Benign notochordal cell tumor of the lung: Report of a case.

A surgical case of a benign notochordal cell tumor of the lung is reported. The patient was an asymptomatic 41-year-old man, who was incidentally found to have a small tumor in the subpleural region of the left lingular segment. Since wedge resection of the tumor, the patient has been free from recurrence. The tumor measured 12 mm in diameter and showed a central cystic change. It consisted of a diffuse proliferation of polygonal cells with abundant, uni- or multi-vacuolated cytoplasm and bland nuclei. The tumor did not show a lobular architecture and lacked a myxoid or fibrous connective tissue containing blood vessels. In the peripheral region of the tumor, a small number of alveolar epithelial cells were entrapped. The nuclei of tumor cells were immunoreactive for brachyury, and the cytoplasm was positive for cytokeratin and S-100 protein. The entrapment of alveolar epithelial cells suggests infiltrative growth of the tumor, and the almost complete absence of blood vessels within the tumor may have restricted tumor growth and induced a cystic change in the central region.

FDG Uptake in Brown Adipose Tissue Activated by a ß3-Adrenergic Receptor Agonist Prescribed for Overactive Bladder.

Brown adipose tissue (BAT), which produces energy and is known to play a role as a hibernating gland, is sometimes visualized on F-FDG PET in children or in slender young adults in a cold environment. Because BAT is activated by catecholamines, FDG uptake in BAT is also observed in patients with pheochromocytoma or paraganglioma. We present the case of an elderly woman with remarkable FDG uptake in BAT. Activation of BAT by a ß3-adrenergic receptor agonist (mirabegron) prescribed for overactive bladder was suspected as the cause of the marked visualization of BAT in this patient.

Ad-shWnt2b Vector Therapy Demonstrates Antitumor Activity in Orthotopic Intrapleural Models as Monitored with the In Vitro Imaging System (IVIS).

AIM: We investigated whether Wnt2B-inhibiting therapy has effective antitumor activity against Wnt2B-overexpressing cells in an orthotopic intrapleural model by monitoring with the in vitro imaging system (IVIS). MATERIALS AND METHODS: Mice for the orthotopic intrapleural model were randomized into 3 groups (control, Ad-shWnt2B and Ad-scramble; 8 mice per group). The respective vector was injected into the intrapleural cavity of mice in the Ad-shWnt2B and Ad-scramble groups. After 6 weeks of vector treatment, all mice were monitored with the IVIS. Additionally, their body weight was measured until all mice died from the tumor or were sacrificed. RESULTS: A549-Luc-positive cells showed cytotoxicity following exposure to the Ad-shWnt2B vector. The percentage of viable cells was significantly lower in A549-Luc cells treated with Ad-shWnt2B than with Ad-scramble (p<0.01 versus control or Ad-scramble, respectively).

Prognostic factors for patients in postoperative brain metastases from surgically resected non-small cell lung cancer.

BACKGROUND: Postoperative recurrence in non-small cell lung cancer (NSCLC) reduces the life expectancy of patients. In this retrospective study, we investigated the prognostic factors in patients with postoperative brain metastases from surgical resected non-small cell lung cancer (NSCLC). METHODS: We conducted a retrospective chart review of patients who had undergone resection for NSCLC between April 2004 and February 2009 and found 65 had experienced postoperative brain metastases by March 2010. We reviewed these patients for clinicopathological information, treatments and responses to treatment, and overall survival. RESULTS: The 5-year survival rate after the diagnosis of brain metastases was 15.4 %. Significantly favorable prognostic factors for patients after a diagnosis of brain metastases included female gender, adenocarcinoma, a small number (1-3) of brain metastases, no extracranial metastasis at the diagnosis of brain metastases, radiation treatment (whole-brain radiation and/or stereotactic irradiation), and local treatment [stereotactic irradiation and/or surgical operation (craniotomy)]. Furthermore, in patients with only brain metastases as the postoperative initial recurrence, the favorable positive prognostic factors included a small number (1-3) of brain metastases, adjuvant chemotherapy, chemotherapy (including adjuvant and other chemotherapy and excluding epidermal growth factor receptor-tyrosine kinase inhibitors), and local treatment. CONCLUSIONS: Our study found that the foregoing clinical characteristics in postoperative brain metastases and the administration of treatment contributed to patient life expectancy.

