Hong Kwan Kim

Integrative and Comparative Genomic Analysis of Lung Squamous Cell Carcinomas in East Asian Patients

PURPOSEnLung squamous cell carcinoma (SCC) is the second most prevalent type of lung cancer. Currently, no targeted therapeutics are approved for treatment of this cancer, largely because of a lack of systematic understanding of the molecular pathogenesis of the disease. To identify therapeutic targets and perform comparative analyses of lung SCC, we probed somatic genome alterations of lung SCC by using samples from Korean patients.nnnPATIENTS AND METHODSnWe performed whole-exome sequencing of DNA from 104 lung SCC samples from Korean patients and matched normal DNA. In addition, copy-number analysis and transcriptome analysis were conducted for a subset of these samples. Clinical association with cancer-specific somatic alterations was investigated.nnnRESULTSnThis cancer cohort is characterized by a high mutational burden with an average of 261 somatic exonic mutations per tumor and a mutational spectrum showing a signature of exposure to cigarette smoke. Seven genes demonstrated statistical enrichment for mutation: TP53, RB1, PTEN, NFE2L2, KEAP1, MLL2, and PIK3CA). Comparative analysis between Korean and North American lung SCC samples demonstrated a similar spectrum of alterations in these two populations in contrast to the differences seen in lung adenocarcinoma. We also uncovered recurrent occurrence of therapeutically actionable FGFR3-TACC3 fusion in lung SCC.nnnCONCLUSIONnThese findings provide new steps toward the identification of genomic target candidates for precision medicine in lung SCC, a disease with significant unmet medical needs.

Management of Multiple Pure Ground-Glass Opacity Lesions in Patients with Bronchioloalveolar Carcinoma

Introduction: The objective of this study was to evaluate the clinical characteristics and long-term outcome of multiple pure ground-glass opacity (GGO) lesions detected in patients undergoing pulmonary resection for bronchioloalveolar carcinoma (BAC). Methods: Between January 2000 and December 2007, 73 patients underwent pulmonary resection for BAC. Of those, 23 patients had multiple pure GGOs on their preoperative computed tomography (CT) scans. Eighty-nine GGO lesions were detected with a median number of 3 (range, 2–11) per patient. Resection included wedge resection in 12 patients, lobectomy in 7, lobectomy with wedge resection in 3, and bilobectomy in 1. Five patients had all GGOs lesions resected (group I), whereas 18 had some of the GGO lesions resected and the remaining lesions followed by serial CT scans (group II). Median follow-up was 40.3 months. Results: No late death occurred during the follow-up period. In group I, four patients had no recurrences and one patient developed a new lesion that was resected and found to be adenocarcinoma. In group II, GGO lesions either did not change in size (n = 15) or disappeared (n = 3) in all patients. No GGO lesions increased in size or developed a solid component during the follow-up period. Conclusions: When multiple pure GGO lesions in patients with BAC remained without surgical resection, there was no change in their size or features during follow-up. When it is not feasible to resect all GGO lesions in patients with multifocal BAC, close follow-up using CT scans represents an alternative to surgical resection.

Management of ground-glass opacity lesions detected in patients with otherwise operable non-small cell lung cancer.

Introduction: When pure ground-glass opacity (GGO) lesions are detected in patients with otherwise operable non-small cell lung cancer, it is controversial whether to resect them simultaneously with the primary tumor or not. Methods: We retrospectively reviewed radiologic features and pathologic diagnoses of pure GGO lesions detected in otherwise operable non-small cell lung cancer. Forty lesions were identified in 23 patients. Four of the eight lesions that were simultaneously resected at surgery for the primary tumor turned out to be malignant. During follow-up, four lesions increased in size and were resected later. The remaining 28 lesions were considered nonmalignant because the size did not change or decreased during follow-up. All the lesions were divided into nonmalignant (n = 32) and malignant groups (n = 8), and their clinical and radiologic features were compared. Results: There was no significant difference in clinical or pathologic findings between the two groups. Median size of the lesions in the nonmalignant group (5 mm) was significantly smaller than in the malignant group (11 mm) (p = 0.001). We tried to predict whether a lesion is benign or malignant based on its size. With a cutoff value of 8 mm, the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 88%, 81%, 53%, 96% and 83%, respectively. Conclusions: When a pure GGO is detected in otherwise operable lung cancer, it should be resected to rule out the possibility of malignancy if the size is greater than 8 mm. Nevertheless, if the size is less than 8 mm, we suggest that it could be closely followed up using imaging studies.

