High-Risk Factors for Recurrence of Stage I Lung Adenocarcinoma: Follow-up Data From JCOG0201.

BACKGROUND: The aim of this study was to identify patients with pathological stage I lung adenocarcinoma at high risk of recurrence. METHODS: We retrieved data from 536 patients with pathological stage I lung adenocarcinoma who underwent lobectomy and were enrolled in a prospective multiinstitutional study (the JCOG0201 study). Invasive component size, excluding lepidic component, was used as the tumor size. Recurrence-free survival (RFS) was estimated by the Kaplan-Meier method, and a multivariable Cox proportional hazards model identified independent prognostic factors associated with worse RFS. RESULTS: The all-patient 10-year RFS was 83.9% (median follow-up 10.2 years). Multivariable Cox analysis revealed that age greater than 65 years (hazard ratio [HR], 2.60; 95% confidence interval (CI), 1.66-4.07), invasive component size greater than 2 cm (HR, 2.70; 95% CI, 1.40-5.23), visceral pleural invasion (HR, 2.17; 95% CI, 1.23-3.81), and vascular invasion (HR, 2.59; 95% CI, 1.47-4.55) were potential independent prognostic factors for RFS. When patients were divided into a high-risk group for recurrence (invasive component size >2 cm or positive for visceral pleural invasion or for vascular invasion; n = 124) and a low-risk group (invasive component size ≤2 cm and negative for visceral pleural invasion and vascular invasion; n = 408), there was a significant difference in RFS between the high-risk and low-risk groups (high-risk group: HR, 3.61; 95% CI, 2.35-5.55). CONCLUSIONS: Pathological stage I lung adenocarcinoma patients with an invasive component size greater than 2 cm, visceral pleural invasion, or vascular invasion were at high risk for recurrence.

Stereotactic body radiotherapy versus lobectomy for operable clinical stage IA lung adenocarcinoma: comparison of survival outcomes in two clinical trials with propensity score analysis (JCOG1313-A).

OBJECTIVE: No randomized controlled trials comparing stereotactic body radiotherapy and lobectomy for operable early-stage non-small-cell lung cancer have been successfully conducted. This study compared survival outcomes in two multi-institutional clinical trials for stereotactic body radiotherapy (Japan Clinical Oncology Group JCOG0403) and lobectomy (Japan Clinical Oncology Group JCOG0201) with propensity score analysis. METHODS: Inclusion criteria were operable, cT1N0M0 and adenocarcinoma diagnosed prior to registration of each trial. Forty of 169 patients from JCOG0403 and 219 of 811 patients from JCOG0201 were included. The primary endpoint was overall survival adjusted with propensity score analysis. The patient selection factors included in the logistic model to estimate the propensity score were age, sex, tumor diameter and consolidation/tumor ratio. RESULTS: Among patient selection factors, age distribution was quite different with little overlap: the median was 79 (interquartile range: 74.5-83.5) in stereotactic body radiotherapy and 62 (interquartile range: 55-68) in lobectomy. In propensity score analysis, 21 patients from each group were matched and the hazard ratio for stereotactic body radiotherapy over lobectomy was 9.00 (95% confidence interval: 1.14-71.04). In the post hoc subgroup analysis with propensity score analysis of inverse probability of treatment weighting, patients were limited to be aged 75 or younger because JCOG0201 only included them when aged 75 or younger. Thirteen patients for stereotactic body radiotherapy and 219 for lobectomy were compared, and the hazard ratio for stereotactic body radiotherapy over lobectomy was 1.19 (95% confidence interval: 0.38-3.73). CONCLUSIONS: The point estimates of hazard ratio favored lobectomy over stereotactic body radiotherapy in the limited number of patients. A randomized controlled study is needed for valid comparison.

Lobectomy Versus Segmentectomy in Radiologically Pure Solid Small-Sized Non-Small Cell Lung Cancer.

