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Objective: To retrospectively assess data on immune checkpoint inhibitors(ICIs)in an actual clinical setting, examine the factors that contribute to response and survival using real-world data, and compare the effectiveness of the 3 types of ICIs for patients with non-small cell lung cancer(NSCLC)., Methods: A retrospective analysis of 127 patients with NSCLC treated with ICIs at our hospital was conducted., Results: Nivolumab(56 patients)showed a 3-year survival rate of 21.6% and a disease control rate of 57.1%. These results are consistent with the clinical trials of Nivolumab. Pembrolizumab(36 patients) showed a 2-year survival rate of 60.3%, a response rate of 50.0%, and a disease control rate of 63.9%. Atezolizumab(35 patients)displayed a particularly low response rate with a 1-year survival rate of 58.4%, response rate of 8.6%, and disease control rate of 25.7%. The treatment results for recurrence after surgery for lung cancer were comparable to those for unresectable lung cancer., Conclusion: Anti-PD-1 antibody displayed better therapeutic results than anti-PD-L1 antibody. The efficacy of ICI administration for postoperative recurrent lung cancer was also shown in this study.

Background: Purely localized, oligometastatic, and widely metastatic tumors are likely to require different therapeutic strategies. Although surgical procedures for isolated pulmonary, brain, or adrenal metastases from lung cancer have been extensively evaluated, most data are from retrospective studies; accordingly, we conducted a prospective multicenter trial., Methods: Patients were eligible if they had previously untreated clinical T1-2N0-1 lung cancer with single-organ metastasis, or single-organ metachronous metastasis after complete resection of pathologic T1-2N0-1 lung cancer. Metastatic lesions were classified into three groups: group A included metastasis in single organs other than brain or lung; group B included synchronous brain metastasis; and group C included pulmonary metastasis. The treatment intervention was surgical resection of metachronous metastasis or of both synchronous metastasis and primary lung cancer., Results: From December 2002 through June 2011, 36 patients were enrolled. Two patients were ineligible, and the remaining 34 were analyzed; 6 (18%) had a benign lesion and no metastasis, 5 patients (15%) underwent incomplete resection of primary lung cancer, and 20 patients (59%) underwent complete resection of both primary lung cancer and metastasis. The 5-year survival rate for these 20 cases was 44.7%., Conclusions: Clinical T1-2N0-1 lung cancer with a single-organ metastatic lesion was a good candidate for surgical resection. A 5-year survival rate of about 40% can be expected, which could be comparable with that for stage II non-small cell lung cancer., (Copyright © 2014 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

In stage I non-small cell lung cancer (NSCLC), the cancer is localized to the lung. For this early stage NSCLC, therefore, surgery is considered to be the treatment of choice. In this report, we reviewed the surgical treatment approaches for stage I NSCLC, placing emphasis on limited resection and video-assisted thoracic surgery (VATS). In regard to limited resection, sublobar resection (wedge resection and segmentectomy) may yield a good long-term outcome in selected cases, as does lobectomy. No strong evidence to recommend this procedure has, however, been published. On the other hand, many descriptive studies have indicated that VATS may be useful for the treatment of NSCLC, although the results have not shown any statistically significant differences from those of resection by conventional open thoracotomy. In addition to the low invasiveness, the curability of NSCLC using the VATS approach has been recognized to be similar to that of the standard thoracotomic approaches in clinical practice. Well-controlled studies with strong statistical results are needed to provide strong supportive evidence for the use of VATS for NSCLC. (Ann Thorac Cardiovasc Surg 2003; 9: 283-9)

Although MDM2, p21/WAF1, and p53 are considered as regulating each other based on in vitro studies, the relation in human lung cancer is not fully understood. The expressions of these proteins were examined immunohistochemically in 112 resected non-small cell lung cancer specimens and the correlation between them were analyzed. MDM2 was expressed in 45% of all lung cancers. In advanced stage, MDM2-positive cases were observed more frequently than in early stage, showing significant difference. No significant difference was observed in the prognosis of the patients regardless of the expression of any protein. Although no correlation was observed between MDM2 expression and p53 expression, or between p21/WAF1 expression and p53 expression, MDM2 expression was strongly related with p21/WAF1 expression. Therefore, MDM2 expression may relate to the progress of the stage of lung cancer, and MDM2 expression and p21/WAF1 expression may be associated not through the p53-related pathway.