A modified Nuss procedure for late adolescent and adult pectus excavatum.

BackgroundAlthough the Nuss procedure has been widely adopted as a standard procedure in children with pectus excavatum, reports focusing on its use in adults are rare. We retrospectively reviewed postoperative results to evaluate the safety and efficacy of the Nuss procedure in late adolescents and adults with pectus excavatum.MethodsBetween 2004 and 2007, a total of 44 patients (M:Fxa0=xa038:6) with a median age of 20 underwent the Nuss procedure. The pectus bar was inserted under thoracoscopic guidance and the depressed sternum was lifted by means of a crane device before rotating the bar. The bar was secured with steel wires laterally at three points. A compound bar and sometimes double bar insertion was performed.ResultsThe median length of hospital stay was three days. Complications occurred in nine patients, including pneumothorax in five, bar rotation in two, wound infection in two, and pericardial effusion in one. Reoperation was performed in three patients to correct bar rotation (nxa0=xa02) and incomplete repair (nxa0=xa01). Three of the 26 patients with a single bar required reoperation, whereas none of the 18 with a double bar had a second operation. There was no recurrence of the chest deformity over median follow-up of 12xa0months, except in one patient from whom the bar was removed prematurely.ConclusionsUsing the thoracoscope, the compound bar technique, the 3-point wire fixation, the crane technique, and sometimes double bar insertion showed that the Nuss procedure could be performed safety and effectively in late adolescent and adult patients with pectus excavatum.

Unplanned Conversion to Thoracotomy During Video-Assisted Thoracic Surgery Lobectomy does not Compromise the Surgical Outcome

BackgroundConcerns remain unresolved regarding the safety of unplanned conversion to open thoracotomy during video-assisted thoracic surgery (VATS) lobectomy. We analyzed both early and late outcomes after thoracotomy conversion from VATS.MethodsFrom December 2003 to December 2008, a total of 738 VATS lobectomies were attempted. Among them were 34 unplanned conversions to open thoracotomy. Patient characteristics, operative data, and early and late postoperative outcomes were analyzed retrospectively.ResultsAmong the 34 conversion cases, 26 patients had lung cancer and 8 had benign lung disease. The conversion rate was 4.61%. Left and right upper lobectomies were most often associated with unplanned conversions. Conversion was classified into five groups: (1) problems related to anthracofibrosis of hilar lymph nodes in 14 patients; (2) intraoperative vessel or bronchus injury in 11 patients; (3) fused interlobar fissure in 4 patients; (4) oncologic problems, including mediastinal or hilar lymph node metastasis in 2 patients; and (5) vascular anomalies in 3 patients. There was one death due to postoperative pneumonia in a patient with multiple co-morbidities. Two patients had an episode of pneumonia. The mean hospital stay was 10xa0days, and the median follow-up period was 30.0xa0±xa011.47xa0months. Three patients with lung cancer developed recurrent disease, all of whom were found to have stage III disease. No cancer-related death occurred. There was no significant difference in survival or recurrence between patients with conversion and those with successful VATS. However, the operating time and hospital stay were significantly longer in conversion patients.ConclusionsOur data support the claim that VATS lobectomy can be safely performed with an acceptable conversion rate. Unplanned conversion to open thoracotomy does not appear to compromise the prognosis.

Diffusion-weighted MRI for distinguishing non-neoplastic cysts from solid masses in the mediastinum: problem-solving in mediastinal masses of indeterminate internal characteristics on CT

