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Introduction: Endobronchial biopsy using forceps is generally performed with a standard bronchoscope, while a needle is used with an endobronchial ultrasound (EBUS) bronchoscope. An EBUS video bronchoscope, such as the EB-530US instrument (Fujifilm, Tokyo, Japan), provides good visibility and may, therefore, enable both forceps biopsies and needle aspirations to be performed., Objectives: The aim of this study was to investigate the feasibility of performing forceps biopsies and needle aspirations using the EBUS video bronchoscope for diagnosing endobronchial lesions., Methods: Seventy patients with suspected endobronchial lesions based on a computed tomography scan were recruited and underwent forceps biopsy using the EB-530US EBUS bronchoscope. If the result of a rapid on-site cytological evaluation was negative, an additional needle aspiration of the same lesion or other target lesions was performed. The primary outcome was the completion rate of bronchoscopy, using only the EBUS bronchoscope without removal., Results: In the 70 patients, forceps biopsies and/or needle aspirations using the EBUS video bronchoscope were performed and completed without removing the EBUS bronchoscope in 67 patients (95.7%). The remaining three patients required the removal of the EBUS bronchoscope from the trachea (blood clot obstruction of the working channel in one patient and change to a thin bronchoscope to sample an EBUS bronchoscope-inaccessible lesion in two others). The EBUS bronchoscope provided diagnostic material in 66 patients (94.3%). One case each of bleeding and pneumonia were observed (1.4%)., Conclusion: Both forceps biopsy and needle aspiration are feasible using a Fujifilm EB-530US EBUS video bronchoscope., (© 2020 John Wiley & Sons Ltd.)

Treatment options for patients with relapsed/refractory small cell lung cancer (R/R SCLC) are limited, and the efficacy of salvage therapies for heavily treated patients should be assessed. Here, we evaluated the efficacy of paclitaxel (PTX) in R/R SCLC patients.A single-institute retrospective chart review was conducted. The primary endpoint was overall survival (OS), whereas the secondary endpoints were progression-free survival (PFS), overall response rate, disease control rate (DCR), and safety.Thirty-one patients (median age, 69 [range, 56-80] years) were analyzed. The median follow-up period was 122 (range, 28-1121) days. The median OS and PFS were 4.4 and 2.2 months, respectively. Adverse events of grade 3 or higher, other than hematological toxicity, were febrile neutropenia and neuropathy. Multivariate analyses identified the following independent predictors of poor OS: performance status and lactate dehydrogenase at the upper limit of normal.PTX monotherapy showed moderate efficacy with acceptable toxicity in heavily treated patients with R/R SCLC patients.

Detection of rare tumor cells circulating in the blood (CTCs) presents technical challenges. CellSearch, the only approved system for clinical use, fails to capture epithelial cell adhesion molecule-negative CTCs such as malignant pleural mesothelioma (MPM). We have developed a novel microfluidic device (CTC-chip) in which any Ab to capture CTCs is conjugated. The CTC-chip was coated with an Ab against podoplanin that is abundantly expressed on MPM. Circulating tumor cell-detection performance was evaluated in experimental models in which MPM cells were spiked in blood sampled from a healthy volunteer and in clinical samples drawn from MPM patients. The CTC-chip showed superior CTC-detection performance over CellSearch in experimental models (sensitivity, 63.3%-64.5% vs 0%-1.1%; P < .001) and in clinical samples (CTC-positivity, 68.8% vs 6.3%; P < .001). A receiver operating characteristic (ROC) analysis showed that the CTC test provided a significant diagnostic performance in discrimination of unresectable disease from resectable disease (area under the ROC curve, 0.851; P = .003). The higher CTC count (≥2 cells/mL) was significantly associated with a poor prognosis (P = .030). The novel CTC-chip enabled sensitive detection of CTCs, which provided significant diagnostic and prognostic information in MPM., (© 2018 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

Background: Surgery for lung cancer invading the spine remains challenging associated with high morbidity and mortality. We describe our surgical approach and assess the outcome of surgical treatment lung cancer invading the spine., Methods: We retrospectively reviewed our recent experiences of lung cancer with vertebral invasion, in which we have performed total or partial vertebrectomy from 2011 through 2015., Results: We experienced 8 patients who were treated with partial or total vertebrectomy for lung cancer. Vertebral invasion was evaluated by chest computed tomography (CT) and magnetic resonance imaging findings. N factors were estimated as cN0 in all patients based on chest CT and PET-CT findings. Two patients were treated by preoperative induction therapy. Total vertebrectomy was performed in 2 patients, hemivertebrectomy in 2 patients and transverse-process resection in 4 patients. In all 8 cases, complete resection was performed. Morbidity was 75% (6 patients) and no mortality occurred. Overall survival rate( 5 years) was 75%., Conclusion: Lung cancer surgery combined with vertebrectomy is highly aggressive suegery associated with high morbidity, however, this procedure is a promising treatment option for selected lung cancer patients, such as N0M0 disease with invasion to the spine.

BACKGROUND Circulating tumor cells (CTCs) are tumor cells that are shed from primary tumors and circulate in the peripheral blood. CTCs, as a surrogate of micro-metastasis, can be a useful clinical marker, but their clinical significance remains unclear in lung cancer. We now report a case of lung cancer in which the count of CTCs was useful in monitoring postoperative recurrence. CASE REPORT A 50-year-old man had undergone right upper lobectomy for lung cancer (pT1bN2M0, stage IIIA adenocarcinoma), followed by cisplatin-based adjuvant chemotherapy. After the patient's operation, we initiated monitoring of CTCs using CellSearch, and documented the change in the CTC count along with the development of cancer recurrence and response or progression to chemotherapy given for recurrent disease. CONCLUSIONS The CTC count may be useful in monitoring blood of patients with lung cancer.

