p62/SQSTM1 is a selective substrate of autophagy, and aberrant accumulation of p62 has been observed in various pathological conditions. To understand the roles p62 plays in non‐small‐cell lung ...cancer (NSCLC), we carried out immunohistochemical analyses of p62 expression in a cohort of patients with annotated clinicopathological data. As analyses of murine and human hepatocellular carcinomas suggested a correlation between p62 and Nrf2 accumulations, we also examined NRF2 expression in the same cohort. The expression of NRF2 and p62 was examined by immunohistochemical methods in 109 NSCLC cases, which included patients with adenocarcinoma (n = 72), squamous cell carcinoma (n = 31), and large cell carcinoma (n = 6). Accumulation of NRF2 and p62 was detected in 34% and 37% of NSCLC patients, respectively. The accumulations of p62 and NRF2 did not correlate with each other, but both were associated with worse lung cancer‐specific survival (P = 0.0003 for NRF2; P = 0.0130 for p62). NRF2 status had an impact on NSCLC prognosis irrespective of histology types, but p62 status did so particularly in adenocarcinoma (P = 0.037). Multivariate analysis indicated that positive immunoreactivities of NRF2 and p62 were both independent factors predicting worse lung cancer‐specific survival (P < 0.0001 for NRF2 and P = 0.04 for p62). This study revealed that both NRF2 and p62 are independent prognostic factors for NSCLC. The prognostic impact of p62 status was pronounced in adenocarcinoma patients, suggesting that molecular mechanisms underlying cancer evolution differ between adenocarcinoma and squamous cell carcinoma. (Cancer Sci 2012; 103: 760–766)
Purely localized, oligometastatic, and widely metastatic tumors are likely to require different therapeutic strategies. Although surgical procedures for isolated pulmonary, brain, or adrenal ...metastases from lung cancer have been extensively evaluated, most data are from retrospective studies; accordingly, we conducted a prospective multicenter trial.
Patients were eligible if they had previously untreated clinical T1-2N0-1 lung cancer with single-organ metastasis, or single-organ metachronous metastasis after complete resection of pathologic T1-2N0-1 lung cancer. Metastatic lesions were classified into three groups: group A included metastasis in single organs other than brain or lung; group B included synchronous brain metastasis; and group C included pulmonary metastasis. The treatment intervention was surgical resection of metachronous metastasis or of both synchronous metastasis and primary lung cancer.
From December 2002 through June 2011, 36 patients were enrolled. Two patients were ineligible, and the remaining 34 were analyzed; 6 (18%) had a benign lesion and no metastasis, 5 patients (15%) underwent incomplete resection of primary lung cancer, and 20 patients (59%) underwent complete resection of both primary lung cancer and metastasis. The 5-year survival rate for these 20 cases was 44.7%.
Clinical T1-2N0-1 lung cancer with a single-organ metastatic lesion was a good candidate for surgical resection. A 5-year survival rate of about 40% can be expected, which could be comparable with that for stage II non-small cell lung cancer.
In patients with completely resected non-small cell lung cancer, recurrence-free survival, postrecurrence survival, and metachronous primary lung cancer have not been well studied at the same time.
A ...total of 315 patients with non-small cell lung cancer who underwent complete resection between 2001 and 2005 were examined. Patients were routinely assessed with computed tomography of the chest and physical checkups every 4 months for the first 2 years and every 6 months from the third to the fifth year. After that, they were examined annually.
The overall 5-year survival was 70%. Of all 315 patients, 107 had recurrent disease. The median recurrence-free survival was 15.7 months. Multivariate analysis showed that pathologic stage and pleural invasion were associated with decreased recurrence-free survival. The median postrecurrence survival was 18.7 months. Multivariate analysis indicated that male sex, pleural invasion, extrathoracic recurrence, and supportive care for recurrence were associated with decreased postrecurrence survival. The cumulative rate of metachronous primary lung cancer at 5 years was 3.7%, and it developed even 8 years after the initial operation.
Only pleural invasion of the original lung cancer was related to both recurrence-free survival and postrecurrence survival. Moreover, postrecurrence survival was related to both site and treatment of the initial recurrence. The incidence of metachronous primary lung cancer was stable over time after the initial operation.
Objectives The purpose of the present study was to retrospectively compare the outcomes of video-assisted thoracic surgery in awake and anesthetized patients in the treatment of secondary spontaneous ...pneumothorax. Methods A total of 57 consecutive patients who underwent video-assisted thoracic surgery for secondary spontaneous pneumothorax was retrospectively analyzed. Of these patients, 15 underwent surgery under epidural and/or local anesthesia (ELA) and 42 under general anesthesia. Using propensity score matching, we identified comparable patient groups: the ELA group and general anesthesia group (n = 8 each). We compared the duration of operating room stay, operating time, postoperative hematologic data on postoperative day 1, postoperative complications, duration of hospital stay, and the incidence of hospital death between the ELA and general anesthesia groups. Results After propensity score matching, the duration of operating room stay was significantly shorter in the ELA group ( P = .006). The incidence of postoperative respiratory complications, including pneumonia and acute respiratory distress syndrome, was lower in the ELA group ( P = .02). The duration of postoperative hospital stay and the incidence of hospital death were not different between the 2 groups. Conclusions The ELA group had a lower incidence of postoperative respiratory complications. Awake video-assisted thoracic surgery can be performed with an acceptable overall morbidity for patients with secondary spontaneous pneumothorax.
