A Case of Tension Subcutaneous Emphysema Treated With Minimally Invasive Open-Window Thoracostomy Using a Wound Protector/Retractor and Three-Sided Taping.

Subcutaneous emphysema is a common complication of thoracic surgery. Tension subcutaneous emphysema that causes airway obstruction is rare but life-threatening. This report presents a patient who developed tension subcutaneous emphysema after recurrent secondary pneumothorax surgery which was treated with minimally invasive open-window thoracostomy. A wound protector/retractor and three-sided taping were successfully used to prevent air from entering the subcutaneous space via the wound while draining trapped air without creating an open pneumothorax. This approach is an option for managing subcutaneous and intrathoracic air leakage in emergency situations.

Prognostic Impact of Central Nervous System Recurrence After Surgery in Patients With Epidermal Growth Factor Receptor Mutation-positive Non-small-cell Lung Cancer.

BACKGROUND/AIM: Adjuvant therapy using third-generation tyrosine kinase inhibitors (TKI) demonstrated improved central nervous system (CNS) disease-free survival after surgery in patients with epidermal growth factor receptor (EGFR) mutation-positive lung cancer. However, the prognostic impact of CNS recurrence in surgical patients remains unknown. We evaluated the effect of CNS recurrence on post-recurrence survival (PRS) in patients with postoperatively recurrent NSCLC. PATIENTS AND METHODS: We assessed the prognostic impact of CNS recurrence using a cohort from a prospective observational study (Kyushu University Lung Surgery Group Study 2: KLSS-2). Based on data from 340 patients in whom EGFR mutations were assessed among 498 total patients in the KLSS-2 cohort, factors related to CNS recurrence and prognosis after postoperative recurrence were analyzed. RESULTS: We noted no marked differences in the presence of EGFR mutations (p=0.14) between patients with CNS recurrence and those without CNS recurrence. Among the patients tested for EGFR mutations with stage IV recurrences (n=219), survival analysis of patients with EGFR mutations showed that the CNS group had a significantly poorer PRS than the no-CNS group (MST: 36.8 vs. 43.9 months, p=0.035). In multivariate survival analysis of stage IV EGFR mutation-positive cases, recurrence in multiple organs and recurrence of brain metastases were independent poor prognostic factors (hazard ratio=2.2, p=0.029; hazard ratio=3.2, p=0.0006, respectively). CONCLUSION: Postoperative CNS recurrence was associated with a poor prognosis among patients with EGFR mutation-positive lung cancer in the period when third-generation EGFR-TKIs were not available. In EGFR mutation-positive lung cancer, prevention of CNS recurrence after surgery may improve post-recurrence prognosis.

Assessment of pleural air leakage using digital chest drainage system after surgical pulmonary resection: Comparison of visible alveolar air leakage with the digital value measured by a digital chest drainage system.

BACKGROUND: The sensitivity of postoperative pleural air leakage (PAL) after pulmonary resection is evaluated by a simple subjective grading method in clinical practice. A new electronic digital chest drainage evaluation system (DCS) recently became clinically available. This study was designed to evaluate the clinical application of the DCS in monitoring the airflow volume and managing postoperative PAL. METHODS: We prospectively enrolled 25 patients who underwent pulmonary resection. Postoperative PAL was evaluated using both conventional PAL grading based on the physician's visual judgment (analog chest drainage evaluation system [ACS]: Level 0 = no leakage to 4 = continuous leakage) and the DCS. The DCS digital measurement was recorded as the flow volume (ml/min), which was taken once daily from postoperative day 1 to the day of chest drainage tube removal. RESULTS: In total, 45 measurements were performed on 25 patients during the evaluation period. Postoperative PAL was observed in five patients (20.0%) and judged as ACS Level >1. The mean DCS values corresponding to ACS Levels 0, 1, 2, and 3 were 2.42 (0.0-11.3), 48.6 (35.4-67.9), 95.6 (79.7-111.5), and 405.3 (150.3-715.6), respectively. The Spearman correlation test showed a significant positive correlation between the ACS PAL level and DCS flow volume (R = 0.8477, p < 0.001). CONCLUSIONS: A relationship between the visual PAL level by the ACS and the digital value by the DCS was identified in this study. The numeric volume obtained by the DCS has been successful in information-sharing with all staff. The digital PAL value evaluated by the DCS is appropriate, and the use of the DCS is promising in the treatment of postoperative PAL after pulmonary resection.