Snail expression is associated with a poor prognosis in malignant pleural mesotheliomas.

BACKGROUND: Malignant pleural mesotheliomas (MPMs) are aggressive tumors with a poor prognosis. We aimed to clarify the mechanisms of epithelial-to-mesenchymal transition (EMT) in MPMs by analyzing the expressions of EMT-associated transcription factors and E-cadherin in relation to tumor proliferation rates and patient survival. METHODS: One hundred nine patients with MPMs were investigated. Among these patients, there were 61 epithelioid tumors, 21 sarcomatoid tumors, 20 biphasic tumors, and 7 desmoplastic tumors. Immunohistochemical analyses were performed to evaluate the expressions of Snail, ZEB1, Twist, E-cadherin, and the Ki-67 proliferation index. RESULTS: The expressions of Snail and ZEB1 were significantly higher in the nonepithelioid tumors than in the epithelioid tumors (p<0.0001 and p=0.0051, respectively). Furthermore, the E-cadherin expression was significantly lower in the Snail-high tumors than in the Snail-low tumors (p=0.0423). The E-cadherin expression was significantly lower in the nonepithelioid tumors than in the epithelioid tumors (p=0.0126). The Ki-67 proliferation index was significantly higher in the nonepithelioid tumors than in the epithelioid tumors (p=0.025). Patient survival was significantly lower in patients with Snail-high MPMs than in those with Snail-low MPMs (p=0.0016), especially in patients with nonepithelioid tumors (p=0.0089). The multivariate analysis also demonstrated that nuclear Snail expression was a significant predictor of poor prognosis in patients with MPMs (p=0.0142). CONCLUSIONS: The Snail expression is associated with EMT and a poor prognosis in MPMs. Snail could be a potential molecular target for the treatment of patients with MPMs.

Higher expression of receptor tyrosine kinase Axl, and differential expression of its ligand, Gas6, predict poor survival in lung adenocarcinoma patients.

BACKGROUND: Downstream activation through receptor tyrosine kinases (RTKs) plays important roles in carcinogenesis. In this study, we assessed the clinical involvement of Axl, an RTK, and its ligand, Gas6, in surgically treated lung adenocarcinoma. METHODS: Axl and Gas6 mRNA and protein expression levels were quantified using quantitative real-time polymerase chain reaction and immunohistochemistry, respectively, in completely resected lung adenocarcinoma tissues (n = 88) and were evaluated for correlation with clinicopathologic features and patient survival. RESULTS: Higher expressions of Axl mRNA/protein and Gas6 protein were significantly related to worse clinicopathological features and prognosis (5-year overall survival rates: Axl mRNA low: 72.3 %, high: 49.7 %, P = 0.047; Axl protein low: 77.5 %, high: 38.6 %, P < 0.001; and Gas6 protein low: 70.5 %, high: 48 %, P = 0.042). On the contrary, higher Gas6 mRNA expression was related to better clinicopathological features and prognosis (5-year overall survival rates: Gas6 mRNA low: 59.2 %, high: 81.8 %, P = 0.054). Multivariate analysis suggests that high Axl mRNA expression may be an independent factor for poor patient prognosis (P = 0.04). CONCLUSIONS: In lung adenocarcinoma, Axl and Gas6 expression levels were associated with tumor advancement and patient survival, thus rendering them as reliable biomarkers and potential targets for treatment of lung adenocarcinoma.

Intratumoral Wnt2B expression affects tumor proliferation and survival in malignant pleural mesothelioma patients.