Aberrant DNA methylation is an important event in carcinogenesis. Of the various regions of a gene that can be methylated in cancers, the promoter is the most important for the regulation of gene ...expression. Here, we describe a microarray analysis of DNA methylation in the promoter regions of genes using a newly developed promoter-associated methylated DNA amplification DNA chip (PMAD). For each sample, methylated Hpa II-resistant DNA fragments and Msp I-cleaved (unmethylated+methylated) DNA fragments were amplified and labeled with Cy3 and Cy5 respectively, then hybridized to a microarray containing the promoters of 288 cancer-related genes. Signals from Hpa II-resistant (methylated) DNA (Cy3) were normalized to signals from Msp I-cleaved (unmethylated+methylated) DNA fragments (Cy5). Normalized signals from lung cancer cell lines were compared to signals from normal lung cells. About 10.9% of the cancer-related genes were hypermethylated in lung cancer cell lines. Notably, HIC1, IRF7, ASC, RIPK3, RASSF1A, FABP3, PRKCDBP, and PAX3 genes were hypermethylated in most lung cancer cell lines examined. The expression profiles of these genes correlated to the methylation profiles of the genes, indicating that the microarray analysis of DNA methylation in the promoter region of the genes is convenient for epigenetic study. Further analysis of primary tumors indicated that the frequency of hypermethylation was high for ASC (82%) and PAX3 (86%) in all tumor types, and high for RIPK3 in small cell carcinoma (57%). This demonstrates that our PMAD method is effective at finding epigenetic changes during cancer.
Overcoming acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR‑TKIs) is an emerging issue in lung cancer treatment. We report evidence that a GTPase-activating ...protein, p190-A RhoGAP (p190), is a potential molecular target for the treatment of lung adenocarcinoma. We documented inhibition of phosphorylation of p190 by EGFR-TKI treatment in lung adenocarcinoma cell lines. Small interfering RNA-mediated knockdown of p190 leads lung adenocarcinoma cells to growth suppression and to inhibition of invasion/migration through inducing cell cycle arrest but not apoptosis. These findings were observed not only in EGFR-TKI-sensitive cells but also in EGFR-TKI-resistant cells; even in cell lines harboring K-ras mutations. The mechanism of this inhibitory effect on growth and invasion/migration was Ras inactivation through disrupting the p190-A RhoGAP/p120RasGAP complex. In addition, a high level of p190 mRNA expression was observed in majority of surgically obtained tissue from lung adenocarcinoma patients. Overexpression of p190 mRNA associated with poor disease-free survival. The results suggest that overexpression of p190 mRNA may be involved in the carcinogenesis of lung adenocarcinoma. These findings indicate that p190 is a possible molecular target for treatment of lung adenocarcinoma.
Background: Photodynamic therapy (PDT) is considered a useful and minimally invasive modality for treating centrally located early lung
cancer. To date, there has been limited information on the ...long-term outcome of patients treated with PDT, especially those
who are medically operable.
Methods: Beginning in 1994, patients with roentgenographically occult bronchogenic squamous cell carcinoma (ROSCC) who met our criteria
underwent PDT at Tohoku University Hospital and were followed up through 2006. Our criteria were as follows: (1) ROSCC without
distant metastasis; (2) medically operable by means of lobectomy or further resection; (3) longitudinal tumor length of â¤
10 mm; and (4) superficial bronchoscopic tumor findings.
Results: A total of 48 patients with ROSCC underwent PDT. The complete response (CR) rate was 94% (45 of 48 of patients). Nine patients
(20%) had local recurrence after CR. A total of 11 deaths was observed, with 6 resulting from multiple primary lung cancer
and only 1 from the original ROSCC. The 5-year and 10-year overall survival rates for all 48 patients were 81% and 71%, respectively.
The Cox proportional hazard model showed that only metachronous multiple primary lung cancer was an independent poor prognostic
factor.
Conclusions: PDT is thought to be a first-line modality for patients who have ROSCC with a tumor length of ⤠10 mm, even if the tumor
is medically operable. Most local recurrence can be cured by active therapy such as surgery, radiotherapy, or PDT. Multiple
primary lung cancer subsequent to PDT is an important issue from the viewpoint of survival.
In solitary fibrous tumors (SFTs) of the pleura, malignant SFTs are uncommon. Although SFTs are known to cause paraneoplastic syndromes through the production of insulin-like growth factor, to the ...best of our knowledge, the production of beta-human chorionic gonadotropin (β-hCG) has been reported only in 1 case involving a patient with a benign SFT. We herein report the first case of the elevation of β-hCG serum levels associated with a malignant SFT in which the β-hCG serum level became a useful indicator of recurrence after the complete resection of the primary mediastinal lesion.
A 44-year-old man with Eisenmenger's syndrome due to ventricular septal defect (VSD) was listed for lung transplantation. The patient's condition was complicated by a giant pulmonary artery (PA) ...aneurysm. Concurrent VSD closure and total reconstruction of the recipient PA with the donor aorta were planned. When the patient underwent bilateral lung transplantation, the aortic graft obtained turned out to be too short to complete the reconstruction. A PA graft made of the recipient's pericardium was successfully interposed between the donor's PA and the donor's aortic graft.
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