[Thymic Cancer Associated with Spontaneous Regression of Multilocular Thymic Cysts].

Thymic cancer associated with spontaneous regression of thymic cysts is a rare disease. A 47-yearold man was referred to our hospital for right chest pain and chest abnormal shadow. Chest computed tomography( CT) revealed a solid lesion 1.3 cm in diameter and a cystic lesion 1.0 cm in diameter at the right anterior mediastinum. A second CT study after six months showed a solid lesion increased to 1.7 cm in diameter and a cystic lesion reduced to 0.7 cm in diameter. A second magnetic resonance imaging (MRI) showed a cystic lesion reduced and high signal intensity region in the thymus enlarged on T2-weighted imaging. Under the diagnosis of thymoma associated with multilocular thymic cysts, total thymectomy was performed for these mediastinal lesions by video-assisted thoracic surgery. Histopathological finding was thymic squamous cell carcinoma (Masaoka stage II) associated with multilocular thymic cysts. Additional postoperative radiotherapy was performed, and there has been no recurrence after one postoperative year.

[Hemorrhage from the subclavian artery after lung cancer resection treated by stent graft placement].

We present a case of a 79-year-old man with right apical invasive lung cancer which was treated by induction radiotherapy followed by right upper lobectomy with chest wall resection. Four days after the operation, hemorrhage from the funicular structure in the cupula of the parietal pleura was observed, and hemostasis was achieved by ligation and fibrin sheet pasting. At the time, we were not able to detect the hemorrhage from the subclavian artery. Two days after the 1st hemostasis, hemorrhage reccurred. Hemorrhage from the inferior border of the subclavian artery was observed, and hemostasis was achieved by direct suture and fibrin sheet pasting. One day after the 2nd hemostasis, re-recurrent hemorrhage occurred. Stent graft placement was performed under local anesthesia. No hemorrhage occurred after the stent graft placement.

[An operative case of thymic cyst with thymoma;report of a case].

Thymic cyst with thymoma is a rare disease. A 67-year-old woman was referred to our hospital for right chest pain and cough. Mass shadow in the right hilum was detected in the chest radiograph. Chest computed tomography( CT) revealed a cystic mass with partially thickened wall suggesting solid tumor at the anterior mediastinum. The tumor was resected by median sternotomy. Histopathological finding was a multilocular thymic cyst with thymoma of spindle cell type.

[Incidence of string-like adhesion between thoracic wall and bullae observed during video-assisted thoracic surgery( VATS) for spontaneous pneumothorax].

It is not rare that string-like adhesion between lung apex and chest wall is observed during videoassisted thoracic surgery (VATS) for spontaneous pneumothorax. This adhesion may cause hemothorax which requires emergency operation, although the precise incidence of such cases is uncertain. We analyzed consecutive 120 spontaneous pneumothorax cases underwent VATS at Suzuka General Hospital from January 2005 to September 2008. Twenty-one out of 120 (17.5%) were such cases receiving partial resection of the lung including the adhesion after dividing it. Pathological study revealed the bullae close to the adhesion in all cases, suggesting that these adhesion caused after possible former pneumothorax. Thus, 21 cases might be recurrent pneumothorax. Even in clinically 1st onset pneumothorax, those cases may be good indication for VATS.

Type A thymoma with simultaneous solitary intrapulmonary metastasis: A case report.

A 79-year-old woman was referred to our facility because of an abnormal chest shadow. Chest computed tomography (CT) showed a solitary right middle lung nodule with a maximum diameter of 3 mm and anterior mediastinal nodule with a maximum diameter of 21 mm. The lung nodule was suspected of being a primary lung cancer rather than a metastatic tumor because there were no primary malignant tumors, apart from an anterior mediastinal tumor visible on diagnostic imaging, including F18 fluorodeoxyglucose-positron emission tomography, and a solitary lung nodule. Partial lung resection by video-assisted thoracoscopic surgery (VATS) was performed, and the intraoperative frozen section of the tumor tissue resulted in a diagnosis of carcinoid tumor. As a result, right middle lobectomy by VATS was performed. The final histological diagnosis of the permanent specimen was intrapulmonary type A thymoma. VATS thymectomy was performed three months later. The histological diagnosis was type A thymoma with intrapulmonary metastasis (Masaoka stage IVb). Additional therapy was not performed because complete resection was achieved. Follow-up CT was performed once every six months after the operation. The patient has been followed up for one year without any further recurrence.

