A prospective observational study of postoperative adjuvant chemotherapy for non-small cell lung cancer in elderly patients (≥ 75 years).

BACKGROUND: To examine the effects of postoperative adjuvant chemotherapy for elderly (≥ 75 years of age) patients with completely resected non-small cell lung cancer (NSCLC), we conducted a multi-institutional and prospective observational study. METHODS: Patients were recruited between January 2014 and December 2017, and assigned to two cohort groups based on the patients' choice either to receive postoperative adjuvant chemotherapy (Cohort B) or not (Cohort A). All the patients were observed for 2 years after enrollment. The primary endpoint was the postoperative change of Karnofsky Performance Status (KPS) at 2 years. The secondary endpoints were postoperative recurrence-free survival (RFS) and overall survival (OS) at 2 years, and the completion rate of the adjuvant chemotherapy. RESULTS: Two hundred and seventy-two patients were enrolled (Cohort A, n = 225; Cohort B, n = 47). At any time point after surgery, no marked difference of KPS was observed between Cohort B and Cohort A. The RFS at 2 years was 70.8% (95% confidence interval [CI], 64.3-76.4) in Cohort A and 76.0% (95% CI 60.8-85.9) in Cohort B. The OS at 2 years was 85.9% (95% CI 80.4-89.9) in Cohort A and 89.1% (95% CI 75.8-95.3) in Cohort B. The completion rate of planned chemotherapy was 49.9% (95% CI 34.1-63.9%). CONCLUSIONS: The elderly patients were not likely to choose to receive postoperative adjuvant chemotherapy; however, no significant adverse effect on postoperative KPS was identified. TRIAL REGISTRATION: Clinical Trial Registration ID: UMIN000020736.

A feasibility trial of postoperative adjuvant chemotherapy with S-1, an oral fluoropyrimidine, for elderly patients with non-small cell lung cancer: a report of the Lung Oncology Group in Kyushu (LOGIK) protocol 0901.

BACKGROUND: The present study was designed to determine whether adjuvant chemotherapy with S-1 after surgical resection is feasible in elderly patients with non-small cell lung cancer (NSCLC), using a multi-institutional trial. METHODS: From July 2009 to July 2011, 25 patients received the following regimen: 2 weeks of administration and 1 week of withdrawal of S-1 at 50-100 mg/body per day in an outpatient setting. The primary endpoint of this trial was the completion rate of eight cycles. RESULTS: The completion rate of eight cycles was 70.8 % [95 % confidence interval (CI) 52.7-89.0 %]. The perfect completion rate of eight cycles on schedule with full doses without delays was 50 % (95 % CI 30.0-70.0 %). The reasons for incomplete cycles were: patient refusal in four cases, anorexia in two cases and thrombocytopenia in one case. As a consequence of delays and/or dose reductions, the relative dose intensity of S-1 was 76.3 %. CONCLUSIONS: Adjuvant chemotherapy with S-1 at a reduced dose and schedule was therefore found to be a feasible treatment for elderly Japanese patients who had undergone surgical resection for NSCLC (UMIN Clinical Trials Registry number UMIN000002383).

Expression of Brachyury gene is a significant prognostic factor for primary lung carcinoma.

BACKGROUND: The clinical significance of Brachyury expression and its relationship to epithelial-mesenchymal transition in primary lung carcinoma is unclear. METHODS: Expression of Brachyury mRNA was investigated in 104 surgically resected primary lung carcinoma tissues. Immunohistochemical analysis of Brachyury transcription factor, Slug, E-cadherin, IL-8, N-cadherin, and Ki67 was performed in 67 of 104 cases, and their expression was correlated to prognoses and clinicopathological factors. RESULTS: Brachyury mRNA expression in primary lung carcinoma tissues was a significant predictor of poor prognosis for 5-year disease-free survival and overall survival rates and was significantly correlated to vascular invasion, lymphatic permeation, histological grade, pathologic T stage, and pathologic N stage (P < 0.05). Brachyury mRNA expression was significantly inversely correlated to E-cadherin expression (P = 0.0252) and positively correlated to IL-8 protein (P = 0.0241) and to Slug protein (P = 0.0243) in adenocarcinoma tissues. CONCLUSIONS: A positive association between Brachyury and Slug and IL-8, and a negative association with E-cadherin may lead to invasiveness and metastasis in primary lung carcinoma. Brachyury mRNA expression is a significant predictor of poor prognosis in primary lung carcinoma.

