Phase III study of adjuvant gemcitabine compared with adjuvant uracil-tegafur in patients with completely resected pathological stage IB-IIIA non-small cell lung cancer (WJTOG0101).

BACKGROUND: Adjuvant oral uracil-tegafur (UFT) has led to significantly longer postoperative survival among patients with non-small-cell lung cancer (NSCLC). Gemcitabine (GEM) monotherapy is also reportedly effective for NSCLC and has minor adverse events (AEs). This study compared the efficacy of GEM- versus UFT-based adjuvant regimens in patients with completely resected pathological stage (p-stage) IB-IIIA NSCLC. PATIENTS AND METHODS: Patients with completely resected p-stage IB-IIIA NSCLC were randomly assigned to GEM or UFT. The primary endpoint was overall survival (OS); secondary endpoints were disease-free survival (DFS), and AEs. RESULTS: We assigned 305 patients to the GEM group and 303 to the UFT group. Baseline factors were balanced between the arms. Of the 608 patients, 293 (48.1%) had p-stage IB disease, 195 (32.0%) had p-stage II disease and 121 (19.9%) had p-stage IIIA disease. AEs were generally mild in both groups, and only one death occurred, in the GEM group. After a median follow-up of 6.8 years, the two groups did not significantly differ in survival: 5 year OS rates were GEM: 70.0%, UFT: 68.8% (hazard ratio 0.948; 95% confidence interval 0.73-1.23; P = 0.69). CONCLUSION: Although GEM-based adjuvant therapy for patients with completely resected stage IB-IIIA NSCLC was associated with acceptable toxicity, it did not provide longer OS than did UFT.

Improved procedures and comparative results for video-assisted thoracoscopic extended thymectomy for myasthenia gravis.

INTRODUCTION: We previously introduced video-assisted thoracoscopic ET (VATS-ET) as a therapeutic option for MG with acceptable results. We have conducted further investigations to improve the procedure without deterioration of operative results, including myasthenia gravis (MG) remission rate and palliation rate. Here, we report the details of our current procedure, as well as surgical results and patient outcomes as compared with the original VATS-ET procedure. MATERIAL AND METHODS: From January 2002 to September 2013, we performed a VATS-ET procedure with an anterior chest wall lifting method for 77 patients who had MG with or without a thymoma. During that period, we investigated the appropriate indications and improved the procedure. RESULTS: Our current indication for this procedure is MG with the anti-acetylcholine receptor antibody or sero-negative type, or MG with a thymoma <5 cm in diameter without invasion to adjacent organs. With our procedure, the thymus and surrounding tissue are sufficiently resected using a bilateral thoracoscopic surgical method without neck incision. Remission and palliation rates were found to be equivalent to those obtained with the original VATS-ET procedure. CONCLUSION: VATS-ET is suitable for select patients with MG with or without a thymoma. In addition, our current method has shown to be effective while also offering cosmetic advantages as compared with the original, neck incision needed, VATS-ET method.

Clinical implications of the margin cytology findings and margin/tumor size ratio in patients who underwent pulmonary excision for peripheral non-small cell lung cancer.

PURPOSE: A pulmonary wedge resection is useful for the treatment of peripheral non-small cell lung cancer (NSCLC). The margin/tumor size ratio (M/T) is a predictor of positive margin cytology findings in these procedures, although the long-term clinical implications remain unclear. This relationship was investigated in this study. METHODS: Thirty-seven cases with a high surgical risk without additional pulmonary resection were selected from those accrued in a multicenter prospective study of optimal margin distance for pulmonary excision of peripheral NSCLC and followed for more than 5 years (range 5.3-14 years). RESULTS: Both the M/T and margin cytology findings were indicators of cancer recurrence and survival. All seven cases of surgical margin recurrence had a cytology-positive surgical margin. The 5-year survival rate was 54.2% (n = 24) for M/T < 1 and 84.6% for M/T ≥ 1 (n = 13, P = 0.05), while it was 38.5% for positive margin (n = 13) and 79.2% for negative margin (n = 24) cases (P = 0.001). In addition, the margin cytology findings were an independent prognostic factor. CONCLUSION: A pulmonary wedge resection for peripheral NSCLC should result in a negative malignant margin, which might be obtained from a sufficient tumor margin ratio of M/T ≥ 1.