The usefulness of fluorodeoxyglucose-positron emission tomography as a preoperative diagnostic tool for thymic epithelial tumors.

BACKGROUND: To investigate the usefulness of 18F-fluorodeoxy glucose-positron emission tomography (18F-FDG PET) for the preoperative imaging diagnosis of malignant grade in thymic epithelial tumors (TETs) and the correlation between the maximum standardized uptake value (SUVmax) and tumor size in TETs. METHODS: We retrospectively investigated 51 patients with TETs performed 18F-FDG PET. The SUVmax was compared between thymic carcinomas and thymomas. We also evaluated the difference in the SUVmax limited to small TETs. In addition, the correlation between the SUVmax and the tumor size was evaluated. RESULTS: The mean SUVmax of thymic carcinomas (n=12) and thymomas (n=39) was 5.71±2.6 and 3.08±1.4, respectively. The SUVmax of thymic carcinomas was significantly higher than that of thymomas (P<0.001). The mean SUVmax of these small thymic carcinomas (n=3) and thymomas (n=13) was 2.97±0.24 and 1.79±0.47, respectively. The SUVmax of the small thymic carcinomas was significantly higher than that of the thymomas (P=0.001). We found a positive correlation between the SUVmax and the maximum tumor size of TETs (correlation coefficient: 0.632, P<0.001). CONCLUSIONS: 18F-FDG PET might be useful for evaluating the preoperative malignancy of TETs. Of note, the maximum tumor size should be considered when performing assessments by 18F-FDG PET.

[A case of metastatic pulmonary cancer from renal cell carcinoma masquerading as pulmonary vein varix].

A 66-year-old woman underwent nephrectomy to treat renal cell carcinoma 5 years previously. Enhanced CT to locate the tumor revealed a lesion very close to the right upper pulmonary vein. Six months later, the nodule grew to 14mm in maximum dimension and it seemed to be a varix of the right upper pulmonary vein on 3D-CT. However, pulmonary artery angiography (PAG) denied this possibility. PET-CT revealed the nodule to be positive for FDG uptake (maxSUV 2.7 in the early phase and 2.2 in the late phase), suggesting that it contained solid tissue with malignant characteristics. Eventually, right upper lobectomy was performed. The nodule was a metastatic renal cell carcinoma with extremely abundant vascular components. This conspicuous feature of the tumor appeared to mimic a pulmonary vein varix on enhanced CT scan and 3D angiogram.

Pericardial immunoglobulin G4-related inflammatory pseudotumor after right upper lobectomy for lung cancer.

A 75-year-old woman underwent thoracoscopic right upper lobectomy for lung cancer. A histopathological examination showed adenocarcinoma, pT1aN0M0 stage IA1. At six months after surgery, chest computed tomography (CT) revealed pericardial nodules that had not been detected before pulmonary resection. Postoperative CT performed two months later revealed that the nodules were growing and F18 fluorodeoxyglucose-positron emission tomography showed a maximum standardized uptake of 9.87. Blood tests revealed no elevated tumor markers, with the exception of a mildly elevated interleukin-2. Based on the above results, thoracoscopic biopsy was performed due to the suspected recurrence of lung cancer or malignant lymphoma. The histopathological examination of the nodule revealed immunoglobulin G4 (IgG4)-related inflammatory pseudotumor. The serum IgG4 levels were elevated (358 mg/dL, normal: 4.5-117.0 mg/dL). No additional treatment was required because all nodules were observed to have disappeared naturally on a follow-up CT scan performed two months after the surgical biopsy. The patient has been followed-up for two years without recurrence. KEY POINTS: SIGNIFICANT FINDINGS OF THE STUDY: We report a case of pericardial immunoglobulin G4-related inflammatory pseudotumor that appeared after right upper lobectomy for lung cancer, and which naturally disappeared without any treatment. WHAT THIS STUDY ADDS: There was an immunoglobulin G4-related inflammatory pseudotumor which appeared as multiple nodules in the pericardial space, and this should be kept in mind when considering the differential diagnosis of intrapericardial nodules.

Long-term survivor of pulmonary combined large cell neuroendocrine carcinoma treated with nivolumab.

