In recent years, the number of patients in whom pneumonectomy is required is gradually decreasing due to advances in diagnostic imaging and increased frequency of health screening that has facilitated relatively early detection of lung cancer, and due to improved techniques for surgery such as bronchoplasty. Considering the marked decreases in QOL after pneumonectomy, most surgeons tend to avoid the indication of pneumonectomy when possible. However, since there are always some patients in whom pneumonectomy is required and is the most appropriate treatment, surgeons should master the procedure of pneumonectomy as a basic surgical technique. In this paper, we described the indications and basic techniques for pneumonectomy under the title of Standard Surgical Techniques of Pneumonectomy.

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Objective. Collagen XVIII, a precursor of endostatin, is an extracellular matrix protein that is a component of vascular and epithelial basement membranes. The aim of this study was to determine whether collagen XVIII expression has any prognostic value in patients with non-small cell lung cancer (NSCLC). Study design. The authors investigated the expression of collagen XVIII in 306 patients who underwent surgery for NSCLC using immunohistochemical methods. The series of patients consisted of 215 men and 91 women ranging in age from 31 to 85, mean 64.8±9.8 years; 114 squamous cell carcinomas, 179 adenocarcinomas, and 13 large cell carcinomas; 130 stage I cases, 47 stage II cases, 113 stage III cases, and 16 stage IV cases. Results. Collagen XVIII expression was detected in 214 of 306 patients with NSCLC (69.9%). Low collagen XVIII expression levels were found in 119 tumor specimens, while high collagen XVIII expression levels were noted in 95 tumor specimens. The overall 5-year survival rates were 40.3%, 56.5%, and 70.4% in the patients who were strongly collagen XVIII-positive, positive, and negative NSCLC, respectively. The prognosis for patients with strongly collagen XVIII-positive NSCLC or collagen XVIII-positive NSCLC was significantly worse than the prognosis for patients with collagen XVIII-negative NSCLC (P<0.0001). Multivariate analysis indicated that age, postsurgical stage, T status, N status, and the overexpression of collagen XVIII were independent prognostic factors. Conclusion. Our results indicate that expression of collagen XVIII in tumor tissue is a crucial prognostic factor in NSCLC.

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Objective and Methods. We retrospectively evaluated the differences of clinicopathological features and surgical outcome with regard to whether the lung cancer was detected by chest X-ray (CXR) without symptoms or by mainly respiratory symptoms. We classified 362 patients with lung cancer into 2 groups. In the mass screening and other disease group (n=225), their lung cancers were discovered by CXR mass screening or during medical examinations for other diseases. In the symptomatic group (n=137), their lung cancers were detected following the appearance of respiratory symptoms. Results. There was no significant difference in the age or gender between the two groups. Both tumor size and smoking index were lower, and pathological T1 (pT1) disease, pathological N0 (pN0) disease, partial resection or lobectomy, non-SCC (squamous cell carcinoma) and complete resection cases were more frequent in the mass screening and other disease group than in the symptomatic group (p<0.01). A multivariate analysis of survival revealed that gender, smoking index, T-factor, N-factor, curativity and the detection method were significant prognostic factors (p<0.05). Histology, operative method, differentiation, operative side and tumor location were not significant prognostic factors. According to the subset analysis, the detection method was a significant prognostic factor in patients with a smoking index of more than 800, pT1 disease, pN0 disease, partial resection or lobectomy and non-SCC cases (p<0.01), but it was no significant in patients with a smoking index of less than 800, advanced disease, extended resection and SCC cases. Conclusion. 1) Early stage lung cancer were more frequent in the mass screening and other disease group. 2) The detection method was a significant prognostic factor in early stage lung cancer. 3) The detection method was not a significant prognostic factor in the extended resection and SCC cases.