We present a rare case of colorectal T1 carcinoma with metastasis of previous lung carcinoma found at the deepest invasive portion. A 61-year-old man presented with cervical lymphadenopathy 18 years after undergoing surgery for right lung carcinoma [poorly differentiated adenocarcinoma stage IIb (T3N0M0)]. Contrast-enhanced computed tomography showed enlarged lymph nodes (LNs) in the neck and mediastinal regions. Combined hybrid-F-fluorodeoxyglucose positron emission-computerized tomography showed increased radionuclide uptake in multiple cervical LNs and mediastinal LNs. LN biopsy revealed a poorly differentiated adenocarcinoma, suspected to be a metastatic tumor of the lung. Subsequent colonoscopy revealed a pedunculated-type lesion with a depressed area in the ascending colon. We performed polypectomy as total excisional biopsy; this tumor was composed mainly of moderately differentiated adenocarcinoma, partially mixed with mucinous adenocarcinoma. The pathological findings of the invasive front of the colorectal carcinoma showed poorly differentiated adenocarcinoma with a morphological pattern similar to that of the previous lung carcinoma. Furthermore, immunohistochemical results for the histological type of the deepest invasive portion of the tissue specimen were positive for thyroid transcription factor-1 but negative for Caudal-type homeobox 2. From these morphological and immunohistochemical findings, the final diagnosis was moderately differentiated lung carcinoma, pTX N3 M1b (LN, colon) Stage IV.

Background/objectives: CD44 is often expressed in various types of tumor cells and involved in a number of biological behaviors of malignancy. The present study focused on the clinical significance of the expression of CD44st and CD44v6 in non-small cell lung cancer (NSCLC)., Methods: The cohort consisted of 261 consecutive patients who had undergone complete resection of NSCLC. CD44 expression was evaluated in surgical specimens by immunohistochemical staining. Serum CD44 levels were determined using a sandwich ELISA (enzyme-linked immunosorbent assay)., Results: In the immunohistochemical analysis, significant correlations were observed between CD44 expression and clinicopathological factors such as the T factor, N factor, pathological stage, and histological type. The 5-year survival rates according to CD44v6 expression were 65.8 and 80.6% in the higher and lower expression groups, respectively (p = 0.0053). According to ELISA, the group with higher expression of serum CD44v6 also showed a significantly more unfavorable prognosis than the lower expression group (p = 0.014). According to multivariate analysis using these significant variables, serum CD44v6 level was found to be an independent prognostic factor (p = 0.048)., Conclusions: CD44v6 overexpression and higher serum CD44v6 levels were found to be significantly unfavorable prognostic factors., (© 2016 S. Karger AG, Basel.)

Intrapericardial vessel management is one of the necessary techniques for respiratory surgeons. We collected cases that had undergone intrapericardial vessel management for lung cancer, and herein discuss the practical performance and safety of this treatment method. We identified 23 (5.6%) of 413 patients who had undergone lung cancer surgery during the 30-month period from January 2011 to June 2013 at our institution. Twenty cases had large sized tumors near the hilum. Three cases demonstrated severe adhesion in the intrathoracic region due to a previous operation. The lung cancer staging was stage ⅠA in 1 case, stage ⅠB in 4 cases, stage ⅡB in 5 cases, stage ⅢA in 11 cases, stage ⅢB in 1 case, and stage Ⅳ in 1 case. We performed lobectomy in 11 cases, bilobectomy in 6 cases, and pneumonectomy in 6 cases. The average operation time was 366 minutes (137-965). Post operative complications were observed in five cases, including two cases of air-leakage and three cases of arrhythmia. All cases were able to walk on foot at discharge. It is important to clearly understand intrapericardial anatomy in order to carry out successful intrapericadial vessel management.

We herein report a very rare case of adenoid cystic carcinoma of the peripheral lungs. A 77-year-old female visited a family physician for aortitis syndrome, diabetes mellitus and hyperlipidemia. A follow-up chest computed tomography scan for aortitis syndrome revealed a nodule in the middle lobe of the right lung. Although a transbronchial lung biopsy was attempted, a definitive diagnosis could not be made. Because the possibility of lung malignancy could not be ruled out, thoracoscopic wedge resection of the middle lobe was performed. The intraoperative pathological diagnosis revealed carcinoma of the lungs and we performed middle lobectomy under complete video-assisted thoracoscopic surgery. A histopathological examination demonstrated an adenoid cystic carcinoma with a characteristic cribriform structure.

A 73-year-old Japanese man visited a local hospital due to palpitations and dyspnea. He was diagnosed as having lung cancer (adenocarcinoma, cT1aN2M1b (BRA), stage Ⅳ), but he did not want to receive any anticancer medications, and was simply being observed. Several months later, he was referred to our hospital due to exacerbation of the dyspnea. His chest computed tomography revealed massive pericardial effusion, therefore he was diagnosed as having cardiac tamponade due to carcinomatous pericarditis and was immediately hospitalized. Upon admission, pericardial fenestration was firstly applied in order to drain pericardial effusion, and intraoperative cardiac findings showed suspicion of myocardial and pericardial metastasis. Immediately after the pericardiotomy, he suffered from cardiac arrest caused by shock. In lung cancer patients with pericardial effusion, even though it is rare, myocardial metastasis in addition to carcinomatous pericarditis and pericardial metastasis should be kept in mind.

Background: Massive lymphadenopathy and direct mediastinal invasion are well-recognized phenomena in patients with small cell lung cancer (SCLC). The aim of this study was to assess the utility of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) in the diagnosis of SCLC., Methods: We retrospectively reviewed the records of 780 patients who underwent EBUS-TBNA at our institution from March 2004 to June 2012. Of these, 101 had a final diagnosis of SCLC. Excluding 3 patients with known SCLC who underwent EBUS-TBNA for staging purposes and including 2 patients who underwent EBUS-TBNA twice for the diagnosis of recurrence after achieving complete response by chemoradiation therapy during the study period, a total of 100 EBUS-TBNA procedures in 98 patients were analyzed., Results: Other diagnostic tests prior to the initial EBUS-TBNA had failed to yield a diagnosis in 41 patients. The overall diagnostic yield of EBUS-TBNA for SCLC was 97% (97 of 100). Rapid on-site cytologic evaluation (ROSE) was performed at the operator's discretion in 77 procedures. ROSE did not have any impact on diagnostic yield (99% with ROSE vs. 90% without ROSE, p=0.1), but the use of ROSE was associated with fewer lesions (mean 1.1 with ROSE vs. 1.6 without ROSE, p<0.01) or aspirates (mean 2.3 with ROSE vs. 4.0 without ROSE, p<0.01)., Conclusions: EBUS-TBNA provided a high diagnostic yield in SCLC with or without ROSE. EBUS-TBNA can be recommended for patients suspected to have SCLC, even if other diagnostic tests have failed., (© 2013 Published by The Japanese Respiratory Society on behalf of The Japanese Respiratory Society.)