BACKGROUND: The indication for limited resection of radiologically pure solid non-small cell lung cancer (NSCLC) is controversial owing to its invasive pathologic characteristics. This study was performed to compare the outcomes after lobectomy and segmentectomy in these NSCLC patients. METHODS: We retrospectively reviewed 251 patients with radiologically pure solid cT1a N0 M0 NSCLC who underwent lobectomy or segmentectomy, and the preoperative characteristics of the patients treated with the two operative techniques were matched using propensity score methods. Overall survival (OS) and disease-free survival (DFS) curves were compared using the log rank test, and differences in survival were also evaluated by the McNemar test. The preoperative factors and surgical procedure were analyzed with the multivariate Cox proportional hazards regression model to identify independent predictors of poor OS and DFS. RESULTS: In the propensity score matched lobectomy and segmentectomy groups (87 patients per group), the 5-year and 10-year OS rates were 85% versus 84% and 66% versus 63%, respectively; and the 5-year and 10-year DFS rates were 80% versus 77% and 64% versus 58%, respectively. There were no significant differences between the two groups in OS or DFS by the log rank test, and also no significant differences in 3-year, 5-year, or 7-year OS or DFS by the McNemar test. Although age, smoking status, pulmonary function, and carcinoembryonic antigen were identified as significant predictors of both OS and DFS, the surgical procedure was not identified. CONCLUSIONS: Similar oncologic outcomes after lobectomy and segmentectomy were indicated among patients with radiologically pure solid small-sized NSCLC.

Lobectomy and limited resection in small-sized peripheral non-small cell lung cancer.

BACKGROUND: Although lobectomy is the standard surgical procedure for non-small cell lung cancer (NSCLC), recent studies show favorable outcomes after limited resection in patients with small-sized peripheral tumors. We conducted a randomized controlled trial of such patients to estimate postoperative outcomes and pulmonary function following these surgical techniques. METHODS: Between 2005 and 2008, eligible patients with tumors of 2 cm or less were randomly assigned 1:1 to undergo lobectomy or limited resection; 32 and 33 NSCLC patients in each group, respectively, were analyzed. The primary end points were 5-year overall survival (OS) and disease-free survival (DFS), while the secondary end points were postoperative pulmonary function including forced vital capacity (FVC) and forced expiratory volume in 1 second (FEV1). RESULTS: The 5-year OS rates were 93.8% and 90.9% in the lobectomy and limited resection groups, respectively (P=0.921). The 5-year DFS rates were 93.8% and 90.9% in the lobectomy and limited resection groups, respectively (P=0.714). These rates did not differ significantly between the two resection groups. The median postoperative/preoperative FVC ratios were 84.1% and 90.0% in the lobectomy and limited resection groups, respectively, while the median postoperative/preoperative FEV1 ratios were 81.9% and 89.1%, respectively. Both ratios were significantly higher in the limited resection group (P=0.032 and P=0.005 for FVC and FEV1 ratios, respectively). CONCLUSIONS: A similar outcome, with more preserved postoperative pulmonary function, was observed in patients who underwent limited resection compared to those who underwent lobectomy. Ongoing large-scale multi-institutional prospective randomized trials of lobar versus sublobar resection in patients with small peripheral NSCLCs will hopefully provide definitive information about intentional limited resection of small peripheral tumors.

[Chest wall reconstruction after resection of chest wall tumors].

Between 1994 and 2012, chest wall resection and reconstruction were performed 15 patients (16 cases) with primary chest wall tumors, metastatic tumors. and chest wall recurrence of breast carcinoma. In all the patients, reconstruction of the chest wall was performed using layers of polypropylene Marlex mesh sheets. In 9 patients, only Marlex mesh sheets were used. The post-operative course was uneventful, and neither paradoxical respiration nor respiratory failure was observed. In 2 patients, reconstructions of the sternum was performed using a Marlex mesh sandwich. A full thickness chest wall defect was reconstructed using Marlex mesh and a pedicled latissimus dorsi musculocutaneous flap. Chest wall recurrence of breast cancer and primary leiomyosarcoma of the chest wall were observed in 4 and 1 patient, respectively. In conclusion, polypropylene Marlex mesh sheets arranged in a layered form appear to be a stable prosthetic material for chest wall reconstruction.

Risk factor analysis of locoregional recurrence after sublobar resection in patients with clinical stage IA non-small cell lung cancer.

