Comparison of 5-fluorouracil-related gene expression levels between adenocarcinomas and squamous cell carcinomas of the lung.

BACKGROUND: A recent meta-analysis study showed that post-operative adjuvant chemotherapy with UFT, an oral combination drug composed of tegafur [prodrug of 5-fluorouracil (5-FU)] and uracil [inhibitor of dihydropyrimidine dehydrogenase (DPD)] was associated with improved survival in patients with lung adenocarcinomas, but not in those with lung squamous cell carcinomas. METHODS: We investigated the 5-FU-related gene expression levels of thymidylate synthase (TS), DPD, thymidine phosphorylase (TP) and orotate phosphoribosyl transferase (OPRT) in resected tumor specimens from 51 patients with adenocarcinomas and 47 with squamous cell carcinomas using quantitative reverse transcription-PCR, and compared those levels between the two histological types. RESULTS: The relative gene expression values of TS, TP and OPRT were significantly lower in adenocarcinomas compared with squamous cell carcinomas, 1.60 +/- 0.86 versus 4.33 +/- 3.40 (P < 0.001), 0.84 +/- 0.52 versus 2.27 +/- 1.16 (P = 0.006) and 9.59 +/- 6.30 versus 16.94 +/- 12.04 (P < 0.001), respectively. The relative gene expression value of DPD was significantly greater in adenocarcinomas than those in squamous cell carcinomas, 2.33 +/- 1.22 versus 1.50 +/- 1.20 (P = 0.01). Lower expressions of TS and TP were observed more in adenocarcinomas (89.8%) than in squamous cell carcinomas (48.9%) (P < 0.001). CONCLUSION: These data may explain that post-operative adjuvant chemotherapy with UFT was associated with improved survival in stage I patients with adenocarcinoma, but less with squamous cell carcinoma.

Tumor-related gene expression levels in thymic carcinoma and Type B3 thymoma.

BACKGROUND: Thymic carcinoma (TC) is a rare type of malignant neoplasm that develops in the anterior mediastinum and associated with poor prognosis. Type B3 thymoma (B3) occasionally demonstrates malignant tumor characteristics, especially in the advanced stage. We investigated the expressions of tumor-related genes in resected TC and B3 specimens. METHODS: TC and B3 specimens resected from 1999 through 2012 were investigated. Tumor segments were collected from the specimens by micro-dissection to extract mRNA, then RT-PCR was performed according to Dannenberg's tumor profile method for semi-quantitation of tumor-related gene mRNA. To compare with other types of cancer, data from lung cancer (LC) cases in our database were also examined. RESULTS: The gene expression levels of thymidylate synthase were significantly higher in TC and B3 as compared to LC specimens (p < 0.02), while no difference were observed between TC and B3 tumors. The ratio of folypolyglutamyl synthase (FPGS) to gamma-glutamyl hydrolase (GGH) mRNA was significantly lower in TC than in B3 (p < 0.05), with lower FPGS/GGH in those tumors related to overall survival. Also, the gene expression of vascular endothelial growth factor (VEGF) was significantly higher in TC as compared to B3 (p = 0.04), with higher VEGF gene expression in TC and B3 specimens related to overall survival of affected patients. Epidermal growth factor receptor (EGFR) expression was significantly higher in B3 as compared to both TC and LC specimens (p < 0.01). However, there were no EGFR gene mutations detected in any of the specimens. CONCLUSIONS: These results indicate that elevated expressions of the tumor-related genes FPGS/GGH and VEGF are correlated with malignancy of TC and B3 tumors. Additional examinations will be necessary to investigate their chemosensitivity.

Tumor-related gene expression levels in pulmonary pleomorphic carcinoma.