A new electrocautery pleural biopsy technique using an insulated-tip diathermic knife during semirigid pleuroscopy.

BACKGROUND: The biopsy size obtained with standard flexible forceps (SFF) during semirigid pleuroscopy is often insufficient for pathological examination. An insulated-tip diathermic knife (IT knife) allows safe resection of a larger lesion during gastrointestinal endoscopy. We sought to validate an electrocautery pleural biopsy technique using the IT knife during semirigid pleuroscopy. We compared the diagnosis of specimens obtained using the IT knife and SFF in 20 subjects with unexplained pleural effusion, and reviewed pleuroscopic parameters such as complications, procedure time, and diameter of the specimens. METHODS: After injecting saline with lidocaine and epinephrine below the affected pleura, the lesion was incised in a circular shape with full thickness by manipulating the IT knife. RESULTS: Diagnostic yields from specimens obtained with the IT knife and SFF were 85% (17 of 20 cases) and 60% (12 of 20 cases), respectively. The IT knife biopsy was superior to SFF in 8 of 20 patients (malignant pleural mesothelioma in three, nonspecific inflammation in two, metastatic breast cancer in one, and tuberculosis in one). These pleural lesions revealed thickened, smooth abnormal appearances. The overall diagnostic yield for both IT knife and SFF was 100%. Median time of the procedure, from first pleural injection to specimen removal, was 21 min (range 12-92 min), and median diameter of specimen was 13 mm (range 6-23 mm). There were no severe complications during the procedure. CONCLUSIONS: Electrocautery biopsy using the IT knife during semirigid pleuroscopy has great potential for diagnosing smooth abnormal pleura which are difficult to biopsy with SFF.

Late sequelae of lobectomy for primary lung cancer: fibrobullous changes in ipsilateral residual lobes.

BACKGROUND: Late complications after lobectomy for primary lung cancer are rare. Progressive fibrobullous changes in the ipsilateral residual lobes were observed in some of the long-surviving patients after lobectomy for lung cancer. We report clinical details of this late complication. METHODS: Between 1975 and 1997, we selected 39 patients (35 males and 4 females) from a total of 1321 patients who underwent lobectomy for primary lung cancer. RESULTS: The incidence rate of this complication was 3%; this increased to 5.6% in patients who had survived for 5 years or more. A chest roentgenogram revealed fibrobullous changes on an average of 2.5 years (range 3 months-6 years) after lobectomy; these changes progressed throughout the ipsilateral lobes over several years. Ten patients (26%) required continuous oxygen therapy. The fibrobullous lungs of 21 (54%) patients were infected with nontuberculous mycobacterium, aspergillus, methicillin-resistant Staphylococcus aureus, and unidentified bacteria in 5, 4, 1, and 11 patients, respectively. Twenty-four patients died of the following causes: cancer (8, 33%), respiratory failure and chronic infections related to this complication (10, 42%), and other diseases (6, 25%). Three patients underwent successful surgical intervention for treating chronic infection of the destroyed lungs (omentopexy 1, completion pneumonectomy 2). CONCLUSIONS: Fibrobullous lung should be recognized as an important late complication that develops in lung cancer patients after lobectomy.

Minimally invasive surgical procedures for thymic disease in Asia.