OBJECTIVE: Although lobectomy is the standard surgical procedure for operable non-small cell lung cancer (NSCLC), sublobar resection also has been undertaken for various reasons. The aim of this study was to identify risk factors of locoregional recurrence and poor disease-specific survival in patients with clinical stage IA NSCLC undergoing sublobar resection. METHODS: We retrospectively reviewed 328 patients with clinical stage IA NSCLC who underwent segmentectomy or wedge resection. Demographic, clinical, and pathologic factors were analyzed using the log-rank test as univariate analyses, and all factors were entered into a Cox proportional hazards regression model for multivariate analyses to identify independent predictors of locoregional recurrence and poor disease-specific survival. RESULTS: The 5- and 10-year locoregional recurrence-free probabilities were 84.8% and 83.6%, respectively, and the 5- and 10-year disease-specific survivals were 83.6% and 73.6%, respectively. Four independent predictors of locoregional recurrence were identified: wedge resection (hazard ratio [HR], 5.787), microscopic positive surgical margin (HR, 3.888), visceral pleural invasion (HR, 2.272), and lymphatic permeation (HR, 3.824). Independent predictors of poor disease-specific survival were identified as follows: smoking status (Brinkman Index; HR, 1.001), wedge resection (HR, 3.183), microscopic positive surgical margin (HR, 3.211), visceral pleural invasion (HR, 2.553), and lymphatic permeation (HR, 3.223). All 4 predictors of locoregional recurrence also were identified as independent predictors of poor disease-specific survival. CONCLUSIONS: Segmentectomy should be the surgical procedure of first choice in patients with clinical stage IA NSCLC who are being considered for sublobar resection. Patients having tumors presenting with no suspicious of pleural involvement would be suitable candidates for sublobar resection.

Radiographically determined noninvasive adenocarcinoma of the lung: survival outcomes of Japan Clinical Oncology Group 0201.

OBJECTIVE: The study objective was to evaluate the long-term survival of patients with radiographically determined noninvasive lung adenocarcinomas. METHODS: A prospective, multi-institutional study on image diagnosis to define early (noninvasive) adenocarcinomas of the lung (Japan Clinical Oncology Group 0201) has shown that a consolidation/tumor ratio on thin-section computed tomography 0.25 or less in cT1a (≤2.0 cm) could be used as a better radiologic criterion for a noninvasive pathology than a consolidation/tumor ratio 0.50 or less in cT1a-b (≤3.0 cm). From the prognostic viewpoints, these criteria were evaluated for 545 patients with adenocarcinoma who underwent lobectomy and lymph node dissection. RESULTS: The subjects consisted of 233 men and 312 women with a median age of 62 years. The median follow-up period among overall patients was 7.1 years (range, 0-8.5 years). The overall and relapse-free 5-year survivals of the overall patients were 90.6% and 84.7%, respectively. When a consolidation/tumor ratio 0.5 or less in cT1a-b was used as a cutoff, the 5-year overall survivals of radiologic noninvasive (121 patients, 22.2%) and invasive (424 patients, 77.8%) adenocarcinomas were 96.7% and 88.9%, respectively, and the difference was statistically significant (P < .001, log-rank test). With the use of a consolidation/tumor ratio 0.25 or less in cT1a, the 5-year overall survivals of radiologic noninvasive (35 patients, 12.1%) and invasive (254 patients, 87.9%) adenocarcinomas were 97.1% and 92.4%, respectively, and the difference was not statistically significant (P = .259). CONCLUSIONS: The radiologic criteria of a consolidation/tumor ratio 0.25 or less in cT1a (≤2.0 cm) and 0.50 in cT1a-b (≤3.0 cm) were both able to define a homogeneous group of patients with an excellent prognosis before surgery.

Predictive risk factors for mediastinal lymph node metastasis in clinical stage IA non-small-cell lung cancer patients.