The overexpression of Arf6 and GEP100 is responsible for the invasive activity that is crucial for the activation of the epidermal growth factor receptor (EGFR) signaling pathways in human cancer. However, whether or not the expression of the EGFR-GEP100-Arf6 axis can be used as a biomarker for the prognosis of lung cancer has yet to be fully determined. Tumor specimens were collected from 182 patients who underwent a complete resection for lung adenocarcinoma. We analyzed phospho-EGFR (p-EGFR), GEP100, and Arf6 expression levels in the primary tumor by immunohistochemical analysis. The expression of p-EGFR, GEP100, and Arf6 was observed in 65 (35.7%), 95 (52.2%), and 20 (11.0%) patients, respectively. Significant associations between p-EGFR and GEP100 expression and vessel invasion were identified. The expression of these individual molecules was not associated with any statistically significant differences in survival. However, triple positive expression of p-EGFR, GEP100, and Arf6 was significantly associated with an increased risk of death based on the multivariate analysis. The EGFR-GEP100-Arf6 axis affected the prognosis of patients with primary lung adenocarcinoma. The combination of p-EGFR, GEP100, and Arf6 staining can predict the prognosis of patients after surgery., (© 2014 S. Karger AG, Basel.)

Background: Regulatory T cells (Tregs) are potent immunosuppressive cells that play a crucial role in tumor immune escape. The purpose of the present study was to evaluate the prognostic significance of the frequency of CD4+CD25+Foxp3+ Tregs in the regional lymph node lymphocytes (RLNL) and peripheral blood lymphocytes (PBL) in patients who underwent surgical resection of non-small cell lung cancer (NSCLC)., Methods: The RLNL and PBL in 158 NSCLC patients who underwent complete surgical resection were collected at the time of surgery. The proportions of CD4+CD25+Foxp3+ cells in the RLNL and PBL were determined by flow cytometry., Results: The average proportions of Tregs in the RLNL and PBL were 1.28% and 0.76%, respectively. The proportion of Tregs in the RLNL was significantly higher than that in the PBL (p < 0.0001). The 5-year overall survival rates of the patients according to the proportion of Tregs in the RLNL were 84.4% and 63.5% in the lower and higher groups, respectively. A significant difference was observed in the survival rate between the higher and lower groups (p = 0.0056). Among the patients with stage I disease, the 5-year survival rate (91.4%) was significantly higher in patients with the lower proportion of Tregs in RLNL that in the higher group (72.1%) (p = 0.0147)., Conclusions: The higher proportion of Tregs in the RLNL was a significant unfavorable prognostic factor, even in patients with node-negative NSCLC. The information about the proportion of Tregs in the RLNL might improve the discriminatory power for assessing the risk of the recurrence of NSCLC., (Crown Copyright © 2013. Published by Elsevier Ireland Ltd. All rights reserved.)

Purpose: Information regarding the treatment of pleural lavage cytology (PLC)-positive patients is still limited. This study evaluated the efficacy of intrapleural chemotherapy (IPC) in PLC-positive patients., Methods: Three hundred eighty-six of the 567 lung cancer patients who underwent surgery had undergone PLC after thoracotomy, following by a complete resection were evaluated. IPC was performed after surgery, and cisplatin or adriamycin was injected intrapleurally through the thoracic tube., Results: The pathological diagnosis showed that 17 patients (4.4 %) were positive for (or suspected to have) malignancy in their PLC. The univariate and multivariate analysis showed that only pleural invasion was a significant predictor of a PLC-positive status. The 5-year overall survival in PLC-positive patients was 38 % and that in PLC-negative patients was 84 %. Both the univariate (p < 0.01) and multivariate (p = 0.045) analyses showed that the status of PLC was significantly associated with the overall survival. Eight of the 17 PLC-positive patients underwent IPC. The 2-year OS rate in the patients treated with IPC was 88 % and that of those without IPC was 44 (p = 0.04)., Conclusion: IPC improved the postoperative survival in PLC-positive NSCLC patients, and a further prospective evaluation regarding this therapy is warranted.

Background: OPN is a multifunctional glycophosphoprotein originally described as a secreted protein from malignant epithelial cells. This study focused on the clinical significance of preoperative serum level of OPN in NSCLC patients who underwent a complete resection., Patients and Methods: The serum OPN level was assayed in 244 patients who underwent a complete resection of NSCLC by commercially available sandwich enzyme-linked immunosorbent assay kits. The patients were considered as a higher group, when the serum OPN levels exceeded 81.3 ng/mL., Results: The patients included 166 male and 78 female subjects. The histologic types included 172 adenocarcinomas, 49 squamous cell carcinomas, and 23 other types of carcinoma. The serum level of OPN in male patients (92.6 ng/mL) was significantly higher than that of female patients (76.9 ng/mL). The OPN level of squamous cell carcinoma was significantly higher than that of adenocarcinoma. The OPN level was significantly elevated in patients with the pleural invasion or microvascular invasion than those without the invasion. The 5-year survival rate after surgery in the lower OPN group (82.0%) was a significant favorable prognosis than that in the higher OPN group (63.7%) (P < .0001). The 5-year survival rates in the lower OPN group at stage I NSCLC (88.1%) was significantly better than that in the higher OPN group (80.5%) (P = .0321)., Conclusion: The preoperative serum OPN level was a useful predictor of an unfavorable prognosis, and it was found to be an independent prognostic determinant of outcome in patients who underwent surgery for NSCLC., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Aim: The purpose of this study was to investigate the clinical significance of expression of cancer/testis (CT) antigen and down-regulation of HLA class-I in patients with stage I non-small cell lung cancer (NSCLC), which underwent complete surgical resection., Patients and Methods: The expression of HLA class-I molecules was evaluated in 136 resected NSCLC specimens by immunohistochemistry. The results were scored as the percentage of stained tumor cells and categorized into two groups: 0-79%, reduced expression; and >80%, normal expression. The expression of CT antigen was performed by reverse transcription-polymerase chain reaction (RT-PCR)., Results: The expression of HLA class-I was normal in 49 tumors (36%), and there was reduced expression in 87 tumors (64%). The expression of Melanoma antigen (MAGE)-A3, MAGE-A4, and Kita-Kyushu lung cancer antigen-1 (KK-LC-1) was positive in 34 (25.0%), 22 (16.2%), and 42 (30.9%) patients, respectively. There was no significant difference in the proportion of HLA class-I expression associated with the expression of any of the CT antigens. Among the patients with positive expression of at least one of the CT antigens, the 5-year survival rate of the patients with the normal expression of HLA class-I was 87.5%; however, it was 63.4% in patients with the reduced expression of HLA class-I (p=0.0477)., Conclusion: Reduced expression of HLA class-I was an unfavorable prognostic factor in patients with positive expression of CT antigen, and represents an important hurdle to antigen-based cancer immunotherapy.

