Kyung Young Chung

Fibroblast Growth Factor Receptor 1 Gene Amplification Is Associated With Poor Survival and Cigarette Smoking Dosage in Patients With Resected Squamous Cell Lung Cancer

PURPOSE To investigate the frequency and the prognostic role of fibroblast growth factor receptor 1 (FGFR1) amplification in patients with surgically resected squamous cell carcinoma of the lung (SCCL) and the association between smoking and FGFR1 amplification. PATIENTS AND METHODS Gene copy number of FGFR1 was investigated in microarrayed tumors from 262 patients with SCCL who had tumor tissue as well as smoking and survival data available. Gene copy number was evaluated by fluorescent in situ hybridization, and an FGFR1-amplified tumor (FGFR1 amp(+)) was prespecified as a tumor with nine or more copies of FGFR1. RESULTS Among 262 patients, the frequency of FGFR1 amp(+) was 13.0%. Patients with FGFR1 amp(+) had significantly shorter disease-free survival (DFS; 26.9 v 94.6 months; P < .001) as well as shorter overall survival (OS; 51.2 v 115.0 months; P = .002) than those without FGFR1 amp(+). Multivariate modeling confirmed that patients with FGFR1 amp(+) had a significantly greater risk of recurrence and death than those without FGFR1 amp(+) after adjusting for sex, smoking status, pathologic stage, and adjuvant chemotherapy (DFS: adjusted hazard ratio [AHR], 2.24; 95% CI, 1.45 to 3.45; P < .001; OS: AHR, 1.83; 95% CI, 1.15 to 2.89; P = .01). The frequency of FGFR1 amp(+) was significantly higher in current smokers than in former smokers and never-smokers (28.9% v 2.5% v 0%; P(trend) < .001). As the smoking dosage increased, so did the incidence of FGFR1 amp(+) (P(trend) = .002). CONCLUSION FGFR1 amplification is an independent negative prognostic factor in surgically resected SCCL and is associated with cigarette smoking in a dose-dependent manner. FGFR1 amplification is a relevant therapeutic target in Asian patients with SCCL.

Identical epidermal growth factor receptor mutations in adenocarcinomatous and squamous cell carcinomatous components of adenosquamous carcinoma of the lung

Adenosquamous carcinoma of the lung is composed of adenocarcinomatous and squamous cell carcinomatous components. The epidermal growth factor receptor (EGFR) mutations occur mostly in adenocarcinomas and rarely in squamous cell carcinoma of lung. Attempts to investigate the EGFR mutation status in each component of adenosquamous carcinoma and to characterize the patients according to mutation status may help to understand the histogenesis of adenosquamous carcinoma.

Thoracoscopic esophagectomy for esophageal cancer: Feasibility and safety of robotic assistance in the prone position

OBJECTIVE To assess the feasibility and safety of robot-assisted thoracoscopic esophagectomy for esophageal cancer in the prone position. METHODS Twenty-one patients underwent robot-assisted thoracoscopic esophagectomy in the prone position by a surgical oncologist who had no prior experience with thoracoscopic esophagectomy. Hemodynamic and respiratory parameters were serially recorded to monitor changes in prone positioning. RESULTS All thoracoscopic procedures were completed with a robot-assisted technique followed by cervical esophagogastrostomy. R0 resection was achieved in 20 patients (95.2%), and the number of dissected nodes was 38.0 + or - 14.2. Robot console time was significantly reduced from 176.3 + or - 12.3 minutes in the initial 6 patients (group 1) to 81.7 + or - 16.5 minutes in the latter 15 patients (group 2) (P = .000). In group 2, there was less blood loss (P = .018), more patients could be extubated in the operating room (P = .004), and the number of dissected mediastinal nodes tended to be increased (P = .093). There was no incidence of pneumonia or 90-day mortality. Major complications included anastomotic leakage in 4 patients, vocal cord palsy in 6 patients, and intra-abdominal bleeding in 1 patient. The prone position led to an elevation of central venous pressure and mean pulmonary arterial pressure and a decrease in static lung compliance. However, cardiac index and mean arterial pressure were well maintained with the acceptable range of partial pressure of arterial oxygen and carbon dioxide. CONCLUSION Robotic assistance in the prone position is technically feasible and safe. Prone positioning was well tolerated, but preoperative risk assessment and meticulous anesthetic manipulation should be carried out.