INTRODUCTION: Even for patients with clinical N0 non-small-cell lung cancer (NSCLC), several invasive tests are available to pathologically confirm the presumptive mediastinal stage by radiologic modalities. The aim of this study was to determine a high-risk population for mediastinal nodal metastasis in patients with clinical stage IA NSCLC, which would be suitable for mediastinal staging by invasive modalities, such as mediastinoscopy or endobronchial ultrasound-guided transbronchial needle aspiration. METHODS: We retrospectively reviewed peripheral clinical stage IA NSCLC patients who had undergone surgical resection with systematic mediastinal lymphadenectomy from 1998 to 2011. To identify predictors for mediastinal nodal metastasis, univariate and multivariate logistic regression analyses were performed. For the significant factors, optimal cutoff points were determined with a receiver operating characteristic analysis. RESULTS: Among the 894 patients eligible for this study, the overall prevalence of mediastinal nodal metastasis was 7.5%. The following four predictors for mediastinal nodal metastasis were identified: age, preoperative serum carcinoembryonic antigen level, tumor size on preoperative radiologic findings, and consolidation/tumor ratio on high-resolution computed tomography. Of the patients with all four predictors identified by the multivariate analyses and receiver operating characteristic analyses (age ≤ 67 years, carcinoembryonic antigen ≥ 3.5 ng/ml, tumor size ≥ 2.0 cm, and consolidation/tumor ratio ≥ 89%), the prevalence of mediastinal nodal metastasis was 33.8%. CONCLUSIONS: Among the clinical stage IA NSCLC patients in whom all four predictors were identified, one third of the patients showed mediastinal nodal metastasis, and thus, those patients should be a target for mediastinal node assessment by invasive modalities, such as mediastinoscopy or endobronchial ultrasound-guided transbronchial needle aspiration.

Prognostic predictors in non-small cell lung cancer patients undergoing intentional segmentectomy.

BACKGROUND: Despite recent studies reporting on the results of prospective intentional sublobar resection for patients with small non-small cell lung cancer (NSCLC), few studies have investigated predictors for prognosis or recurrence exclusively in patients undergoing intentional sublobar resection. METHODS: We retrospectively reviewed 223 patients with small (2 cm or less) peripheral NSCLC who underwent intentional segmentectomy at the Niigata Cancer Center Hospital between 1992 and 2009. The significant demographic, clinical, and pathologic factors identified with the log rank test in univariate analyses were analyzed with the Cox proportional hazards regression model to examine independent predictors for prognosis and recurrence in multivariate analysis. RESULTS: The 5-year and 10-year overall survival rates were 89.6% and 81.0%, respectively, and the 5-year and 10-year recurrence-free probabilities were 91.1% and 91.1%, respectively. Eight patients had locoregional recurrence, and 12 had distant recurrence. Multivariate analyses revealed that age more than 70 years (hazard ratio [HR] 2.389), male (HR 2.750), more than 75% consolidation/tumor ratio on high-resolution computed tomography (HR 2.750), and lymphatic permeation (HR 5.618) were independent poor prognostic factors, and lymphatic permeation (HR 16.257) was an independent predictor for recurrence. CONCLUSIONS: The factors related to upstaging on pathologic diagnosis were not identified as independent predictors; therefore, the current patient selection criterion seems reasonable. If lymphatic permeation is present on pathologic findings, careful follow-up is recommended. The predictors identified in this study will support assessment and interpretation of the results of ongoing prospective randomized trials of lobar versus sublobar resection in patients with small peripheral NSCLC.

Factors influencing long-term survival and surgical indications for pulmonary metastasectomy for metastases from colorectal cancer.

BACKGROUND: This study examined the prognostic factors and surgical indications for pulmonary metastasectomy for metastases from colorectal cancer. METHODS: We retrospectively reviewed 142 patients treated between 1985 and 2005 who had undergone complete resections of pulmonary metastases from colorectal cancer. RESULTS: Overall 5-year and 10-year survival rates were 42.4% and 32.0%, respectively. The 5-year survival rate for patients with a solitary metastasis was 55.1%, compared with 24.0% for patients with multiple metastases (P= 0.013). The 5-year survival rate for patients with a disease-free interval (DFI) ≥ 1000 days was 55.1%, compared with 31.6% for patients with a DFI < 1000 days (P= 0.008). No significant differences in survival rate according to the location of the primary lesion, maximum tumor size, preoperative serum carcinoembryonic antigen level, or surgical procedure were observed. Prior resection for liver metastases and repeated resection for recurrent pulmonary metastases did not influence the survival rate. A multivariate analysis demonstrated that the number of metastases was an independent, significant prognostic factor for survival. The survival rate of patients with three or more metastases was significantly lower than that of patients with two or fewer metastases. CONCLUSIONS: The number of metastases is an independent prognostic factor after pulmonary metastasectomy for metastases from colorectal cancer. Patients with a solitary pulmonary metastasis benefit the most from pulmonary metastasectomy. The pulmonary resection of three or more metastases is associated with a reduced survival rate. Pulmonary metastasectomy is recommended even for patients with a prior hepatic metastasectomy or patients with recurrent pulmonary metastases.