BioKnife, a uPA activity-dependent oncolytic Sendai virus, eliminates pleural spread of malignant mesothelioma via simultaneous stimulation of uPA expression.

Malignant pleural mesothelioma (MPM) is highly intractable and readily spreads throughout the surface of the pleural cavity, and these cells have been shown to express urokinase-type plasminogen activator receptor (uPAR). We here examined the potential of our new and powerful recombinant Sendai virus (rSeV), which shows uPAR-specific cell-to-cell fusion activity (rSeV/dMFct14 (uPA2), named "BioKnife"), for tumor cell killing in two independent orthotopic xenograft models of human. Multicycle treatment using BioKnife resulted in the efficient rescue of these models, in association with tumor-specific fusion and apoptosis. Such an effect was also seen on both MSTO-211H and H226 cells in vitro; however, we confirmed that the latter expressed uPAR but not uPA. Of interest, infection with BioKnife strongly facilitated the uPA release from H226 cells, and this effect was completely abolished by use of either pyrrolidine dithiocarbamate (PDTC) or BioKnife expressing the C-terminus-deleted dominant negative inhibitor for retinoic acid-inducible gene-I (RIG-IC), indicating that BioKnife-dependent expression of uPA was mediated by the RIG-I/nuclear factor-κB (NF-κB) axis, detecting RNA viral genome replication. Therefore, these results suggest a proof of concept that the tumor cell-killing mechanism via BioKnife may have significant potential to treat patients with MPM that is characterized by frequent uPAR expression in a clinical setting.

Differences in the expression of epithelial-mesenchymal transition related molecules between primary tumors and pulmonary metastatic tumors in colorectal cancer.

PURPOSE: Epithelial-mesenchymal transition (EMT) is a key event in cancer metastasis. This study immunohistochemically examined the expression of EMT-related molecules in both primary colorectal cancer and pulmonary metastases, and analyzed the expression pattern. METHODS: Ten patients with colorectal cancer that underwent surgical resections for both the primary tumor and metastatic pulmonary tumors were included. The expression status of EMT-related molecules was examined using immunohistochemical staining. RESULTS: Nine of the 10 cases maintained the expression of both E-cadherin and ß-catenin in the primary site. The expression of E-cadherin and ß-catenin in the pulmonary metastatic site was preserved in 10 and 12 out of 15 metastatic lesions, respectively. The EMT-related transcription factor, Twist, was positively expressed in all 10 cases, Smad interacting protein 1 (Sip1) in 9, Snail in 4 and Slug in 3 of the primary sites. On the other hand, staining for Twist, Sip1 and Snail at the metastatic pulmonary site, was negative in all 10 cases. CONCLUSION: The expression of EMT-related transcription factors in metastatic pulmonary tumors from colorectal cancer decreased in comparison to the primary tumors. These findings suggested that the expression status of EMT-related transcription factors might play an important role in the implantation of metastatic foci.

[Chest surgery in patients with pulmonary metastasis from head and neck cancer].