Video-assisted thoracic surgery (VATS) procedures for thymic tumors and myasthenia gravis were introduced in Asia in the middle 1990s in at least two regions, Hong Kong and Japan. To overcome difficulties in obtaining a wide view of the anterior mediastinum, several methods for lifting the sternum or anterior chest wall have been presented, mainly by Japanese surgeons. More recently, single port VATS through a subxiphoid incision was also introduced in Japan. The long-term outcome of a VATS extended thymectomy for myasthenia gravis has been shown to be comparable to that of a trans-sternal extended thymectomy, while the long-term outcome of a VATS thymectomy for thymic epithelial tumors remains to be elucidated. Nevertheless, its indication for tumors in an early stage is now widely accepted, and the number of VATS procedures is steadily increasing in Japan and China. Single-port VATS through a subxiphoid incision was developed in Japan and might become accepted as a useful approach in the near future when combined with robot-assisted thoracoscopic surgery. In addition, robot-assisted thoracoscopic surgery for the thymus has also been introduced in some areas in Asia. Although few of those surgical procedures for the thymus have been performed, results obtained thus far indicate that it might be preferable to lung resection. Several novel minimally invasive thymectomy techniques have been invented and developed in Asia, and further advancements in this field by Asian surgeons are anticipated.

Surgical resection for advanced lung cancer using the hemi-clamshell approach.

OBJECTIVES: The hemi-clamshell (HCS) approach consists of partial sternotomy with antero-lateral thoracotomy. This study evaluated the utilities and outcomes of the HCS approach in advanced lung cancer patients. METHODS: We retrospectively investigated 45 patients who underwent surgery for advanced lung cancer via the HCS procedure between 2000 and 2014, the indications for surgery being tumour invasion extending to the aorta arch in 5, descending aorta in 9, main pulmonary artery in 5, superior vena cava in 6, right or left atrium in 4, apical thoracic dome in 7 patients and mediastinal lymphadenopathy for left-sided lung cancer in 12. Preoperative chemo-radiation induction therapy was given to 33 of these patients. RESULTS: We performed 34 lobectomies, including 8 sleeve lobectomies, 10 pneumonectomies and 1 wedge resection of the lung. Cardiovascular reconstruction of the aortic arch was performed in 3, descending aorta in 4, subclavian arteries in 4, superior vena cava in 5, atrial wall in 4 and pulmonary artery in 12 patients with some overlap. En bloc chest wall resection was performed in 7 patients. Lymphadenectomy in the pre-tracheal and subcarinal areas was routinely performed. Forty-two operations (93%) were complete resections. No postoperative mortalities occurred and the 5-year survival rate for all patients was 53%. CONCLUSIONS: The HCS approach is suitable for advanced lung cancer, including invasion of mediastinal structures, the apical dome and mediastinal lymph nodes. It provides a wide view of the mediastinum and apex of the chest, and safe access to the thoracic great vessels, resulting in better long-term survival rates.

Amelioration of pulmonary emphysema by in vivo gene transfection with hepatocyte growth factor in rats.

BACKGROUND: Hepatocyte growth factor (HGF) is an important mitogen and morphogen that contributes to the repair process after lung injury. The goal of the present study was to characterize its role in pulmonary emphysema, which may lead to the development of new treatment strategies with HGF. METHODS AND RESULTS: HGF mRNA and protein levels in lung tissue and plasma from elastase-induced emphysema rats transiently increased, then declined significantly to below the basal level in a time-dependent manner (P<0.01). Furthermore, changes in HGF were correlated with histologically progressive emphysematous changes and deterioration in pulmonary physiology. Use of the HVJ (hemagglutinating virus of Japan) envelope method resulted in successful transfection of cDNA encoding human HGF, as demonstrated by an efficient expression of HGF in alveolar endothelial and epithelial cells. Transfection of HGF resulted in a more extensive pulmonary vasculature and inhibition of alveolar wall cell apoptosis, and those effects led to improved exercise tolerance and gas exchange (P<0.05), which persisted for more than 1 month. CONCLUSIONS: Decreased HGF expression due to a failure in sustained endogenous production after injury was associated with emphysema-related histopathologic and physiological changes in the present rat model. In addition, induction of HGF expression by a gene-transfection method resulted in improved pulmonary function via inhibition of alveolar cell apoptosis, enhancement of alveolar regeneration, and promotion of angiogenesis.

Detection of occult tumor cells in lymph nodes from non-small cell lung cancer patients using reverse transcription-polymerase chain reaction for carcinoembryonic antigen mRNA with the evaluation of its sensitivity.