A prospective radiological study of thin-section computed tomography to predict pathological noninvasiveness in peripheral clinical IA lung cancer (Japan Clinical Oncology Group 0201).

PURPOSE: Pathological noninvasiveness needs to be precisely predicted in preoperative radiological examinations of patients with early lung cancer for the application of limited surgery. PATIENTS AND METHODS: Patients with clinical T1N0M0 peripheral lung cancer were recruited. Radiological findings of the main tumor were evaluated as to ground-glass opacity with thin-section computed tomography. The primary end point was specificity, i.e., the proportion of patients with radiologically diagnosed invasive lung cancer to patients with pathologically diagnosed invasive lung cancer. The precision-based planned sample size was 450. We expected that the lower limit of the 95% confidence interval (CI) for specificity should be satisfied in ≥97% of patients. RESULTS: We enrolled 811 patients from 31 institutions between December 2002 and May 2004. The primary end point was evaluated in 545 patients. The specificity and sensitivity for the diagnosis of pathologically diagnosed invasive cancer were 96.4% (161/167, 95% CI: 92.3-98.7%) and 30.4% (115/378, 95% CI: 25.8-35.3%), respectively, i.e., a negative result. Nevertheless, the specificity for lung adenocarcinoma ≤2.0 cm with ≤0.25 consolidation to the maximum tumor diameter was 98.7% (95% CI: 93.2-100.0%), and this criterion could be used to radiologically define early adenocarcinoma of the lung. CONCLUSIONS: Although our predetermined criterion for specificity was not statistically confirmed, radiological diagnosis of noninvasive lung cancer with a thin-section computed tomography scan corresponded well with pathological invasiveness. Radiological noninvasive peripheral lung adenocarcinoma could be defined as an adenocarcinoma ≤2.0 cm with ≤0.25 consolidation.

Operative treatment for metachronous pulmonary metastasis from esophageal carcinoma.

BACKGROUND: The clinical significance of operative treatment for metachronous pulmonary metastasis from esophageal carcinoma is unclear. METHODS: We retrospectively reviewed 23 consecutive patients who underwent operative resection for metachronous pulmonary metastasis from esophageal carcinoma from 1991 to 2008. Patient baseline characteristics, survival probability, and prognostic factors were analyzed. The median follow-up period was 31 months for surviving patients. RESULTS: There were 19 men and 4 women, with a median age of 66 years at the time of pulmonary resection. The median disease-free interval was 15.5 months. Cervical or mediastinal lymph node metastases preceded pulmonary metastases in 4 patients. Seven patients (30.4%) had multiple metastases with a maximum number of 4. The median operative time and blood loss were 94.5 minutes and 18 mL, respectively. The median length of postoperative stay was 12.5 days. The predicted 1-, 3-, and 5-year survival rates using the Kaplan-Meier method were 73.9%, 43.5%, and 43.5%, respectively, with a median survival time of 28.7 months. Univariate analysis revealed that an extrapulmonary metastasis as the initial recurrence site was an unfavorable prognostic factor (P = .0411). Multivariate analyses, however, did not identify the initial recurrence site as an independent prognostic factor (P = .0542). CONCLUSION: Operative resection for metachronous pulmonary metastasis from esophageal carcinoma is an acceptable treatment. This study of a limited number of patients may have created a constitutional selection bias. An antecedent extrapulmonary metastasis was found to be an unfavorable prognostic factor.

Diagnostic yield of preoperative computed tomography imaging and the importance of a clinical decision for lung cancer surgery.