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Objective. The reported incidence of second primary lung cancer has increased steadily, because the proportion of early-stage lung cancer has increased and long-term surgical results for early-stage lung cancer have improved. In this report, we reviewed surgical results for second primary lung cancer. Methods. The data from the lung cancer registry on patients with multiple primary lung cancer from January 1996 to December 2003 were reviewed. Results. During the 8-year period, a total of 523 patients underwent pulmonary resection for primary lung cancer. Nineteen patients developed a second primary lung cancer. Of those 19 patients, 16 patients underwent pulmonary resection for second primary lung cancer. There were 10 men and 6 women patients. The average age at the second operation was 75. The initial pulmonary resection was lobectomy in 14 patients and segmentectomy in 2. The second pulmonary resection was lobectomy in 4 patients, segmentectomy in 4 and wedge resection in 8. The second primary lung cancer was preoperative stage IA in 11 patients and stage IB in 5. The second primary cancer was postoperative stage IA in 13 patients, stage IB in 1, and stage IIB in 2. There were no postoperative complications or perioperative deaths among the 16 patients. The overall actuarial 5-year survival for second primary lung cancers was 56.8%, while the actuarial 5-year survival for second primary lung cancers treated with limited resection was 71.1%. Conclusion. We conclude that an aggressive surgical approach is effective and is linked with good outcome for patients with a second primary lung cancer if the tumor is detected within stage I, which has the possibility of cure by performing limited resection. Moreover, careful follow-up at regular intervals should be continued after the first resection.

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Objective. We examined the clinical features, diagnosis, treatment, prognosis and prognostic factors of diffuse malignant pleural mesothelioma. Subjects. Fifty-one patients from the institutions of our study group with a pathological diagnosis of diffuse malignant pleural mesothelioma were enrolled. Results. Out of the 51 patients, 47 cases were male and four cases were female with an average age of 60 years old. A past history of exposure to asbestos was identified in 19 patients (37%). Forty-five patients (88%) presented symptoms such as chest pain, shortness of breath, and cough. Thoracoscopic pleural biopsy was the most effective method for diagnosis. It required 60 days (median) from the first visit to establish the diagnosis of malignant pleural mesothelioma. Cytodiagnosis and hyaluronic acid values of pleural effusion were not useful for the diagnosis in half of the cases. Operation was performed in 28 cases (pleuropneumonectomy for 26 cases and other operations for two cases). Chemotherapy and/or radiotherapy were performed in 13 cases, while supportive care alone was carried out in 10 cases. The 1-year, 2-year, and 3-year survival rates of the overall patients were 50.6%, 25.0% and 12.7%, respectively, while the median survival was 12.3 months. Statistically, significant differences of survival were seen according to age, clinical stage and surgery with univariate analysis, but only for clinical stage with multivariate analysis. Some cases undergoing intrathoracic perfusion chemohyperthermia as a postoperative adjuvant therapy showed better survival. Conclusion. For definitive diagnosis, thoracoscopic pleural biopsy should be done promptly in cases with pleural effusion of unknown origin. Establishment of the appropriate indications for surgery, the development of postoperative adjuvant therapy and the development of effective chemotherapy are required for the improvement of survival in diffuse malignant pleural mesothelioma.

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Background. Lymphomatoid granulomatosis is a very rare disease, with only 11 cases having been reported in Japan. We report different outcomes in two cases of pulmonary lymphomatoid granulomatosis. Cases. Case 1 involved a 68-year-old woman who had an abnormal pulmonary hilar shadow on chest radiography. Bronchoscopy did not assist diagnosis, so partial resection of the lung was performed under video-assisted thoracic surgery. Frozen section examination suggested lung cancer. Right middle lobectomy with dissection of the mediastinal lymph nodes was performed. Histopathology revealed grade III lymphomatoid granulomatosis. Adjuvant chemotherapy proved ineffective and the patient died 10 months postoperatively. Case 2 involved a 71-year-old woman who also had an abnormal shadow on chest radiography. Bronchoscopy again proved unhelpful, so partial resection of the lung was performed under video-assisted thoracic surgery. Frozen section examination yielded a diagnosis of lymphomatoid granulomatosis, and histopathology confirmed grade I lymphomatoid granulomatosis. The patient remains alive without any sign of recurrence at 1 year postoperatively. Conclusion. We report these 2 cases and review the reports of lymphomatoid granulomatosis in Japan.