A randomized phase II study to assess the effect of adjuvant immunotherapy using α-GalCer-pulsed dendritic cells in the patients with completely resected stage II-IIIA non-small cell lung cancer: study protocol for a randomized controlled trial.

BACKGROUND: As the toxicity associated with the α-GalCer-pulsed dendritic cell (DC) therapy could be considered to be negligible, its addition to postoperative adjuvant chemotherapy would be expected to greatly improve the therapeutic effect, and could result in prolonged survival. The aim of the present study is to compare the therapeutic efficacy of alpha-galactosylceramide-pulsed DC therapy in patients who have undergone a complete resection of stage II-IIIA non-small-cell lung cancer (NSCLC) followed by postoperative adjuvant therapy with cisplatin plus vinorelbine, to that in patients who did not receive additional treatment (surgical resection plus postoperative adjuvant chemotherapy only). METHODS: Subsequent to the complete resection of NSCLC, followed by the administration of cisplatin plus vinorelbine dual-agent combination adjuvant chemotherapy, patients who satisfy the inclusion criteria will be randomly allocated to either the α-GalCer-pulsed DC immune therapy group, or the standard treatment group. In total, 56 patients will be included in the study. The primary endpoint is recurrence-free survival, and the secondary endpoints are natural killer T-cell-specific immune response, the frequency of toxic effects and safety, and overall survival. DISCUSSION: In order to determine the efficacy of α-GalCer-pulsed DC therapy, the present study compares patients with stage II-III NSCLC who underwent complete surgical resection followed by postoperative adjuvant therapy with cisplatin plus vinorelbine, to those who did not receive additional treatment (surgical resection plus postoperative adjuvant chemotherapy only). TRIAL REGISTRATION: UMIN000010386 ( R000012145 ). Registered on 1 April 2013. UMIN-CTR is officially recognized as a registration site which satisfies ICMJE criteria.

The Impact of Pleural Lavage Cytology Both Before and After Lung Resection on Recurrence of Non-Small Cell Lung Cancer.

BACKGROUND: Pleural lavage cytology (PLC) involves cytologic examination during surgery for non-small cell lung cancer (NSCLC). The timing regarding the performance of PLC is potentially important; however, a consensus remains to be established. We sought to retrospectively analyze the impact of PLC both before (pre-PLC) and after (post-PLC) lung resection on recurrence in NSCLC. METHODS: From July 1994 to December 2011, 700 consecutive patients with surgically resected NSCLC were selected. Both pre-PLC and post-PLC status was tested using univariate and multivariate Cox regression analyses of recurrence-free survival (RFS). RESULTS: By analyzing RFS, post-PLC status but not pre-PLC status together with pathologic N factor and pathologic stage, was identified as an independent factor for poor prognosis (p = 0.0040). A statistically significant association was observed between positive post-PLC status and pleural invasion, pathologic T factor, pathologic N factor, pathologic stage, and postoperative recurrence (p = 0.0004, p = 0.0033, p = 0.0001, p < 0.0001, and p < 0.0001, respectively). The RFS was similarly worse for patients with positive post-PLC status regardless of pre-PLC status. Conversely, the RFS was similarly better for patients with negative post-PLC status regardless of pre-PLC status. CONCLUSIONS: Positive post-PLC status was found to be a predictive factor for postoperative recurrence in patients with surgically resected NSCLC. Moreover, post-PLC status might be an additional factor not only for identifying a patient group with a high risk of postoperative recurrence, but also to avoid unnecessary treatment of patients with low risk of postoperative recurrence.

