Thymoma is the most common neoplasm of the anterior mediastinum. This neoplasm is composed with neoplastic epithelial cells and non-neoplastic T lymphocytes with varying degrees. In the advanced stage of thymomas, recurrence is not uncommon, and treatment for recurrent lesions— especially disseminated lesions—is not easy. In addition, thymoma is often associated with autoimmune diseases. The representative disorder is myasthenia gravis (MG). Combined treatment for recurrence and complex autoimmune diseases is often difficult. The efficacy of thymectomy for early-onset MG without thymomas was demonstrated in a recent clinical trial, and it may be effective for MG patients associated with thymoma. However, thymectomy or thymomectomy usually does not affect other non-MG autoimmune diseases. Thymectomy has been performed via median sternotomy for many years, and thoracoscopic or mediastinoscopic thymectomy has been reported often. We established a subxiphoid approach to thoracoscopic thymectomy, and its usefulness and efficacy have been reported. In this section, the detailed procedures of thymectomy using this subxiphoid approach are introduced.
Acute exacerbation (AE) of idiopathic pulmonary fibrosis (IPF) in lung cancer patients is a critical factor in post-operative mortality. The cause of AE development is unknown and AE may occur in patients without the diagnosis of IPF. We have conducted a retrospective study of consecutive patients who underwent lung cancer surgery since January 2004. Sixty-two patients with fibrous findings in preoperative high-resolution computed tomography were enrolled in the present study and clinicopathological factors were analysed. AE was observed in 6 of 62 patients. The frequency of AE according to the type of fibrous changes classification was 1/7 in the usual interstitial pneumonia (UIP) pattern, 1/16 in the cellular non-specific interstitial pneumonia (NSIP) pattern, 4/25 in the fibrotic NSIP pattern and 0/14 in the unclassified or focal fibrous changes pattern. Preoperative Krebs von den Lungen-6 (KL-6) was higher in patients with AE than in those without AE. In patients who underwent partial resection, AE did not develop even with high KL-6 levels. In conclusion, in patients with both the UIP and the NSIP patterns, AE development is possible. In patients with a high risk of AE, such as those with high KL-6 values, limited surgery may be an option to prevent AE development.
Abstract Purpose: Recently, somatic mutations of the epidermal growth factor receptor (EGFR) gene were found in ∼25% of Japanese lung cancer patients. These EGFR mutations are reported to be correlated with clinical response to gefitinib therapy. However, DNA sequencing using the PCR methods described to date is time-consuming and requires significant quantities of DNA; thus, this existing approach is not suitable for a routine pretherapeutic screening program. Experimental Design: We have genotyped EGFR mutation status in Japanese lung cancer patients, including 102 surgically treated lung cancer cases from Nagoya City University Hospital and 16 gefitinib-treated lung cancer cases from Kinki-chuo Chest Medical Center. The presence or absence of three common EGFR mutations were analyzed by real-time quantitative PCR with mutation-specific sensor and anchor probes. Results: In exon 21, EGFR mutations (CTG → CGG; L858R) were found from 8 of 102 patients from Nagoya and 1 of 16 from Kinki. We also detected the deletion mutations in exon 19 from 7 of 102 patients from Nagoya (all were deletion type 1a) and 4 of 16 patients from Kinki (one was type 1a and three were type 1b). In exon 18, one example of G719S mutation was found from both Nagoya and Kinki. The L858R mutation was significantly correlated with gender (women versus men, P < 0.0001), Brinkman index (600 ≤ versus 600>, P = 0.001), pathologic subtypes (adenocarcinoma versus nonadenocarcinoma, P = 0.007), and differentiation status of the lung cancers (well versus moderately or poorly, P = 0.0439), whereas the deletion mutants were not. EGFR gene status, including the type of EGFR somatic mutation, was correlated with sensitivity to gefitinib therapy. For example, some of our gefitinib-responsive patients had L858R or deletion type 1a mutations. On the other hand, one of our gefitinib-resistant patients had a G719S mutation. Conclusions: Using the LightCycler PCR assay, the EGFR L858R mutation status might correlate with gender, pathologic subtypes, and gefitinib sensitivity of lung cancers. However, further genotyping studies are needed to confirm the mechanisms of EGFR mutations for the sensitivity or resistance of gefitinib therapy for the lung cancer.
Background: The presence of epidermal growth factor receptor (EGFR) mutations in gefitinib-naive lung cancer patients has been reported to be higher in females, in non-smokers, in Japanese, and in adenocarcinoma patients, especially in bronchioloalveolar carcinoma (BAC). To further investigate the prevalence of EGFR mutations in relation to pathological factors, we evaluated EGFR mutations in series of Japanese adenocarcinoma patients who had never been treated with gefitinib.
Nuclear factor (erythroid-derived 2)-like 2 (NRF2) is a transcription factor belonging to the cap 'n' collar subfamily of the basic-leucine zipper (bZIP) family of transcription factors, which plays a significant role in adaptive responses to oxidative stress. Previously, we reported that NRF2 gene (NFE2L2) mutations correlate with poor prognosis of lung squamous cell carcinomas. We therefore hypothesized that an increased NRF2 gene copy number may correlate with clinicopathological features in lung cancer patients. In this study, the increased copy number of the NRF2 gene was analyzed by real-time polymerase chain reaction (real-time‑PCR) amplifications in 90 surgically-treated non-small cell lung cancer (NSCLC) cases. In total, 16 NRF2 mutation cases were included. An increased NRF2 gene copy number was found in 7 (7.8%) lung squamous cell carcinoma patients. Increased NRF2 copy number status significantly correlated with mutation status (mutant, 31.25% vs. wild‑type, 2.7%; p=0.0017). The mean NRF2 gene copy number was significantly higher in mutant (2.478±0.668) compared to wild-type NRF2 (1.917±0.737) (p=0.0048). However, the copy number did not correlate with smoking status (p=0.3741), gender (p=0.1545), age (≥65 vs. <65, p=0.1237) and pathological stage. Although an increased NRF2 copy number correlates with mutations in squamous cell carcinoma, the percentage of the increased copy number was low; therefore, another mechanism may exist for the activation of NRF2 mutations in cancer.