Several authors have previously reported that patients with pulmonary combined large cell neuroendocrine cancer ( LCNEC) have a poor prognosis and there is no consensus on the treatment strategy for combined LCNEC as well as LCNEC. Here, we report the case of a long-term survivor with pulmonary combined LCNEC. The patient was a 60-year-old man who underwent thoracoscopic right lower lobectomy. The final histopathology and staging of the tumor showed LCNEC combined with squamous cell carcinoma and T2aN0M0 stage IB. Multimodality treatments including chemotherapy, radiotherapy and surgery for several recurrences were performed after the pulmonary surgery. After immune checkpoint inhibitor (ICI) therapy with nivolumab, all the metastatic lesions shrunk and a partial response was maintained at five years after the first surgery. In our case, ICI after multimodality therapy combining cytotoxic anticancer drugs and radiotherapy was effective in LCNEC with metachronous multiple metastases. KEY POINTS: SIGNIFICANT FINDINGS OF THE STUDY: Immune checkpoint inhibitor after multimodality therapy combining cytotoxic anticancer drugs and radiotherapy was effective in LCNEC with metachronous multiple metastases. The patient survived over five-years after the first surgery. WHAT THIS STUDY ADDS: Immune checkpoint inhibitor may be effective in some LCNEC patients.

Epidermal growth factor receptor gene amplification and gefitinib sensitivity in patients with recurrent lung cancer.

To evaluate the epidermal growth factor receptor (EGFR) protein expression, gene mutations and amplification as predictors of clinical outcome in patients with non-small-cell lung cancer (NSCLC) receiving gefitinib, we have performed fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC). We investigated the EGFR amplification and EGFR protein expression statuses in 27 surgically treated non-small-cell lung cancer (NSCLC) cases. These patients experienced relapse after surgery and received gefitinib 250 mg/day. The presence or absence of EGFR mutations of kinase domains was analyzed by genotyping analysis and sequences, and already reported. EGFR mutations were found from 15/27 lung cancer patients. EGFR mutation status was significantly correlated with better prognosis (log-rank test P=0.0023). Smoking status (never smoker vs. smoker, P=0.0032), and pathological subtypes (adenocarcinoma vs. non-adenocarcinoma, P=0.0011), but not EGFR amplification (P=0.1278), were correlated with survival of lung cancers. EGFR IHC results were correlated with FISH results (P=0.0125), but not correlated with prognosis (P=0.7921). Thus, the EGFR gene amplification or protein expression is not a predictor of gefitinib efficacy in Japanese patients with NSCLC. We have also evaluated the EGFR mutation status and clinico-pathological features for 27 NSCLC patients who had undergone surgery followed by treatment with gefitinib at the National Hospital Organization, Kinki-chuo Chest Medical Center. The EGFR mutation status, especially exon19 mutation was correlated with good response to gefitinib than exon 21 point mutation.

EGFR polymorphism of the kinase domain in Japanese lung cancer.

BACKGROUND: Mutations of the epidermal growth factor receptor (EGFR) gene at kinase domain have been reported in non-small-cell lung cancer (NSCLC), and some common somatic mutations in EGFR have been examined for their ability to predict sensitivity to gefitinib or erlotinib. However, EGFR mutations at exon 20 have been reported to predict resistance to gefitinib therapy. MATERIALS AND METHODS: We investigated the EGFR mutations and/or polymorphism statuses at kinase domain in 303 surgically treated non-small cell lung cancer (NSCLC) cases. One hundred ninety-four adenocarcinoma cases were included. The presence or absence of EGFR polymorphism of kinase domains was analyzed by direct sequences. We have also investigated EGFR polymorphism status at exon 20 for 23 NSCLC patients who had undergone surgery followed by treatment with gefitinib at the National Hospital Organization, Kinki-chuo Chest Medical Center. RESULTS: EGFR mutations at kinase domain were found in 75 of 303 lung cancer patients. During sequencing of EGFR tyrosine kinase domain in tumors, 86 EGFR polymorphism (G2607A) cases were identified at exon 20. G2067A polymorphism was significantly higher in nonadenocarcinomas (37.4%) than in adenocarcinoma (25.3%, P = 0.0415). The polymorphism status did not correlate with gender, smoking (never smoker versus smoker), and EGFR mutations. In 46 total gefitinib treated NSCLC patients, there was a tendency toward better prognosis in EGFR wild type (GG) patients than AG + AA patients. EGFR polymorphism in Japanese lung cancers seemed to be less frequent than Caucasian lung cancers. CONCLUSIONS: EGFR-tyrosine kinase polymorphism might be associated with clinicopathological background of lung cancers.

