Tracing Oncogene Rearrangements in the Mutational History of Lung Adenocarcinoma.

Mutational processes giving rise to lung adenocarcinomas (LADCs) in non-smokers remain elusive. We analyzed 138 LADC whole genomes, including 83 cases with minimal contribution of smoking-associated mutational signature. Genomic rearrangements were not correlated with smoking-associated mutations and frequently served as driver events of smoking-signature-low LADCs. Complex genomic rearrangements, including chromothripsis and chromoplexy, generated 74% of known fusion oncogenes, including EML4-ALK, CD74-ROS1, and KIF5B-RET. Unlike other collateral rearrangements, these fusion-oncogene-associated rearrangements were frequently copy-number-balanced, representing a genomic signature of early oncogenesis. Analysis of mutation timing revealed that fusions and point mutations of canonical oncogenes were often acquired in the early decades of life. During a long latency, cancer-related genes were disrupted or amplified by complex rearrangements. The genomic landscape was different between subgroups-EGFR-mutant LADCs had frequent whole-genome duplications with p53 mutations, whereas fusion-oncogene-driven LADCs had frequent SETD2 mutations. Our study highlights LADC oncogenesis driven by endogenous mutational processes.

Long-term survival analysis of robotic esophagectomy for esophageal cancer.

Robotic esophagectomy has improved early outcomes and enhanced the quality of lymphadenectomy for esophageal cancer surgery. This study aimed to determine risk factors for long-term survival following robotic esophagectomy and the causes of long-term mortality. We included patients who underwent robotic esophagectomy at our institute between 2010 and 2022. Robotic esophagectomy was defined as a surgical procedure performed robotically in both the abdomen and thorax. Robotic esophagectomy was performed in patients at all stages, including advanced stages, even in patients with stage IV and supraclavicular lymph node metastasis. A total of 340 patients underwent robotic esophagectomy during the study period. Ivor-Lewis operation and McKeown operation were performed on 153 (45.0%) and 187 (55.0%) patients, respectively. The five-year survival rates based on clinical stages were as follows: 85.2% in stage I, 62.0% in stage II, 54.5% in stage III, and 40.3% in stage IV. Risk factors for long-term survival included body mass index, Charlson comorbidity index, clinical stages, and postoperative complications of grade 4 or higher. Among the cases of long-term mortality, recurrence accounted for 42 patients (61.7%), while non-cancer-related death occurred in 26 patients (38.2%). The most common cause of non-cancer-related death was malnutrition and poor general condition, observed in 11 patients (16.2%). Robotic esophagectomy has demonstrated the ability to achieve acceptable long-term survival rates, even in patients with cervical lymph node metastasis. However, addressing high-grade postoperative complications and long-term malnutrition remains crucial for further improving the long-term survival outcomes of patients with esophageal cancer.

Thoracic duct embolization in treating postoperative chylothorax: does bail-out retrograde access improve outcomes?

OBJECTIVES: To evaluate clinical outcomes of thoracic duct embolization (TDE) for the management of postoperative chylothorax with the aid of the bail-out retrograde approach for thoracic duct cannulation (TDC). MATERIALS AND METHODS: Forty-five patients with postoperative chylothorax underwent Lipiodol lymphangiography (LLG) between February 2016 and November 2019. If targetable central lymphatic vessels were identified in LLG, TDC, a prerequisite for TDE, was attempted. While the conventional antegrade transabdominal approach was the standard TDC method, the retrograde approach was applied as a bail-out method. Embolization, the last step of TDE, was performed after confirming leakages in the trans-TDC catheter lymphangiography. Technical and clinical success rates were determined retrospectively. RESULTS: TDC was attempted in 40 among 45 patients based on LLG findings. The technical success rate of TDC with the conventional antegrade approach was 78% (31/40). In addition, six more patients were cannulated using the bail-out retrograde approach, which raised the technical success rate to 93% (37/40). While 35 patients underwent embolization (TDE group), ten patients did not (non-TDE group) for the following reasons: (1) lack of targetable lymphatics for TDC in LLG (n = 5), (2) technical failure of TDC (n = 3), and (3) lack of discernible leakages in the transcatheter lymphangiography (n = 2). The clinical success of the TDE group was 89% (31/35), compared with 50% (5/10) of the non-TDE group. One major procedure-related complication was bile peritonitis caused by the needle passage of the distended gallbladder. CONCLUSIONS: Bail-out retrograde approach for TDC could improve the overall technical success of TDC significantly. KEY POINTS: • Bail-out retrograde thoracic duct access may improve the overall technical success of thoracic duct access, thus improving the clinical success of thoracic duct embolization.