Background: The post-surgical follow-up strategy in non-small cell lung cancer (NSCLC) is still controversial. Data on factors that affect the interval between surgery and recurrence or predict survival after recurrence in NSCLC patients are still limited., Methods: From a group of 775 NSCLC patients who consecutively underwent curative surgery, 133 patients showing recurrence were retrospectively analyzed., Results: Recurrence was most often seen in smokers and patients with advanced stage disease. In patients experiencing relapse, the 1- and 2-year recurrence rates were 58% and 84%, respectively. A multivariate analysis showed that patients who underwent limited surgery, had non-adenocarcinoma disease, or had metastatic lymph node involvement showed early recurrence (p-values: <0.01, 0.04, and 0.04, respectively). Among all relapsed patients, the 2-year overall survival rate after recurrence was 37%. A multivariate analysis demonstrated that patients with lymph node metastasis at the time of surgery and patients who experienced early recurrence were significantly more likely to have a shorter survival time after recurrence (hazard ratio, 1.73; p=0.03; hazard ratio, 2.56; p<0.001, respectively)., Conclusions: Patients who are node-positive, show non-adenocarcinoma disease, and/or undergo limited surgery should receive careful follow-up during the first year after surgery for NSCLC. The present data provide additional information about postoperative recurrence in NSCLC patients., (Copyright © 2012 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.)

We evaluated the tumour shape as a potential prognostic indicator in lung adenocarcinoma patients. Among 994 patients who underwent curative surgery, 78 cases of adenocarcinoma (N0M0) with tumours ≥ 31 mm in diameter were reviewed. The patients were divided into two groups based on the ratio between the longest and the smallest axis length. The patients who had tumours whose ratios were > 0.5 were defined as the globular shape group (GL) and the others, whose ratio was 0.5 or less, were defined as the ellipse shape group (EL). The 78 patients were divided into two subgroups (57 in the GL and 21 in the EL). The tumour shape was related to the prognosis, and the 5-year overall survival (OS) rate in the GL was 51.5%, and that in the EL was 85.5% (P = 0.018). The 5-year disease-free survival rate of the GL was 46.6% and that of the EL patients was 85.0% (P = 0.04). The multivariate analysis showed that the shape of the tumour and the presence of pleural invasion were the independent and significant factors predicting the OS (P = 0.04 and P < 0.01, respectively). In adenocarcinoma patients, the shape of the tumour is related to the postoperative survival.

Purpose: This study retrospectively investigated the clinical significance of surgical treatment for stage IV non-small-cell lung cancer (NSCLC)., Subjects: There were 36 patients who underwent surgical resection for stage IV NSCLC between 1999 and 2008., Results: The patients included 22 males and 14 females. All patients had either synchronous distant metastasis or pleural dissemination. The mean age of the patients was 65.8 years (range, 18 to 90 years). The histological types included 29 adenocarcinomas, 5 squamous-cell carcinomas and 2 large-cell carcinomas. The organs of metastasis were bone in 5 patients, brain in 4, adrenal gland in 4, axillary lymph nodes in 3, liver in 2, and 1 patient had a contralateral pulmonary metastasis. The number of metastases was one site in 13, two sites in 3, three sites in 1, and five sites in 2 patients. The patients with bone metastasis were treated with radiation, and the patients with brain metastasis underwent stereotaxic radiosurgery. The patients with either adrenal metastasis, axillary lymph node metastasis, or contralateral lung metastasis underwent surgical resection. Among the patients with distant metastasis, the 5-year survival rate was 30.1 %. There were 17 patients with pleural dissemination. The 5-year survival rate in these patients was 25.3%. The overall 5-year survival rate after surgery in the patients with stage IV disease was 26.8%., Conclusion: Selected patients who can undergo surgical resection for the primary tumor and effective local therapy for metastatic lesions still have a chance to obtain long-term survival. Surgical treatment for NSCLC with oligometastatic disease can be considered as one arm of multidisciplinary treatment., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Background: The purpose of the current study was to clarify the clinical role of insulin-like growth factor receptor-1 (IGF1R) in NSCLC., Patients and Methods: Tumor specimens were collected from 285 patients who underwent complete resection for adenocarcinoma (AD, n = 182), squamous cell carcinoma (SCC, n = 77), and other histologic types of cancer (n = 26) of the lung. The expression of IGF1R and Ki-67 was evaluated by immunohistochemical (IHC) analysis., Results: Positive expression of IGF1R was detected in 87 (30.5%) of 285 cases, of which 43 (23.6%) of 182 cases were AD, 36 (46.8%) of 77 cases were SCC, and 8 (30.8%) of 26 cases were other histologic types (SCC vs. AD, p < .001; SCC vs. non-SCC, p < .001). Positive IGF1R expression was also identified in 20 (44.4%) and 67 (27.9%) of the patients with and without recurrence, respectively (p = .027). Multivariate logistic regression models indicated that positive staining for IGF1R expression was an independent factor in AD associated with tumor recurrence (p = .040) but not in NSCLC, SCC, and other types of cancer. A positive IGF1R expression tended to demonstrate a poor disease-free survival (DFS) in NSCLC according to the Kaplan-Meier DFS curves (p = .053). The tumors showing a positive expression of IGF1R were observed more frequently in tumors with a positive expression of Ki-67 than in the tumors with a negative expression of Ki-67 (p = .010)., Conclusion: IGF1R expression was associated with reduced DFS correlating with postoperative recurrence. In addition, a significant relationship was also observed between IGF1R and Ki-67 expression in NSCLC. However, in subgroup analysis, a significant correlation was not observed. IGF1R expression predicts postoperative recurrence in patients with AD, but not in those with non-AD of NSCLC., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Background: The epithelial-mesenchymal transition (EMT) is also involved in cancer progression and metastasis. The expression of mesenchymal marker genes might be associated with a more aggressive form of the disease. CD146 is a marker of mesenchymal cells, a potentially metastasis-promoting cell adhesion molecule, and its expression has been described in various types of solid tumors. We, herein, evaluated the expression of CD146 in patients with adenocarcinoma of the lung by using immunohistochemistry to clarify its clinical significance., Materials and Methods: Tumor specimens were collected from 183 consecutive patients who underwent complete resection for lung adenocarcinoma from 2003 to 2007 in our Department. We analyzed the CD146 expression levels in the primary lung adenocarcinoma by immunohistochemistry., Results: Positive expression of CD146 was identified in 16 (8.7%) patients. A significant association was only observed between the CD146 expression level and male patient gender (p=0.03); other factors were not associated with CD146 expression. The 5-year overall survival (OS) rate in patients with tumors that were negative and positive for CD146 expression was 84.4% and 50.0%, respectively (p<0.01). A positive CD146 expression was found to be associated with the OS based on a univariate survival analysis (p=0.013)., Conclusion: CD146 expression was more frequently detected in males than in females. The positive expression of CD146 was associated with a poorer OS according to the survival analysis. CD146 may be a useful marker for predicting poor prognosis in patients with NSCLC following complete resection.