Role of the yellow spot around the urogenital opening of female mosquitofish (Gambusia affinis) as a cue for copulation.

Males of the viviparous teleost fish Gambusia affinis copulate with females by using a specialized anal fin, or gonopodium. When female G. affinis were placed in a shallow transparent tank which was then floated on the surface of a larger aquarium housing male G. affinis , the males frequently attempted to copulate with females housed in the smaller quarantine tank. This copulatory behavior in male G. affinis was only observed to be elicited by visual stimuli; female G. affinis have a yellow spot and black anal spots around their urogenital opening. To investigate the function of the yellow spot of the female, we examined male copulatory behavior directed towards artificial female models having a yellow, black, gray, or white spot in the genital region. Of the differently colored females tested, males spent a significantly longer time in the vicinity of the artificial model with a yellow spot. In addition, males attempted to copulate with the yellow-spotted female model more frequently than with the models of different colors. These findings revealed that the yellow spot around the female urogenital opening of G. affinis attracts males and functions as a cue for copulation.

Mutation of epidermal growth factor receptor gene in adenosquamous carcinoma of the lung.

We have investigated 26 adenosquamous lung cancer tissues and found that four EGFR mutations were mainly in female and non-smoker lung cancer. However, EGFR mutation at kinase domain was exclusive with K-ras mutation. However, smoking and gender status could affect the occurrence of EGFR mutation. There was no difference in EGFR mutation status if analysis was performed in never smoker female subgroup.

EGFR exon 20 insertion mutation in Japanese lung cancer.

Mutations of the epidermal growth factor receptor (EGFR) gene have been reported in non-small cell lung cancer (NSCLC), especially in female, never smoker patients with adenocarcinoma. Some common somatic mutations in EGFR, including deletion mutations in exon 19 and leucine to arginine substitution at amino acid position 858 (L858R) in exon 21, have been examined for their ability to predict sensitivity to gefitinib or erlotinib. On the other hand, previous report has shown that the insertion mutation at exon 20 is related to gefitinib resistance. We investigated the exon 20 EGFR mutation statuses in 322 surgically treated non-small cell lung cancer cases. Two hundred and five adenocarcinoma cases were included. The presence or absence of EGFR mutations of kinase domains was analyzed by direct sequences. EGFR insertion mutations at exon 20 were found from 7 of 322 (2.17%) lung cancer patients. We also detected the 18 deletion type mutations in exon 19, and 25 L858R type mutations in exon 21. There was a tendency towards higher exon 20 insertion ratio in never smoker (never smoker 4.4% versus smoker 1.3%, p=0.0996) and female (female 4.5% versus male 1.3%, p=0.0917). Two exon 20 insertion cases were treated with gefitinib and failed to response. EGFR insertion mutation in exon 20 could not be ignored from Japanese lung cancers.

ErbB4 expression and mutation in Japanese patients with lung cancer.

BACKGROUND: Much evidence has accumulated that the epidermal growth factor receptor (EGFR) and its family members are strongly implicated in the development and progression of lung cancers. Recently, erbB4 kinase domain mutations were reported in Korean patients with lung cancer. We hypothesized that erbB4 mutations correlate with clinicopathologic features of lung cancers. PATIENTS AND METHODS: The presence or absence of erbB4 kinase domain mutations was analyzed by reverse-transcription polymerase chain reaction amplification and direct sequencing in 105 surgically treated non-small-cell lung cancer cases from Nagoya City University Hospital. Sixty-three adenocarcinoma cases were included. The EGFR mutation status for these 105 samples were already reported. We have investigated erbB4 expression status by immunohistochemistry in 40 non-small cell lung cancer cases. RESULTS: ErbB4 mutation was not found in 105 patients with lung cancer. The EGFR mutation status was significantly correlated with sex (women, 74.2% vs. men, 9.5%; P < 0.0001), smoking status (never-smokers, 68.8% vs. smokers, 11%; P < 0.0001), pathologic subtype (adenocarcinoma, 44.4% vs. non-adenocarcinoma, 4.8%; P < 0.0001), and differentiation status of the lung cancer (well-differentiated, 47.4% vs. others, 14.8%; P = 0.0004). We detected ErbB4 protein positivity in 20 samples. The ErbB4 protein status was not significantly correlated with sex (women, 28.6% vs. men, 54.5%; P = 0.4075), smoking status (never-smokers, 69.4% vs. smokers, 16.9%; P < 0.0001), pathologic subtype (adenocarcinoma, 46.2% vs. nonadenocarcinoma, 51.9%; P > 0.9999), or differentiation status of the lung cancer (well-differentiated, 54.5% vs. others, 48.3%; P > 0.9999). CONCLUSION: Thus, erbB4 mutations are rare in Japanese people with lung cancer and of limited value for molecular-targeted therapy.