CT-defined visual emphysema in smokers with normal spirometry: association with prolonged air leak and other respiratory complications after lobectomy for lung cancer.

OBJECTIVES: To evaluate the association of visual emphysema on preoperative CT with respiratory complications and prolonged air leak (PAL) in smokers with normal spirometry who underwent lobectomy for lung cancer. METHODS: Among patients who underwent lobectomy for lung cancer between 2018 and 2019 at a single center, ever-smokers with normal spirometry were identified retrospectively. Visual emphysema was graded for centrilobular emphysema (CLE) and paraseptal emphysema (PSE), respectively, by two thoracic radiologists. The associations of visual emphysema with PAL and respiratory complications (except PAL) were investigated. RESULTS: In total, 282 patients were evaluated (257 men; mean age, 64.6 ± 9.8 years). Visual emphysema was present in 126 patients (44.7%) (CLE, 26; PSE, 40; combined CLE and PSE, 60). PAL and respiratory complications occurred in 34 (12.1%) and 26 patients (26.9%), respectively. Greater frequency of PAL and respiratory complications were observed in patients with higher grades of CLE (p = 0.002 for PAL; p = 0.039 for respiratory complications) and PSE (p < 0.001 for PAL; p < 0.001 for respiratory complications). For reader 1 evaluation, the presence of both CLE and PSE was associated with PAL (adjusted odds ratio [OR], 4.94; 95% confidence interval [CI], 1.75-13.95; p = 0.003). For reader 2 evaluation, PSE (adjusted OR, 4.26; 95% CI, 1.22-14.97; p = 0.024) and combined CLE and PSE (adjusted OR, 3.49; 95% CI, 12.1-10.06; p = 0.020) were associated with PAL. The presence of solely CLE was not associated with any adverse outcome (all p > 0.05) for both readers. CONCLUSIONS: Visual assessment of PSE in smokers with normal spirometry may help identify those who develop PAL after lobectomy. KEY POINTS: • Visual emphysema was highly prevalent (44.7%) in smokers with normal lung function who underwent lobectomy for lung cancer. • Increasing tendency of postoperative complications was observed as the grade of visual emphysema increased. • The presence of paraseptal emphysema was associated with prolonged air leak.

Association of Adipopenia at Preoperative PET/CT with Mortality in Stage I Non-Small Cell Lung Cancer.

Background Body mass index (BMI) and sarcopenia status are well-established prognostic factors in patients with lung cancer. However, the relationship between the amount of adipose tissue and survival remains unclear. Purpose To investigate the association between baseline adipopenia and outcomes in patients with early-stage non-small cell lung cancer (NSCLC). Materials and Methods Consecutive patients who underwent surgical resection for stage I NSCLC between 2011 and 2015 at a single tertiary care center were retrospectively identified. The primary outcome was the 5-year overall survival (OS) rate, and secondary outcomes were the 5-year disease-free survival (DFS) rate and the major postoperative complication rate. The abdominal total fat volume at the waist and the skeletal muscle area at the L3 level were obtained from preoperative PET/CT data and were normalized by the height squared to calculate the fat volume index (FVI) and skeletal muscle index. Adipopenia was defined as the sex-specific lowest quartile of the FVI for the study sample, and sarcopenia was determined using the skeletal muscle index reference value (men, <55 cm2/m2; women, <39 cm2/m2). The association between body composition and outcomes was evaluated using Cox regression analysis. Results A total of 440 patients (median age, 65 years [interquartile range, 58-72 years]; 243 men) were evaluated. Most underweight patients (<20 kg/m2) had adipopenia (97%, 36 of 37 patients), but overweight patients (25-30 kg/m2, n = 138) and obese patients (>30 kg/m2, n = 14) did not have adipopenia (3%, four of 152 patients). In the group with a normal BMI (20-25 kg/m2), 28% (70 of 251 patients) had adipopenia and 67% (168 of 251 patients) had sarcopenia. After adjusting for age, sex, smoking history, surgical procedure, stage, histologic type, BMI, and sarcopenia, adipopenia was associated with reduced 5-year OS (hazard ratio [HR] = 2.2; 95% CI: 1.1, 3.8; P = .02) and 5-year non-cancer-specific OS rates (HR = 3.2; 95% CI: 1.2, 8.7; P = .02). There was no association between adipopenia and postoperative complications (P = .45) or between adipopenia and the 5-year DFS rate (P = .18). Conclusion Baseline adipopenia was associated with a reduced 5-year overall survival rate in patients with early-stage non-small cell lung cancer and may indicate risk for non-cancer-related death. © RSNA, 2021 Online supplemental material is available for this article.