Impact of Environmental Tobacco Smoke on the Incidence of Mutations in Epidermal Growth Factor Receptor Gene in Never-Smoker Patients With Non–Small-Cell Lung Cancer

PURPOSE Active tobacco smoking has been associated with the incidence of epidermal growth factor receptor (EGFR) mutations. However, the impact of environmental tobacco smoke (ETS) on EGFR mutations has been unknown. We investigated an association between ETS exposure and EGFR mutations in never smokers with non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS We enrolled 179 consecutive never smokers who were newly diagnosed with NSCLC. The history of ETS exposure was obtained with a standardized questionnaire that included exposure period, place, and duration. The nucleotide sequences of exons 18 to 21 on EGFR gene were determined using nested polymerase chain reaction amplification. RESULTS The incidence of EGFR mutations was significantly lower in patients with ETS exposure than in those without (38.5% v 61.4%; P = .008). In a logistic regression model that adjusted for sex and histology, an adjusted odds ratio (AOR) for the risk of EGFR mutations with exposure to ETS was 0.40 (95% CI, 0.20 to 0.81; P = .011). In quartile groups based on total smoker-year, the AORs for the lowest- to highest-quartile groups were 0.59 (95% CI, 0.23 to 1.49), 0.50 (95% CI, 0.17 to 1.50), 0.48 (95% CI, 0.20 to 1.18), and 0.22 (95% CI, 0.08 to 0.62; P(trend) = .028). Among the types of ETS exposure, adulthood ETS and household ETS were significantly associated with the incidence of EGFR mutations. Patients with ETS exposure showed a lower response rate to EGFR tyrosine kinase inhibitors than did patients without ETS exposure (24.6% v 44.8%; P = .053). CONCLUSION ETS exposure is negatively associated with EGFR mutations in never smokers with NSCLC.

Prognostic value of visceral pleura invasion in non-small cell lung cancer.

OBJECTIVES The purpose of this study was to clarify the prognostic significance of visceral pleura invasion in T2 non-small cell lung cancer (NSCLC). MATERIALS AND METHODS Between 1990 and 2001, 439 consecutive patients with T2 NSCLC underwent curative surgical resection. The subjects included 234 patients with stage IB, 95 with stage IIB, and 110 with stage IIIA and B disease. The patients were divided into two groups according to the existence of visceral pleura invasion (group I without, group II with). Both groups were compared with regard to tumor size, histology, associated mediastinal lymph node involvement, and survival rates. RESULTS Visceral pleura invasion (group II) was identified in 114 patients (26%), and was present in 22% of patients with NSCLC with a tumor size of 3 cm or less and in 27% of those with a tumor larger than 3 cm (P=0.37). Visceral pleura invasion was associated with a higher frequency of mediastinal lymph node involvement (group I=22%, group II=34%, P=0.009). Five- and 10-year survival rates were 50 and 45% in group I, and 36 and 22% in group II (P=0.0006). In stage IB, visceral pleura invasion was identified in 53 patients (23%), and 5- and 10-year survival rates were 63 and 60% in the visceral pleura non-invasion group, and 44 and 28% in visceral pleura invasion group (P=0.0018). By multivariate Cox model analysis, age at intervention (relative risk=1.03, P=0.0017), N status (relative risk=1.53, P<0.0001), tumor size (relative risk=1.83, P=0.0452) and visceral pleura invasion (relative risk=1.42, P=0.0291) were independent predictors of poor prognosis. CONCLUSIONS We were able to demonstrate that visceral pleura invasion was a factor of poor prognosis in T2 NSCLC. It was found to correlate with more extensive mediastinal lymph node involvement and a decreased survival rates. Therefore, the patients with visceral pleura invasion should be closely followed up especially.

Pulmonary aspergilloma: Analysis of prognosis in relation to symptoms and treatment

BACKGROUND This study was conducted to assess the risk of surgical treatment and to evaluate surgical resection in patients with pulmonary aspergilloma. METHOD We reviewed 240 patients with pulmonary aspergilloma who were diagnosed between 1990 and 2006. Of these, 135 patients underwent surgical procedure (group A) and 105 patients were managed with conservative treatment (group B). RESULT Forty complications (29.6%) and 6 operative mortalities (4.4%) developed in group A. During the follow-up period, there were 5 recurrences (3.9%) after surgical procedure. The overall 10-year survival rates of group A and group B were 84.8% and 56.7% (P < .001). In multivariate analysis, age, sex, and surgical treatment were favorable prognostic factors. Symptoms of hemoptysis and blood-tinged sputum were not significant prognostic factor even in univariate analysis. CONCLUSION Our results indicate that (1) early morbidity and mortality rates of surgical treatment for pulmonary aspergilloma are acceptable, and (2) surgical treatment is helpful not only to reduce symptoms but also to prolong the survival of patients with pulmonary aspergilloma. Although more studies are needed, our data support the conclusion that surgical resection should be considered for all patients with pulmonary aspergilloma who have acceptable pulmonary reserve.