Predictive Impact for Postoperative Recurrence of Preoperative Serum Krebs von den Lungen-6 Concentration in Pathologic Stage IA Non-Small Cell Lung Cancer.

BACKGROUND: Although stage IA non-small cell lung cancer has an optimistic survival rate, up to 10% of these patients relapse after surgical procedures and die. We retrospectively analyzed clinicopathologic features of patients with stage IA non-small cell lung cancer to identify recurrence predictors and to investigate effects of preoperative serum Krebs von den Lungen-6 (PS-KL-6) concentrations. METHODS: We selected 204 consecutive patients with stage IA non-small cell lung cancer treated from December 2003 to December 2009 for this study and tested their PS-KL-6 concentrations in univariate and multivariate Cox regression analyses of recurrence-free survival (RFS). RESULTS: High PS-KL-6 concentration (PS-KL6(High)) was significantly associated with sex (p = 0.0006), smoking status (p = 0.0438), histology (p = 0.0049), and postoperative recurrence (p = 0.0058). Both intratumoral blood vessel invasion (p = 0.0345) and PS-KL6(High) (p = 0.0021) were identified as independent predictors of shorter RFS. Relative risk of patients with PS-KL6(High) was 3.478 compared with patients with low PS-KL-6 concentration (PS-KL6(Low); 95% confidence interval: 1.576 to 8.013). Among patients with tumors larger than 2 cm (T1b), the PS-KL6(High) group had significantly shorter RFS than the PS-KL6(Low) group (p = 0.0040). CONCLUSIONS: PS-KL-6 concentration is a simple and novel predictor of recurrence in patients with stage IA non-small cell lung cancer and might help to identify patients who will need more careful follow-up among T1bN0M0 series.

Clinicopathological Features and Outcome of Lung Cancer Patients with Hematological Malignancy.

PURPOSE: The aim of this study was to report the incidence of lung cancer in patients with hematological malignancy (HM), as well as patient characteristics and outcome. METHODS: We investigated 1503 consecutive patients treated for HM and 1208 patients who underwent surgical resection for lung cancer. RESULTS: Lung cancer with HM was observed in 12 patients (0.8 % of HM cases and 1.0 % of lung cancer cases), including eight men who were smokers and four women who had never smoked. The average Brinkman index was 1010, which suggested heavy smokers. In synchronous cases, all four patients preceded to HM treatment; however, three patients died from HM. In metachronous cases, during a mean 52.7 months after treatment of lung cancer, three patients had HM. At a mean 41.4 months after HM treatment, five patients had lung cancer and underwent surgery without serious postoperative events. CONCLUSIONS: A second cancer tended to be detected within 5 years after treatment of the first cancer. Men with a history of heavy smoking might be at risk for combined lung cancer and HM. Careful follow-up is recommended within 5 years after treatment of the first cancer. Most lung cancer detected synchronously with HM had poor prognosis. In metachronous cases, surgical resection of lung cancer after treatment of HM was feasible and safe.

Initial Experience of Single-Incision Thoracoscopic Surgery for 100 Patients with Primary Spontaneous Pneumothorax.

PURPOSE: The aim of this retrospective study was to evaluate single-incision thoracoscopic surgery (SITS) for primary spontaneous pneumothorax (PSP). METHODS: Among 141 patients who underwent surgery for PSP from July 2009 to December 2013, a total of 100 patients underwent SITS. Their data were examined for clinical characteristics and surgical results. RESULTS: More patients with younger age, female sex, and who had social indications were treated by SITS than by three-port video-assisted thoracic surgery (VATS). The mean operative time for SITS was 48.8 min. There were no conversions from SITS to three-port VATS or thoracotomy. After SITS, the median duration of chest drainage was 1 day, and the median hospital stay was 2 days. Early complications included one surgical-site infection and one case of air leakage. Four patients (4.0%) had ipsilateral recurrence of PSP. CONCLUSION: SITS is feasible when performed for selected patients with PSP. Long-term follow-up and further examinations are required to evaluate patient selection, efficacy, and comparability of SITS with conventional open and three-port VATS approaches.