AbstractObjectivesTo evaluate the usefulness of diffusion-weighted (DW) magnetic resonance images for distinguishing non-neoplastic cysts from solid masses of indeterminate internal characteristics on computed tomography (CT) in the mediastinum.MethodsWe enrolled 25 patients with pathologically proved mediastinal masses who underwent both thoracic CT and magnetic resonance imaging (MRI) including diffusion-weighted imaging (DWI). MRI was performed in patients with mediastinal masses of indeterminate internal characteristics on CT. Two thoracic radiologists evaluated the morphological features and quantitatively measured the net enhancement of the masses at CT. They also reviewed MR images including unenhanced T1- and T2-weighted images, gadolinium-enhanced images and DW images.ResultsThe enrolled patients had 15 solid masses and ten non-neoplastic cysts. Although the morphological features and the extent of enhancement on CT did not differ significantly between solid and cystic masses in the mediastinum (Pu2009>u20090.05), non-neoplastic cysts were distinguishable from solid masses by showing signal suppression on high-b-value DW images or high apparent diffusion coefficient (ADC) values of more than 2.5u2009×u200910-3xa0mm2/s (Pu2009<u20090.001). ADC values of non-neoplastic cysts (3.67u2009±u20090.87u2009×u200910-3xa0mm2/s) were significantly higher than that of solid masses (1.46u2009±u20090.50u2009×u200910-3xa0mm2/s) (Pu2009<u20090.001).ConclusionsDWI can help differentiate solid and cystic masses in the mediastinum, even when CT findings are questionable.Key Points• Non-invasive diagnosis of non-neoplastic cysts can save surgical biopsy or excision.n • Conventional CT or MRI findings cannot always provide a confident diagnosis.n • Mediastinal masses can be well-characterised with DWI.n • Non-neoplastic mediastinal cysts show significantly higher ADC values than cystic tumours.n • DWI is useful to determine treatment strategy.

Outcomes of Mediastinoscopy and Surgery with or without Neoadjuvant Therapy in Patients with Non-small Cell Lung Cancer Who are N2 Negative on Positron Emission Tomography and Computed Tomography

Introduction: The objectives of this study were (1) to assess the results of mediastinoscopy and mediastinal lymphadenectomy and (2) to compare outcomes of surgical treatment with or without neoadjuvant therapy in patients with non-small cell lung cancer who are N2 negative on integrated positron emission tomography and computed tomography (PET/CT). Methods: This was a retrospective, single-institution review of patients with non-small cell lung cancer who were N2 negative on CT and PET/CT. All patients underwent mediastinoscopy; if N2 positive, patients underwent neoadjuvant therapy followed by pulmonary resection, and if N2 negative, patients underwent pulmonary resection with mediastinal lymphadenectomy. Results: Between 2003 and 2007, there were 750 patients (547 men). Of these, 51 patients were N2 positive at mediastinoscopy and then underwent neoadjuvant therapy (mediastinoscopy N2 group), and 699 were N2 negative at mediastinoscopy and then underwent mediastinal lymphadenectomy. Mediastinal lymphadenectomy revealed that 635 had N0 or N1 disease (N2-negative group), and 64 had N2 disease (surgery N2 group). Overall 5-year survival was 73% for the N2-negative group, 44% for the surgery N2 group, and 47% for the mediastinoscopy N2 group. Disease-free 5-year survival was 59% for the N2-negative group, 27% for the surgery N2 group, and 29% for the mediastinoscopy N2 group. Conclusions: We found that there were no significant differences in overall and disease-free survivals between the surgery N2 group and the mediastinoscopy N2 group. The benefit of neoadjuvant therapy in patients with PET/CT-negative but mediastinoscopy-positive N2 disease should be confirmed by randomized studies.

Prognostic impact of nomogram based on whole tumour size, tumour disappearance ratio on CT and SUVmax on PET in lung adenocarcinoma.

AbstractObjectivesLung adenocarcinoma frequently manifests as subsolid nodules, and the solid portion and ground-glass-opacity (GGO) portion on CT have different prognostic significance. Therefore, current T descriptor, defined as the whole tumour diameter without discrimination between solid and GGO, is insufficient. We aimed to determine the prognostic significance of solid tumour size and attempt to include prognostic factors such as tumour disappearance rate (TDR) on CT and SUVmax on PET/CT.MethodsFive hundred and ninety-five patients with completely resected lung adenocarcinoma were analyzed. We developed a nomogram using whole tumour size, TDR, and SUVmax. External validation was performed in another 102 patients.ResultsIn patients with tumours measuring ≤2xa0cm and >2 to 3xa0cm, disease free survival (DFS) was significantly associated with solid tumour size (Pu2009<u20090.001), but not with whole tumour size (Pu2009=u20090.052). Developed nomogram was significantly superior to the conventional T stage (area under the curve of survival ROC; Pu2009=u20090.013 by net reclassification improvement) in stratification of patient survival. In the external validation group, significant difference was noted in DFS according to proposed T stage (Pu2009=u20090.009).ConclusionsNomogram-based T descriptors provide better prediction of survival and assessment of individual risks than conventional T descriptors.Key points• Current measurement of whole tumour diameter including ground-glass opacity is insufficientn • TDR enables differentiation between invasive solid portion and non-invasive GGO portionn • SUVmax demonstrates the biological aggressiveness of the tumourn • We developed a nomogram using whole tumour size, TDR, and SUVmaxn • Nomogram-based clinical T descriptors provide better prediction of survival

