• Journal of Chest Surgery
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• v.39 no.2 s.259
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• pp.106-110
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• 2006

Background: Bronchioloalveolar carcinoma (BAC) is an uncommon primary malignancy of the lung, and it accounts for $2{\~}14\%$ of all pulmonary malignancies. According to World Health Organization (WHO) categorisation, BAC is a subtype of adenocarcinoma. The current definition of BAC includes the following: malignant neoplasms of the lung that have no evidence of extrathoracic primary adenocarcinoma, an absence of a central bronchogenic source, a peripheral parenchymal location, and neoplastic cells growing along the alveolar septa. Previous reports had demonstrated a better prognosis following surgery for patients affected by BAC than those affected by other type of non-small cell lung cancer (NSCLC). We aim to analyse Asan Medical Center experiences of BAC. Material and Method: Between 1990 and 2002, 31 patients were received operations for BAC. We analyse retrosepectively sex, age, disease location, preoperative clinical stage, postoperative pathologic stage & complications, survival according to medical record. Result: There were 12 men and 19 women, the average age was 61.09$\pm$10.63 ($31{\~}79$) years. Tumor locations were 7 in RUL, 1 in RML, 4 in RLL, 8 in LUL, 11 in LLL. Operations were 28 lobectomies, 2 pneumonectomies. Postoperative pathologic stage were 12 T1N0M0, 15 T2N0M0, 1 T1N1M0, 1 T1N2M0, 1 T2N2M0, 1 T1N0M1. Mortality were 4 cases ($12.9\%$) and there were no early mortality. Cancer free death was 1 cases, other 3 were cancer related deaths. All of them were affected by distal metastasis and received chemotherapy and each metastatic locations were right rib, brain, and both lung field. The average follow up periods were 50.87$\pm$24.77 months. The overall 3, 5-year survival rate among all patients was $97.1\%,\;83.7\%$, stage I patients overall 2, 5year survival rate was $96.3\%$. The overall disease free 1, 2, 5-year survival rate among all patients was $100\%,\;90\%,\;76\%$ and 2, 5-year survival rate in cases of stage I was $96.4\%,\;90.6\%$. 7 cases ($22.58\%$) were chemotherapies, 1 case ($3.22\%$) was radiation therapy, and 2 cases ($6.45\%$) were chemoradiation therapies. Metastatic locations were 3 cases in lung, 1 case in bone, 1 cases in brain. Conclusion: BAC has a favourable survival and low recurrence rate compare with reported other NSCLC after operative resections.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.5
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• pp.1803-1811
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• 2015

Hepatoma-derived growth factor (HDGF) is a novel jack-of-all-trades in cancer. Here we quantify the prognostic impact of this biomarker and assess how consistent is its expression in solid tumors. A comprehensive search strategy was used to search relevant literature updated on October 3, 2014 in PubMed, EMBASE and WEB of Science. Correlations between HDGF expression and clinicopathological features or cancer prognosis was analyzed. All pooled HRs or ORs were derived from random-effects models. Twenty-six studies, primarily in Eastern Asia, covering 2,803 patients were included in the analysis, all of them published during the past decade. We found that HDGF overexpression was significantly associated with overall survival (OS) ($HR_{OS}=2.35$, 95%CI=2.04-2.71, p<0.001) and disease free survival (DFS) ($HR_{DFS}=2.25$, 95%CI =1.81-2.79, p<0.001) in solid tumors, especially in non-small cell lung cancer, hepatocellular carcinoma and cholangiocarcinoma (CCA). Moreover, multivariate survival analysis showed that HDGF overexpression was an independent predictor of poor prognosis ($HR_{OS}=2.41$, 95%CI: 2.02-2.81, p<0.001; $HR_{DFS}=2.39$, 95%CI: 1.77-3.24, p<0.001). In addition, HDGF overexpression was significantly associated with tumor category (T3-4 versus T1-2, OR=2.12, 95%CI: 1.17-3.83, p=0.013) and lymph node status (N+ versus N-, OR=2.37, 95%CI: 1.31-4.29, p=0.03) in CCA. This study provides a comprehensive examination of the literature available on the association of HDGF overexpression with OS, DFS and some clinicopathological features in solid tumors. Meta-analysis results provide evidence that HDGF may be a new indicator of poor cancer prognosis. Considering the limitations of the eligible studies, other large-scale prospective trials must be conducted to clarify the prognostic value of HDGF in predicting cancer survival.