A case of middle mediastinal cavernous hemangioma.

A 51-year-old female was referred to our clinic for investigation of abnormal chest X-ray findings during a routine health examination. Chest computed tomography showed a middle mediastinal tumor, and she was admitted to hospital for surgical treatment. The tumor was removed using thoracoscopic surgery, without significant blood loss. Pathological examination showed that the tumor was composed of blood vessels with relatively thick vascular walls containing smooth muscle. Immunohistochemical staining was positive for CD34 and Factor VIII, and negative for D2-40. Based on these findings, the tumor was diagnosed as a cavernous hemangioma. We herein present this very rare case of middle mediastinal cavernous hemangioma.

Primary intrapulmonary thymoma.

Primary intrapulmonary thymoma (PIT), which is an intrapulmonary tumor without an associated mediastinal component, is rare. We herein report a resected case of PIT in a 55-year-old female who presented with a 2.5 × 2.4 cm mass in the left upper lobe. We also summarize the clinicopathological features and discuss the diagnosis, pathogenesis, and treatment of PIT.

Differences in the expression of epithelial-mesenchymal transition related molecules between primary tumors and pulmonary metastatic tumors in colorectal cancer.

PURPOSE: Epithelial-mesenchymal transition (EMT) is a key event in cancer metastasis. This study immunohistochemically examined the expression of EMT-related molecules in both primary colorectal cancer and pulmonary metastases, and analyzed the expression pattern. METHODS: Ten patients with colorectal cancer that underwent surgical resections for both the primary tumor and metastatic pulmonary tumors were included. The expression status of EMT-related molecules was examined using immunohistochemical staining. RESULTS: Nine of the 10 cases maintained the expression of both E-cadherin and ß-catenin in the primary site. The expression of E-cadherin and ß-catenin in the pulmonary metastatic site was preserved in 10 and 12 out of 15 metastatic lesions, respectively. The EMT-related transcription factor, Twist, was positively expressed in all 10 cases, Smad interacting protein 1 (Sip1) in 9, Snail in 4 and Slug in 3 of the primary sites. On the other hand, staining for Twist, Sip1 and Snail at the metastatic pulmonary site, was negative in all 10 cases. CONCLUSION: The expression of EMT-related transcription factors in metastatic pulmonary tumors from colorectal cancer decreased in comparison to the primary tumors. These findings suggested that the expression status of EMT-related transcription factors might play an important role in the implantation of metastatic foci.

[Investigation of preoperative respiratory evaluation in four cases of myasthenia gravis undergoing extended thymectomy in the past two years].

BACKGROUND: Myasthenia gravis (MG) is an autoimmune disease. The MG patients undergoing extended thymectomy under general anesthesia are at risk for postoperative complications, such as respiratory insufficiency and crisis (cholinergic and myasthenic). We evaluated the preoperative predictive factors, which are important for postoperative respiratory control. METHODS: Four patients undergoing extended thymectomy under general anesthesia in our hospital within the last two years (2008-2010) were studied. All patients were graded with Ossermann Classification (I, IIa, IIb, IIb), MGFA Clinical Classification (Class I, IIIb, IIIb, IIIb) and Fuchu Hospital Scoring System (2, 4, 5, 10). RESULTS: One patient was re-intubated in postoperative 5 days due to myasthenic crisis. The patient had a high values in Fuchu Hospital Scoring System (10), longer duration of myasthenia (84 months) and higher preoperative anti-acetylcholine receptor antibody value (1,200 nmol x l(-1)). CONCLUSIONS: This finding suggests that Fuchu Hospital Scoring System, duration of myasthenia and preoperative anti-acetylcholine receptor antibody are valuable for MG patients undergoing extended thymectomy as preoperative predictive factors. These factors are important for postoperative respiratory control.