There have been only a few reports about a surgical resection of pulmonary metastasis from malignant head and neck tumors. Here we reviewed the literatures concerning the surgical results of pulmonary metastasectomy from malignant head and neck tumors, and discussed the indication for surgery. The 5-year overall survival after a metastasectomy was approximately 50.0% including all the histological types of head and neck cancer. Limiting to the squamous cell carcinoma (SCC), the 5-year overall survival was approximately 30.0%. Of the head and neck SCCs, the oral cavity SCC such as SCC of the tongue showed an extremely poor survival after metastasectomy. A pulmonary metastasectomy of squamous cell carcinoma is thus justified with the exception of oral cavity origin. Both adenoid cystic carcinoma of salivary glands and thyroid cancer are of low malignant nature, and the progression after occurrence of distant metastases is also very slow. Therefore, the survival benefit by those pulmonary metastasectomy is not evident.

Prognostic Impact of Central Nervous System Recurrence After Surgery in Patients With Epidermal Growth Factor Receptor Mutation-positive Non-small-cell Lung Cancer.

BACKGROUND/AIM: Adjuvant therapy using third-generation tyrosine kinase inhibitors (TKI) demonstrated improved central nervous system (CNS) disease-free survival after surgery in patients with epidermal growth factor receptor (EGFR) mutation-positive lung cancer. However, the prognostic impact of CNS recurrence in surgical patients remains unknown. We evaluated the effect of CNS recurrence on post-recurrence survival (PRS) in patients with postoperatively recurrent NSCLC. PATIENTS AND METHODS: We assessed the prognostic impact of CNS recurrence using a cohort from a prospective observational study (Kyushu University Lung Surgery Group Study 2: KLSS-2). Based on data from 340 patients in whom EGFR mutations were assessed among 498 total patients in the KLSS-2 cohort, factors related to CNS recurrence and prognosis after postoperative recurrence were analyzed. RESULTS: We noted no marked differences in the presence of EGFR mutations (p=0.14) between patients with CNS recurrence and those without CNS recurrence. Among the patients tested for EGFR mutations with stage IV recurrences (n=219), survival analysis of patients with EGFR mutations showed that the CNS group had a significantly poorer PRS than the no-CNS group (MST: 36.8 vs. 43.9 months, p=0.035). In multivariate survival analysis of stage IV EGFR mutation-positive cases, recurrence in multiple organs and recurrence of brain metastases were independent poor prognostic factors (hazard ratio=2.2, p=0.029; hazard ratio=3.2, p=0.0006, respectively). CONCLUSION: Postoperative CNS recurrence was associated with a poor prognosis among patients with EGFR mutation-positive lung cancer in the period when third-generation EGFR-TKIs were not available. In EGFR mutation-positive lung cancer, prevention of CNS recurrence after surgery may improve post-recurrence prognosis.

Oncological Impact of the Level of Inferior Mesenteric Artery Ligation in Low Rectal Cancer Surgery.

BACKGROUND/AIM: This study aimed to evaluate the clinical impact of the level of inferior mesenteric artery (IMA) ligation in patients with advanced low rectal cancer. PATIENTS AND METHODS: All enrolled patients (n=350) underwent curative resection of rectal cancer with D3 lymph node dissection, with either IMA (high-tie) or superior rectal artery (SRA) (low-tie) ligation. RESULTS: There were 27 and 65 patients in the high-tie and low-tie groups, respectively. There was no significant difference in the postoperative complication rate. Postoperative anastomotic leakage developed in five patients in the low-tie group and none in the high-tie group. The overall recurrence rates were 37.0% (n=10) and 40.0% (n=26) in the high-tie and low-tie groups, respectively, with no significant difference between the two groups (p=0.748). Local recurrences and lymph node metastases developed in five and no patients in the high-tie group and in 13 and one patient in the low-tie group, respectively. In the multivariate analysis, pathological T4 and pathological N2 and N3 were independent poor prognostic factors for overall survival (OS), whereas left colic artery (LCA) preservation was not significant. CONCLUSION: No significant difference in oncological outcomes was observed in advanced low rectal cancer surgery with respect to the level of the IMA ligation. Thus, the less complicated high-tie procedure should be adopted as a standard procedure.

Is radical local therapy effective in postoperative recurrent EGFR-mutated non-small cell lung cancer?