• Tuberculosis and Respiratory Diseases
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• v.56 no.6
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• pp.646-656
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• 2004

Background : The aim of this study was to elucidate the mediastinal lymphatic drainage of nonsmall- cell lung cancer (NSCLC). Methods : We retrospectively analyzed the frequency of enlarged mediastinal lymph node (LN) in 256 NSCLC patients with N2 or N3 diseases on CT scan, especially with respect to the location of primary tumor. Results : In 57 patients with right upper lobe (RUL) tumors, right lower paratracheal LN (89.5%) was the most commonly enlarged, followed by subcarinal LN (54.4%). In 61 patients with left upper lobe (LUL) tumors, left lower paratracheal (70.5%) and subaortic LNs (52.5%) were commonly enlarged. Subcarinal LN enlargement without ipsilateral superior mediastinal LN enlargement was rarely found in both upper lobe tumors; RUL 8.8%, LUL 6.6%. In patients with right or left lower lobe (RLL or LLL) tumors, the most commonly enlarged LN was subcarinal; 88.2%, 65.7%, respectively. In RLL tumors with both subcarinal and superior mediastinal LN enlargements, the frequency of ipsilateral superior mediastinal LN involvement was similar to that of bilateral superior mediastinal involvement. In LLL tumors with both subcarinal and superior mediastinal LN enlargements, bilateral superior mediastinal involvement was more frequent than ipsilateral superior mediastinal involvement. Conclusion : The results of this study suggest that both upper lobe tumors are mainly drained directly to ipsilateral superior mediastinal LNs, and that both lower lobe lesions are drained to superior mediastinal LN via subcarinal LNs.

• Journal of Chest Surgery
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• v.43 no.5
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• pp.506-512
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• 2010

Background: This study was designed to evaluate the FDG uptake ratio of mediastinal node and primary tumors using integrated PET/CT imaging combined with Glut-1 expression of the primary tumor in order to predict the N2 status more accurately in NSCLC patients. Material and Method: Patients who underwent integrated PET/CT scanning with a detectable mSUV for both primary tumors and mediastinal lymph nodes were eligible for this study. The FDG uptake ratio between the mediastinal node and the primary tumor was calculated. Result: The average mSUV of primary tumors and mediastinal nodes were, respectively, $7.4{\pm}2.2$ and $4.2{\pm}2.2$ in N2-positive patients and $7.6{\pm}3.7$ and $2.8{\pm}6.9$ in N2-negative patients. The mean FDG uptake ratio of mediastinal node to primary tumor were $0.58{\pm}0.23$ for malignant N2 lymph nodes and $0.45{\pm}0.20$ for benign lymph nodes (p<0.05). Models which combined Glut-1 expression with an FDG ratio have better diagnostic power than models that use the FDG uptake ratio alone. Conclusion: In some patients with a previous history of pulmonary tuberculosis or other inflammatory lung diseases, an FDG uptake ratio combined with Glut-1 expression may be useful in diagnosing mediastinal node metastasis more exactly.

• Journal of Chest Surgery
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• v.37 no.10
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• pp.845-855
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• 2004

Background: No general consensus has been available regarding the necessity of postoperative radiation therapy (PORT) and its optimal techniques in the patients with chest wall invasion (pT3cw) and node negative (N0) non-small cell lung cancer (NSCLC). We did retrospective analyses on the pT3cwN0 NSCLC patients who received PORT because of presumed inadequate resection margin on surgical findings. And we compared them with the pT3cwN0 NSCLC patients who did not received PORT during the same period. Material and Method: From Aug. of 1994 till June of 2002, 22 pT3cwN0 NSCLC patients received PORT-PORT (＋) group- and 16 pT3cwN0 NSCLC patients had no PORT-PORT (-) group. The radiation target volume for PORT (＋) group was confined to the tumor bed plus the immediate adjacent tissue only, and no regional lymphatics were included. The prognostic factors for all patients were analyzed and survival rates, failure patterns were compared with two groups. Result: Age, tumor size, depth of chest wall invasion, postoperative mobidities were greater in PORT (-) group than PORT (＋) group. In PORT (-) group, four patients who were consulted for PORT did not receive the PORT because of self refusal (3 patients) and delay in the wound repair (1 patient). For all patients, overall survival (OS), disease-free survival (DFS), loco-regional recurrence-free survival (LRFS), and distant metastases-free survival (DMFS) rates at 5 years were 35.3%, 30.3%, 80.9%, 36.3%. In univariate and multivariate analysis, only PORT significantly affect the survival. The 5 year as rates were 43.3% in the PORT (＋) group and 25.0% in PORT (-) group (p=0.03). DFS, LRFS, DMFS rates were 36.9%, 84.9%, 43.1 % in PORT (＋) group and 18.8%, 79.4%, 21.9% in PORT(-) group respectively. Three patients in PORT (-) group died of intercurrent disease without the evidence of recurrence. Few suffered from acute and late radiation side effects, all of which were RTOG grade 2 or lower. Conclusion: The strategy of adding PORT to surgery to improve the probability not only of local control but also of survival could be justified, considering that local control was the most important component in the successful treatment of pT3cw NSCLC patients, especially when the resection margin was not adequate. Authors were successful in the marked reduction of the incidence as well as the severity of the acute and late side effects of PORT, without taking too high risk of the regional failures by eliminating the regional lymphatics from the radiation target volume.