Pulmonary hamartoma is the most common tumor in benign lung neoplasm. We reviewed the clinical characteristics of 9 patients who had undergone surgical resection for pulmonary hamartoma between 2000 and 2009. There were 1 male and 8 female patients. The age of the patients ranged from 42 to 77 years old (mean 59). Calcification was not observed by computed tomography scan except in 1 patient. Although transbronchial lung biopsy (TBLB) was performed in 5 patients, no definitive diagnosis was obtained. Six patients underwent 18F-fluorodeoxyglucose (FDG)-positron emission tomography, and none of them showed any accumulation of FDG except for 1 patient. Concerning the operative procedures, a sleeve lobectomy was performed in 1 patient, a segmentectomy in 1, a lobectomy in 2, a partial resection of the lung in 3, and a nucleation in 2 patients. The postoperative courses were uneventful, and no findings of recurrence were observed in any of the patients after surgery. As a preoperative diagnosis of pulmonary hamartoma is often difficult in TBLB, it is necessary to perform surgical resection in the differential diagnosis of lung cancer or metastatic lung tumor, unless there are typical findings of pulmonary hamartoma in clinical imaging.

Aim: The human epidermal growth factor receptor HER-2/neu (HER2) gene is a proto-oncogene involved in the signal transduction pathways leading to cell growth and differentiation. The present study focused on the clinical significance of the expression of HER2 in non-small cell lung cancer (NSCLC)., Patients and Methods: Consecutive specimens of 159 adenocarcinomas and 77 squamous cell carcinomas, from patients who had been treated by complete resection of NSCLC in our department between 2003 and 2005, were studied. The HER2 expression was evaluated by immunohistochemical staining with score of membranous staining being 0=none, 1=weak, 2=10-30% cells, 3≥30% cells stained., Results: The staining scores in adenocarcinoma were 0 in 121 patients (76.1%), 1 in 16 (10.0%), 2 in 17 (10.7%), and 3 in 5 patients (3.1%). The HER2 expression scores in squamous cell carcinoma were 0 in 74 patients (96.1%), 1 in 1 (1.2%), 2 in 1 (1.2%), and 3 in 1 patient (1.2%). The postoperative 5-year survival rate of patients with adenocarcinoma according to the expression of HER2 scores 0, 1, 2 and 3 was 75.3%, 77.8%, 76.5% and 20.0%, respectively. Patients with adenocarcinoma with score 3 staining had a significantly unfavorable prognosis compared to those with staining scores of 0-2 (p=0.0216)., Conclusion: HER2 overexpression (score 3) in adenocaricinoma was a significantly unfavorable prognostic factor. Since the number of NSCLC patients with HER2 overexpression was small, further investigations will be necessary to clarify the efficacy of molecular targeted therapy for this subgroup.

Background: Ki-67 expression has been established as a predictive marker for recurrence in breast cancer, and proliferating cell nuclear antigen (PCNA) which is also a proliferation marker, is also herein discussed regarding its role in the prognosis of various types of cancer. However, no useful data are presently available regarding the biological significance of both molecules in lung cancer., Patients and Methods: Tumor specimens were collected from 183 consecutive patients who underwent a complete resection for lung adenocarcinoma from 2003 to 2007 in our Department. We analyzed the Ki-67 and PCNA expression levels in primary lung adenocarcinoma by immunohistochemistry., Results: Positive expression of Ki-67 and PCNA was identified in 41 (22.4%) and 149 (81.4%) patients, respectively. The positive expression of Ki-67 was identified in 14 (50.0%) out of 28 patients and 27 (18.1%) out of 155 patients with and without recurrence, respectively (p<0.001). PCNA expression was not correlated with recurrence. Positive expression of Ki-67 was associated with a poorer disease-free survival according to the survival analysis. A multivariate analysis also demonstrated that Ki-67 expression was independently associated with an increased risk of poor disease-free survival., Conclusion: Ki-67 may be a useful marker for predicting postoperative recurrence in patients with non-small cell lung cancer following complete resection.