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Objective. The long-term result of video-assisted thoracic surgery (VATS) lobectomy combined with lymphadenectomy, was evaluated as a new modality for the treatment of lung cancer. Materials and Methods. Between September 1992 and August 2004, we performed 378 VATS lobectomies. Of the 324 cases of lung cancer, 247 clinical stage I patients with no major complications underwent extended lymph node dissection (lymphadenectomy). Results. The number of resected lymph nodes ranged from 5 to 73 (25 on average). Among these 247 patients, pathological examination revealed N0 in 159 patients (64.4%), N1 in 32 patients (13.0%), and N2 in 56 (22.6%), and 152 were finally diagnosed as pathologically stage I. Among these patients, 5 died of multiple bone metastases, pleuritis carcinomatosa or brain metastasis. However, the remaining patients are alive with no signs of metastasis for 1 to 130 months after the operation. The 5-year and 10-year survival rates after VATS lobectomy combined with lymphadenectomy for pathological stage I lung cancer have been 94.4% and 87.9%, respectively, which are far better than those after open surgery (78.5% and 65.0%). Comparison between pre- and post-operative pulmonary function revealed less of a decrease for VATS compared with open thoracotomy; in the VATS group, the 3-year postoperative scores were 0.92 for vital capacity and 0.88 for FEV_1.0. Conclusion. VATS was evaluated as setting a new gold standard in the treatment of lung cancer in appropriate patients.

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The significant principle of surgical intervention in practice for lung cancer is considered striking a balance between oncological radicality and less invasive surgery. The former is a major premise and the latter consists of lesser parenchyma resection and minimally invasive approach. During the past decades, the common technique for primary non-small cell lung cancers has been an anatomic lobectomy and a complete hilar/mediastinal dissection using traditional open thoracotomy with very few and very infrequent variations. This is still recommended even though small-sized peripheral cancers are increasingly detected with recent advances in radiologic investigation. We have great doubts as to whether the conventional procedure is really necessary for treatment of small lesions, and so extended segmentectomy with lymph node assessment can be generated as an alternative to lobectomy for clinical stage I cancers 2 cm or smaller. Although video-assisted thoracic surgery (VATS) can be performed more with the introduction of minimally invasive access, arguments among thoracic surgeons continue regarding the appropriateness of “pure” VATS to pulmonary resection for lung cancer. We have made some refinements concerning the access to apply the benefits to as many cases as we can, and thus utilize a integrated combination of muscle-sparing minithoracotomy with video-assisted technique (Hybrid VATS). Current general trends toward less invasive techniques imply that great changes of surgical practice could take place for lung cancer.

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Background. Postoperative adjuvant chemotherapy for patients with IIIA-N2 non-small cell lung cancer (NSCLC) has been elucidated to improve their 5-year survival rate by 4-5% by a metaanalysis or a recent mega-clinical trial. However, it is still yet to be clarified what population among heterogeneous IIIA-N2 NSCLC or should be indicated or what chemotherapy regimen should be selected. Aim. To consider indication of adjuvant chemotherapy for IIIA-N2 NSCLC, surgical results were retrospectively analyzed. Patients and methods. For 293 patients with IIIA-N2 NSCLC who underwent surgical treatment during 1974-2003, postoperative prognosis was investigated in terms of clinical N (cN) status, period, adjuvant treatments and completeness of resection. Results. Overall survival at 5 years was 21%, and median survival period was 24 months. One hundred and seventy four patients who underwent a complete resection showed a 30% 5-year survival rate whereas the 5-year survival rate was 8% in 110 patients who underwent an incomplete resection (p<0.001). A pleural dissemination and an extranodal invasion of mediastinal lymph node metastasis to surrounding organs were the main reason for incomplete resection, and these were observed in 42 (35%) and 41 patients (34%), respectively. As to the historical periods when the operations were performed, the complete resection rate was 40% in the 1970s, 52% in the 1980s, 68% in the 1990s and 90% in the 2000s, and 3-year survival rates were 13% in the 1970s, 35% in the 1980s, 31% in the 1990s and 70% in the 2000s. Single station N2 cases showed a 36% 5-year survival rate if complete resections were performed. Thirteen patients who underwent an induction chemotherapy exhibited a 100% complete resection rate and 75% 3-year survival rate even though their mediastinal node metastases were bulky or multiple. Conclusions. 1) Complete resection is the most dominant prognostic factor. 2) High resolution CT might improve selection of resectable cases. 3) Resectable single station N2 cases showed an outcome equivalent to the cN0-pN2 population, and may be a candidate for postoperative adjuvant chemotherapy. 4) Induction chemotherapy for marginally respectable cN2 population is hopeful.

