[Show abstract][Hide abstract] ABSTRACT: Purpose: To better understand the complete genomic architecture of lung adenocarcinoma (LA). Experimental Design: We used array experiments to determine copy number variations and sequenced the complete exomes of the 247 LA tumor samples along with matched normal cells obtained from the same patients. Fully annotated clinical data were also available, providing an unprecedented opportunity to assess the impact of genomic alterations on clinical outcomes. Results: We discovered that genomic alternations in the RB pathway are associated with significantly shorter disease-free survival in early-stage LA patients. This association was also observed in our independent validation cohort. The current treatment guidelines for early-stage LA patients recommend follow-up without adjuvant therapy after complete resection, except for high-risk patients. However, our findings raise the interesting possibility that additional clinical interventions might provide medical benefits to early-stage LA patients with genomic alterations in the RB pathway. When examining the association between genomic mutation and histological subtype, we uncovered the characteristic genomic signatures of various histological subtypes. Notably, the solid and the micropapillary subtypes demonstrated great diversity in the mutated genes, while the mucinous subtype exhibited the most unique landscape. This suggests that a more tailored therapeutic approach should be used to treat LA patients. Conclusion: Our analysis of the genomic and clinical data for 247 LAs should help provide a more comprehensive genomic portrait of LA, define molecular signatures of LA subtypes, and lead to the discovery of useful prognostic markers that could be used in personalized treatments for early-stage LA patients.
Clinical cancer research : an official journal of the American Association for Cancer Research. 10/2014;
[Show abstract][Hide abstract] ABSTRACT: The role of non-surgical treatments (NS), such as chemoradiotherapy or radiotherapy, for clinical T1N0M0 esophageal cancer (cT1N0M0 EC) has not been well delineated. The aim of this study was to evaluate and compare the feasibility and efficacy of NS and Surgical treatment (S) in cT1N0M0 EC patients.
Cancer Chemotherapy and Pharmacology 09/2014; · 2.80 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Although there is no consensus on the management of bronchogenic cyst, most surgeons advocate early removal, even in asymptomatic patients. To evaluate the feasibility and safety of video-assisted thoracic surgery (VATS) in the management of bronchogenic cysts and long-term follow-up, a retrospective analysis was performed.
Interactive Cardiovascular and Thoracic Surgery 07/2014; · 1.11 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background We aimed to investigate the value of routine flexible bronchoscopy (FB) for the preoperative assessment of early-stage non-small cell lung cancer (NSCLC) diagnosed using percutaneous core needle biopsy (PCNB). Methods We enrolled 688 NSCLC patients who were treated at our hospital between January 2003 and December 2012 and who met the following criteria: (1) early-stage lung cancer (stage I or II); (2) lung cancer had been diagnosed using PCNB; and (3) no evidence of endobronchial disease in the airways other than the primary cancer site on both chest computed tomography (CT) and positron emission tomography-CT (PET-CT). All NSCLC patients were from the same tertiary referral center, where FB is routinely performed preoperatively for this disease, and their medical records were reviewed retrospectively. Results Of the 688 patients included in the study, 451 (65.6%) were male and the median age was 65 years. Pathology analysis revealed that adenocarcinoma was the most frequently observed cell type (516/688, 75.0%). The distribution of preoperative clinical staging for the 688 patients was (1) IA (54.5%, 375/688); (2) IB (22.1%, 152/688); (3) IIA (18.2%, 125/688); and (4) IIB (5.2%, 36/688). The majority of these patients (95.2%, 655/688) underwent surgical resection. Unsuspected malignant endobronchial lesion on FB was found in only two cases (0.3%), and the surgical strategy had to be modified for both of these patients. Conclusion Preoperative FB is not beneficial for screening the airways of almost any patient with early-stage NSCLC, provided that neither PET-CT nor CT reveal any evidence of endobronchial malignant involvement other than at the primary cancer site.
[Show abstract][Hide abstract] ABSTRACT: This study was performed to assess the incidence, survival, and risk factors associated with unsuspected pathologic N2 disease in patients with resectable clinical N0-1 non-small cell lung cancer.
Between January 2002 and December 2010, 1,821 patients with clinical N0-1 non-small cell lung cancer underwent pulmonary resection and mediastinal lymph node dissection. Clinical outcomes and risk factors for pathologic N2 disease were retrospectively analyzed for this cohort.