BACKGROUND: Pulmonary pleomorphic carcinoma (PPC) is a rare type of non-small-cell lung cancer that belongs to the family of sarcomatoid carcinomas and is associated with poor prognosis. We investigated the expressions of tumor-related genes in resected PPC specimens. METHODS: Specimens resected from patients with PPC from July 2006 through April 2012 were investigated. Tumor segments were collected from the specimens by micro-dissection to extract mRNA, then RT-PCR was performed according to Dannenberg's tumor profile method for semi-quantitation of tumor-related gene mRNA. To compare with other types of lung cancer, data from stage-matched adenocarcinoma (AC) and squamous cell carcinoma (SCC) cases in our database were also examined. RESULTS: The gene expression levels of thymidylate synthase were significantly higher in PPC and SCC as compared to the AC specimens (p < 0.001). The levels of dihydropyrimidine dehydrogenase and thymidine phosphorylase mRNA in PPC showed a similar tendency to those in SCC, in contrast to AC. Furthermore, the expression level of excision repair cross-complementation group 1 mRNA in PPC specimens was similar to that reported in NSCLC, while the level of vascular endothelial growth factor (VEGF) expression was higher as compared to that reported for colorectal cancer. CONCLUSIONS: Although gene expression of tumor cannot be directly correlated to its sensitivity for anti-cancer drugs, it is likely that PPC tumors are not sensitive to anti-metabolic drugs. Anti-VEGF therapy may be a candidate for PPC, while cisplatin also remains a viable option.

¹8F-fluorodeoxyglucose positron emission tomography for evaluation of thymic epithelial tumors: utility for World Health Organization classification and predicting recurrence-free survival.

OBJECTIVES: (18)F-fluorodeoxyglucose positron emission tomography (FDG-PET) plays an important role in many oncological settings. In this study, we assessed the utility of (18)F-FDG-PET for predicting the histological classification, stage and survival of thymic epithelial tumors. METHODS: We retrospectively analyzed 37 patients with thymic epithelial tumors who underwent PET before surgical resection and investigated the relationship between the maximum of standardized uptake value (SUVmax) of each tumor and the WHO classification, recurrence-free survival, and tumor-related gene expressions. RESULTS: The study included 15 males and 22 females, ranging in age from 22 to 81 years (mean 64 years). The tumor histology of 31 tumors was thymoma and that of the remaining tumors was thymic carcinoma. The Masaoka tumor stage was as follows: stage I in 18, II in 9, III in 5 and IV in 5 patients. The patients were divided into three groups according to a simplified histologic classification: low-risk thymoma (types A, AB and B1, n = 21), high-risk thymoma (types B2 and B3, n = 10) and thymic carcinoma (n = 6). The SUVmax of low-risk group (SUVmax ≤4.27) was significantly lower than that of high-risk group (p = 0.0114) and that of thymic carcinomas (SUVmax >4.27) was also significantly higher than that of thymomas (p < 0.0001). The group of high SUVmax (SUVmax >4.27) had significantly inferior recurrence-free survival to that of less value (SUVmax ≤4.27) (p = 0.0009). The SUVmax were not correlated with tumor-related gene expressions. CONCLUSION: The SUVmax of (18)F-FDG-PET reflects WHO classification of thymic epithelial tumors. High SUVmax predicts lower recurrence-free survival of the tumors.

Benefits of rib head resection via costotransverse ligament release method for T3 lung cancer in the paravertebral space.

OBJECTIVE: Lung cancer located in the paravertebral region occasionally invades the rib head (T3) and not the spine (T4). In such cases, a costotransverse ligament release (CTLR) method may be useful for complete resection without performing a vertebrectomy. METHODS: Eighteen patients with lung cancer underwent chest wall resection between 2001 and 2009 at our institutions. Of those, 7 who underwent chest wall removal with rib head resection via a CTLR method (group A) and 11 without rib head resection(conventional distal rib resection, group B) were retrospectively analyzed. RESULTS: Three patients in group A underwent induction chemoradiotherapy. All rib head resections were performed via a CTLR approach without postoperative complications. There were no deaths within 30 day in group A and 1 in group B. The mean number of resected rib heads was 2.1 in group A, while 2.0 ribs were removed in group B. There was no significant difference for operation time between groups A and B(332±112 vs. 287±114 mins, p = 0.449). Local recurrence was seen in 0 patients in group A and 3 in group B(p = 0.13). The median survival time was 1489 and 727 day, respectively, while 5-year survival rates were 0.48 and 0.41, respectively. CONCLUSION: A rib head resection via a CTLR method is an effective procedure for T3 lung cancer infiltrating the rib head.