Risk factors for developing post-thymectomy myasthenia gravis in patients with thymoma.

BACKGROUND: Thymectomy is required for the treatment of thymoma-associated myasthenia gravis (MG). However, MG may develop only after thymectomy, a condition known as post-thymectomy MG. This study aimed to investigate the risk factors for post-thymectomy MG in patients with thymoma. METHODS: We retrospectively identified 235 patients with thymoma who underwent thymectomy at a single hospital from January 2008 to December 2017: 44 with preoperatively diagnosed MG were excluded, leaving 191 patients in the final analysis. Univariable survival analyses using Cox proportional hazards regression model and Kaplan-Meier estimate were conducted to identify risk factors for post-thymectomy MG. RESULTS: Post-thymectomy MG developed in 4.2% (8/191) of the patients with thymoma between 18 days and 108 mo after surgery. Hazard ratios (HRs) of pre- and postoperative anti-acetylcholine receptor antibody (AChR-Ab) titers were 2.267 (P = .002) and 1.506 (P < .001), respectively. Patients with extended thymectomy had a low chance of post-thymectomy MG (HR 0.035, P = .007). Larger thymoma (HR, 1.359; P = .005) and type A or AB thymoma according to World Health Organization histological classification (HR, 11.92; P = .021) were associated with higher chances of post-thymectomy MG. Within the subgroup of preoperatively AChR-Ab seropositive patients, post-thymectomy MG developed in 22.2% (6/27). CONCLUSIONS: Pre- and postoperative AChR-Ab levels should be measured in patients with thymoma. A large thymoma and partial thymectomy appear to be associated with a higher probability of post-thymectomy MG.

Outcomes of adjunctive surgery for nontuberculous mycobacterial pulmonary disease.

BACKGROUND: Owing to the unsatisfactory results of antibiotic treatment alone, surgical resection is currently considered as adjunctive therapy in patients with nontuberculous mycobacterial pulmonary disease (NTM-PD). However, reports regarding the outcomes of surgery vary considerably by institution. Here, we investigated the surgical outcomes and risk factors associated with unfavorable outcomes after surgery. METHODS: We analyzed patients with NTM-PD who underwent pulmonary resection at Seoul National University Hospital between January 1, 2006, and December 31, 2020, and assessed the types of surgical procedures, complications, and long-term outcomes. Multivariate logistic regression analysis was used to identify the risk factors associated with treatment refractoriness or recurrence after surgery. RESULTS: Among 67 patients who underwent surgery during the study period, the most common indication for surgery was persistent culture positivity despite rigorous medical treatment (80.6%), followed by longstanding cavitary lesions or radiographic aggravation (10.4%) and massive hemoptysis (4.5%). Among 53 patients with positive mycobacterial cultures at the time of surgery, 38 (71.7%) achieved initial negative culture conversion, 9 (17.0%) of whom experienced recurrence. Nine (13.4%) patients experienced postoperative complications, which were managed without lasting morbidity and mortality. Female sex (adjusted odds ratio [aOR] 6.63; 95% confidence interval [CI] 1.04-42.4; P = .046), preoperative positive mycobacterial culture (aOR 5.87; 95 %CI 1.04-33.08; P = .045), and residual lesions (aOR 6.86; 95 %CI 1.49-31.56; P = .013) were associated with refractoriness or recurrence. CONCLUSIONS: Pulmonary resection is a reasonable treatment modality for patients with refractory NTM-PD or major complications such as massive hemoptysis. The potential risk factors associated with unfavorable outcomes included female sex, preoperative positive mycobacterial culture, and residual lesions after surgery.