Purpose: This study investigated whether the number of involved lymph nodes is associated with the prognosis in patients that underwent surgery for pathological stage (p-stage) III/N2 NSCLC., Subjects: This study evaluated 121 patients with p-stage III/N2 NSCLC., Results: The histological types included 65 adenocarcinomas, 39 squamous cell carcinomas and 17 others. The average number of dissected lymph nodes was 23.8 (range: 6-55). The average number of involved lymph nodes was 5.9 (range: 1-23). The 5-year survival rate of the patients was 51.0% for single lymph node positive, 58.9% for 2 lymph nodes positive, 34.2% for 3 lymph nodes positive, and 30.0% for 4 lymph nodes positive, and 20.4% for more than 5 lymph nodes positive. The patients with either single or 2 lymph nodes positive had a significantly more favorable prognosis than the patients with more than 5 lymph nodes positive. A multivariate analysis revealed that the number of involved lymph nodes was a significant independent prognostic factor., Conclusion: Surgery appears to be preferable as a one arm of multimodality therapy in p-stage III/N2 patients with single or 2 involved lymph nodes. The optimal incorporation of surgery into the multimodality approach therefore requires further clinical investigation.

Purpose: This study investigated the preoperative serum levels of CYFRA 21-1 and CEA as prognostic factors in patients with stage I non-small cell lung cancer., Subjects: This study evaluated 341 patients who had undergone a complete resection for stage I NSCLC between 2002 and 2008., Results: The patients included 193 males and 148 females. The mean age of the patients was 69.2 years (range: 19-88). The histological types included 264 adenocarcinomas, 56 squamous cell carcinomas, 11 large cell carcinomas, and 10 other types of carcinoma. A pneumonectomy was performed in 2 patients, a bilobectomy in 7, a lobectomy in 255, a segmentectomy in 46, and partial resection of the lung in 31 patients. The positive rates for CYFRA 21-1 in the adenocarcinoma and squamous cell carcinoma patients were 33.3% and 76.8%, respectively. The positive rates for CEA in adenocarcinoma and squamous cell carcinoma patients were 23.8% and 26.8%, respectively. The 5-year survival rate after surgery in the normal CYFRA 21-1 group and the high CYFRA 21-1 groups were 92.8% and 75.4%, respectively, in the patients with stage I NSCLC. There was a significant difference between the 2 groups (p<0.0001). The 5-year survival rate according to the serum level of CEA in the patients with stage I NSCLC were 88.3% for the normal group and 76.3% for the high group. In a multivariate analysis using the variables found to be significant prognostic factors in univariate analysis, a high CYFRA 21-1 level was found to be a significant independent prognostic factor (95% confidence interval 1.213-5.442, p=0.014)., Conclusion: A high preoperative CYFRA 21-1 level was a significant independent prognostic factor in patients with stage I NSCLC. The patients with a high CYFRA 21-1 level should carefully followed-up to rule out occult metastasis. Further clinical studies will be necessary to evaluate the efficacy of adjuvant therapy for the patients selected according to this criterion., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

This study evaluated 325 patients who had undergone pleural lavage cytology (PLC) immediately after thoracotomy following a complete resection for non-small cell lung cancer (NSCLC) between 2004 and 2008. The number of patients with negative and positive findings in PLC was 309 and 13, respectively. The proportion of T1 in the PLC-positive group was significantly smaller than that of the PLC-negative group. The pathologic examinations revealed that the parietal pleural invasion was significantly more severe in the PLC-positive group than in the PLC-negative group. Pathologic lymphovascular invasion was also significantly more prominent in the PLC-positive group than in the PLC-negative group. The 5-year survival rate after surgery in the PLC-positive group and PLC-negative group was 54.7% and 79.0%, respectively. The positive finding in PLC showed a tendency of an unfavorable prognosis for NSCLC patents following complete resection. Further clinical studies will be necessary to evaluate the efficacy of adjuvant therapy for PLC-positive patients.

Background and Aims: The widespread use of high resolution computed tomography has increased the number of small peripheral lung cancers. This study reviewed the clinicopathological features of the patients with non-small cell lung cancer (NSCLC) with a tumor diameter of 1 cm or less, in order to explore the adequate management of such small sized lung cancers., Material and Methods: This study was a retrospective analysis of consecutive 58 patients (5.3% out of 1095 patients) who underwent a complete resection for a peripheral NSCLC with a diameter of 1.0 cm or less. The clinical features and outcomes were compared with 203 patients with NSCLC with a diameter between 1.1 and 2.0 cm., Results: The mean age was 64.5 years and there were 26 males and 32 females. Clinical stage was IA in 57 (98%) and IIIA in 1. Lobectomy was performed in 39 patients, segmentectomy in nine, and nonanatomic wedge resection in ten. Two patients, who underwent systemic lymph node dissection, had mediastinal lymph node metastasis and were diagnosed as pathological stage IIIA; however they did not relapse after surgery. One patient with pathological stage IA papillary adenocarcinoma died due to brain metastases. The five-year overall survival rate and disease free survival rate was 95.0% and 95.3%, respectively. Patients with NSCLC of 1.0 cm or less showed significantly better survival than those with tumors measuring 1.1-2.0 cm in size (p = 0.048)., Discussion: The indications for avoiding systemic lymph node dissection for operable NSCLC should not be based on the size of the tumor. A small-sized lung cancer might be surgically treated before the tumor enlarges to more than 1.0 cm in size.

Aims: This study retrospectively investigated the clinical significance of lymphovascular invasion (LVI) following a complete resection for stage I non-small cell lung cancer (NSCLC)., Methods: A total of 226 patients who underwent a complete resection for pathological stage I NSCLC were examined., Results: Lymphatic invasion was pathologically diagnosed as ly0 in 156 patients, ly1 in 65, and ly2 in 5 patients. The pathological vascular invasion was diagnosed as v0 in 178 patients, v1 in 35, v2 in 10, and v3 in 3 patients. The 5-year survival rate after surgery of the patients with and without lymphatic invasion was 76.8 and 90.6%, respectively. There was a significantly more unfavorable prognosis in patients with lymphatic invasion (p = 0.042). The 5-year survival rate of the patients with vascular invasion was also significantly more unfavorable (67.8%) than that of patients without vascular invasion (90.4%; p = 0.004). LVI was found to significantly correlate with tumor size and the presence of pleural invasion., Conclusion: The LVI of NSCLC is a significant prognostic factor in patients with stage I tumors. In future clinical trials, it is necessary to evaluate the efficacy of adjuvant therapy for the selection of patients according to this criterion., (Copyright © 2011 S. Karger AG, Basel.)