Incidence of acute exacerbation of interstitial pneumonia in operated lung cancer: institutional report and review.

PURPOSE: Several small studies have reported that acute exacerbation (AE) of idiopathic interstitial pneumonia (IIP) can occur after lung resection for patients with non-small cell lung cancer, though the incidence rate is unclear. METHODS: We examined our institutional data and performed a search of the MEDLINE database for publications regarding AE of IIP following surgery for lung cancer. Studies reporting the incidence rates of IIP and AE were included. RESULTS: Eleven studies including our institutional data were determined to be eligible. Seven studies designated the incidence of IIP. Of 4749 patients (from 7 studies) who underwent lung resection for NSCLC, 277 had IIP, for an incidence rate of 5.8% (range 1.1%-11.7%). Eleven studies designated the incidence of AE from IIP patient, 67 (15.8%) of 424 IIP patients (from 11 studies) developed AE after surgery, of whom 38 (56.7%) died during the postoperative course. CONCLUSION: Coexistent IIP in patients with lung cancer increases the risk of lung cancer surgery. Furthermore, AE of IIP may be a major cause of operation-related death.

Efficacy of functional operability algorithm for octogenarians with primary lung cancer.

PURPOSE: The number of lung cancer patients is increasing in association with the aging of society, and age is associated with the risk of undergoing a thoracotomy procedure. We prospectively investigated the efficacy of a functional operability algorithm that included pulmonary function and exercise test results for determining the indication for surgery in octogenarians. METHODS: From April 2001 to October 2008, surgical indications for a total of 45 octogenarians were assessed using our algorithm, including forced expiratory volume in 1 s/forced vital capacity ratio, predicted postoperative percent of forced expiratory volume in 1 s, Hugh-Jones dyspneic index, and empirical anaerobic threshold obtained during an exercise test. Then the surgical results were reviewed. RESULTS: Thoracotomy was contraindicated in one patient; the remaining 44 patients underwent surgery. Axilloanterior thoracotomy (75%), lobectomy (84%), and mediastinal lymph node dissection (73%) were the major procedures. Altogether, 37 postthoracotomy complica-Received: 13 February 2011 / Accepted: 30 May 2011 © The Japanese Association for Thoracic Surgery 2012 tions occurred in 29 (65.9%) patients. The 30-day and hospital mortality rates were 2.3% and 4.5%, respectively, and overall and disease-specific 5-year survival rates for the 42 patients were 54.5% and 79.6%, respectively. CONCLUSION: Following careful selection with our functional operability algorithm, octogenarians were able to tolerate a standard lung resection for primary lung cancer with acceptable morbidity and mortality. Their survival was consistent with that of younger cancer patients.

Cytologically malignant margin without continuous pulmonary tumor lesion: cases of wedge resection, segmentectomy and lobectomy.

The surgical margin is usually investigated during the operation using a pathological method, though cytological methods are also used to identify remaining malignant cells. We reviewed cases of pulmonary resection for a malignant tumor. At our institution, an on-site surgical margin examination using a cytological method is mandated for cases of wedge resection and segmentectomy, and an option in lobectomy cases. We examined 21 wedge resection (3 primary lung cancer, 18 metastasis), 17 segmentectomy (13 primary lung cancer, 4 metastasis), and 4 lobectomy (all primarily lung cancer) cases. Six cases showed malignant cells in the surgical margin, of which one had a microscopic skip lesion pattern and five an 'occult' pattern (positive cytology, negative pathology). Cytological malignancy occurred even in cases of wedge resection of a tiny (4 mm in diameter) lesion metastasized from colon cancer, as well as segmentectomy with a sufficient gross margin containing microscopic skip lesions and right middle lobectomy with an additional right upper lobectomy due to two previous cytological malignancies in a residual lobe. Surgical margin cytology revealed remaining malignancy in the residual lobe, which provided important information for deciding additional procedures during surgery.