We evaluated the usefulness of a real-time quantitative reverse transcription-polymerase chain reaction (RT-PCR) method for detecting occult tumor cells in histologically malignant-negative lymph nodes resected from patients with non-small cell lung cancer. First, we examined the relationship between tumor cell number and carcinoembryonic antigen (CEA) mRNA copy number using a PCR method with a cancer cell line (A549) in a serial dilution study. Next, we evaluated the relationship between nodal metastatic area size and CEA mRNA copy number using lymph nodes with histologically proven metastasis in a serial slice study. On the basis of those results, we performed RT-PCR analyses with 28 primary tumors and 211 lymph nodes from 28 patients who underwent a lobectomy with systematic node dissection. Our results in the serial dilution study showed that the detectable limitation by quantitative RT-PCR was 25-100 neoplastic cells and 20-100 CEA mRNA copy numbers. In the serial slice study, we found a correlation between CEA mRNA copy number and nodal metastatic area. In the clinical samples, amplification of CEA mRNA was obtained with all 28 primary tumors and 13 of the lymph nodes with metastasis shown by hematoxylin-eosin staining. Furthermore, 52 (25%) of 211 histologically negative lymph nodes and the specimens from 14 (64%) of the 22 pN0 patients revealed a significant level of CEA mRNA. These results indicate that micrometastases, which are not detectable with conventional examinations, can be detected by the present method of RT-PCR for CEA mRNA in a proportion of patients with resected pN0 non-small cell lung cancer.

Comparison of surgical results after pneumonectomy and sleeve lobectomy for non-small cell lung cancer: trends over time and 20-year institutional experience.

OBJECTIVE: Sleeve lobectomy is a lung-saving procedure for central tumors for which the alternative is pneumonectomy. The purpose of this study was to report the clinical characteristics, operative results, survival, and late outcomes over 20 years in patients who underwent sleeve lobectomy and pneumonectomy at our institution. METHODS: There were 62 patients who underwent sleeve lobectomy (SL group) and 110 who underwent pneumonectomy (PN group). Comparisons of the demographics, morbidity, and survivals between the groups were performed by unpaired t-test, chi(2)-test, and log-rank test. RESULTS: Patients who underwent a pneumonectomy showed a significantly advanced pathological stage, and a larger tumor size than those who received a sleeve lobectomy, whereas there were no significant differences in histology, ratio of combined resection and induction therapy, or total morbidity. There were three in-hospital deaths (4.8%) in the SL group and four (3.6%) in the PN group. Local relapse and distant recurrence incidence were similar between the two groups. The 5-year-survival rates of the SL and PN groups were 54% and 33%, respectively (p<0.0001). However, there were no differences in 5-year survivals in patients with pathological stage I/II (SL, 59% vs PN, 63%) and those who received induction therapy (SL, 22% vs PN, 52%) between the groups. CONCLUSIONS: Both pneumonectomy and sleeve lobectomy were performed with an acceptable risk of operative mortality and satisfactory 5-year survival rate. The indication of pneumonectomy is aimed to perform a curative resection for locally advanced lung cancer, particularly after induction therapy that is otherwise unresectable, and the selected patients will likely benefit from a complete resection.

Results of pulmonary resection following neoadjuvant therapy for locally advanced (IIIA-IIIB) lung cancer.