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Objectives. The therapeutic results for c-N2 non-small cell lung cancer (NSCLC) are extremely bad. To improve these results, we performed induction chemoradiotherapy (ICRT). Materials and methods. 50 patients with c-N2 NSCLC underwent operation following ICRT from January 1992 to April 2004. Until 1998, MVP (mitomycin C, vindesine, cisplatin) or EP (etoposide, cisplatin) (n=27, group-A). After that, Taxan+CBDCA (carboplatin) (Tx+P) (n=23, group-B). Two cycles of chemotherapy were performed with concurrent radiation (50 Gy). Results. In all 50 cases, complete resection was performed with no operative mortality. Response rate was 74%. Histological response rate of Ef2 or Ef3 was 78% (38 cases of 50 cases). Complete histological response was observed in 10 cases (20%). Three-year survival was 54%. Three-year survival of Ef3 patients in group B (Tx+p) was 80% and three patients survived more than 40 months. Conclusions. Surgery after ICRT for c-N2 NSCLC could be performed safely with promising results. Better outcome is anticipated for patients who exhibit good histological response.

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Over 10 years have elapsed since video-assisted thoracic surgery and thoracoscopic surgery came into clinical use and the characteristics have become clarified. With the use of VATS, damage to pulmonary function in the early postoperative stage is minimized and, within one week postoperatively, dosages of analgesics can be kept low and the period of hospital stay can be shortened in comparison with conventional thoracotomy. These features are generally recognized. At present, thoracotomy that used to be called “standard” has changed significantly to muscle sparing thoracotomy or to minimal thoracotomy and these procedures have enabled a great decrease in invasiveness. Comparative studies VATS and minimal thoracotomy have revealed no differences in invasiveness and postoperative quality of life between the two procedures. Recent data illustrate the need for critical evaluation of video-assisted thoracic surgery before the procedure is accepted as a superior approach for thoracotomy, based on unproved advantages. With the wide use of lung cancer CT screening systems, it can be anticipated that small or even minute lung cancer cases will increase in the near future. Consequently, the establishment of a surgical procedure with radicality and less invasiveness will be strongly demanded for lung cancer.

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Objective. Cisplatin-based combinations are standard regiments in the treatment of advanced non-small cell lung cancer. However, the high toxicity by cisplatin-based combinations requires investigation of alternative treatments without cisplatin. Phase III studies of platinum-based vs non-platinum-based chemotherapy are reviewed. Study Design (Methods). Phase III studies published or reported in meetings are compiled and reviewed. Results. Although some studies did not show a statistically significant difference, a survival benefit for platinum-based doublet including non-platinum new agents was demonstrated compared with single non-platinum agents. Platinum-based doublets were associated with almost equivalent or better response rates and survival compared with non-platinum doublets, although there's one recent study showing a significant survival benefit in a non-platinum doublet. Generally, the toxicity profiles associated with non-platinum combinations were not markedly improved except for upper gastrointestinal tract toxicity such as nausea and vomiting. Conclusion. Although platinum-based doublets are still standard for the treatment of non-small cell lung cancer, non-platinum-based doublets may be considered alternative treatment in selected patients. The accrual of a randomized study of non-platinum triplet with platinum doublet (JMTO LC0003) was completed on April, 2005.

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Purpose. To define the state of the art and explore the future direction of combined modality therapy (CMT) with chemotherapy and radiotherapy for unresectable stage III non-small-cell lung cancer (NSCLC). Methods. Published papers and meeting abstracts regarding CMT with chemoradiotherapy for stage III NSCLC were reviewed and analyzed. Results. Phase III studies comparing sequential with concurrent chemoradiotherapy using a full dose of cisplatin-based chemotherapy demonstrated significantly better overall and long-term survival favoring concurrent chemoradiotherapy. Clinical trials with “third generation” chemotherapy regimen, “target-based” agents in the setting of CMT are ongoing. Conclusion. Cisplatin-based chemotherapy and concurrent thoracic radiotherapy is the standard of care for patients with unresectable stage III NSCLC. Further studies are needed to clarify the role of new agents.

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