoma gene expression has been found in various types of cancers including non-small cell lung cancer (NSCLC) and some reports have shown it also to be associated with a poor clinical prognosis in NSCLC. MATERIALS AND METHODS: We evaluated the expression of Rb protein by immunohistochemistry in 90 patients with lung adenocarcinoma who underwent surgical resection and determined its prognostic significance. Also, the expression of p27 by immunohistochemistry and the mutations of the p53 gene by PCR-SSCP were evaluated. RESULTS: Fifty-one out of 90 tumors (56.7%) had reduced expression of the Rb gene. There were no statistical differences between the Rb expression level and clinicopathological status. There was no correlation between the Rb expression level and the p53 mutations or the p27 expression level. The 5-year survival rate in the normal group was 55.1%, which was poorer than that of 73.0% in the reduced group, but showed no statistical difference (p=0.0981). In patients with a reduced Rb-expression, the survival rate of the p53 mutation group tended to show a poorer prognosis than that of the p53 normal group (p=0.0880). In addition, the survival rate of the negative p27 expression group tended to show a poorer prognosis than that of the positive p27 expression group (p=0.0537). CONCLUSIONS: The Rb expression status was not significant as an individual factor for evaluating the prognosis in adenocarcinoma of the lung. Analyses of the accumulation of genetic alteration are necessary to identify the subset of patients with a poor prognosis.

[Anesthetic management of tracheal stent insertion under total intravenous anesthesia--a report of two cases].

Tracheal stent insertion is a useful method for patients with malignant tracheal stenosis. Expandable metal stents were inserted in two patients with severe dyspnea due to tracheal stenosis caused by lung cancer and esophageal cancer. The tracheas were intubated after spraying the pharynx with 4% lidocaine solution. The respiration was assisted. Anesthesia was maintained by intravenous propofol. There were no episodes of coughing during and after the procedure.

Expression of the isoamylase gene of Flavobacterium odoratum KU in Escherichia coli and identification of essential residues of the enzyme by site-directed mutagenesis.

The isoamylase gene from Flavobacterium odoratum KU was cloned into and expressed in Escherichia coli JM109. The promoter of the gene was successful in E. coli, and the enzyme produced was excreted into the culture medium, depending on the amount of the enzyme expressed. The enzyme found in the culture medium showed almost the same M(r), heat-inactivating constant, and N-terminal sequence as those of the enzyme accumulated in the periplasmic space. This result indicated that the enzyme accumulated in an active form at the periplasm was transported out of the cell. The primary sequence of the enzyme, which was deduced from its nucleotide sequence, showed that the mature enzyme consisted of 741 amino acid residues. By changing five possible residues to Ala independently, it was found that Asp-374, Glu-422, and Asp-497 were essential. The sequences around those residues were highly conserved in isoamylases of different origins and the glycogen operon protein X, GlgX. The comparison of the distance between these essential residues with those of various amylases suggested that the bacterial and plant isoamylase but not GlgX had a longer fourth loop than the other amylases. This longer fourth loop had a possible role in accommodating the long branched chains of native glycogens and starches.

UFT plus cisplatin with concurrent radiotherapy for locally advanced non-small-cell lung cancer.

A phase II study of combined-modality treatment consisting of uracil and tegafur (in a molar ratio of 4:1 [UFT]) plus cisplatin (Platinol) and concurrent radiotherapy was conducted to evaluate the activity of this regimen in patients with locally advanced non-small-cell lung cancer. Eligible patients with cytologically or histologically confirmed, unresectable stage III non-small-cell lung cancer received UFT (400 mg/m2 orally on days 1 through 52) and cisplatin (80 mg/m2 intravenously on days 8, 29, and 50). Radiotherapy, with a total dose of 60.8 Gy, was delivered in 38 fractions on days 1 through 52. Among the 17 patients entered, 16 experienced partial responses (94%; 95% confidence interval, 83% to 100%). The median time to tumor progression was 30 weeks (range, 8 to 87 weeks), and the 1-year survival rate was 80%. Hematologic toxicity was moderate. Grade 3 leukopenia occurred in 10 patients (59%), but no grade 4 hematologic toxicity was observed. No grades 3 or 4 nonhematologic toxicities were reported. These observations suggest that oral UFT plus cisplatin with concurrent radiotherapy can be safely administered to patients with locally advanced non-small-cell lung cancer. The demonstrated antitumor activity is high, making this combined-modality treatment worthy of further investigation in a multi-institution trial.

Invasive thymoma with long-term survival by extensive reoperation.

The recurrence of invasive thymoma is often observed; however, no accepted treatment of recurrent invasive thymoma has yet been established. We herein report a 41-year-old woman with invasive thymoma and pleural dissemination who demonstrated long-term survival after undergoing 4 operations. Based on our findings, reoperation is thus suggested in patients with intrathoracic recurrence and long-term survival can be expected.

Second primary cancers after resection of lung adenocarcinoma with ras gene mutation.

BACKGROUND: Ras gene mutations are associated with a poor prognosis in patients with adenocarcinoma of the lung. However, the association between cases with ras gene mutation and an occurrence of second primary cancer is unknown. MATERIALS AND METHODS: We examined 89 adenocarcinoma of the lung obtained from patients treated by curative resection, and four second primary cancers, for mutation at codons 12, 13, and 61 of three ras oncogenes using polymerase chain reaction and oligonucleotide hybridization techniques. RESULTS: Ras gene mutations were detected in 13 cases. Six patients died from recurrent disease within 3 years. Of the seven patients who survived over 5 years, three patients demonstrated a metachronous second primary cancer after the operation for lung cancer, and one patient had synchronous laryngeal cancer. Two of the cases with second primary cancer demonstrated the ras gene mutation. One had the same mutation as that of the primary lung cancer, and the other had a different mutation from the first lung cancer. CONCLUSION: Ras gene mutations play an important role in tumor progression of lung adenocarcinoma and also might have an role in the carcinogenesis in respiratory tract cancer.

Spontaneous pneumothorax complicating lung metastasis from lingual carcinoma.

We report a patient with pneumothorax caused by a metastatic tumour from carcinoma of the tongue, which had given rise to a bronchopleural fistula with subsequent induction of pneumothorax. Although rare, pulmonary metastasis should be considered in the aetiology of spontaneous pneumothorax. Despite advanced disease, surgical treatment may be feasible.