Risk Associated with Bilobectomy after Neoadjuvant Concurrent Chemoradiotherapy for Stage IIIA-N2 Non-small-cell Lung Cancer

BackgroundThe aim of the present study was to evaluate the outcomes of surgical resection, especially bilobectomy, after chemoradiation therapy to treat stage IIIA-N2 non-small-cell lung cancer.MethodsData from all patients who underwent surgical resection after neoadjuvant chemoradiation therapy for stage IIIA-N2 non-small-cell lung cancer between 1998 and 2007 were analyzed retrospectively. The chemotherapy regimen consisted of weekly paclitaxel plus cisplatin or weekly paclitaxel plus carboplatin for 5xa0weeks. The concurrent thoracic radiotherapy dose was 45xa0Gy over 5xa0weeks. Surgical resection was planned at around 4xa0weeks following the completion of neoadjuvant therapy.ResultsOf 186 patients who underwent neoadjuvant therapy, 23 bilobectomies, 28 pneumonectomies, and 135 lobectomies were performed. The early postoperative mortality rate (within 30xa0days after operation) was 7.1, 8.7, and 1.5% for the pneumonectomy, bilobectomy, and lobectomy groups, respectively. The late postoperative mortality rate (within 90xa0days) of the lobectomy, bilobectomy, and pneumonectomy groups was 5.9, 13, and 10.7%, respectively. Overall survival was significantly higher among patients treated by lobectomy than among those treated by bilobectomy (pxa0=xa00.041) or pneumonectomy (pxa0=xa00.010). Recurrence was significantly lower in patients treated by lobectomy than in those treated by pneumonectomy (pxa0=xa00.034).ConclusionsBilobectomy is associated with high operative mortality and poor long-term survival after neoadjuvant concurrent chemoradiotherapy for stage IIIA-N2 non-small-cell lung cancer. The outcomes of bilobectomy were similar to those of pneumonectomy in terms of overall survival, disease-free survival, and postoperative mortality.

Outcomes of Curative-Intent Surgery and Adjuvant Treatment for Pulmonary Large Cell Neuroendocrine Carcinoma

BackgroundPulmonary large cell neuroendocrine carcinoma (LCNEC) is pathologically classified as non-small-cell lung cancer (NSCLC), but its clinical behavior is more aggressive than other types of NSCLC. Accordingly, the optimal treatment strategy for LCNEC, including the indication of adjuvant treatment, remains controversial.MethodsA retrospective review of 139 patients who underwent curative-intent surgery for LCNEC was performed to investigate clinicopathologic features and survival outcomes and to evaluate whether adjuvant treatment affected survival outcomes.ResultsThe mean patient age was 64xa0years (126 men, 90.6%). Operative procedures included 111 lobectomies (79.8%), 12 pneumonectomies (8.6%), and 2 sublobar resections. Pathologic stage was IA in 31 (22%), IB in 36 (26%), IIA in 34 (24%), IIB in 9 (6%), IIIA in 19 (14%), IIIB in 2 (1.4%), and IV in 4 patients (2.9%). Postoperatively, 50 patients (36%) received adjuvant treatment. The median follow-up duration was 33xa0months. The 5-year overall survival (OS) rate was 53%, and 5-year disease-free survival (DFS) rate was 39%. In patients with pathologic stage I, there was no significant difference in either OS or DFS according to the addition of adjuvant treatment. However, in patients with pathologic stage II or higher, patients who underwent adjuvant treatment showed significantly better OS (pxa0=xa00.023) and DFS (pxa0=xa00.038).ConclusionsOur findings showed that patients who underwent curative-intent surgery for LCNEC benefitted from the use of adjuvant treatment especially in pathologic stage II or higher.