Human MOB1 expression in non-small-cell lung cancer.

PURPOSE: Human MOB1 (hMOB1) is a recently isolated gene that is a human homologue of the Schizosaccharomyces mitotic checkpoint gene MOB1. The loss of checkpoint control in mammalian cells results in genomic instability, leading to the amplification, rearrangement, or loss of chromosomes, events associated with tumor progression. We hypothesized that hMOB1 might be expressed in non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: We attempted to determine the influence of hMOB1 expression on clinicopathologic features in patients with NSCLC who had undergone surgery. Expression of hMOB1 messenger RNA (mRNA) was evaluated by reverse transcription-polymerase chain reaction in 60 NSCLCs and adjacent histologic normal lung samples using LightCycler. RESULTS: Human MOB1/glyseraldehyde-3-phosphate dehydrogenase (GAPDH) mRNA expression was significantly decreased in the tumor of lung cancer tissue (3.347 +/- 4.306) compared with normal lung tissue (4.833 +/- 4.306; P = 0.0437), although 22 of 60 lung cancer tissue samples had > 1 tumor-normal ratio of MOB1/GAPDH mRNA expression. There was no relationship between hMOB1 gene expression and age, sex, pathologic stages, or pN status. However, decreased hMOB1/GAPDH expression was especially seen in pT1 lung cancer (tumor-normal ratio; 0.318 +/- 0.328) when compared with pT4 lung cancer (1.915 +/- 1.895; P = 0.0362). CONCLUSION: The decreased expression of hMOB1 mRNA might be the early phase phenomenon for tumor invasion from NSCLC. Alternatively, loss of mitotic checkpoint might play a role in oncogenesis for lung cancer.

CCND1 messenger RNA expression is correlated with EGFR mutation status in lung cancer.

BACKGROUND: Epidermal growth factor receptor (EGFR) stimulation markedly increases cyclin D1 protein expression. Recently, it has been reported that cyclin D1 expression was increased in EGFR mutant cell lines; however, the expression status of CCND1 in EGFR mutant lung cancer tissues has not been reported. PATIENTS AND METHODS: We have investigated the CCND1 messenger RNA (mRNA) levels and other clinicopathologic data in 74 lung cancers. The CCND1 mRNA levels were quantified by real-time reverse-transcriptase polymerase chain reaction using LightCycler. RESULTS: The CCND1/GAPDH mRNA levels were significantly higher in adenocarcinoma (35.125 +/- 37.387) than in non-adenocarcinoma (15.2 +/- 24.699; P = .0158), and CCND1/GAPDH mRNA levels were not significantly different among smoking status, sex, or pathologic stage. The CCND1/GAPDH mRNA levels were significantly higher in lung cancer with EGFR mutation (39.713 +/- 41.265) than in lung cancer without EGFR mutation (21.805 +/- 29.152; P = .0338). CCND/GAPDH mRNA expression did not correlate with prognosis of lung cancer. CONCLUSION: Using the LightCycler real-time reverse-transcriptase polymerase chain reaction assay, CCND1 gene expression might correlate with EGFR mutation in lung cancer. However, further studies are needed to confirm the impact of cyclin D1 for a molecular target of lung cancer.

EGFRvIII mutation in lung cancer correlates with increased EGFR copy number.