To evaluate the optimum treatment strategy for metastatic adrenal tumors derived from non-small cell lung cancer (NSCLC), we retrospectively analyzed 17 consecutive cases (8 resection cases: 4 synchronous and 4 metachronous: 9 non-resection cases: 3 synchronous and 6 metachronous) who received surgical resection for NSCLC. The patients included 12 males and 5 females with a mean age of 63.9 years. Of these, 9, 3, 2, 2, and 1 patient (s) were diagnosed as having adenocarcinoma, squamous cell carcinoma, pleomorphic carcinoma, large cell carcinoma, and adenosquamous cell carcinoma, respectively. The mean interval after lung resection and treatment of metachronous adrenal metastasis was 9.9 months. The mean time to progression from treatment of metachronous adrenal metastasis to disease progression was 8.9 months. A survival analysis showed no significant prognostic difference between the patient age, gender, pathological stage, synchronous/metachronous classification, CEA, and site of metastases. However, patients who received an adrenalectomy had a more favorable prognosis. The 2-year survival of patients following resection versus those who did not undergo a resection for adrenal metastasis was 62.5 and 22.8%, respectively. These data indicate that metastatic adrenal tumors should be resected if the patient can tolerate surgery after appropriate selection.

Background: The clinical features of mucinous bronchioloalveolar carcinoma (BAC) have remained unclear due to the low incidence of this disease. This study investigated the clinicopathological features and the surgical outcome in patients with mucinous BAC., Methods: We clinicopathologically evaluated 782 patients who underwent resection for nonsmall cell carcinoma between 1999 and 2008, of whom, 13 (1.6%) demonstrated to have mucinous BAC., Results: The patients with mucinous BAC included six men and seven women. The mean age was 69.1 years (range: 55-78 years). Eight patients (61.5%) had a smoking habit. No patients had any subjective symptoms. The tumour diameter ranged from 1.2 cm to 10 cm. The surgical procedures included 11 lobectomies, and two partial resections of affected lobes. The pathological stage was IA in eight patients, IB in two, IIA in two, and IIIA in one. None of the patients had lymph node metastases or lymphovascular invasion. The overall postoperative 5-year survival rate was 52.5%. The 5-year survival rate according to tumour diameter was 100% in patients with tumours ≤ 3 cm, and 25.1% in patients with tumours > 3 cm. Two patients died due to pulmonary metastases, and one died from carcinomatous pleuritis and pulmonary metastases., Conclusion: Patients with small mucinous BAC (≤ 3 cm) in diameter showed excellent prognosis after surgical resection. However, mucinous BAC > 3 cm in diameter tended to recur with pulmonary metastasis., (Copyright © 2010 Asian Surgical Association. Published by Elsevier B.V. All rights reserved.)

Purpose: The clinical features of large cell carcinoma (LCC) of the lung have remained unclear due to the low incidence of the disease. This study investigated the clinicopathological features and the surgical outcome in patients with LCC., Subjects: This study clinicopathologically evaluated 975 patients who had undergone a resection for non-small cell carcinoma between 1994 and 2007. There were 57 (5.8%) patients with LCC among them., Results: The LCC patients included 49 males and 8 females and included 9 patients with large cell neuroendocrine carcinoma. All patients excluding 1 had a smoking habit. The mean smoking pack-year index was 49.9 in the patients with LCC, 27.1 in 625 patients with adenocarcinoma, and 52.5 in 266 patients with squamous cell carcinoma, and this was significantly higher in the patients with LCC than in those with adenocarcinoma. The mean tumor diameter was 38 mm for LCC, 28 mm for adenocarcinoma, and 39 mm for squamous cell carcinoma. The pathological stage was IA in 11 patients, IB in 11, II in 12, IIIA in 16, IIIB in 5, and IV in 2. The post-operative 5-year survival rate was 60.5% for LCC, 64.3% for large cell neuroendocrine carcinoma, 67.0% for adenocarcinoma, and 50.1% for squamous cell carcinoma., Conclusion: The tumor diameter was significantly larger for LCC than for adenocarcinoma at the time of diagnosis. The proportion of smokers and the smoking pack-year index in patients with LCC were significantly higher than those of adenocarcinoma. The surgical results were similar between LCC and other non-small cell lung carcinomas., (Copyright 2010 Surgical Associates Ltd. Published by Elsevier Ltd. All rights reserved.)

Background: This pilot study aimed to examine the technical feasibility and safety of video-assisted thoracic surgery (VATS) involving major pulmonary resection for central tumors compared with the perioperative data obtained from historical cohorts who underwent open thoracotomy., Methods: Between April 2002 and June 2008, 26 consecutive patients with centrally located lung tumors 6 cm in size or smaller with histologically confirmed or radiologically suspected non-small cell lung cancer were prospectively registered for VATS involving major pulmonary resection at a single institution. These patients were compared with 20 historical cohorts who underwent comparable surgical procedures by open thoracotomy in terms of demographic, perioperative, histopathologic, and outcome variables., Results: One conversion was performed because of the patient's inability to tolerate single-lung ventilation, and this patient was excluded from this study. The two groups showed no differences in terms of demographic, operative, or histopathologic variables. Both groups presented with no mortality. The VATS group demonstrated a significantly lower C-reactive protein level (p = 0.0166), shorter chest tube drainage time (p = 0.0141), shorter epidural tube anesthesia (p < 0.0001), lower analgesic requirements (p = 0.0001), shorter hospital stay (p < 0.0001), and fewer postoperative complications (p = 0.0157) than the open thoracotomy group. Despite the short follow-up time, the two groups were comparable in terms of both recurrence and survival rates., Conclusions: The results indicate that VATS involving major pulmonary resection is technically feasible and safe for selected patients with central lung tumors, with an acceptable perioperative outcome compared with open thoracotomy.