Unsuspected pathologic N2 disease was identified in 196 patients (10.8%). The most common type of resection was lobectomy (81.6%). Adjuvant therapy was administered in 177 patients (90.3%). The median follow-up time was 28 months (range, 1 to 101 months). N2 involvement was single-station in 121 (66.8%) and multiple-station in 65 (33.2%). The 5-year overall and disease-free survival rates were 56.1% and 35.0%, respectively. The 5-year survival rates of single-station and multiple-station N2 were 66.6% and 36.4%, respectively (p < 0.001). Adenocarcinoma, clinical N1, tumor size (>3 cm), and a right middle lobe tumor were identified as independent risk factors for unsuspected multiple-station N2 disease by multivariate analysis. Incidence of unsuspected multiple-station N2 disease in low-risk classes (aggregate score, 0 to ≤2) was only 5.5%.
The incidence of unsuspected N2 disease in our cohort was similar to that of previous reports. Survival outcomes were favorable for unsuspected single-station N2 disease but were poor for unsuspected multiple-station N2 disease. Clinical N0-1 non-small cell lung cancer patients with risk class of low score for unsuspected multiple-station N2 disease can be exempted from aggressive mediastinal staging.
The Annals of thoracic surgery 04/2014; · 3.45 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Pulmonary and/or bronchial aneurysm with systemic thrombophlebitis can be seen in the case of both Behcet's disease and Hughes-Stovin syndrome. These two diseases may be indistinguishable since the clinical, radiological, and histopathological findings are similar in both cases. In particular, from the perspective of pulmonary involvement, hemoptysis is the leading cause of death in both conditions and is followed by aneurysmal rupture. Here, we report a case in which surgical resection was performed for a patient presenting recurrent hemoptysis as an atypical presentation of Behcet's disease.
The Korean journal of thoracic and cardiovascular surgery. 04/2014; 47(2):178-180.
[Show abstract][Hide abstract] ABSTRACT: We report a rare case of granular cell tumor arising in the left lower lobe (LLL) bronchus with secondary obstructive change in a 60-year-old male. The patient was found to have a nodule in the LLL on a computed tomography scan, three months prior to his presentation to the Asan Medical Center. Bronchoscopic biopsies revealed a granular cell tumor. After undergoing LLL lobectomy with bronchoplasty, the patient has not experienced any tumor recurrence.
The Korean journal of thoracic and cardiovascular surgery. 04/2014; 47(2):193-196.
[Show abstract][Hide abstract] ABSTRACT: The purpose of this study was to identify perioperative risk factors for postoperative acute kidney injury (AKI) in patients undergoing esophageal cancer surgery.
A retrospective analysis of the prospectively collected medical data.
A tertiary care university hospital.
All consecutive adult patients (n = 595) who underwent elective esophageal surgery for cancer between January 2005 and April 2012.
AKI was defined by the AKI Network criteria based on serum creatinine changes within the first 48 hours after esophageal cancer surgery. The relationship between perioperative variables and AKI was evaluated using multivariate logistic regression. Postoperative AKI developed in 210 (35.3%) patients. Risk factors for AKI were body mass index (odds ratio [OR] 1.07; 95% confidence interval [CI] 1.01-1.14), preoperative serum albumin level (OR 0.52; 95% CI 0.33-0.84), use of angiotensin-converting enzyme inhibitors or angiotensin-receptor blockers (OR 1.35; 95% CI 1.05-1.75), colloid infusion during surgery (OR 1.11; 95% CI 1.06-1.18), and postoperative 2-day C-reactive protein (OR 1.05; 95% CI 1.01-1.09). Postoperative AKI was associated with prolonged length of hospital stay.
Postoperative AKI is common in patients undergoing esophageal surgery for cancer. Closer evaluation and monitoring in patients with risk factors for AKI may be warranted.
Journal of cardiothoracic and vascular anesthesia 03/2014; · 1.06 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Melanoma that involves the upper gastrointestinal (GI) tract is rare and studies relating to endoscopic and pathologic findings with clinical outcomes are lacking. We reviewed the gross and microscopic patterns of the upper GI tract in primary and metastatic melanoma, and examined their association with clinical outcomes.
Twenty-nine cases of primary esophageal (n = 19) and metastatic gastric and/or duodenal melanoma (n = 10) that were detected during upper GI endoscopy between 1995 and 2011 were retrospectively analyzed.