Effects of excision repair cross-complementation group 1 (ERCC1) single nucleotide polymorphisms on the prognosis of non-small cell lung cancer patients.

BACKGROUND: Excision repair cross-complementation group 1 (ERCC1) is the lead enzyme in the nucleotide excision repair process. Two polymorphisms of ERCC1, T19007C (rs11615) and C8092A (rs3212986), have been reported to affect both the carcinogenesis and the survival of the patients who received platinum-based chemotherapy, but the mechanism by which these polymorphisms influence the survival is unclear. In this study, we determined the function of these ERCC1 polymorphisms in the survival of NSCLC patients. METHOD: The ERCC1 T19007C and C8092A single nucleotide polymorphisms (SNPs) were evaluated in 122 Japanese non-small cell lung cancer (NSCLC) patients who underwent a complete resection and analyzed the clinicopathological significance of these SNPs. None of the patients received peri-operative platinum-based chemotherapy. The relationship between these SNPs and ERCC1 protein expression and the platinum sensitivity of the primary tumors were also examined. RESULT: Regarding T19007C SNP, the distribution of the CC, CT, and TT genotypes was 45%, 48% and 7%, respectively. As for C8092A SNP, the distribution of CC and CA genotypes was 70% and 30%, respectively. The patients with C8092A CA genotype were significantly poorer disease-free survival (DFS) and overall survival (OS) than those with the CC genotype (p=0.037 and 0.004). In addition, no relationship was observed between T19007C SNP and DFS or OS. These two SNPs also did not correlate with either ERCC1 protein expression or platinum sensitivity. CONCLUSION: The ERCC1 C8092A polymorphism may influence the NSCLC prognosis regardless of the ERCC1 protein expression and platinum sensitivity.

Castleman's disease of the chest wall.

Primary Castleman's disease of the chest wall is unusual. Furthermore, such tumors arising from a surgical wound are extremely rare. We report a 33-year-old female with a history of a thoracic surgery at 5 years of age. A round, homogenous 4 x 3.5-cm mass protruded into the thoracic cavity on the posterior portion of the previous posterolateral incision. The tumor was completely removed, with combined rib resection. The resected specimen showed Angiofollicular Lymph Node Hyperplasia (Castleman's disease), hyaline-vascular type. No recurrence has been found for 10 years. This is the first report of primary chest wall Castleman's disease arising from the surgical wound.

Never-smoking nonsmall cell lung cancer as a separate entity: clinicopathologic features and survival.

BACKGROUND: To propose 'never-smoking nonsmall cell lung cancer (NSCLC)' as a separate entity, the clinicopathologic differences of operable NSCLC between never-smoking patients and patients with a history of smoking were investigated. METHODS: The medical records of 1405 patients with primary NSCLC who underwent a complete resection at the study institution from 1974 through 2004 were reviewed for clinicopathologic variables and postoperative survival. RESULTS: The proportion of never-smoking patients with NSCLC has been significantly increasing over 30 years, from 15.9% in the 1970s to 32.8% in the 2000s. A significantly greater proportion of female patients or adenocarcinoma patients was found in the 'never-smoking NSCLC' group in comparison to the 'smoking NSCLC' group (85.8% vs 11.2% and 87.8% vs 49.1%, respectively). The proportion of pathologic stage IA disease for the 'never-smoking NSCLC' group was significantly higher than that for the 'smoking NSCLC' group (40.1% vs 25.4%; P < .0001). With regard to both overall and cancer-specific survival, the 'never-smoking NSCLC' patient group was significantly superior to the 'smoking NSCLC' group. In addition to smoking status, the factors found to be significantly associated with the postoperative survival rate were sex, histologic type, T classification, and N classification by univariate analyses. A multivariate analysis revealed never-smoking status to be an independent prognostic factor in addition to pathologic T and N classification. CONCLUSIONS: The differences in the clinicopathologic factors and survivals between the 'never-smoking NSCLC' patient group and the 'smoking NSCLC' group suggest that NSCLC in never-smokers should be considered a separate disease entity.