Introduction: We evaluated the feasibility and safety of the video-assisted thoracic surgery (VATS) lobectomy for non-small cell lung cancer (NSCLC) in patients with comorbidity., Methods: Between April 2000 and December 2006, a prospective database of 58 consecutive patients undergoing a VATS lobectomy for NSCLC, who had a Charlson comorbidity index score of 2 or more, was retrospectively analyzed. The demographic, perioperative, histopathologic, and outcome variables, including the recurrence and survival, were assessed., Results: The VATS lobectomy was successfully performed in 57 patients (16 women and 41 men; median age, 70 years). Twenty-three patients (40.4%) were aged 75 years or older. The total score of the Charlson comorbidity index was as follows: 2 in 26 patients, 3 in 13 patients, 4 in 12 patients, 5 in five patients, and 6 in one patient. None of the patients required a blood transfusion during surgery or during the postoperative course. We observed no intraoperative or in-hospital deaths, and no complications occurred in the 45 patients (78.9%). At a median follow-up of 34 months, a recurrence was observed in five patients who had advanced stages: a local recurrence in one and a distant recurrence in four. The overall 5-year survival rates for postoperative stage IA (n = 25) and IB (n = 16) were 100% and 94%, respectively., Conclusions: We believe that a VATS lobectomy is a feasible and safe procedure for NSCLC in patients with comorbidity because this modality demonstrates an acceptable morbidity and a favorable oncologic outcome.

The purpose of this study is to examine the feasibility and safety of thoracoscopic major pulmonary resection requiring the cross-clamping of the main pulmonary artery (PA), in comparison to an open thoracotomy performed in patients with lung cancer. A retrospective database of 27 consecutive lung cancer patients, who underwent either video-assisted thoracic surgery (VATS) (n=13) or open thoracotomy (n=14) for a major pulmonary resection using these procedures, was analyzed regarding the demographic, perioperative, histopathologic, and outcome variables. The thoracoscopic procedures were successfully performed in 12 of 13 patients (92.3%). Two groups showed no differences in the demographic, perioperative, histopathologic and staging variables. Both groups presented with no mortality. The VATS group showed better results regarding the length of epidural anesthesia (P=0.0066), additional analgesic requirements (P=0.0009), and morbidity (P=0.0213) than the open thoracotomy group. Despite the short follow-up time, the two groups were comparable regarding both the recurrence and survival rates. The results indicate that VATS is feasible and safe for selected lung cancer patients requiring the cross-clamping of the main PA, with acceptable perioperative results in comparison to an open thoracotomy.

Objectives: We prospectively analyzed the association between drainage volume and development of complications to clarify the safety of early removal of chest tube after thoracoscopic lobectomy., Methods: Between November 2001 and October 2007, 136 patients with suspected or histologically documented lung cancer were enrolled. Patients with no air leak and increased drainage underwent removal of the chest tube on the day after thoracoscopic lobectomy independent of the drainage volume. Patients were classified into three groups as tertiles according to the drainage volume. Demographic and perioperative variables were compared among the three groups. Age-sex adjusted odds ratios of the clinical variables associated with development of complications were estimated. In addition, the odds ratios of the drainage volume for development of complications were estimated after adjusting for potentially important factors., Results: One hundred patients underwent early removal of the chest tube. Almost all demographic and perioperative variables showed no differences among the three groups (0-289 mL, n = 33; 290-399 mL, n = 33; and >or=400 mL, n = 34). Tumors in a lower lobe, preoperative stage II or higher, 5 or more anatomic segments resected, and advanced disease were all factors that were associated with higher odds ratios for complications. The drainage volume was not associated with an increased morbidity, even after adjusting for these factors., Conclusions: Early removal of chest tube on the day after thoracoscopic lobectomy, independently of the drainage volume, appears to be safe in well-selected patients.

A lobectomy with a resection of the pulmonary artery is less invasive than a pneumonectomy. However, it seems to be extremely difficult to perform this technique using video-assisted thoracic surgery with technical limitations because this technique is associated with an increased operative risk even in an open thoracotomy. Between April 2002 and December 2006, a curative video-assisted thoracic surgery lobectomy including a mediastinal lymphadenectomy was performed in 121 patients with primary non-small cell lung cancer. Five of those patients underwent a thoracoscopic lobectomy with the partial removal and reconstruction of the pulmonary artery. The causes of the pulmonary artery resection included two direct invasions of the artery, two invasions of the arterial branch, and one calcified lymphadenopathy involving the branch. No patients required a blood transfusion. No complications attributable to the technique or mortality were seen. No patients showed an abnormal blood flow through the reconstructed vessel. There were no local recurrences on the pulmonary artery. A video-assisted thoracic surgery lobectomy including a partial resection and reconstruction of the pulmonary artery is a complex procedure for patients with non-small cell lung cancer. It is feasible when all associated technical issues are properly addressed.

Objective: The optimal surgical treatment for non-small cell lung cancer (NSCLC) with vertebral body invasion remains both controversial and challenging. We reviewed our experiences of NSCLC with vertebral body invasion, in which we have performed induction chemoradiotherapy followed by lung resection with en bloc partial vertebrectomy., Methods: Six NSCLC patients with vertebral invasion underwent an operation following chemoradiotherapy from January 2001 to July 2006. Vertebral invasion was evaluated by the chest CT and MRI findings. Either carboplatin-paclitaxel (n=3) or carboplatin-docetaxel (n=3) was used. Two cycles of chemotherapy were performed with concurrent radiation (50 Gy) treatment., Results: In all of the six cases, a complete resection with en bloc partial vertebrectomy was performed with no operative mortality. The histological complete response rate and major response rate were 16.7% (1/6) and 83.3% (5/6), respectively. The 5-year overall survival rate was 67.7%. In addition, no local failure was observed after surgery., Conclusions: Surgery after chemoradiotherapy (carboplatin/paclitaxel or docetaxel and 50 Gy radiation) for NSCLC with vertebral invasion could thus be performed with acceptable morbidity.

A 53-yr-old woman developed a dry cough after the completion of multi-agent chemotherapy. The biopsy specimens showed diffuse infiltrates with multiple myeloma (MM) cells. Immunohistochemistry revealed positive staining in MM cells with surface CD20, surface CD38, and cytoplasmic IgG. This report represents the first reported case of pulmonary parenchymal infiltrates in a patient with CD20-positive MM.