CD8+ T cells infiltrating within cancer cell nests in human colorectal cancer were associated with a favorable patients' survival, suggesting the presence of anti-tumor immunity. The present study was designed to examine this concept in non-small cell lung cancer (NSCLC) by a retrospective analysis of 128 surgically resected cases. Immunohistochemical analysis showed that the number of CD8+ T cells within cancer cell nests in NSCLC was related to the histological subtype (large cell carcinoma or squamous cell carcinoma > adenocarcinoma) and the degree of dedifferentiation (undifferentiated type > differentiated type). In contrast to colorectal cancer, the number of CD8+ T cells in NSCLC had no statistically significant impact on the patients' survival. The present study demonstrated that the degree of infiltration of CD8+ T cells within cancer cell nests is dependent on the dedifferentiation of cancer cells in NSCLC, which could be one of the important aspects for the study of tumor immunity.

To clarify the pathway of the metastases from each pulmonary lobe to mediastinal nodes, we examined the pattern of mediastinal nodal involvement in 462 resected pN2 non-small cell lung cancer. Carcinomas of the right upper lobe frequently involved #3 (78/133) and #4 (70/133) nodes, whereas those of the right middle or lower lobe frequently metastasized to #7 nodes (18/23 and 86/113, respectively). On the other hand, carcinoma of left upper lobe frequently involved #5 nodes (81/118), whereas those of the left lower lobe most frequently metastasized to #7 nodes (50/75). Of 462 pN2 patients, 95 (20.6%) had skip metastases to the mediastinal nodes. Skip metastasis was observed more frequently in carcinomas of right upper and middle lobe. One of the reasons of skip metastasis may be the direct lymph drainage through subpleural space to mediastinum.

Background: In order to elucidate the roles of tumor angiogenesis in lung carcinogenesis, the expressions of several angiogenic factors in lung carcinoma tissues were examined., Materials and Methods: Tissue specimens from 112 cases of resected non-small cell lung cancer (NSCLC) were studied. The expressions of platelet-derived endothelial cell growth factor (PD-ECGF) and vascular endothelial growth factor (VEGF) were examined immunohistochemically. Microvessel density (MVD) was also evaluated., Results: VEGF-positive cases were observed more frequently in advanced stage lung cancers than in early cancers, and VEGF-positive tumors had higher MVD than VEGF-negative tumors, while such differences were not observed for PD-ECGF. In squamous cell carcinoma, the patients with high-MVD tumor had significantly worse survival than those with low-MVD tumor., Conclusions: Our results suggest that VEGF plays an important role in angiogenesis of lung cancers, while the contribution of PD-ECGF may be limited.

Background: Some patients with resected pN2 lung carcinoma were long term survivors. To determine appropriate therapeutic modalities for the selected patients, the clinicopathologic characteristics of these patients were examined using the actual number of survivors rather than the cumulative survival rate because the cumulative survival rate occasionally is confounded due to patients with short follow-up periods., Methods: Between 1981-1990, 178 patients with pN2 nonsmall cell lung carcinoma underwent complete resection with systemic lymph node dissection. The ratios of 5-year survivors to all patients in groups with several clinicopathologic factors were compared., Results: Gender, the side that was operated on, location of the tumor, histologic type, or surgical procedure were not related to the ratio of 5-year survivors. However, T classification, skip metastasis, and the number of levels involved were associated with the ratio significantly. The authors also found that the location of the involved lymph node(s) affected the ratio., Conclusions: Even in the presence of pN2 disease, lung carcinoma patients with T1 tumors, skip metastasis, or single level mediastinal lymph node involvement, especially Level 4, Level 5, or Level 6 lymph nodes, had a relatively favorable prognosis and may be candidates for primary resection.