Malignant pleural mesothelioma (MPM) is an aggressive thoracic tumor with a poor prognosis. We performed a comprehensive clinical study on the intratumoral expression of Wnt1, Wnt2B and Wnt5A in MPM. One hundred and seven MPM patients were investigated. Immunohistochemistry was performed to evaluate the intratumoral expression of Wnt1, Wnt2B, Wnt5A, survivin and c-Myc, and the Ki-67 proliferation index. The apoptotic index was evaluated by the TUNEL method. Among the 107 MPMs, 23 MPMs (21.5%) were Wnt1-high tumors, 72 MPMs (67.3%) were Wnt2B-high tumors and 54 MPMs (50.5%) were Wnt5A-high tumors. There was no correlation among the levels of Wnt expression. The percentage of Wnt2B-positive tumors was significantly higher compared to that of the other Wnts (p<0.0001). Furthermore, intratumoral Wnt2B expression significantly correlated with the expression of survivin (p<0.001) and c-Myc (p<0.001). Regarding tumor biology, the Ki-67 proliferation index was significantly higher in the Wnt2B-high tumors than in the Wnt2B-low tumors (p=0.0438). In addition, the overall survival was significantly lower in patients with Wnt2B-high tumors than in those with Wnt2B-low tumors (p=0.0238). A Cox multivariate analysis also demonstrated the Wnt2B status to be a significant prognostic factor in MPM patients (p=0.0042). Intratumoral Wnt2B expression was associated with the expression of survivin and c-Myc, tumor proliferation and patient survival in MPM. Wnt2B is a potential molecular target for the treatment of Wnt2B-overexpressing MPMs.

Protective effect of pre-recovery surfactant inhalation on lungs donated after cardiac death in a canine lung transplantation model.

BACKGROUND: Warm ischemia-reperfusion injury related to donation after cardiac death is a crucial issue in transplantation. Because surfactant function deteriorates in lungs during warm ischemia, we hypothesized pre-recovery surfactant inhalation would mitigate warm ischemia-reperfusion injury. METHODS: We rendered donor dogs cardiac dead and left them at room temperature. All animals received ventilation for 60 minutes starting at 240 minutes after cardiac arrest. The animals were divided into 2 groups: NS (normal saline, n = 7) group, which received aerosolized normal saline, and SF (surfactant; n = 5), which received aerosolized surfactant. The lungs were flushed and procured, and the left lung was transplanted into recipient dogs. At 45 minutes of reperfusion, the right pulmonary artery was ligated, and the left transplanted lung function was evaluated. RESULTS: In the NS group, 2 of 7 dogs died at 75 minutes after reperfusion, whereas all 5 animals in the SF group survived for 240 minutes after reperfusion. The SF group showed significantly better dynamic compliance, oxygenation, and wet-to-dry weight ratio. Furthermore, the SF group had higher levels of high-energy phosphates in the lung tissues and lower levels of interleukin-8, tumor necrosis factor-α, and protein in the bronchoalveolar lavage fluid. Histologically, the lungs in the SF group showed fewer signs of interstitial edema and hemorrhage and significantly less neutrophilic sequestration than those of the NS group. CONCLUSIONS: Our results indicated pre-recovery surfactant inhalation improved graft function, maintained adenine nucleotide levels, and prevented alveolar-capillary barrier leakage, resulting in the attenuation of warm ischemia-reperfusion injury.

Detection of ALK fusion in lung cancer using fluorescence in situ hybridization.

OBJECTIVE: To develop an easy-to-use technique for EML4-ALK detection and establish the effective selection of candidates for screening. BACKGROUND: We previously reported clinicopathological findings of patients with lung cancer harboring the EML4-ALK fusion gene. Anaplastic lymphoma kinase inhibitors have therapeutic effects in lung cancer patients with EML4-ALK, accounting for merely 1%-5% of lung cancers. METHODS: We investigated EML4-ALK in tumors from 581 patients. EML4-ALK was detected by a reverse transcription polymerase-chain reaction and by the newly established criteria and algorithm using a fluorescence in situ hybridization method. To establish an algorithm to restrict candidates chosen for ALK fusion gene detection, clinicopathological findings as well as EGFR, ERBB2, and KRAS mutations were analyzed. RESULTS: 8 (1.3%) tumors had EML4-ALK, EGFR, KRAS, and ERBB2 mutations, which were mutually exclusive and were detected in 191 (32.8%), 56 (9.6%), and 11 (1.8%) tumors, respectively. We screened 581 patients with tumors and another 27 who were nonsmokers or mild smokers (<20 packs per year) lacking EGFR, KRAS, and ERBB2 mutations and who had adenocarcinomas exhibiting an acinar component with moderate or poor differentiation. Of the 27 patients, 8 (29.6%) had EML4-ALK. CONCLUSIONS: We propose criteria for selecting candidates for efficient detection of the fusion gene.

Higher expression of EphA2 and ephrin-A1 is related to favorable clinicopathological features in pathological stage I non-small cell lung carcinoma.