Tumor necrosis as a prognostic factor for stage IA non-small cell lung cancer

BACKGROUND In stage IA non-small cell lung cancer (NSCLC), lobectomy and mediastinal lymph node dissection is considered the standard treatment. However, 20% to 30% of patients have cancer recurrences. The purpose of this study was to determine the patterns and risk factors for recurrence in patients with stage IA NSCLC. METHODS We retrospectively reviewed the medical records of 201 patients who had confirmed stage IA NSCLC by lobectomy and complete lymph node dissection. RESULTS There were 131 male patients with a mean age of 60.68±9.26 years. The median follow-up period was 41.4 months. Recurrences were reported in 16 patients. One hundred fourteen and 87 patients were T1a (≤2 cm) and T1b (>2 cm to ≤3 cm), respectively. The pathologic results were as follows: adenocarcinomas and bronchioloalveolar carcinomas (n=134); squamous cell carcinomas (n=57); and other diagnoses (n=10). Tumor necrosis and lymphatic invasion were significant adverse risk factors for recurrence based on univariate analysis. Multivariate analysis showed that tumor necrosis was the only significant risk factor to predict cancer recurrence (hazard ratio, 4.336; p=0.032). The 5-year overall survival was 94.8% for necrosis-negative patients and 86.2% for necrosis-positive patients (p=0.04). The 5-year disease-free survival was 92.1% for necrosis-negative patients and 78.9% for necrosis-positive patients (p=0.016). CONCLUSIONS Tumor necrosis was shown to be an adverse risk factor for survival and recurrence in patients with stage IA NSCLC. Thus, close observation and individualized adjuvant therapy might be helpful for patients with stage IA NSCLC with tumor necrosis.

Adenosine triphosphate-based chemotherapy response assay (ATP-CRA)-guided platinum-based 2-drug chemotherapy for unresectable nonsmall-cell lung cancer†

The study investigated correlations between adenosine triphosphate / chemotherapy response assay (ATP‐CRA) and clinical outcomes after ATP‐CRA‐guided platinum‐based chemotherapy for unresectable nonsmall‐cell lung cancer (NSCLC).

Preoperative C-reactive protein levels are associated with tumor size and lymphovascular invasion in resected non-small cell lung cancer

BACKGROUND This study focused on the association between preoperative serum C-reactive protein (CRP) levels and pathologic parameters in patients with resected non-small cell lung cancer (NSCLC). Our primary objective was to find pathologic factors that may explain poor prognosis in patients with preoperative serum CRP elevation. METHODS The records of 102 patients who had undergone pulmonary resection of NSCLC were reviewed. The association between preoperative serum CRP levels and variables that had p-values of less than 0.05 in t-test or one-way ANOVA was examined using multiple linear regression analysis. RESULTS Mean serum CRP level prior to surgery was 3.8+/-4.9 (range, 0.1-19.8) mg/dL. The Pearson correlation coefficient indicated that serum CRP level and pathologic tumor diameter are positively correlated (r=0.487, p<0.001). Serum CRP levels were associated with sex (male vs. female, p=0.003), smoking status (smoker vs. never smoker, p=0.007), histology (squamous vs. non-squamous, p=0.001), tumor size (size>3 cm vs. size< or =3, p<0.001), tumor necrosis (yes vs. no, p<0.001), lymphovascular invasion (yes vs. no, p<0.001), and pleural invasion (P0 vs. P1 vs. P2 vs. P3, p=0.013), but not with age (age>64.5 vs. age< or =64.5, p=0.508), atelectasis or obstructive pneumonia (yes vs. no, p=0.119), location of tumor (peripheral vs. central, p=0.474), and lymph node involvement (N0 vs. N1 vs. N2 vs. N3, p=0.558). Multiple linear regression analysis indicated that pathologic tumor size (beta=0.583, p=0.005) and lymphovascular invasion (beta=3.002, p=0.009) were associated with preoperative serum CRP level. CONCLUSION Our results indicate that lymphovascular invasion and pathologic tumor size are associated with preoperative serum CRP level, which may be considered a prognostic factor in patients with NSCLC. This additional information might serve as a basis to explain poor prognosis in patients with preoperative serum CRP elevation.

Basaloid carcinoma of the lung: a really dismal histologic variant?

BACKGROUND Basaloid carcinoma of the lung has been reported as an uncommon and highly aggressive form of nonsmall cell lung cancers. Even in stage I and II of basaloid carcinoma, a 5-year survival rate of only 15% has been reported and it has been suggested that different treatment modalities for basaloid carcinoma should be considered. The aim of this study was to determine the prognostic implications of a basaloid carcinoma of the lung. METHODS This study included a series of 291 surgically resected lung tumors, which were originally diagnosed as a poorly or undifferentiated carcinoma, a small cell carcinoma, or an atypical carcinoid. Of these, 35 basaloid carcinoma patients were identified and compared with 167 poorly differentiated squamous cell carcinoma (PDSC) patients in terms of the preoperative clinical data, the procedure performed, and the survival outcome. RESULTS The overall incidence of basaloid carcinoma was 4.8%. The actuarial 5-year survival rate was 40.6% in patients with PDSC and 36.5% in those with basaloid carcinoma (p = 0.86). In stage I and II patients, the actuarial 5-year survival rate was 53.9% in the PDSC group and 57.2% in the basaloid group (p = 0.97). There were no differences in the recurrence rate and the relapse pattern (p = 0.584). Coxs proportional hazards model revealed that an age equal to 60 years old (hazard ratio 2.179, p = 0.000) and an advanced stage (hazard ratio 2.264, p = 0.000) were the risk factors for postoperative survival in both groups. CONCLUSIONS Basaloid carcinoma of the lung does not have a worse prognosis than the other nonsmall cell lung cancers. Although it is obvious that a basaloid carcinoma is a unique histologic entity, it does not require a different treatment modality due to the similar clinical behavior with other nonsmall cell lung cancers.