Expression of mismatch repair proteins, hMLH1/hMSH2, in non-small cell lung cancer tissues and its clinical significance.

BACKGROUND: hMLH1 and hMSH2 have been implicated to be involved in the DNA mismatch repair (MMR) system. The purpose of this study is to investigate the expression of hMLH1 and hMSH2 DNA MMR proteins in non-small cell lung cancer (NSCLC) tissue and to elucidate their clinical significance. METHODS: The hMLH1 and hMSH2 protein expression was evaluated by immunohistochemistry for a consecutive series of 113 NSCLC patients. The expressions of each protein were examined for an association with the clinicopathological variables, including genetic alterations analyzed by high resolution fluorescent microsatellite analysis. RESULTS: Regarding the hMLH1 expression, the MSI-positive patients showed significantly lower scores than the MSI-negative patients. For hMSH2 expression, the patients with a 20 or higher pack-year index (PYI) showed significantly higher scores than the patients with a PYI less than 20. The expression status of proteins did not affect both the disease free and overall survival of the patients. No significant correlation was observed among the scores for the proteins. CONCLUSIONS: The expressions of hMLH1 and hMSH2 are independently regulated and play different roles in NSCLC. The genetic instability is possibly due to the reduced expression of hMLH1 protein, and hMSH2 expression is associated with smoking status.

CHFR expression is preferentially impaired in smoking-related squamous cell carcinoma of the lung, and the diminished expression significantly harms outcomes.

Loss of tumor suppressors and activation of oncogenes lead to carcinogenesis. Abnormal expression of CHFR, a novel checkpoint gene, or of Aurora kinases, key regulators of mitosis, has been detected in a variety of solid tumors. Recently, CHFR has been revealed to ensure chromosomal stability by controlling the expression level of Aurora-A in vitro. However, the frequency of aberrant expression of these proteins and the association with clinicopathologic parameters remain poorly defined in nonsmall-cell lung cancer (NSCLC). In this study, we investigated the immunohistochemical protein expression of CHFR and Aurora-A in 157 NSCLC cases and evaluated the association between clinicopathologic parameters statistically. The relationship between CHFR protein and mRNA levels and the association between this relationship and promoter methylation of the CHFR gene were also examined in 20 frozen sections of NSCLC. Overexpression of Aurora-A and reduced expression of CHFR were found in 94 cases (59.8%) and 62 cases (39%) of NSCLC, respectively, and those were significantly correlated with tumor differentiation and size. Moreover, diminished CHFR expression was significantly associated with smoking-related squamous cell carcinoma cases and poor prognosis. Multivariate analysis revealed that CHFR expression was an independent prognostic factor. A statistical correlation was evident between CHFR protein and mRNA expression. In conclusion, our results suggest the aberrant expression of Aurora-A and/or of CHFR contributed to the increase in the malignant potential of NSCLC. We also revealed that CHFR expression was predominantly impaired in smoking-related squamous cell carcinoma and might be a useful prognostic marker in NSCLC.

Serum carcinoembryonic antigen level is associated with epidermal growth factor receptor mutations in recurrent lung adenocarcinomas.