Three types of gross patterns were recognized-nodular pattern in 7 cases, mass-forming pattern in 18 cases, and flat pigmented pattern in 4 cases. In primary esophageal melanoma, 13 patients (68.4 %) underwent surgery and 9 received palliative therapy. Of all cases, 22 patients (75.9 %) died of disease progression; the median overall survival period was 12 months (interquartile range [IQR] 4.5-24.5 months), and from recognition of upper GI tract melanoma the median overall survival period was 9 months (IQR 3.5-17.0 months). In primary esophageal cases, skin melanoma stage better discriminated the patients with good prognosis than the esophageal cancer stage. The flat pigmented gross pattern proved to be a good prognostic factor in primary and metastatic GI tract melanomas (p = 0.016 and p = 0.046, respectively).
Melanoma of the GI tract is a highly aggressive disease with a poor prognosis, both in primary and metastatic cases. However, in primary esophageal melanoma, careful inspection of the mucosa during endoscopic examination followed by surgical resection may result in extended survival.
Annals of Surgical Oncology 03/2014; · 4.12 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: With recent advances in radiology, the detection of ground-glass nodules (GGNs) has become increasingly common. However, there still is no consensus on management, especially on the need for systemic lymph node (LN) dissection. The purpose of this study was to evaluate the surgical outcomes on the basis of the extent of resection of the primary lesion and mediastinal LN dissection and to carefully suggest appropriate treatment strategies in the patients with pulmonary adenocarcinoma presenting as pure ground-glass opacities.
From January 2006 to December 2010, 1267 patients with pulmonary adenocarcinoma, including adenocarcinoma in situ, underwent curative-intent surgical resection. Among these patients, pure GGNs were confirmed in 48 patients on preoperative chest computed tomography (CT) by an experienced radiologist, and 42 underwent systemic LN dissection or sampling. We retrospectively reviewed the perioperative data and postoperative outcomes.
The median age of the patients was 56 (range, 35-78) years, and 26 (54.2%) patients were male. The median size of the nodules was 12 (5-30) mm, and 8 (16.7%) had multiple lesions at the time of operation. The median duration between the initial diagnosis and operation was 4 (0-45) months. Preoperative positron emission tomography/CT was taken in 36 (75.0%) patients, which showed no significant metabolic uptake. For curative resection, lobectomy was performed in 32 (66.7%) patients, segmentectomy in 4, and wedge resection in 12. Clear resection margins were reported in all patients. Forty-two patients underwent systemic mediastinal LN dissection or sampling, and the median number of dissected LNs was 23 (7-53). No LN was reported as positive for malignancy. The median follow-up duration after the first operation was 39 (23-77) months, and there were no cases of late mortality, local recurrence or nodal recurrence. Recurrent GGNs have been developed in 6 (12.5%) patients.
For pure GGNs, limited resection can be performed when complete resection is obtained, as it was sufficient for cure and especially because there is high probability of multiple lesions. We were unable to demonstrate any additional therapeutic benefit with mediastinal LN dissection in patients with pure GGNs.
European journal of cardio-thoracic surgery: official journal of the European Association for Cardio-thoracic Surgery 02/2014; · 2.40 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Most cases of Ewing's sarcoma are reported in the bone, and extraosseous Ewing's sarcoma is an extremely rare disease. Here, we report a rare case of primary pulmonary Ewing's sarcoma in a patient with hemoptysis. The patient underwent right upper lung lobe lobectomy with adjuvant chemotherapy and radiation therapy and has been free of recurrent disease for 4 years.
The Korean journal of thoracic and cardiovascular surgery. 02/2014; 47(1):47-50.
[Show abstract][Hide abstract] ABSTRACT: Chylothorax associated with pulmonary resection for lung cancer, although rare, must be considered as a potential complication during thoracic surgery. In the present study, we investigated the effectiveness of a conservative approach (diet or pleurodesis) to the management of chylothorax.
Between January 2000 and December 2010, 3,120 consecutive patients underwent pulmonary resection and mediastinal lymph node dissection at our institution. Among them, 67 patients with confirmed chylothorax were retrospectively reviewed.