BACKGROUND: The overexpression of receptor tyrosine kinase EphA2 has been reported in various cancers. In non-small cell lung cancer (NSCLC), a positive correlation has been reported between high EphA2 immunohistochemical staining level and poor prognosis. However, its ligand, ephrin-A1, is supposed to act as a tumor suppressor via the kinase activity of EphA2. Thus, the biphasic roles of this system are not fully elucidated. We retrospectively evaluated the expression levels of EphA2 and ephrin-A1 in surgically treated pathological (p-) stage I NSCLC tumor samples, and their relation to clinicopathologic features or postoperative prognoses. METHODS: The levels of EphA2 and ephrin-A1 mRNA expression were quantified by real-time reverse-transcription polymerase chain reaction in tissue samples from p-stage I NSCLC patients who had undergone complete resection in our facility (n=195). They were divided into two (EphA2/ephrin-A1-Low and -High) groups based on the median expression level, and their respective clinicopathologic features and prognoses were analyzed. Furthermore, samples were stained immunohistochemically and classified into four groups according to their staining levels, and their prognoses analyzed. RESULTS: Marked demographic differences were found between EphA2/ephrin-A1-Low and -High groups. Both EphA2-High and ephrin-A1-High groups had more females, no smoking history, adenocarcinoma histology, well-differentiated carcinomas, p-stage IA patients, and patients with EGFR gene mutations. Five-year overall survival rates of the EphA2-Low and the EphA2-High patient groups were 68.9% and 86.1%, respectively (P=0.017), and five-year disease-free survival rates were 69.9% and 83.2%, respectively (P=0.035). There were no statistical differences between ephrin-A1-Low and ephrin-A1-High groups concerning postoperative survival. Although showing smaller differences, the findings from the immunohistochemical analyses supported the above results. CONCLUSIONS: Higher expression of EphA2 and ephrin-A1 was more related to the female sex, reduced smoking status, adenocarcinoma, well differentiated carcinomas, p-stage IA, and EGFR gene mutations. Higher EphA2 mRNA expression in p-stage I NSCLC patients was positively related to improved prognoses. These results may reflect a tumor suppressive role for the EphA2/ephrin-A1 system in a population of patients restricted to p-stage I NSCLC.

Expression of IGF1R is associated with tumor differentiation and survival in patients with lung adenocarcinoma.

PURPOSE: The insulin-like growth factor 1 receptor (IGF1R) is widely expressed in normal tissues and many malignancies in humans. We investigated the clinical significance of the expression of the IGF1R gene in human lung adenocarcinoma. METHODS: A total of 238 patients with lung adenocarcinoma were investigated. Quantitative real-time reverse-transcription polymerase chain reaction (RT-PCR) assays were performed to evaluate the gene expression of IGF1R, and immunohistochemical staining was done to evaluate the protein expression of IGF1R. RESULTS: Among the 238 patients with lung adenocarcinoma, 107 tumors (45.0%) were IGF1R-low and 131 tumors (55.0%) were IGF1R-high. The IGF1R gene expression ratio was significantly lower in moderately to poorly differentiated adenocarcinomas than in well-differentiated adenocarcinomas (P = 0.0388). Gene expression of IGF1R was significantly correlated with protein expression of IGF1R (r = 0.7163, P < 0.0001). Regarding patient survival, overall survival was significantly lower in patients with IGF1R-low tumors than in those with IGF1R-high tumors (63.2% versus 76.1% 5-year survival, P = 0.0188). Multivariate analysis using a Cox proportional-hazards model demonstrated that IGF1R gene status was a significant prognostic factor predicting overall survival of patients with lung adenocarcinoma (hazard ratio 1.800; P = 0.0321). Moreover, the disease-free survival rate was significantly lower in patients with IGF1R-low tumors than in those with IGF1R-high tumors (49.2% versus 64.6% 5-year survival, P = 0.0084). CONCLUSION: The present study suggests the level of IGF1R expression to be a useful prognostic marker for patients with dedifferentiated lung adenocarcinoma.

Impact of KRAS and EGFR gene mutations on recurrence and survival in patients with surgically resected lung adenocarcinomas.