BACKGROUND: Long-term survival can be achieved with radical local therapy in some cases of postoperative recurrence of non-small cell lung cancer (NSCLC). Here, we evaluated post-recurrence survival (PRS) after treatment of postoperative recurrent epidermal growth factor receptor (EGFR) mutated NSCLC and examined the effectiveness of radical local therapy. METHODS: This multicenter prospective cohort study was conducted in 14 hospitals. The inclusion criteria for this study were patients with recurrence after radical resection for NSCLC. Information about the patient characteristics at recurrence, tumor-related variables, primary surgery, and treatment for recurrence was collected. After registration, follow-up data (e.g., treatment and survival outcomes) were obtained and analyzed. RESULTS: From 2010 to 2015, 505 patients with recurrent NSCLC were enrolled into the study, and 154 EGFR mutation-positive cases were included. As the initial treatment for recurrence, 111 patients (72%) received chemotherapy, 14 (9%) received chemoradiotherapy, 14 (9%) received definitive radiotherapy, and seven (5%) received surgical resection. The remaining eight patients (5%) received supportive care. The median PRS and 5-year survival rates for all cases were 64 months and 53.2%, respectively. The 5-year survival rate according to the initial treatment was as follows: supportive care, 0%; chemotherapy, 53.3% and radical local therapy, 60.1%. The six patients who received radical local treatment remained recurrence-free for more than 3 years after recurrence with only initial treatment. CONCLUSIONS: Although radical local therapy may be curative in some patients, chemotherapy including EGFR-TKI treatment is expected to provide long-term survival comparable to that of radical local therapy.

A unique method for repairing intraoperative pulmonary air leakage with both polyglycolic acid sheets and fibrin glue.

BACKGROUND: In the present study we present a unique maneuver, using both fibrin glue and polyglycolic acid (PGA) sheets, for repairing intraoperative pulmonary air leakage, and report our clinical results. METHODS: Based on the results from in vitro experiments, we retrospectively investigated the clinical effects of our method for repairing intraoperative pulmonary air leakage in 377 consecutive patients, who underwent a pulmonary resection for primary lung cancer or metastatic lung tumors from 2004 to 2009. From April 2004 through September 2007, repair of intraoperative pulmonary air leakage was performed in 204 patients using only fibrin glue. From October 2007 through December 2009, the repair was performed in 173 patients with a unique application of both fibrin glue and PGA sheets, i.e., (1) rubbing fibrin glue A solution, (2) applying a PGA sheet cut to an appropriate size, (3) rubbing fibrin glue B solution on the PGA sheet, and (4) reapplying fibrin glue A solution and rubbing. RESULTS: The mean duration of postoperative pleural drainage was significantly shorter in the latter time period when both fibrin glue and PGA sheets were used than in the former period when fibrin glue was used alone. The incidence of prolonged air leakage longer than 1 week was also significantly lower in the latter era than in the former era. CONCLUSION: Our unique application of both fibrin glue and PGA sheets for the intraoperative repair of pulmonary air leakage effectively resulted in a shortening of the duration of postoperative pleural drainage.

Localized pleural amyloidosis: report of a case.

We herein describe an asymptomatic 31-year-old male who was admitted for an investigation of an abnormal pleural tumor detected by chest radiography. We performed various preoperative investigations including fluorodeoxyglucose-positron emission tomography. The maximum standardized uptake value (SUVmax) was 2.2, and malignancy could not be ruled out. We therefore carried out a thoracoscopy-assisted partial resection of the right upper lobe combined with a parietal pleurectomy. The pathological examination showed that there was a tumor localized with pleural amyloidosis.

Results of a surgical resection of pulmonary metastasis from hepatocellular carcinoma: prognostic impact of the preoperative serum alpha-fetoprotein level.