Right-sided chylothorax was more common than left-sided chylothorax (p = 0.033). All patients were initially treated with nil per os (NPO; n = 46) or a low long-chain triglyceride (LCT) diet (n = 21). In the NPO group, 24 patients were successfully treated with diet alone and 20 underwent pleurodesis. In the LCT group, 10 patients were successfully treated with diet alone; of the 11 remaining patients, 4 patients improved after NPO. The 7 patients who did not improve with NPO underwent pleurodesis. No significant differences in chest tube output before and after initial treatment, length of stay, or success rate were observed between patients initially treated with NPO and those receiving low LCT. All 32 pleurodeses performed in 27 patients were successful. Two patients underwent surgery without pleurodesis after dietary treatment failure. Postoperative air leakage or drainage for 5 days greater than 21.6 mL/kg were independent risk factors for dietary treatment failure.
Conservative treatment, including pleurodesis, should be the first choice of treatment for chylothorax complicating pulmonary resection.
The Annals of thoracic surgery 12/2013; · 3.45 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Extrauterine epithelioid trophoblastic tumors constitute an extremely rare gestational trophoblastic disease. We report the case of an extrauterine trophoblastic tumor that was incidentally detected in the left lung. Squamous cell carcinoma was suspected after microscopically examining the specimen obtained upon preoperative needle biopsy. After surgery, the tumor was confirmed by microscopic findings and immunohistochemical features.
The Korean journal of thoracic and cardiovascular surgery. 12/2013; 46(6):471-4.
[Show abstract][Hide abstract] ABSTRACT: Gastric conduit cancer (GCC), which is a carcinoma that arises in the gastric conduit after oesophagectomy, often negatively affects long-term survivors of oesophageal cancer. The aim of this study was to evaluate the incidence and clinical implications of GCC.
We reviewed data for 863 patients who underwent an oesophagectomy and a reconstruction of the gastric conduit from 1993 to 2011 for oesophageal cancer.
A total of 18 cases of GCC in 18 patients were identified. Cumulative incidence rates of GCC were 2.4% at 5 years and 5.7% at 10 years. The median interval between oesophagectomy and detection of gastric tube cancer was 5.0 years (range, 1-16 years). Ten patients were incidentally diagnosed with GCC under periodic endoscopy. All cases of gastric tube cancer were adenocarcinoma and 12 cases were located at the antrum of the gastric conduit. For GCC treatment, endoscopic submucosal dissection was performed in 6 patients, total gastric conduit gastrectomy with colon interposition in 3 patients and chemotherapy in 6 patients. Five patients received conservative treatment alone. The 5-year survival rate of all patients was 22.2%. The 3-year survival rates of the patients who underwent endoscopic resection, total gastrectomy with colon interposition or chemotherapy or conservative treatment were 100, 50, and 9.1%, respectively (P = 0.003).
Patients had a constant risk of GCC occurrence after oesophagectomy for oesophageal cancer. Endoscopic or surgical resection for early GCC showed favourable outcomes compared with chemotherapy or conservative treatment for advanced GCC. A regular and long-term follow-up, including detailed endoscopy, is essential for the early detection of GCC in patients who underwent oesophagectomy for oesophageal cancer.
European journal of cardio-thoracic surgery: official journal of the European Association for Cardio-thoracic Surgery 10/2013; · 2.40 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Epithelial-mesenchymal transition (EMT) is associated with reduced sensitivity to many chemotherapeutic drugs, including EGFR tyrosine kinase inhibitors. Here, we investigated if this reduced sensitivity also contributes to resistance to crizotinib, an ALK inhibitor of lung cancer that exhibits the EML4-ALK translocation. We established a crizotinib-resistant subline (H2228/CR), which was derived from the parental H2228 cell line by long-term exposure to increasing concentrations of crizotinib. Characteristics associated with EMT, including morphology, EMT marker proteins, and cellular mobility, were analyzed. Compared with H2228 cells, the growth of H2228/CR cells was independent of EML4-ALK, and H2228/CR cells showed cross-resistance to TAE-684 (a second-generation ALK inhibitor). Phenotypic changes to the spindle-cell shape were noted in H2228/CR cells, which were accompanied by a decrease in E-cadherin and increase in vimentin and AXL. In addition, H2228/CR cells showed increased secretion and expression of TGF-β1. Invasion and migration capabilities were dramatically increased in H2228/CR cells. Applying TGF-β1 treatment to parental H2228 cells for 72 h induced reversible EMT, leading to crizotinib resistance, but this was reversed by the removal of TGF-β1. Suppression of vimentin in H2228/CR cells by siRNA treatment restored sensitivity to crizotinib. Furthermore, these resistant cells remained highly sensitive to the Hsp90 inhibitors, similar to the parental H2228 cells. In conclusion, we suggest EMT is possibly involved in acquired resistance to crizotinib, and that HSP90 inhibitors could be a promising option for the treatment of EMT.