Cardiopulmonary resuscitation in pediatric pectus excavatum patients-Where is the heart?

BACKGROUND: In children with pectus excavatum, the posteriorly depressed sternum compresses and displaces the heart. However, the currently recommended compression site and depth for cardiopulmonary resuscitation have not been studied in this population. AIM: This retrospective study investigated the location of the center of ventricles with the largest cross-sectional area to determine the optimal site and depth for chest compressions in pediatric pectus excavatum patients. METHODS: Chest computed tomography images of 94 pediatric pectus excavatum patients before and after correction surgery were compared with normal patients. The caudal displacement of the ventricles was calculated by dividing the length of sternum by the length from the suprasternal notch to the transverse level of the largest cross-sectional area of the ventricles. The proportional leftward deviation of the center of the ventricles from the midline versus transverse diameter of the thorax was calculated. The remaining internal thickness was calculated at the midline assuming the recommended compression depth of one-third of the anterior to posterior diameter. RESULTS: Compared with the normal population (mean = 81% [SD = 10.3%]), pediatric pectus excavatum patients showed caudal displacement of ventricles before (98.2% [15.1%], 95% CI of mean difference; 13.7%-20.5%, P < .001) and after correction (100.4% [13.5%], 95% CI of mean difference; 16.2%-22.5%, P < .001). Compared with the normal population (6.9% [2.7%]), pediatric pectus excavatum patients showed leftward deviation of ventricles before (16.2% [5.5%], 95% CI of mean difference; 8.2%-10.4%, P < .001) and after correction (13.3% [4.8%], 95% CI of mean difference; 5.3%-7.3%, P < .001). The remaining internal thickness assuming the recommended chest compression was <10 mm in 54/94(57.4%) and 18/94 (19.1%) of pediatric pectus excavatum patients before and after correction, respectively. CONCLUSIONS: Pediatric pectus excavatum patients showed significant caudal displacement and leftward deviation of the ventricles compared with the normal population despite correction surgery and the currently recommended compression site and depth might injure intrathoracic structures without effective cardiac compression during cardiopulmonary resuscitation.

Efficacy and Cost-effectiveness of Surgical Biopsy for Histologic Diagnosis of Indeterminate Nodules Suspected for Early Stage Lung Cancer: Comparison with Percutaneous Needle Biopsy.

BACKGROUND: Indeterminate pulmonary nodules (IPN) suspected for early stage lung cancer mandate accurate diagnosis. Both percutaneous needle biopsy (PCNB) and surgical biopsy (SB) are valuable options. The present study aimed to compare the efficacy and cost-effectiveness between PCNB and SB for IPN suspected for early stage lung cancer. METHODS: During January-November 2018, patients who underwent operation for IPN suspected for early stage lung cancer (SB group, n = 245) or operation after PCNB (PCNB group, n = 113) were included. Patient-level cost data were extracted from medical bills from the institution. Propensity score matching was performed between the two groups from a retrospectively-collected database. RESULTS: Fifteen patients (11.5%) had complications after PCNB; thirteen (11.5%) were not confirmed to have lung cancer through PCNB but underwent operation for IPN. In SB group, 172 (70.2%) and 7 (2.9%) patients underwent wedge resection and segmentectomy for SB, respectively; 66 patients (26.9%) underwent direct lobectomy without SB. After propensity score matching, 58 paired samples were produced. Most patients in PCNB group were admitted twice (n = 55, 94.8%). The average hospital stay was longer in PCNB group (12.9 ± 5.3 vs. 7.3 ± 3.0, P < 0.001). Though the cost of the operation was comparable (USD 12,509 ± 2,909 vs. 12,669 ± 3,334; P = 0.782), the total cost was higher for PCNB group (USD 14,403 ± 3,085 vs. 12,669 ± 3,334; P = 0.006). The average subcategory cost, which increases proportional to hospital stay, was higher in PCNB group, whereas the cost of operation and surgical materials were comparable between the two groups. CONCLUSION: Lung cancer operation following SB for IPN was associated with lesser cost, shorter hospital stays, and lesser admission time than lung cancer operation after PCNB. The increased cost and longer hospital stay appear largely related to the admission for PCNB.