BACKGROUND: Oncogenic gene mutations observed in lung adenocarcinomas, such as epidermal growth factor receptor (EGFR) and KRAS, have some predictive value for chemotherapeutic drugs or EGFR-tyrosine kinase inhibitors. However, the influence of these gene alterations on patients' prognosis remains controversial. METHODS: We retrospectively analyzed the tumors of 180 patients with completely resected pathological stage I-III lung adenocarcinoma which harbored either KRAS codon 12 mutation or EGFR gene mutations within exons 18-21 to investigate the impact of these gene mutations on the patients' survival. Gene mutations were detected by established methods. RESULTS: Of 180 patients, 32 had KRAS codon 12 mutations (KRAS group), 148 had EGFR mutations within exon 18-21 (EGFR group). Pathological stage and operation mode were independent factors for disease-free survival. However, the EGFR group had better overall survival than the KRAS group (P = 0.0271). Cox proportional hazard model revealed pathological stage (P = 0.0001) and presence of EGFR gene mutations (P = 0.0408) were independent factors for overall survival. In survival after tumor recurrence, the EGFR group had a better median survival time (46.7 months) after recurrence than the KRAS group (26.0 months). CONCLUSIONS: In patients with completely resected lung adenocarcinomas, KRAS and EGFR gene mutation status of tumors was not associated with disease-free survival. However, the presence of an EGFR gene mutation boded well for the patient's overall survival, and thus patients with EGFR mutations have a better prognosis than those with KRAS mutations.

Clinical significance of BRAF gene mutations in patients with non-small cell lung cancer.

BACKGROUND: V-raf murine sarcoma viral oncogene homolog B1 (BRAF) mutations are attractive molecular targets for cancer treatment. Detection of BRAF gene mutation and analyses in non-small cell lung cancer (NSCLC) are of great scientific interest. PATIENTS AND METHODS: The study included 581 NSCLC patients (377 males, 204 female) undergoing pulmonary resection. BRAF gene mutations were screened using the PCR-SSCP method and were confirmed by direct DNA sequencing. Mutations of epidermal growth factor receptor (EGFR), v-erb-b2 erythroblastic leukemia viral oncogene homolog 2 (ERBB2), and v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) gene were also analyzed. RESULTS: Five patients (0.8%) had BRAF mutations within exon 15. In 581 NSCLC patients, EGFR gene mutations within exons 18 to 21 were detected in 191 (32.8%) patients, KRAS codon 12 mutations in 56 (9.6%) patients, and ERBB2 codon 20 mutations in 11 (1.8%) patients. All mutations were mutually exclusive. The NSCLC patients with BRAF mutations were proved to be men who were heavy smokers. CONCLUSIONS: PCR-SSCP analysis of BRAF exon 15 in NSCLC patients without other gene mutations may be sufficient to identify candidates for treatment.

Effect of preprocurement ventilation on lungs donated after cardiac death in a canine lung transplantation model.

BACKGROUND: One method of countering chronic lung donor shortages is the practice of donation after cardiac death (DCD). However, this technique inevitably leads to pulmonary dysfunction related to warm ischemia. One promising method of alleviating this problem is ventilation. However, it can rarely be initiated from the onset of cardiac arrest, particularly in uncontrolled DCD donors. We investigated the protective effect of the last 60 min of ventilation during a 240-min warm ischemic time. METHODS: We rendered donor dogs cardiac dead and left them at room temperature. Six dogs received ventilation with 100% oxygen for 60 min starting at 180 min after cardiac arrest (ventilation group). Eight dogs received no ventilation. Lungs were harvested 240 min after cardiac arrest, then transplanted into recipient dogs. At 60 min after reperfusion, the right pulmonary artery was ligated, and the function of the left transplanted lung was evaluated. RESULTS: In the ventilation group, all six animals survived for 240 min after reperfusion, whereas in the nonventilation group, only four of eight survived. The ventilation group demonstrated significantly better pulmonary oxygenation, shunt fraction, and wet-to-dry weight ratio. Furthermore, the ventilation group revealed significantly higher levels of high-energy phosphates in the lung tissues, fewer apoptotic cells, lower levels of tumor necrosis factor-α and interleukin-8 messenger RNA in the lung tissues, and lower levels of interleukin-6 messenger RNA in the serum. CONCLUSION: Our results suggest that ventilation during the late phase of the preprocurement period may ameliorate ischemia-reperfusion injury in DCD donors.

A case of Good's syndrome: a rare acquired immunodeficiency associated with thymoma.