OBJECTIVE: We performed this study to determine the role and prognostic factors of neoadjuvant therapy followed by surgery for locally advanced non-small cell cancer. METHODS: One hundred patients with clinical stage III non-small cell lung cancer (79 IIIA, 21 IIIB; 78 males, 22 females; average age 60.5 years) received neoadjuvant therapy, of whom 84 received two cycles of platinum chemotherapy combined with an average radiation dose of 41.5Gy, and 16 patients underwent chemotherapy alone. The mean follow-up duration was 80.9 months. Survival rate was estimated by the Kaplan-Meier method, and a Cox proportional hazards model was applied to determine the prognostic factors. RESULTS: The operative procedures included 74 lobectomies, 7 bi-lobectomies, and 19 pneumonectomies. Two patients died within 30 days due to adult respiratory distress syndrome and acute pulmonary embolism, respectively. The overall 5-year survival rate was 39.7% with a median survival time (MST) of 39.6 months. The 5-year survival rate for downstaged (pN1,2) patients was 53.5% while it was 16.3% for patients with residual N2. There was no difference in survival between lobectomy and pneumonectomy (MST 38 months vs 42 months). Univariate and multivariate analyses revealed that nodal status and tumor size after neoadjuvant therapy were independent prognostic factors. CONCLUSIONS: Neoadjuvant therapy was shown to deliver the optimal effect for surgery for cIIIA/IIIB NSCLC with acceptable mortality. Re-staging to exclude the residual multiple nodal metastasis can lead to the proper patient selection. A pneumonectomy, as a last option, following neoadjuvant therapy did not affect the mortality.

Overexpression of ADAM9 in non-small cell lung cancer correlates with brain metastasis.

The "a disintegrin and metalloprotease" (ADAM) family contributes to regulation of the cell-cell and cell-matrix interactions that are critical determinants of malignancy. To determine the relationship between metastasis and ADAM proteins, we compared the mRNA levels of ADAM9, -10, -12, -15, and -17 in sublines of an EBC-1 lung cancer cell line that were highly metastatic to either brain or bone. ADAM9 mRNA levels were significantly higher in highly brain-metastatic sublines than in the parent or highly bone-metastatic sublines. To elucidate the role of ADAM9 in brain metastasis, we stably transfected A549 and EBC-1 cells with a full-length ADAM9 expression vector. Compared with mock-transfectants, ADAM9 overexpression resulted in increased invasive capacity in response to nerve growth factor, increased adhesion to brain tissue, and increased expression of integrin alpha 3 and beta 1 subunits. Administration of the anti-beta 1 monoclonal antibody attenuated this increase in invasive and adhesive activity. Intravenous administration of ADAM9-overexpressing A549 cells to mice resulted in micrometastatic foci in the brain and multiple metastatic colonies in the lungs. In contrast, administration of parent and mock-transfected A549 cells to mice resulted in lung tumors without brain metastasis. These results suggest that ADAM9 overexpression enhances cell adhesion and invasion of non-small cell lung cancer cells via modulation of other adhesion molecules and changes in sensitivity to growth factors, thereby promoting metastatic capacity to the brain.

Total pleural covering technique for intractable pneumothorax in patient with Ehlers-Danlos syndrome.

We report a patient with vascular-type Ehlers-Danlos syndrome (vEDS) who developed pneumothorax and was treated with a total pleural covering technique (TPC). A 24-year-old man developed repeat pneumothorax with intermittent hemo-sputum. Based on unusual radiological manifestations of lung lesions and physical findings, EDS was suspected as an underlying cause of the pneumothorax. Surgical treatment was performed using a mediastinal fat pad and TPC, and no relapse was seen up to 2 years after surgery. TPC is a less invasive surgical approach for selected patients with vEDS. Accurate underlying diagnosis of vEDS and systemic evaluation of vascular complications are necessary before planning surgery.

Surgical resection for lung cancer with infiltration of the thoracic aorta.

OBJECTIVE: The purpose of this study was to evaluate the results of a combined resection of the thoracic aorta and primary lung cancer. METHODS: Sixteen patients underwent thoracic aorta resection along with a left pneumonectomy (n = 6), left upper lobectomy (n = 9), or partial lung resection (n = 1), of whom 10 also received preoperative induction therapy. Cardiopulmonary bypass was used in 10 patients, and a passive shunt between the ascending aorta and the descending aorta was used in 4 patients. RESULTS: Six postoperative major complications occurred in 5 patients, including postoperative bleeding (n = 3), intraoperative bleeding (n = 1), chylothorax (n = 1), and respiratory failure (n = 1). The postoperative morbidity rate was 31%, and the mortality rate was 12.5% (2/16). Furthermore, 4 patients died of systemic tumor relapse, and 1 patient died of intrapleural recurrence. Nine patients were alive after a median follow-up of 54 months (range, 12-199 months). The median survival time of patients with postoperative pathologic N0 disease was 31 months, whereas it was 10 months for those with pathologic N2 or N3 disease. Five-year survivals were 70% for patients with N0 disease and 16.7% for patients with N2 or N3 disease ( P = .0070). CONCLUSIONS: Although pulmonary resection with the involved aorta might cause high surgical morbidity and mortality rates, encouraging long-term survivals were obtained in patients without mediastinal nodal involvement.