A nomogram for predicting recurrence after complete resection for thymic epithelial tumors based on the TNM classification: A multi-institutional retrospective analysis.

OBJECTIVES: This study aimed to compare the predictive ability between the Masaoka-Koga (M-K) staging system and the 8th TNM staging system for the recurrence of thymic epithelial tumors (TETs). In addition, a nomogram was developed on the basis of the proposed TNM classification to predict individual recurrence rate. METHODS: A retrospective study was performed on 445 patients who underwent complete resection (R0) of TETs between January 2000 and February 2013. Concordance index (C-index) was used as a statistical indicator to quantify the prediction power of the prediction models. RESULTS: In multivariate analysis, tumor stage and WHO classification were independent recurrence factors in a predictive model on the basis of M-K and TNM stage. The TNM model showed higher C-index than the M-K model (0.837 vs 0.817). The nomogram, on the basis of the TNM model, revealed a highly predictive performance, with a bootstrap-corrected C-index of 0.85 (95% CI, 0.76 to 0.93). CONCLUSIONS: A predictive model based on the 8th TNM stage was slightly better than that based on M-K stage with respect to recurrence after R0 of TETs. The proposed nomogram could be applied to estimate the individual recurrence rate and make decisions for proper surveillance.

Sleeve Lobectomy for Non-Small Cell Lung Cancers: Predictive CT Features for Resectability and Outcome Analysis.

OBJECTIVE. The purpose of this study was to investigate the CT features predictive of resectability in sleeve lobectomy (SL) for patients with non-small cell lung cancers (NSCLCs) and the outcomes of this procedure. MATERIALS AND METHODS. The study included 45 patients with NSCLCs who planned to undergo SL as a first-line surgical option and underwent SL or pneumonectomy between February 2014 and July 2017. The patients were dichotomized according to whether SL was achieved without residual disease. ROC curve and logistic regression analyses were performed to identify CT features predictive of resectability in SL without residual disease. For outcome analysis, postoperative complications and survival were compared between the two patient groups. RESULTS. SL was successfully performed in 25 patients (55.6%), whereas eight patients underwent SL but had a positive resection margin and 12 required pneumonectomy. The AUC value of the tumor-involved length of the salvage bronchus for SL without residual disease was 0.802, with 5 mm considered the optimal cutoff for this tumor-involved length. A tumor-involved length of 5 mm or less for the salvage bronchus representing the distal anastomosis end in SL was the sole significant predictor for resectability in SL without residual disease in logistic regression analysis (odds ratio, 16.0; 95% CI, 3.7-69.6; p < 0.001). The group of patients who underwent SL without residual disease tended to have a more favorable survival outcome than patients who underwent SL but had residual disease or those who underwent pneumonectomy (p = 0.110), but postoperative complication rates were similar between the two patient groups (20.0% vs 25.0%, respectively). CONCLUSION. A tumor-involved salvage bronchus length of 5 mm or less was a CT feature predictive of resectability in SL without residual disease, which may improve the survival of patients with NSCLCs.

Dual-time point 18F-FDG PET/CT for the staging of oesophageal cancer: the best diagnostic performance by retention index for N-staging in non-calcified lymph nodes.