The patient was a 76-year-old man who had a prior history of recurrent pneumonia and severe, chronic sinusitis. Computed tomography showed a thymoma, and laboratory results revealed hypogammaglobulinemia. Therefore, Good's Syndrome (GS, rare adult-onset immunodeficiency with thymoma) was diagnosed. To treat his sinusitis, we started the patient on long-term clarithromycin therapy, preoperatively. A thymothymectomy was performed, but the immunological disorder was not resolved. Although standard gamma globulin replacement was not given, his sinusitis symptoms were ameliorated, and he has not had pneumonia since the operation. Long-term macrolide therapy probably plays some role in managing sino-pulmonary infections associated with GS.

Simultaneous double thymic carcinoids: a rare initial manifestation of multiple endocrine neoplasia type 1.

A 53-year-old man was referred to our hospital for treatment of two anterior mediastinal tumors. The anterior mediastinal tumors were resected by thymectomy under the probable diagnosis of double thymomas. The final pathological diagnosis was multiple thymic carcinoids. Although 20%-25% of patients with thymic carcinoid have a family history of multiple endocrine neoplasia type 1 (MEN-1), radiographic screening just after the operation did not detect any endocrine tumors. However, the patient had a urinary calculus 4 months 7 months after the operation. Endocrinological examination then revealed mild hypercalcemia, hypophosphatemia, hyperinsulinemia, and hyperprolactinemia. Radiologically, a parathyroid tumor and a pancreatic tumor were found. The patient was referred to a university hospital and a mutation of MEN-1 gene was detected. The diagnosis of MEN-1 was confirmed about 1 year after the operation.

Resected osteochondroma of the rib in an elderly patient.

Solitary osteochondroma of the rib is a rare primary chest wall tumor. Herein, we report a case of a successfully resected osteochondroma of the rib. The patient was a 73-year-old asymptomatic woman who came to our hospital regularly for treatment of hypertension and hyperlipidemia. A checkup chest roentgenogram showed a shadow at the right anterior chest wall consistent with a mass, and computed tomography showed a tumor arising from the right fourth rib. Because it was impossible to exclude completely the diagnosis of a well-differentiated chondrosarcoma, we performed resection of the right anterior chest wall and a re construction with a rigid prosthesis. The post operative course of the patient was unremarkable. The final pathological diagnosis of the rib tumor was osteochondroma.

Three cases of resected pleomorphic carcinoma.

Pleomorphic carcinoma (PC) is a rare malignancy of the lung. We present 3 cases that were resected. Case 1: The patient was a 75-year-old asymptomatic man whose chest roentgenogram showed a cavity at the right apex. A right upper lobectomy was performed, and the pathological stage was IB (pT2N0M0). After 3 courses of adjuvant chemotherapy, he is alive without relapse 56 months after the operation. Case 2: The patient was a 60-year-old man with left high back pain whose chest roentgenogram showed a mass shadow in the left upper lung field. A left upper lobectomy with partial resection of S6 was performed after induction chemotherapy. The pathological stage was IIIA (pT2N2M0). He died of infection 4 months after the operation during adjuvant chemotherapy. Case 3: A 78-year-old man with hemoptysis underwent aortic arch replacement after a diagnosis of impending rupture of an aortic aneurysm. During the operation, a tumor in the left upper lung lobe was detected. A left upper division segmentectomy was performed one month later. The pathological stage was IIB (pT3N0M0). Despite adjuvant radiotherapy, the patient died of cancer 9 months after the segmentectomy. The final pathological diagnoses for all 3 cases were PC. More cases of PC should be reported to establish optimal management.

Intraoperative migration of a nail from the left B10b to the main bronchus.

OBJECTIVES: We report a rare case in which an intrapulmonary foreign body underwent a large intraoperative migration. METHOD: A 57-year-old man with an intrapulmonary nail in the left S(10) was admitted into our hospital. Since the removal by a flexible bronchoscopy was unsuccessful, a thoracotomy was performed. RESULT: Preoperative chest roentgenograms and a bronchoscopy after an endotracheal intubation confirmed that the nail had not migrated. During the operation, however, the nail moved from the periphery of B(10)b to the main bronchus. CONCLUSION: It is mandatory to confirm the precise location of a foreign body even during an operation to avoid unnecessary pulmonary resections.