Long-term graft patency after replacement of the brachiocephalic veins combined with resection of mediastinal tumors.

OBJECTIVE: We sought to investigate the correlation between type of vascular reconstruction and long-term graft patency after replacement of brachiocephalic veins combined with resection of mediastinal malignancies. METHODS: Eighteen patients underwent surgical resection of tumors and the superior vena cava with concomitant vascular reconstruction using ringed polytetrafluoroethylene grafts. Graft patency was verified by means of venography or contrast-enhanced computed tomography at time points ranging from 3 to 77 months (median, 33 months) postoperatively. RESULTS: Seven patients underwent sole reconstruction of the right brachiocephalic vein, with occlusion observed in only 1 patient. In 6 patients who underwent reconstruction of the bilateral brachiocephalic veins with 2 separate grafts, the grafts remained patent in 2, whereas 4 patients experienced occlusion of one of the two grafts yet remained asymptomatic. Both patients who underwent reconstruction with a Y graft experienced left brachiocephalic vein graft occlusion. In the 3 patients who underwent reconstruction of a left brachiocephalic vein, the graft became occluded, and superior vena cava syndrome developed in 2 of these patients. CONCLUSION: When replacing the superior vena cava, reconstruction of a left brachiocephalic vein alone results in a significant rate of occlusion and development of superior vena cava syndrome. Thus we advocate sole right brachiocephalic vein reconstruction or bilateral brachiocephalic vein reconstruction in this setting, and separate reconstruction of the veins is preferable to use of a Y graft.

Glucocorticoids induce G1 cell cycle arrest in human neoplastic thymic epithelial cells.

PURPOSE: Glucocorticoids exert anti-proliferative effects in various cell types and have long been known to induce apoptosis in thymocytes. Although a few reports have described the regression of human thymoma with glucocorticoid therapy, its effects on neoplastic thymic epithelial cells (TECs) have not been reported. In the present study, we investigated glucocorticoid receptor (GR) expression on neoplastic TECs and the effects of glucocorticoids in vitro on the cell cycle progression of tumor cells. PATIENTS AND METHODS: Thymoma specimens were obtained during surgery from 21 patients. Three of the specimens with glucocorticoid therapy were examined using the TdT-mediated dUTP-biotin nick-end labeling method. Primary tumor specimens from ten untreated thymomas were examined for GR expression by immunohistochemistry. Isolated neoplastic TECs from the remaining eight untreated thymomas were examined using immunohistochemistry, flow cytometric and cell cycle analysis. RESULTS: GR are expressed on neoplastic TECs as well as on non-neoplastic thymocytes in thymomas, regardless of WHO histological classification. Glucocorticoids caused an accumulation of TEC in G0/G1 phase in all cases examined (n = 6), and also induced apoptosis in the three with the lowest levels of Bcl-2 expression. CONCLUSIONS: Our results indicate that neoplastic TECs express GR and that glucocorticoids directly suppress their in vitro proliferation.

Attenuation of lung injury in allograft rejection using NF-kappaB decoy transfection-novel strategy for use in lung transplantation.