PURPOSE: Pulmonary metastasis is the most common type of extrahepatic recurrence of hepatocellular carcinoma (HCC). The outcome of pulmonary metastasectomy of HCC has not yet been thoroughly investigated. The outcomes of surgical treatment of pulmonary metastases from HCC were reviewed in order to analyze the postoperative survival and the relevant prognostic factors. METHODS: This study retrospectively reviewed 20 patients who underwent pulmonary metastasectomy from an HCC between 1990 and 2007 at two institutions. The surgical outcome was evaluated by both the overall survival and cancer-specific survival after pulmonary resection. The association between various clinico-pathological factors and the survival outcome was analyzed. RESULTS: The overall survival rate after the initial pulmonary metastasectomy was 46.9% at 5 years, and the cancer-specific 5-year survival rate was 63.2%. One patient died of surgery-related events 19 days after the pulmonary resection. The preoperative AFP (alpha-fetoprotein) level was found to be a significant prognostic factor for both overall and cancer-specific survival for patients undergoing pulmonary metastasectomy. Both the overall and cancer-specific survival rates were significantly worse for the patients with AFP ≥ 500 ng/ml in comparison to those with AFP < 500 ng/ml (p < 0.05). No other factors were associated with the survival after pulmonary metastasectomy. CONCLUSION: The serum level of AFP might be a valuable predictor for the outcome of pulmonary metastasectomy required for metastasis of HCC.

Relationship between expression of apoptosis-related proteins and the efficacy of postoperative chemotherapy in patients with T3 gastric cancer.

PURPOSE: We investigated the relationship between the p53-dependent apoptotic pathway and the survival of patients with gastric cancer, retrospectively, to elucidate new biomarkers of uracil/tegafur (UFT) chemotherapy. METHODS: We examined the expression of p53, p21, Bax, and myeloid cell leukemia 1 (Mcl-1) proteins immunohistochemically in 105 patients who underwent curative gastrectomy for gastric cancer invading the serosa. Postoperative oral UFT was prescribed for 1 year. Kaplan-Meier survival curves were compared with the two-sided log-rank test. RESULTS: Positive staining for p53, p21, Bax, and Mcl-1 proteins was found in 63.8, 52.4, 39.0, and 72.4% of the subjects, respectively. Survival time did not differ significantly between the patients with and those without p53, p21, and Bax expression. However, patients with Mcl-1- tumors survived longer than those with Mcl-1+ tumors. Postoperative UFT treatment did not improve survival; however, adjuvant UFT significantly prolonged the survival of patients with p53-, p21-), Bax+, or Mcl-1+ tumors, but not of patients with p53+, p21+, Bax-, or Mcl-1- tumors. CONCLUSIONS: The efficacy of adjuvant chemotherapy for gastric cancer may be affected by the status of apoptosis-related proteins such as p53, p21, Bax, and Mcl-1. However, because susceptibility to apoptosis did not explain the sensitivity of chemotherapeutic agents, further investigation of the mutual interaction between apoptosis-related proteins is required.

Prediction of true-negative lymph node metastasis in clinical IA non-small cell lung cancer by measuring standardized uptake values on positron emission tomography.

PURPOSE: We developed a method for predicting true-negative lymph node metastases in clinical IA non-small lung cancer (NSCLC) by the combined evaluation of computed tomography (CT), 2-[18F]-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) findings and the maximum standardized uptake value (SUVmax) of primary tumors. METHODS: The subjects of this study were 94 patients with clinical stage IA NSCLC who underwent both preoperative CT and FDG-PET. We analyzed the relationship between the SUVmax of primary tumors and various clinicopathological factors to find the best method available for assessing true-negative lymph node metastasis. RESULTS: The pathological stages were IA (n = 80), IB (n = 4), IIA (n = 5), IIIA (n = 4), and IV (n = 1). Pathologic lymph node metastasis was recognized in nine patients and the SUVmax of these tumors ranged from 3.3 to 20.3. A SUVmax of 3.0 was defined as the cut-off point and patients were dichotomized according to this point. Tumors with SUVmax of 3.0 or less were associated with a significantly lower incidence of pleural and vascular invasion and were characterized by the degree of differentiation. CONCLUSION: The SUVmax of primary tumors reflects the grade of malignancy; therefore, the combined evaluation of FDG-PET/CT findings with the SUVmax of primary tumors may help predict lymph node metastasis negativity.