We investigated the prognosis of completely resected 119 non-small cell lung cancer patients according to the invaded organs. There was no significant difference in prognosis between T3N0M0 and T3N1M0 patients (5-year survival rate: 34% vs. 38%). However, the prognosis of T3N2M0 patients (5-year survival rate: 11%) was too poor to be regarded as the same category. Therefore, we investigated only T3N0M0 and T3N1M0 patients to assess the contribution of the invaded organs to prognosis. Of the 5 patients with diaphragm invasion, there was no 3-year survivor, and the prognosis of patients with diaphragm invasion was very poor. The chest wall invasion was divided into three parts: parietal pleural invasion, subpleural tissue invasion and intercostal muscular invasion. The 5-year survival rates of patients with such invasion was 35%, 29% and 27%, respectively. The patients with Pancoast tumor had very poor prognosis. T3 factor was heterogeneous, and the prognosis of the patients with T3 tumor was various according to invaded organs.

Objective: The TNM staging system of lung cancer is widely used as a guide for estimating prognosis and selecting treatment modality. In 1997, the International Union Against Cancer and the American Joint Committee on Cancer have adopted a revised stage grouping for lung cancer. However, the validity of the new stage grouping has not been fully established. We investigated the prognoses of patients who had resection of non-small-cell lung cancer to confirm the validity of the revised classification., Methods: A total of 1310 patients with non-small-cell lung cancer underwent complete resection and pathologic staging of the disease in our hospitals from 1980 through 1993. A pulmonary resection was performed with a systematic nodal dissection. The survivals were calculated with the Kaplan-Meier method on the basis of overall deaths, and the survival curves were compared by log rank test., Results: There were significant differences in survival between patients with T1 N0 M0 and T2 N0 M0 disease and between those with T1 N1 M0 and T2 N1 M0 disease. However, there was no significant difference between patients with T2 NO M0 disease and those with T1 N1 M0 disease. No significant difference in survival was observed among patients with T2 N1 M0, T3 NO M0, and T3 N1 M0 cancer. Patients with different invaded organs of T3 subdivision (pleura, chest wall, pericardium, or diaphragm) had a different prognosis. There was no significant difference between patients with T3 N2 M0 disease and those with stage IIIB disease., Conclusions: We supported most of the revision, such as dividing stage I, dividing stage II, and putting T3 N0 M0 to stage IIB. Furthermore, we found some candidates for a subsequent revision, such as putting T3 N1 M0 to stage IIB, putting T2 N0 M0 and T1 N1 M0 together, regarding diaphragm invasion as T4, and putting T3 N2 M0 to stage IIIB.

Results of surgical treatment for 33 intrathoracic recurrence after complete resection of non-small cell lung cancer were analyzed. Prognosis of the second surgical treatment were favorable in patients with subsequent cancer with in situ component and solitary lesion in lung parenchyma. Retrospective study of 53 patients who recurred and were thoroughly followed up their clinical course until lung cancer death revealed that the solitary one tends to be confined to the intrathoracic location, and the multiple one did not confined to the intrathoracic location but also extended to the extrathoracic distant metastasis or to the supraclavicular lymph nodes.

#12u nodes are peribronchial lymph nodes around the upper lobe bronchus which should not be routinely dissected in cases with middle lobe carcinoma or lower lobe carcinoma. In this paper, #12u were examined histologically in 152 lung cancer cases. As a results, 14 of 152 (9.2%) had nodal diseases in #12 nodes. #12u nodes were involved in 3 of 30 N1 diseases (10%), and in 11 of 35 N2 diseases (31.4%). There was a case which had no nodal involvement except for #12u node. And in three cases, we found only one nodal metastasis except for #12u nodes. If we did not dissect #12u nodes, these cases will be relapse in near future. Thus, for curative operation, #12u nodes should be dissected as a standard operation.

In order to improve the management of lung cancer at various stages, we analyzed results of treatment in 928 of 1024 patients who were registered at our Hospital Tumor Registry of 1952-1983 with a pathological diagnosis of TNM for carcinoma of the lung after pulmonary resection. The 5-year-survival rate was 43% in 928 patients excluded the cases who were lost follow-up or succumbed within post-operative 1 month. The 5-year-survival rate was 77% for the stage I, 54.7% for the stage II, 17% for the stage III and 4% for the stage IV. The 5-year-survival rate by therapeutic modality was as follows: 52% for the group with chemotherapy, 35% for the one without adjuvant therapies, 29% for the one with irradiation and 15% for the one with radiochemotherapy. Patients with adenocarcinoma who underwent curative surgery showed improvement of survival by postoperative chemotherapy. No increase in survival time was noticed in the irradiated group with N2.