PURPOSE: The purpose of this study is to investigate the role of dual time point (DTP) 18F-FDG PET/CT in the staging of oesophageal cancer, especially in lymph node metastasis. METHODS: A total of 35 patients with oesophageal squamous cell carcinoma who underwent surgical treatment without neoadjuvant chemotherapy were enrolled as a test set and another 19 patients were enrolled as a validation set. The DTP PET/CT scans were obtained in dual time points at 60 and 120 min each, following the administration of 18F-FDG. Visual analysis was performed and semiquantitative analysis was performed using several PET parameters such as maximal standardized uptake values (SUVmax), peak SUV (SUVpeak) and retention indexes using SUVmax (RImax) and SUVpeak (RIpeak). RESULTS: Primary oesophageal lesions exhibited a significant difference for SUVmax at each time point scan (ANOVA, p < 0.001). For nodal staging, a total of 276 non-calcified nodal stations of the test set were evaluated. Sensitivity, specificity and accuracy of visual analysis were 32.0% (8 of 25), 96.8% (243 of 251) and 90.9% (251 of 276) in the test set. Using ROC analysis, RImax had the largest area under the curve (AUC) to detect metastatic lymphadenopathy at the optimal cut-off value of 6% (AUC 0.853, P < 0.001) in the test set (sensitivity, specificity and accuracy; 80.0% (20 of 25), 94.8% (238 of 251) and 93.5% (258 of 276)). In the validation set (179 non-calcified nodal stations), sensitivity, specificity and accuracy of RImax at the optimal cut-off of 6% were 71.4% (5 of 7), 99.4% (171 of 172) and 98.4% (176 of 179), whereas those of visual analysis were 14.3% (1 of 7), 98.8% (170 of 172) and 95.5% (171 of 179). CONCLUSIONS: The best diagnostic performance of nodal staging in patients with oesophageal cancer was achieved by application of RImax with a cut-off of more than 6% on DTP 18F-FDG PET/CT with the exclusion of calcified lymph nodes. Optimal clinical management in surgically-candidate oesophageal cancer patients could be achieved using the diagnostic flow on DTP 18F-FDG PET/CT.

Serial improvement of quality metrics in pediatric thoracoscopic lobectomy for congenital lung malformation: an analysis of learning curve.

BACKGROUND: Video-assisted thoracic surgery (VATS) pulmonary resection in children is a technically demanding procedure that requires a relatively long learning period. This study aimed to evaluate the serial improvement of quality metrics according to case volume experience in pediatric VATS pulmonary resection of congenital lung malformation (CLM). Methods VATS anatomical resection in CLM was attempted in 200 consecutive patients. The learning curve for the operative time was modeled by cumulative sum analysis. Quality metrics were used to measure technical achievement and efficiency outcomes. Results The median operative time was 95 min. The median length of hospital stay and chest tube indwelling time was 4 and 2 days, respectively. The improvement of operation time was observed persistently until 200 cases. However, two cut-off points, the 50th case and 110th case, were identified in the learning curve for operative time, and the 110th case was the turning point for stable outcomes with short operation time. Significant reduction of length of hospital stay and chest tube indwelling time was observed after 50 cases (p = .002 and p = .021, respectively). The complication rate decreased but continued at a low rate for entire study period and the interval decrease was not statistically significant. Conversion rate decreased significantly (p = .001), and technically challenging procedures were performed more frequently in later cases. Conclusions Improvements of quality metrics in operation time, conversion rate, length of hospital stay, and chest tube indwelling time were observed in proportion to case volume. Minimum experience of 50 is necessary for stable outcomes of pediatric VATS pulmonary resection.

Malignant peripheral nerve sheath tumor in children: A single-institute retrospective analysis.

Malignant peripheral nerve sheath tumors are rare tumors that originate from Schwann cells. Patients with neurofibromatosis type 1 are prone to develop these tumors. Due to their rarity and lack of established treatment, the prognosis of malignant peripheral nerve sheath tumors is poor. A retrospective study was conducted on children treated for malignant peripheral nerve sheath tumors at the Seoul National University Children's Hospital between 2007 and 2016. Eleven patients were diagnosed with malignant nerve sheath tumors at a median age of 12 years, eight of whom had neurofibromatosis type 1. All the patients underwent chemotherapy and received surgical resection, and 5 patients relapsed. The 2-year overall survival rate was 72.7%, and the 2-year event-free survival rate was 58.2%. Univariate analysis was performed to assess the correlations between the clinical factors. There was no statistically significant difference in the overall survival rate according to the patients' clinical factors. However, there was a decreasing trend in the relationship between the event-free survival rate and the prevalence of neurofibromatosis type 1. Regular follow up of neurofibromatosis type 1. Regular follow-up of neurofibromatosis type 1 patients may identify detection of early relapse of malignant peripheral nerve sheath tumors. Genetic studies of these patients and tumors may identify opportunities for targeted therapy.