• The Korean Journal of Nuclear Medicine
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• v.39 no.4
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• pp.231-238
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• 2005

Purpose: We investigated prospectively whether the interpretation considering the patterns of FDG uptake and the findings of unenhanced CT for attenuation correction can improve the diagnostic accuracy for assessing malignant lymph node (LN) and N stage in non-small cell lung cancor (NSCLC) using CT-corrected FDG-PET (PET/CT). Materials & Methods: Subjects were 91 NSCLC patients (M/F 62/29, age: $60{\pm}9$ yr) who underwent PET/CT before in dissection. We evaluated the maximum SUV (maxSUV), patterns of FDG uptake, short axis diameter, and calcification of LN showing abnormally increased FDG uptake. Then we investigated criteria improving the diagnostic accuracy and correlated results with postoperative pathology. In step 1, in was classified as benign or malignant based on maxSUV only. In step 2, LN was regarded as benign if it had lower maxSUV than the cut-off value of step 1 or it had calcification irrespective of its maxSUV. In step 3, LN regarded as malignant in step 2 was classified as benign if they had indiscrete margin of FDG uptake. Results: Among 432 LN groups surgically resected (28 malignant, 404 benign), 71 showed abnormally increased FDG uptake. We determined the cut-off as maxSUV=3.5 using ROC curve analysis. The sensitivity, specificity, and accuracy for assessing malignant LN were 64.3%, 86.9%, 85.4% in step 1, 64.3%, 95.0%, 93.1% in step 2, and 57.1%, 98.0%, 95.4% in step3, respectively. The accuracy for assessing N stage was 64.8% in step 1, 80.2% in step 2, and 85.7% in step 3. Conclusion: interpreting PET/CT, consideration of calcification and shape of the FDG uptake margin along with maxSUV can improve the diagnostic accuracy for assessing malignant involvement and N stage of hilar and mediastinal LNs in NSCLC.

• Journal of Chest Surgery
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• v.42 no.5
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• pp.615-623
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• 2009

Background: We evaluated the feasibility and the efficacy of Video-Assisted Thoracic Surgery (VATS) lobectomy for treating patients with non-small cell lung cancer (NSCLC) and we compared the outcomes of VATS lobectomy with those of open lobectomy. Material and Method: From 2003 to March 2008, 133 NSCLC patients underwent VATS lobectomy. The patients were selected on the basis of having clinical stage I disease on the chest CT and PET scan. The outcomes of 202 patients who underwent open lobectomy (OL group) for clinical stage I NSCLC were evaluated to compare their results with those of the patients who underwent VATS lobectomy (the VL group). Result: The number of females and the number of patients with adenocarcinoma and stage IA disease were greater in VL group (p<0.05). There was no operative mortality or major complications in the VL group. Conversion to thoracotomy was needed in 8 cases (6%), which was mostly due to bleeding. The chest tube indwelling time and the length of the postoperative hospital stay were significantly shorter in the VL group (p<0.001). The number of dissected lymph nodes and the size of tumor were significantly smaller in the VL group (p<0.001). For the pathologic stage I patients, there was no significant difference in the three-year survival rates between the two groups (p=0.15). Conclusion: VATS lobectomy is a safe procedure with low operative mortality and morbidity. VATS lobectomy is feasible for early stage NSCLC and it provides outcomes that are comparable to those for open lobectomy. Further long-term data are needed.

• Tuberculosis and Respiratory Diseases
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• v.64 no.4
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• pp.278-284
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• 2008