PURPOSE: This study aimed to evaluate the diagnostic yield of preoperative computed tomography (CT) imaging and the validity of surgical intervention based on the clinical decision to perform surgery for lung cancer or suspected lung cancer. METHODS: We retrospectively evaluated 1755 patients who had undergone pulmonary resection for lung cancer or suspected lung cancer. CT scans were performed on all patients. Surgical intervention to diagnose and treat was based on a medical staff conference evaluation for the suspected lung cancer patients who were pathologically undiagnosed. We evaluated the relation between resected specimens and preoperative CT imaging in detail. RESULTS: A total of 1289 patients were diagnosed with lung cancer by preoperative pathology examination; another 466 were not pathologically diagnosed preoperatively. Among the 1289 patients preoperatively diagnosed with lung cancer, the diagnoses were confirmed postoperatively in 1282. Among the 466 patients preoperatively undiagnosed, 435 were definitively diagnosed with lung cancer, and there were 383 p-stage I disease patients. There were 38 noncancerous patients who underwent surgery with a diagnosis of confirmed or suspected lung cancer. Among the 1755 patients who underwent surgery, 1717 were pathologically confirmed with lung cancer, and the diagnostic yield of preoperative CT imaging was 97.8%. Among the 466 patients who were preoperatively undiagnosed, 435 were compatible with the predicted findings of lung cancer. CONCLUSION: Diagnostic yields of preoperative CT imaging based on clinical evaluation are sufficiently reliable. Diagnostic surgical intervention was acceptable when the clinical probability of malignancy was high and the malignancy was pathologically undiagnosed.

Ciliated muconodular papillary tumour of the lung: a newly defined low-grade malignant tumour.

We present two cases of ciliated muconodular papillary tumour (CMPT) in this report. CMPT is a newly defined low-grade malignant tumour with ciliated columnar epithelial cells, occurring in the peripheral lung. Both patients underwent pulmonary resection due to an enlarged solitary pulmonary nodule. Pathological findings in both cases confirmed a papillary tumour with a mixture of ciliated columnar and goblet cells. The tumours were rich in mucous and had spread along the alveolar walls, as observed in bronchioloalveolar carcinoma. Nuclear atypia was mild, and no mitotic activity was observed. Immunohistochemically, tumour cells stained positive for carcinoembryonic antigen, thyroid transcription factor-1 and cytokeratin 7 but not for cytokeratin 20. The immunohistochemical staining patterns were almost identical to those of pulmonary adenocarcinoma. We definitively diagnosed as CMPT. Both patients remained relapse-free.

A case of rapidly growing pulmonary carcinosarcoma.

We report herein a case of rapidly growing pulmonary carcinosarcoma, a rare and highly malignant lung neoplasm characterized by a biphasic histopathological pattern consisting of both epithelial and sarcomatous components, and we also summarize the clinical features of this entity based on previously reported cases. A 65-year-old man was referred for further examination of a lung tumor after a routine chest X-ray (CXR) showed a tumor shadow in the right upper lung zone. Chest computed tomography (CT) found a 2.0 cm pulmonary mass with suspected chest wall invasion in the right upper lobe, although cytological evidence of malignancy could not be obtained despite repeated preoperative bronchoscopy. The tumor grew rapidly, indicating the possibility of lung cancer. A right upper lobectomy with chest wall excision was performed. The postoperative definitive diagnosis was carcinosarcoma consisting of adenocarcinoma and chondrosarcoma. The pathological stage was p-T3N0M0. The patient subsequently received adjuvant chemotherapy with cisplatin and vinorelbine. Routine follow-up chest CT 7 months after the surgery showed pleural dissemination. Consequently he underwent radiotherapy, but the disseminated tumors enlarged further while he received this treatment. The patient is receiving best supportive care at present. Findings based on previously reported cases and our case suggest that early surgical intervention and combined therapeutic strategy are the most important aspects of treatment for pulmonary carcinosarcoma.

Improvements in surgical results for lung cancer from 1989 to 1999 in Japan.