BACKGROUND: The presence of epidermal growth factor receptor (EGFR) gene mutations is a good indicator of the clinical efficacy of gefitinib in patients with nonsmall cell lung cancer. It was recently reported that the serum carcinoembryonic antigen (CEA) level could be a predictive factor for the efficacy of gefitinib treatment; therefore, it is suggested that the EGFR gene mutation is associated with the serum CEA level. The current study analyzed the association between EGFR gene mutations and clinical features, including the serum CEA level, in patients with recurrent lung adenocarcinomas. METHODS: A total of 48 lung adenocarcinoma patients with postoperative disease recurrence who underwent chemotherapy were investigated. EGFR gene mutations at exons 18, 19, and 21 were measured using surgical specimens taken from the primary tumor. RESULTS: Mutations of the EGFR gene were detected in 25 of the 48 patients and the abnormal serum CEA concentration at the time of disease recurrence was found to be significantly associated with the incidence of EGFR gene mutations (P = .045). The rate of EGFR gene mutations significantly increased as the serum CEA level increased (serum CEA level; <5 vs > or =5 <20 vs > or =20 = 35% vs 55% vs 87.5%, respectively, P = .040). A multivariate analysis revealed that a higher serum CEA level at the time of disease recurrence is independently associated with EGFR gene mutations (P = .036) with an odds ratio of 4.70 (95% confidence interval, 1.1-21.1). CONCLUSIONS: The serum CEA level appears to be closely associated with the presence of EGFR gene mutations in patients with pulmonary adenocarcinomas.

Induction of epithelial-mesenchymal transition-related genes by benzo[a]pyrene in lung cancer cells.

BACKGROUND: It is believed that epithelial-mesenchymal transition (EMT) occurs during the development and progression of cancer; however, the correlation between tobacco smoking and EMT remains to be elucidated. METHODS: Cells from the bronchioloalveolar carcinoma cell line A549 were exposed to benzo(a)pyrene (B[a]P) for 24 weeks, and morphology, proliferative activity, and gene expression profiles were analyzed. RESULTS: Although no apparent morphologic changes were observed, the B[a]P-exposed A549 cells exhibited enhanced proliferative activity in 1% bovine serum that contained medium, and dramatic changes in expression levels were observed in a large number of genes. Of those, the expression of EMT-related genes, such as migration-stimulating factor, plasminogen activator inhibitor-1, fibronectin, twist, transforming growth factor-beta2, basic fibroblast growth factor, and electron transport system, were up-regulated; whereas gene expression of E-cadherin was decreased. Most enhanced expression levels remained 8 weeks after the retrieval of B[a]P in culture. CONCLUSIONS: The current results indicated that B[a]P seems to induce EMT in lung cancer cells, and it also may drive disease progression in patients with lung cancer.

Relationship between the loss of heterozygosity and tobacco smoking in pulmonary adenocarcinoma.

A loss of heterozygosity (LOH) is a major cause of lung carcinogenesis, and it is considered to be related to tobacco smoking in central type lung cancer. We investigated the relationship between LOH in lung adenocarcinoma and tobacco smoking. In a consecutive series of 50 patients with lung adenocarcinoma who underwent a surgical resection, cancer tissue specimens and corresponding normal peripheral lung and central bronchial tissue specimens were analyzed for LOH at the regions of D3S1234 (FHIT), D3S1300 (FHIT), D9S171 (CDKN2), and D17S796 (p53) by polymerase chain reaction using four fluorescence-labeled dinucleotide markers. To examine how cells are influenced by smoking, the A549 cell line was exposed to benzo[a]pyrene (B[a]P) for 24 weeks and then was subjected to the above analysis. The LOH in cancer tissue was thus detected in four (17%) patients at D3S1234, six (14%) at D3S1300, and seven (18%) at D17S796, but no LOH was detected in any normal tissue specimens. The incidence of LOHs in cancer tissue specimens from active smokers was 21% at D3S1234, 11% at D3S1300, and 19% at D17S796, whereas that of LOHs from nonactive smokers was 0% at D3S1234, 19% at D3S1300, and 14% at D17S796. Analyzing the relationship between the pack-year index and the presence of LOH, a significant difference was found among the active smokers. Besides, in the A549 cell line exposed to B[a]P, LOH was de novo detected in one (D2S123) of the nine regions examined. The incidence of LOH could be influenced by tobacco smoking in lung adenocarcinoma, thus suggesting the presence of an important event in the carcinogenesis of this disease.