Masaru Takenaka

Preoperative CYFRA 21-1 and CEA as prognostic factors in patients with stage I non-small cell lung cancer

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.

Clinical significance of the frequency of regulatory T cells in regional lymph node lymphocytes as a prognostic factor for non-small-cell lung cancer.

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.

Results of a surgical resection for patients with stage IV non--small-cell lung cancer.

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.

Serum Level of Osteopontin as a Prognostic Factor in Patients Who Underwent Surgical Resection for Non-Small-Cell Lung Cancer

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.

Surgical Resection for Patients With Mucinous Bronchioloalveolar Carcinoma

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.

Evaluation of undiagnosed solitary lung nodules according to the probability of malignancy in the American College of Chest Physicians (ACCP) evidence-based clinical practice guidelines

Abstract Background. This study retrospectively investigated the clinical significance of undiagnosed solitary lung nodules removed by surgical resection. Patients and methods. We retrospectively collected data on the age, smoking, cancer history, nodule size, location and spiculation of 241 patients who had nodules measuring 7 mm to 30 mm and a final diagnosis established by histopathology. We compared the final diagnosis of each patient with the probability of malignancy (POM) which was proposed by the American College of Chest Physicians (ACCP) guidelines. Results. Of the 241 patients, 203 patients were diagnosed to have a malignant lung tumor, while 38 patients were diagnosed with benign disease. There were significant differences in the patients with malignant and benign disease in terms of their age, smoking history, nodule size and spiculation. The mean value and the standard deviation of the POM in patients with malignant tumors were 51.7 + 26.1%, and that of patients with benign lesions was 34.6 + 26.7%. The area under the receiver operating characteristic (ROC) curve (AUC) was 0.67. The best cut-off value provided from the ROC curve was 22.6. When the cut-off value was set at 22.6, the sensitivity was 83%, specificity 52%, positive predictive value 90%, negative predictive value 36% and accuracy 77%, respectively. Conclusions. The clinical prediction model proposed in the ACCP guidelines showed unsatisfactory results in terms of the differential diagnosis between malignant disease and benign disease of solitary lung nodules in our study, because the specificity, negative predictive value and AUC were relatively low.

Discriminative features of thin-slice computed tomography for peripheral intrapulmonary lymph nodes.

BACKGROUND The use of computed tomography (CT) scans has increased the opportunities to detect small nodular shadows in peripheral lung fields. Intrapulmonary lymph nodes (IPLNs) are sometimes identified among these nodular shadows, and a differential diagnosis is often difficult. However, few descriptions of the CT findings of IPLNs, with regard to their potential for the differential diagnosis of lung cancer, have been published. METHODS From 2006 through 2011, 606 patients underwent thoracic surgery for pulmonary nodules. Nine patients (1.5%) had pathologically diagnosed IPLNs. We retrospectively reviewed the clinicopathological features and thin-section CT findings of the patients with IPLNs. We also compared these IPLN patients with 17 patients having small-sized lung cancer. RESULTS In six cases, the nodules were round, and linear density extending from the IPLNs was visualized in seven nodules. The nodules in IPLNs were located in the lower lobe, and the nodule borders were clearer than those of lung cancers. Six out of nine nodules were round, and linear densities were more easily visualized for the IPLNs. CONCLUSION Medical specialists need to be familiar with the discriminative features of thin-slice CT for IPLNs not only to avoid performing unnecessary operations, but also to prevent the mis-staging of lung cancer.

Esophageal Bypass Using a Gastric Tube for a Malignant Tracheoesophageal/ Bronchoesophageal Fistula: A Report of 4 Cases

Tracheoesophageal/bronchoesophageal fistulas are often caused by locally advanced esophageal cancer and lung cancer, and result in life-threatening conditions such as severe cough and dyspnea due to pneumonia. We herein report the clinical characteristics of 4 patients with tracheoesophageal/bronchoesophageal fistulas. All patients were men, and ranged in age from 40-69 years. Three patients had esophageal cancer and 1 had lung cancer. All 4 underwent esophageal bypass using a gastric tube with tube drainage of the distal side of the esophagus. Three patients died at 3, 4, and 5 months after surgery. However, these patients were allowed to enjoy food orally up until the last few days of life. One patient who underwent esophageal bypass and chemoradiotherapy has remained well for 5 years without any evidence of recurrence. This bypass procedure is therefore considered to be a feasible treatment choice for patients with tracheoesophageal/bronchoesophageal fistulas.

The impact of covering the bulla with an absorbable polyglycolic acid (PGA) sheet during pneumothorax surgery

We herein present the pathological findings of a bulla covered using an absorbable polyglycolic acid sheet applied with fibrin glue. These findings indicated that the membrane of the bulla was reinforced. Covering the bulla with an absorbable polyglycolic acid sheet (Neoveil, Gunze Ltd, Kyoto, Japan) and applying fibrin glue was effective to prevent the recurrence of the pneumothorax. Moreover, this report is the first case report showing the pathological findings of a bulla which was covered with an absorbable polyglycolic acid sheet and fibrin glue.

Possible familial case of Birt–Hogg–Dubé syndrome complicated with lung cancer: A possible link between these two disease entities

A 65-year-old Japanese woman was introduced to our hospital for an examination of multiple pulmonary cystic lesions and a pulmonary nodule in the left lower lobe. She had a smoking history of 25 pack-years, and her two younger brothers had suffered from pneumothorax; one of them additionally had lung cancer with pulmonary multiple cystic lesions. A surgical biopsy specimen obtained from her left lower lobe revealed adenocarcinoma surrounded by a single epithelial layer that was covered with collagen fibers. The pathological features were compatible with the findings of the cystic lesions in the patients with Birt-Hogg-Dubé syndrome (BHDS). A diagnosis of BHDS was eventually made according to the detection of a folliculin gene mutation. This is the first report of a possible familial case of BHDS complicated with primary lung cancer. We herein reviewed the previously reported cases of BHDS with lung cancer and other tumors and discussed a potential mechanism of tumorigenesis and carcinogenesis in the lung in the patients with BHDS.