BACKGROUND: In 1986, Japanese Association for Thoracic Surgery started a nationwide survey of the number of primary lung cancer undergoing resection and this survey was continued annually. Thereafter, investigations of lung cancer surgical results have been conducted three times. The postoperative overall 5-year survival rate was 47.8% in resected cases in 1989, 52.3% in 1994, and 62.0% in 1999, showing improvement over the decade (p < 0.01). OBJECTIVE: To clarify the factors influencing survival improvements retrospectively. PATIENTS AND METHODS: The subjects of the investigation are the patients who underwent resection for primary lung cancers in 1989, 1994, and 1999. Postoperatively, after 5 years, surveys of surgical results were sent to institutes where lung cancer resection had been performed. The subjects undergoing resection who provided 10 items (age, sex, pathologic T factor, pathologic N factor, pathologic M factor, date of resection, histology, curability, prognosis, and survival time) numbered 3004 in 1989, 6895 in 1994, and 12,235 in 1999. They were classified according to the Union International Contre le Cancer 1997 revised tumor, node, and metastasis classification. Differences in age, gender, histology, pathologic stage, curability, and operative death rates were analyzed for each survey year. RESULTS: According to the changes in proportions, the cases over 70 years of age, women, and pathologic stage I increased significantly (p < 0.001), whereas in cases with small cell lung cancer, incomplete resection and operative death decreased significantly over time (p < 0.001). CONCLUSION: The postoperative 5-year survival rate in Japan improved between 1989 and 1999. The main cause of this improvement was the increase in early stage lung cancer, especially cases with tumors 2 cm or less in size.

Long-term survival after removal of a malignant peripheral nerve sheath tumor originating in the anterior mediastinum.

Malignant peripheral nerve sheath tumors (MPNSTs; malignant schwannomas) rarely occur in the anterior mediastinum, and their prognosis is poor. A 75-year-old man was referred to our hospital for examination of an anterior mediastinal tumor. A computed tomography-guided percutaneous needle biopsy revealed only fibrosis. The tumor was completely excised via a median sternotomy with partial resection of the pericardium and right upper lobe of the lung. Thereafter, the tumor was diagnosed as a storiform-pleomorphic type of malignant fibrous histiocytoma. At 1 year after the surgery, a distant metastasis was found in the interlobular space between the right middle and lower lobes. The tumor was completely excised via a right posterolateral thoracotomy. Reexamination of the primary and secondary tumors revealed an MPNST. No recurrence was found up to 5 years after the second surgery without adjuvant chemotherapy or radiation therapy. However, he died from multiple lung metastases after 6 years.

Expression of 5-fluorouracil-related enzymes in lung cancer: ELISA characterizes enzyme activity and messenger RNA expression.

The enzymes thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD) and orotate phosphoribosyl transferase (OPRT) are involved in the metabolism of the anticancer drug 5-fluorouracil (FU). Expression of TS, DPD and OPRT in cancer tissue has been reported to be associated with sensitivity and/or resistance to 5-FU therapy. However, the role of TS, DPD and OPRT expression in lung cancer has not been fully established. Furthermore, among several measuring methods, it is not clear which method effectively predicts the response to 5-FU therapy. The aim of this study was to analyze the expression of 5-FU-related enzymes using enzyme-linked immunosorbent assay (ELISA) and to examine the correlation of ELISA and the results obtained using different measuring methods such as reverse transcript polymerase chain reaction (RT-PCR), immunohistochemistry, and enzymatic activity. Lung cancer specimens were obtained from 134 patients who underwent curative resection for lung cancer. As a pilot study, enzyme expression of 11 samples was measured using 4 different methods for DPD: RT-PCR, immunohistochemistry, enzymatic activity and ELISA. The relationships between pairs of results were compared, and then enzyme protein expression was measured using ELISA in 119 patients with adenocarcinoma. Of the 4 independent methods, the highest correlation was observed between protein expression measured by ELISA and enzyme activity. The correlation of gene expression and ELISA was also significant. The protein level in stage I adenocarcinoma measured using ELISA was 13.0+/-24.8 ng/mg protein for TS, 362.2+/-264.3 ng/mg protein for DPD and 4.5+/-2.0 ng/mg protein for OPRT. The predictive value of the enzymes for prognosis and the effectiveness of 5-FU was not determined as few recurrences were observed during the short follow-up period. In conclusion, ELISA is a simple and reliable method to measure key enzymes related to 5-FU therapy.