Overexpression of the epidermal growth factor receptor (EGFR) is caused by EGFR gene amplification and is sometimes associated with expression of a variant EGFR (deletion exon 2-7 or EGFRvIII). EGFRvIII mutation has oncogenic potential and is investigated as a potential therapeutic target. We genotyped the EGFRvIII mutation status in 252 surgically treated lung cancer cases. The presence or absence of EGFRvIII mutation was analyzed by real-time quantitative polymerase chain reaction (PCR) with mutation specific sensor and anchor probes. EGFR copy number was evaluated with PCR-based assay. EGFR mutation status at kinase domain has been examined and reported. EGFRvIII mutation was found on 8 of 252 patients. All patients were male, smokers, and 7 had squamous cell carcinoma. The mutation status was significantly correlated with pathological subtypes (squamous cell carcinoma vs. adenocarcinoma, p=0.0114). Sixty EGFR mutations at kinase domain exclusively existed with EGFRvIII mutations. EGFR gene copy number was significantly higher in EGFRvIII mutant (4.711+/-4.968) than in non-EGFRvIII mutant (2.284+/-1.224) (p=0.0001). EGFRvIII gene mutation might be one of the mechanisms of increased EGFR copy number. Further studies are needed to confirm the mechanisms of EGFRvIII mutations for possible anti-EGFR therapy for lung cancer.

Nras and Kras mutation in Japanese lung cancer patients: Genotyping analysis using LightCycler.

Activating mutations of Ras gene families have been found in a variety of human malignancies, including lung cancer, suggesting their dominant role in tumorigenesis. Many studies have showed that the Kras gene is activated by point mutations in approximately 15-20% of non-small cell lung cancers (NSCLCs), however, there are only a few reports on Nras mutations in NSCLC. We have genotyped Nras mutation status (n=195) and Kras mutation status (n=190) in surgically treated lung adenocarcinoma cases. The presence or absence of Nras and Kras mutations was analyzed by real-time quantitative polymerase chain reaction (PCR) with mutation-specific sensor and anchor probes. EGFR mutation status at kinase domain has already been reported. Nras mutation was found in 1 of 195 patients. This mutation was a G-to-T transversion, involving the substitution of the normal glycine (GGT) with cystein (TGT) and thought to be a somatic mutation. The patient was male and a smoker. Kras mutant patients (11.1%; 21/190) had a significantly worse prognosis than wild-type patients (p=0.0013). Eighty-two EGFR mutations at kinase domain had exclusively Nras or Kras mutations. Although Nras gene mutation might be one of the mechanisms of oncogenesis of lung adenocarcinoma, this was a very rare event. Further studies are needed to confirm the mechanisms of Nras mutations for the sensitivity of molecular target therapy for lung cancer.

L858R EGFR mutation status correlated with clinico-pathological features of Japanese lung cancer.

Somatic mutations of the epidermal growth factor receptor (EGFR) gene were found in about 25-40% of Japanese lung cancer patients. These mutations are associated with clinical and radiographic responses to EGFR tyrosine kinase inhibitors. Most common mutation are arginine for leucine substitution at amino acid 858 (L858R) and exon 19 deletions, especially deletion type 1 mutation. We investigated these EGFR mutation statuses in 575 surgically treated non-small cell lung cancer (NSCLC) cases. Three-hundred and sixty-two adenocarcinoma cases were included. The presence or absence of EGFR mutations of kinase domains was analyzed by genotyping analysis (TaqMan assay; n=386, and LightCycler assay; n=98) and sequences (n=91). EGFR mutations (CTG; CGG; L858R) were found from 63 of 575 lung cancer patients. We also detected the deletion 1a type mutations (2235-2249 del GGAATTAAGAGAAGC) from 39 patients and deletion 1b type mutations (2236-2250 del GAATTAAGAGAAGCA) from 15 patients in exon 19. These mutation statuses were significantly correlated with gender, smoking status (never smoker versus smoker), and pathological subtypes (adenocarcinoma versus non-adenocarcinoma). L858R mutation (p<0.0001), but not deletion 1 type mutation (p=0.0665), was correlated with differentiation status (well versus moderately or poorly) of lung cancers. L858R mutation ratio was significantly higher in non-smoker (p=0.0496) and adenocaicinoma (p=0.0136) when compared to deletion 1 type mutations. The EGFR mutation status, especially L858R mutation might be correlated with the clinico-pathological features related to good response to gefitinib, such as gender, smoking history, and pathological subtypes of Japanese lung cancers.