OBJECTIVE: Increased production of nitric oxide (NO) is known to be a marker of lung allograft rejection and lung injury. NO production is up-regulated directly or indirectly by nuclear factor-kappa B (NF-kappaB), a transcriptional factor of inflammatory cytokines and iNOS. We attempted to determine whether transfection of an NF-kappaB decoy into allografts could reduce NO production and ameliorate acute lung injury during allograft rejection. METHODS: Left lung transplantation was performed in pairs of Brown Norway (RT1n) and Lewis (RT1) rats. In Group NF (n=6), the allografts were flushed with 20 ml of PBS solution containing a hemagglutinating virus of Japan (HVJ) liposome-ODN complex as an NF-kappaB decoy and preserved for 60 min at 4 degrees C. A scramble decoy was used in the positive control (Group S, n=5) and simple PBS solution in the negative control (Group C, n=5). Five days after transplantation without use of immuno-suppressants, exhaled NO, gas exchange, and graft histological rejection score were determined. RESULTS: The exhaled NO level was significantly reduced in Group NF as compared with Group S (445+/-162 vs 1305+/-123 ppb, P<0.02), while improvements in PaO2 (197+/-28 vs. 60+/-18 mmHg, P<0.02) and rejection score (1.8+/-0.3 vs. 2.5+/-0.4) were also observed. There were no differences in these parameters between Groups S and C. CONCLUSIONS: Inhibition of NF-kappaB activation in the allograft by ODN decoy transfection into the donor lung ameliorated lung injury during acute allograft rejection. Our results imply a possible therapeutic target for the inflammation process in lung transplantation clinical settings.

Application of HVJ-liposome mediated gene transfer in lung transplantation-distribution and transfection efficiency in the lung.

OBJECTIVE: A novel hemagglutinating virus of Japan (HVJ)-liposome-mediated gene transfer system has been shown to have benefits of a high efficiency of transfection and low immunogenicity. The aims of this study were to determine the effect of re-transfection of the HVJ-liposome system via the airway, and to quantify the distribution of gene expression between transtracheal and transplantation approaches. METHODS: Beta-galactosidase (beta-gal) plasmid DNA was introduced into lung tissues using the HVJ-liposome method. Two groups of Sprague-Dawley (SD) rats received intratracheal instillation of 10 microg of the beta-gal gene, once on Day 0 in 1 group (Group Tb-1, n=4) and 3 times on Days 0-2 in another (Group Tb-3, n=4). In a third group of SD rats (Group Tx, n=5), an orthotopic left lung transplantation was performed after the donor lung was flushed with an HVJ-liposome complex solution and preserved for 1h. Gene expression and distribution in lung tissue was then quantified by counting the X-gal stained cells. RESULTS: Both the transtracheal and transplantation approaches resulted in low levels of transfection in the vascular endothelial cells (0.2+/-0.1 and 4.0+/-1.8%), respectively, but a moderate degree of transfection to the airway (11.0+/-7.1 and 28.0+/-20.7%) and alveolar cells (3.0+/-1.8 and 6.0+/-3.6%). Three repetitive injections via the airway increased gene expression in airway epithelial cells of 41.0+/-12.0% compared with the single administration of 11.0+/-4.3%. CONCLUSIONS: Our results suggest that the repeated transtracheal gene transfection using HVJ-liposome may have benefits for treatment of problems after lung transplantation. In addition, gene transfer using a flushing solution during harvest may provide an opportunity for gene manipulation in the setting of lung transplantation.

False positive accumulation in 18F fluorodeoxyglucose positron emission tomography scan due to sarcoid reaction following induction chemotherapy for lung cancer.

We present a case of lung cancer that showed false positive accumulation in an 18F fluorodeoxyglucose positron emission tomography (FDG-PET) scan following induction chemotherapy for suspected metastasis and progression of malignancy. A 66-year-old man was diagnosed with squamous cell carcinoma in the lung, classified as clinical stage IIIA (T2N2M0), and underwent induction chemotherapy. An FDG-PET scan prior to chemotherapy demonstrated accumulation only in the tumor, whereas following treatment it revealed a strong accumulation not only in the tumor, but also in the supraclavicular lymph nodes, which indicated lymph node metastasis. The patient underwent a biopsy of the right supraclavicular lymph node and mediastinoscopy, after which all dissected lymph nodes showed sarcoid reactions and no tumor cells were found pathologically. We concluded that when evaluating the effect of induction chemotherapy for malignancy, a sarcoid reaction might lead to the false positive accumulation of FDG.