Background: TRAIL is a promising anticancer agent which induces selective tumor cell death due to a unique receptor system that includes death receptors and decoy receptors. DR5 TRAIL receptor is an originally identified p53-regulated death receptor gene that was induced, by doxorubicine, only in cells with a wild-type p53 status. We investigated that focused on the correlation between the DR5 and p53 expressions in non-small cell lung cancer (NSCLC). Methods: Immunohistochemical analysis, with using avidin-biotinylated horseradish peroxidase complex, was carried out in 89 surgically resected NSCLC formalin-fixed paraffin-embedded tissue sections. As primary antibodies, we used anti-DR5 polyclonal antibody and anti-p53 monoclonal antibody. A negative control was processed with each slide. The positive tumor cells were quantified twice and these values were expressed as percentage of the total number of tumor cells, and the intensity of immunostaining was expressed. The analysis of the DR5 expression was done separately in tumor area and in a nearby region of normal tissue. Results: The DR5 expression was high in the bronchial epithelium (89% of cases) but this was almost absent in type I & II pneumocytes, lymphocytes and smooth muscle cells. High DR5 expression rate in tumor was seen in 28% (15/53) of squamous cell carcinomas, in 47% (15/32) of adenocarcinomas and, in 50% (2/4) of large cell carcinomas. The DR5 expression did not show any statistical significance relationship with the T stage, N stage, or survival. However, the DR5 expression showed significant inverse correlation with the p53 expression. (p< 0.01). Conclusion: We demonstrated that the DR5 expression in NSCLC via immunohistochemical analysis is relatively tumor-specific except for that in the normal bronchial epithelium and it is significantly dependent on the p53 status. This might be in vivo evidence for the significance of the DR5 gene as a p53 downstream gene.

• Journal of Chest Surgery
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• v.41 no.5
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• pp.586-590
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• 2008

Background: Non-small cell lung cancer (NSCLC) patients histologically proven to have stage N2 disease by media-stinoscope or thoracoscope underwent subsequent neoadjuvant chemoradiotherapy. This study was designed to find out if there were any differences in survival or recurrence rates between N2 positive and N2 negative patients. Material and Method: Between January 1998 and December 2005, we retrospectively analyzed 69 patients who were divided into three groups. Group A consisted of patients whose N stage was downstaged, group B of patients whose N stage was the same, and Group C of patients who could not undergo surgery because of disease progression during neoadjuvant chemoradiotherapy. We analyzed and compared the mean survival, three-year survival, mean disease-free survival, and three-year disease-free survival rates for the three groups. Result: There were no demographic differences among the groups. The mean survival was 58, 47, and 21 months for groups A, B, and C, respectively. The mean survival was longest in group A, but no statistically significant difference was found on A-B or B-C group comparison (p>0.05). However, a significant difference was noted between group A and group C (p : 0.01). Three-year survival rates were 67%, 41%, and 21.6% for groups A, B, and C, respectively, with a statistical difference similar to that seen in mean survival. The mean disease-free survival was 44 months in group A and 45 months in group B, with no statistically significant difference noted. No significant differences were noted in the three-year disease-free survival rates (55.1%, 46.8%). Conclusion: There were no significant differences in survival or recurrence rates with changes in N stage after neoadjuvant chemoradiotherapy. However, mean survival, three-year survival, and three-year disease-free survival rates tended to be higher in downstaged patients. Nevertheless, the difference was statistically insignificant, and therefore further studies with more patients and longer follow-up are necessary to clarify the positive effects on the survival and prognosis of downstaged patients.

• Radiation Oncology Journal
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• v.27 no.3
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• pp.126-132
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• 2009

Purpose: We wanted to evaluate the prognostic factors for the pathologic N2 non-small cell lung cancer (NSCLC) patients who were treated by postoperative radiotherapy. Materials and Methods: We retrospectively reviewed 112 pN2 NSCLC patients who underwent surgery and postoperative radiotherapy (PORT) From January 1999 to February 2008. Seventy-five (67%) patients received segmentectomy or lobectomy and 37 (33%) patients received pneumonectomy. The resection margin was negative in 94 patients, and it was positive or close in 18 patients. Chemotherapy was administered to 103 (92%) patients. Nine (8%) patients received PORT alone. The median radiation dose was 54 Gy (range, 45 to 66), and the fraction size was 1.8~2 Gy. Results: The 2-year overall survival (OS) rate was 60.2% and the disease free survival (DFS) rate was 44.7% for all the patients. Univariate analysis showed that the patients with multiple-station N2 disease had significantly reduced OS and DFS (p=0.047, p=0.007) and the patients with an advanced T stage ($\geq$T3) had significantly reduced OS and DFS (p<0.001, p=0.025). A large tumor size ($\geq$5 cm) and positive lymphovascular invasion reduced the OS (p=0.035, 0.034). Using multivariate analysis, we found that multiple-station N2 disease and an advanced T stage ($\geq$T3) significantly reduced the OS and DFS. Seventy one patients (63.4%) had recurrence of disease. The patterns of failure were loco-regional in 23 (20.5%) patients, distant failure in 62 (55.4%) and combined loco-regional and distant failure in 14 (12.5%) patients. Conclusion: Multiple involvement of mediastinal nodal stations for the pN2 NSCLC patients with PORT was a poor prognostic factor in this study. A prospective study is necessary to evaluate the N2 subclassification and to optimize the adjuvant treatment.