Biological mechanism and clinical effect of protein-bound polysaccharide K (KRESTIN(®)): review of development and future perspectives.

The mechanism of action of protein-bound polysaccharide K (PSK; KRESTIN(®)) involves the following actions: (1) recovery from immunosuppression induced by humoral factors such as transforming growth factor (TGF)-ß or as a result of surgery and chemotherapy; (2) activation of antitumor immune responses including maturation of dendritic cells, correction of Th1/Th2 imbalance, and promotion of interleukin-15 production by monocytes; and (3) enhancement of the antitumor effect of chemotherapy by induction of apoptosis and inhibition of metastasis through direct actions on tumor cells. The clinical effectiveness of PSK has been demonstrated for various cancers. In patients with gastric or colorectal cancer, combined use of PSK with postoperative adjuvant chemotherapy prolongs survival, and this effect has been confirmed in multiple meta-analyses. For small-cell lung carcinoma, PSK in conjunction with chemotherapy prolongs the remission period. In addition, PSK has been shown to be effective against various other cancers, reduce the adverse effects of chemotherapy, and improve quality of life. Future studies should examine the effects of PSK under different host immune conditions and tumor properties, elucidate the mechanism of action exhibited in each situation, and identify biomarkers.

Survival after recurrence following surgical resected non-small cell lung cancer: A multicenter, prospective cohort study.

Objectives: The optimal treatment for recurrent non-small cell lung cancer (NSCLC) has not been standardized. In this prospective cohort study, we evaluated post-recurrence survival (PRS) after treatment of recurrent NSCLC and identified prognostic factors after recurrence. Methods: This multicenter prospective cohort study was conducted in 14 hospitals. The inclusion criteria for this study were patients with recurrence after radical resection for NSCLC. Information about the patient characteristics at recurrence, tumor-related variables, primary surgery, and treatment for recurrence was collected. After registration, follow-up data, such as treatment and survival outcomes, were obtained every 3 months. Results: From 2010 to 2015, 505 cases were enrolled, and 495 cases were analyzed. As initial treatment for recurrence, 263 patients (53%) received chemotherapy, 46 (9%) received chemoradiotherapy, 98 (20%) had definitive radiotherapy, 14 (3%) received palliative radiotherapy, and 31 (6%) underwent surgical resection. The remaining 43 patients (9%) received supportive care. The median PRS and 5-year survival rates for all cases were 30 months and 31.9%, respectively. The median PRS according to the initial treatment was as follows: supportive care, 8 months; palliative radiotherapy, 16 months; definitive radiotherapy, 30 months; chemotherapy, 31 months; chemoradiotherapy, 35 months; and surgery, not reached. A multivariate analysis showed that the age, gender, performance status, histology presence of symptoms, duration from primary surgery to recurrence, and number of recurrent foci were independent prognostic factors for PRS. Conclusions: The PRS of patients with recurrent NSCLC was different depending on the patient's background characteristics and initial treatment for recurrence.

CHFR hypermethylation and EGFR mutation are mutually exclusive and exhibit contrastive clinical backgrounds and outcomes in non-small cell lung cancer.