[Show abstract][Hide abstract] ABSTRACT: The presence of multiple primary cancers (MPCs) in patients with esophageal cancer often presents physicians with a difficult therapeutic decision, because little is known about the appropriate treatment and long-term survival. The purpose of this study was to evaluate appropriate surgical approaches and long-term survival after surgery for esophageal cancer associated with MPCs.
Data from 622 patients who underwent surgery for primary esophageal cancer between 1989 and 2008 were reviewed retrospectively to identify the presence of MPCs.
A total of 96 MPCs were identified in 90 (14.5 %) patients. The three leading MPCs were stomach cancer (n = 36, 37.5 %), head and neck cancer (n = 18, 18.8 %), and lung cancer (n = 18, 18.8 %). The rate of curative resections for both esophageal cancer and MPCs was 87.5 % (28/32) in patients with stomach cancer, 47.1 % (8/17) in head and neck cancer, and 52.9 % (9/17) in lung cancer (P = 0.006). The 5-year survival rates after surgery for esophageal cancer in patients associated with stomach, lung, and head and neck cancer were 52.7, 27.0, and 9.2 %, respectively (P = 0.011).
A range of surgical approaches for esophageal cancer is available in patients associated with MPCs. However, curative resections for primary esophageal cancer associated with MPCs are feasible in highly selected patients. Therefore, a multidisciplinary team management approach is essential for customized treatment strategies in patients with esophageal cancer associated with MPCs.
Annals of Surgical Oncology 08/2013; · 4.12 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Ectopic mediastinal parathyroid adenomas are rare, but can be life-threatening. Resection is indicated in those cases accompanied by hypercalcemia, especially in young patients. Although most mediastinal parathyroid adenomas can be removed by a cervical approach, a transthoracic approach is needed when the adenoid tissues are located deep within the thoracic cavity. We describe the case of a 37-year-old female who underwent excision of an intrathoracic ectopic parathyroid adenoma after parathyroidectomy four months earlier.
The Korean journal of thoracic and cardiovascular surgery. 08/2013; 46(4):302-4.
[Show abstract][Hide abstract] ABSTRACT: We report a rare case of rhabdomyosarcoma spontaneously arising in an anterior mediastinal teratoma in a 47-year-old male. The patient was found to have an anterior mediastinal mass on a chest X-ray, which was taken two months before his presentation to Asan Medical Center. A subsequent computed tomography scan revealed an 8.9×7.1×8.0 cm heterogeneous mass in the anterior mediastinum. He underwent an excision via median sternotomy. The histopathologic study identified a mature teratoma with embryonal rhabdomyosarcoma.
The Korean journal of thoracic and cardiovascular surgery. 08/2013; 46(4):305-8.
[Show abstract][Hide abstract] ABSTRACT: Background The aim of the present study was to evaluate the oncologic characteristics of pulmonary mucoepidermoid carcinoma (PMEC) and the efficacy of surgical resections.Materials and Methods The surgery for PMEC was performed in 23 patients at Asan Medical Center from January 2000 to December 2010. They accounted for 0.8% of all surgically resected pulmonary neoplasm in the center. The medical records of these patients were reviewed retrospectively.Results This study group was composed of 13 males (56.5%) and 10 females (43.5%). Median age was 41 years (range, 10 to 75 years). Complete resection with systematic mediastinal lymph node dissection was performed in all patients. There were three postoperative complications: atelectasis in one patient and chylothorax in two patients. There was no postoperative mortality. The median follow-up duration was 68 months (range, 13 to 115 months). In one patient, recurrent disease was found 73 months after surgery. All patients were followed without mortality until the end of this study. The 5- and 8-year disease-free survival rates were 100 and 90.9%, respectively.Conclusion Complete surgical resection with systematic lymph node dissection is an effective treatment for patients with PMEC and provides favorable prognosis.
The Thoracic and Cardiovascular Surgeon 04/2013; · 0.93 Impact Factor