The transcriptional landscape and mutational profile of lung adenocarcinoma.

All cancers harbor molecular alterations in their genomes. The transcriptional consequences of these somatic mutations have not yet been comprehensively explored in lung cancer. Here we present the first large scale RNA sequencing study of lung adenocarcinoma, demonstrating its power to identify somatic point mutations as well as transcriptional variants such as gene fusions, alternative splicing events, and expression outliers. Our results reveal the genetic basis of 200 lung adenocarcinomas in Koreans including deep characterization of 87 surgical specimens by transcriptome sequencing. We identified driver somatic mutations in cancer genes including EGFR, KRAS, NRAS, BRAF, PIK3CA, MET, and CTNNB1. Candidates for novel driver mutations were also identified in genes newly implicated in lung adenocarcinoma such as LMTK2, ARID1A, NOTCH2, and SMARCA4. We found 45 fusion genes, eight of which were chimeric tyrosine kinases involving ALK, RET, ROS1, FGFR2, AXL, and PDGFRA. Among 17 recurrent alternative splicing events, we identified exon 14 skipping in the proto-oncogene MET as highly likely to be a cancer driver. The number of somatic mutations and expression outliers varied markedly between individual cancers and was strongly correlated with smoking history of patients. We identified genomic blocks within which gene expression levels were consistently increased or decreased that could be explained by copy number alterations in samples. We also found an association between lymph node metastasis and somatic mutations in TP53. These findings broaden our understanding of lung adenocarcinoma and may also lead to new diagnostic and therapeutic approaches.

Multifocal synchronous mucinous adenocarcinomas arising in congenital pulmonary airway malformation: a case report with molecular study.

AIMS: Congenital pulmonary airway malformation (CPAM) is a rare developmental anomaly of the lung. Here, we report a case of mucinous adenocarcinoma arising in CPAM. A 23-month-old boy underwent a thoracoscopic lobectomy of the left upper lobe of the lung based on a presumptive diagnosis of asymptomatic CPAM, found in antenatal sonogram. METHODS AND RESULTS: Histologically, the lesion was consistent with CPAM, Stocker type I. In addition, multiple foci ranging from mucinous epithelial hyperplasia to mucinous adenocarcinoma were detected. All lesions shared the same immunoprofile with the expression of cytokeratin (CK) 20, MUC5AC, and human epidermal growth factor receptor2 (HER2), but were negative for CK7, transcription factor 1 (TTF-1), MUC1, CDX2, BRAF (VE1) and anaplastic lymphoma kinase (ALK). K-RAS point mutation (G12V) was also detected in all micro-dissected mucinous lesions but EGFR mutation was not found. All lesions were consistent with mucinous adenocarcinoma. The patient's clinical course has been uneventful during the 12-months follow-up period. CONCLUSIONS: This interesting case demonstrated that multiple foci in CPAM can synchronously transform into malignancies.

Safety of Perioperative Maintenance of Antiplatelet Agents in Elderly Patients Undergoing Lung Cancer Surgery.