Aberrant promoter methylation of the checkpoint gene with forkhead-associated domain and ring finger (CHFR) gene is frequently detected in human cancer. We previously demonstrated that diminished CHFR expression was significantly correlated with both poor prognosis and heavy smoking in nonsmall cell lung cancer (NSCLC). Conversely, epidermal growth receptor (EGFR) mutation is detected in NSCLC among those who have never smoked or smoked lightly. To address the frequency of CHFR hypermethylation as well as differences in the distributions and clinicopathologic backgrounds against EGFR mutation in NSCLC, we investigated a large group of 208 NSCLC patients, including 165 with adenocarcinoma (ADC), 40 with squamous cell carcinoma and three others. We found that CHFR hypermethylation and EGFR mutation are mutually exclusive and have contrastive clinicopathologic backgrounds in NSCLC. Methylation-specific polymerase chain reaction (MSP) and direct DNA sequencing were performed to detect CHFR hypermethylation and EGFR mutation, respectively. CHFR hypermethylation was found in 29 cases (14%) (16 ADC (8%), 12 SCC (6%) and one adenosquamous carcinoma), while EGFR mutation was detected in 48 (23%) cases, all of which were ADC. CHFR hypermethylation and EGFR mutation were mutually exclusive (p = 0.004). NSCLC with altered CHFR was significantly correlated with smoking history, poor differentiation, lymphatic invasion, and poor prognosis; this contrasted sharply with EGFR mutation, which had statistically better clinical outcomes. Our results demonstrate that CHFR loss might be critical for the tumorigenesis of NSCLC in patients with a history of smoking and induces tumors of a more malignant phenotype than the EGFR mutation. Thus, CHFR alteration should be considered a therapeutic target against NSCLC in patients with poor prognoses.

Non-small cell lung cancer in never smokers as a representative 'non-smoking-associated lung cancer': epidemiology and clinical features.

Recent interest in lung cancer without a history of tobacco smoking has led to the classification of a distinct disease entity of 'non-smoking-associated lung cancer'. In this review article, we have made an overview of the recent literature concerning both the epidemiology and clinical features of lung cancer in never smokers, and have brought 'non-smoking-associated lung cancer' into relief. The etiology of lung cancer in never smokers remains indefinite although many putative risk factors have been described including secondhand smoking, occupational exposures, pre-existing lung diseases, diet, estrogen exposure, etc. Non-small cell lung cancer (NSCLC) in never smokers is clinically characterized by an increased incidence in females and a higher occurrence of adenocarcinoma in comparison to NSCLC in ever smokers in both surgical patients and non-resectable advanced-stage patients. Furthermore, the prognosis of never-smoking NSCLC is better than that of smoking-related NSCLC in both surgical patients and non-resectable advanced-stage patients. Recently recognized novel gene mutations such as EGFR (epidermal growth factor receptor) mutations are largely limited to never smokers or light smokers, and the expression of this gene is responsible for the clinical efficacy of gefitinib, an epidermal growth factor receptor-tyrosine kinase inhibitor. NSCLC with the EML4 (echinoderm microtubule-associated protein-like 4)-ALK (anaplastic lymphoma kinase) fusion gene is also more likely to occur in never smokers and in those with adenocarcinoma histology, and is expected to benefit from ALK inhibitors. In consideration of the future increase in never-smoking NSCLC or 'non-smoking-associated lung cancer', both clinical trials and investigations are needed.

Intraoperative radiofrequency ablation in an open thoracotomy setting for the new treatment of mediastinal liposarcoma: report of a case.

This report presents the case of a patient with mediastinal liposarcoma treated by radiofrequency ablation (RFA) in an open thoracotomy setting. This procedure is safe and feasible, and it appears to be an effective option for patients with soft tissue sarcoma originating from the mediastinum, especially for patients who are not well suited to undergo a further surgical resection. This report on a new type of RFA treatment for mediastinal liposarcoma may therefore be informative for general thoracic surgeons.

Dedifferentiated chondrosarcoma of the lung: report of a case.

This report presents a rare case of pulmonary sarcoma with regional anaplastic changes. A 73-year-old Japanese man with a hamartoma-like nodule of the left lung accompanied by interstitial pneumonia was followed up for 30 months. He underwent a surgical resection due to the rapid growth of the lung nodule. A pathological examination revealed a dedifferentiated sarcoma arising from the chondrosarcoma.