Background: The maintenance of antiplatelet therapy increases the risk of bleeding during lung cancer surgery. Conversely, the perioperative interruption of antiplatelet therapy may result in serious thrombotic complications. This study aimed to investigate the safety of continuing antiplatelet therapy in the context of lung cancer surgery. Methods: We retrospectively reviewed a cohort of 498 elderly patients who underwent surgery for lung cancer. These patients were categorized into 2 groups: group N, which did not receive antiplatelet therapy, and group A, which did. Group A was subsequently subdivided into group Am, where antiplatelet therapy was maintained, and group Ai, where antiplatelet therapy was interrupted. We compared the incidence of bleeding-related and thrombotic complications across the 3 groups. Results: There were 387 patients in group N and 101 patients in group A (Ai: 70, Am: 31). No significant differences were found in intraoperative blood loss, thoracotomy conversion rates, transfusion requirements, volume of chest tube drainage, or reoperation rates for bleeding control between groups N and A or between groups Am and Ai. The duration of hospital stay was longer for group A compared to group N (7 days vs. 6 days, p=0.005), but there was no significant difference between groups Ai and Am. The incidence of cardiovascular or cerebrovascular complications did not differ significantly between groups Ai and Am. However, group Ai included a severe case of in-hospital ST-elevation myocardial infarction. Conclusion: The maintenance of antiplatelet therapy was found to be safe in terms of perioperative bleeding and thrombotic complications in elderly lung cancer surgery patients.

Treatment of Fanconi anemia patient with synchronous esophageal and tongue cancer in COVID-19 era: a case report.

Although Fanconi anemia patients accompany a high risk of multiple cancers, radiation therapy on these patients has been carried out only in limited cases due to the concern for radiation toxicity that stems from their susceptibility to radiation. We report a case of a 28-year-old female patient diagnosed as synchronous esophageal and tongue cancer, and underwent two cycles of radiation therapy, inevitably in the condition of coronavirus disease 2019 infection. She received radiation therapy of 30 Gy to esophageal mass with neoadjuvant aim in her first-round radiation therapy, and later received 27 Gy to tongue cancer surgical bed with adjuvant aim in her second-round radiation therapy. With no further treatment, she has been maintaining no evidence of disease state for 7 months. Managing Fanconi anemia patients with multiple cancers using radiation therapy is feasible, in which cases a dose de-escalation may be important considering the radiation toxicity and possible future re-treatment.

Fetal Lung Interstitial Tumor: A Comprehensive Case Study with an Emphasis on Next-Generation Sequencing.

Fetal lung interstitial tumor (FLIT), which is characterized by immature interstitial cells resembling the fetal lung parenchyma of 20 to 24 weeks of gestation, is a rare respiratory neoplasm. This study presents the first reported FLIT in Korea. It also aims to refine the diagnostic method of FLIT and increase the accuracy of prognostic assessment by using next-generation sequencing to check for anaplastic lymphoma receptor tyrosine kinase (anaplastic lymphoma kinase) gene rearrangement. Although the initial prognosis for FLIT has been promising since its first report in 2010, certain pathological features are associated with poorer outcomes. Therefore, achieving an accurate diagnosis of FLIT is crucial for avoiding unnecessary treatments beyond surgical resection.

Safety of lung resection surgery after severe acute respiratory syndrome coronavirus 2 infection in the post-vaccination era.

OBJECTIVES: To investigate the postoperative outcomes of lung resection in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and determine the optimal timing of surgery. METHODS: This retrospective, single-centre cohort study included patients who underwent lung resection between June 2021 and June 2022. Patients were divided into the coronavirus disease 2019 (COVID-19) and non-COVID-19 groups based on their preoperative SARS-CoV-2 infection history, and postoperative outcomes were compared. Logistic regression analysis was conducted to identify the risk factors of complications after lung resection surgery. RESULTS: In total, 1194 patients were enrolled, of whom, 79 had a history of SARS-CoV-2 infection. In the COVID-19 group, 66 patients (90.4%) had received at least 1 vaccination dose. The average interval between infection and surgery was 67 days, with no significant impact on postoperative outcomes. Regarding postoperative outcomes, there were no significant differences in major complication rate (6.3% vs 5.4%, P = 0.613), respiratory complication rate (19.0% vs 12.2%, P = 0.079) or length of stays (4.9 ± 3.4 vs 5.0 ± 5.6, P = 0.992) between the 2 groups. Multivariate logistic regression analysis revealed that age, male sex, poor pulmonary function test, open surgery and extensive lung resection were risk factors for postoperative complications, while preoperative COVID-19 infection status was not a statistically significant risk factor. CONCLUSIONS: In the post-vaccination era, lung resection surgery can be safely performed shortly after SARS-CoV-2 infection, even within 4 weeks of infection.