Proteogenomics of Non-smoking Lung Cancer in East Asia Delineates Molecular Signatures of Pathogenesis and Progression.

Lung cancer in East Asia is characterized by a high percentage of never-smokers, early onset and predominant EGFR mutations. To illuminate the molecular phenotype of this demographically distinct disease, we performed a deep comprehensive proteogenomic study on a prospectively collected cohort in Taiwan, representing early stage, predominantly female, non-smoking lung adenocarcinoma. Integrated genomic, proteomic, and phosphoproteomic analysis delineated the demographically distinct molecular attributes and hallmarks of tumor progression. Mutational signature analysis revealed age- and gender-related mutagenesis mechanisms, characterized by high prevalence of APOBEC mutational signature in younger females and over-representation of environmental carcinogen-like mutational signatures in older females. A proteomics-informed classification distinguished the clinical characteristics of early stage patients with EGFR mutations. Furthermore, integrated protein network analysis revealed the cellular remodeling underpinning clinical trajectories and nominated candidate biomarkers for patient stratification and therapeutic intervention. This multi-omic molecular architecture may help develop strategies for management of early stage never-smoker lung adenocarcinoma.

CT-Based Deep-Learning Model for Spread-Through-Air-Spaces Prediction in Ground Glass-Predominant Lung Adenocarcinoma.

BACKGROUND: Sublobar resection is strongly associated with poor prognosis in early-stage lung adenocarcinoma, with the presence of tumor spread through air spaces (STAS). Thus, preoperative prediction of STAS is important for surgical planning. This study aimed to develop a STAS deep-learning (STAS-DL) prediction model in lung adenocarcinoma with tumor smaller than 3 cm and a consolidation-to-tumor (C/T) ratio less than 0.5. METHODS: The study retrospectively enrolled of 581 patients from two institutions between 2015 and 2019. The STAS-DL model was developed to extract the feature of solid components through solid components gated (SCG) for predicting STAS. The STAS-DL model was assessed with external validation in the testing sets and compared with the deep-learning model without SCG (STAS-DLwoSCG), the radiomics-based model, the C/T ratio, and five thoracic surgeons. The performance of the models was evaluated using area under the curve (AUC), accuracy and standardized net benefit of the decision curve analysis. RESULTS: The study evaluated 458 patients (institute 1) in the training set and 123 patients (institute 2) in the testing set. The proposed STAS-DL yielded the best performance compared with the other methods in the testing set, with an AUC of 0.82 and an accuracy of 74%, outperformed the STAS-DLwoSCG with an accuracy of 70%, and was superior to the physicians with an AUC of 0.68. Moreover, STAS-DL achieved the highest standardized net benefit compared with the other methods. CONCLUSION: The proposed STAS-DL model has great potential for the preoperative prediction of STAS and may support decision-making for surgical planning in early-stage, ground glass-predominant lung adenocarcinoma.

Stented cryopreserved aortic allograft for reconstruction of long-segment post-tuberculosis tracheal stenosis.

Tracheobronchial tuberculosis is one of the conditions causing long segment tracheal stenosis and is a clinically challenging scenario. This report describes a successful tracheal reconstruction in a 44-year-old man with long-segment post-tuberculosis tracheobronchial stenosis, utilizing a stented cryopreserved aortic allograft. The procedure was necessitated by the failure of conventional treatments. The stenotic segment was resected and replaced with a cryopreserved aortic allograft, supported by a metallic stent to maintain airway patency. Post-surgery, the patient experienced resolution of dyspnea without major complications. Currently, at 33 months post-operation, the patient enjoys an enhanced quality of life with effective breathing, speaking, swallowing abilities, and has resumed normal daily activities, with regular bronchoscopic follow-ups. This report demonstrates a novel approach for managing challenging tuberculosis-induced long segment airway stenosis.

Dexmedetomidine for enhanced recovery after non-intubated video-assisted thoracoscopic surgery.

BACKGROUND: Non-intubated video-assisted thoracoscopic surgery combines a minimally invasive technique with multimodal locoregional analgesia to enhance recovery. The mainstay sedation protocol involves propofol and fentanyl. Dexmedetomidine, given its opioid-sparing effect with minimal respiratory depression, facilitates sedation in non-intubated patients. This study aimed to evaluate the efficacy of dexmedetomidine during non-intubated video-assisted thoracoscopic surgery. METHODS: A total of 114 patients who underwent non-intubated video-assisted thoracoscopic surgery between June 2015 and September 2017 were retrospectively evaluated. Of these, 34 were maintained with dexmedetomidine, propofol, and fentanyl, and 80 were maintained with propofol and fentanyl. After a 1:1 propensity score-matched analysis incorporating sex, body mass index, American Society of Anesthesiologists classification, pulmonary disease and hypertension, the clinical outcomes of 34 pairs of patients were assessed. RESULTS: The dexmedetomidine group showed a significantly lower opioid consumption [10.3 (5.7-15.1) vs. 18.8 (10.0-31.0) mg, median (interquartile range); P = 0.001] on postoperative day 0 and a significantly shorter postoperative length of stay [3 (2-4) vs. 4 (3-5) days, median (interquartile range), P = 0.006] than the control group. During operation, the proportion of vasopressor administration was significantly higher in the dexmedetomidine group [18 (53) vs. 7 (21), patient number (%), P = 0.01]. On the other hand, the difference of the hypotension and bradycardia incidence, short-term morbidity and mortality rates between each group were nonsignificant. CONCLUSIONS: Adding adjuvant dexmedetomidine to propofol and fentanyl is safe and feasible for non-intubated video-assisted thoracoscopic surgery. With its opioid-sparing effect and shorter postoperative length of stay, dexmedetomidine may enhance recovery after surgery.

Tissue Proteogenomic Landscape Reveals the Role of Uncharacterized SEL1L3 in Progression and Immunotherapy Response in Lung Adenocarcinoma.

The fundamental pursuit to complete the human proteome atlas and the unmet clinical needs in lung adenocarcinoma have prompted us to study the functional role of uncharacterized proteins and explore their implications in cancer biology. In this study, we characterized SEL1L3, a previously uncharacterized protein encoded from chromosome 4 as a dysregulated protein in lung adenocarcinoma from the large-scale tissue proteogenomics data set established using the cohort of Taiwan Cancer Moonshot. SEL1L3 was expressed in abundance in the tumor parts compared with paired adjacent normal tissues in 90% of the lung adenocarcinoma patients in our cohorts. Moreover, survival analysis revealed the association of SEL1L3 with better clinical outcomes. Intriguingly, silencing of SEL1L3 imposed a reduction in cell viability and activation of ER stress response pathways, indicating a role of SEL1L3 in the regulation of cell stress. Furthermore, the immune profiles of patients with higher SEL1L3 expression were corroborated with its active role in immunophenotype and favorable clinical outcomes in lung adenocarcinoma. Taken together, our study revealed that SEL1L3 might play a vital role in the regulation of cell stress, interaction with cancer cells and the immune microenvironment. Our research findings provide promising insights for further investigation of its molecular signaling network and also suggest SEL1L3 as a potential emerging adjuvant for immunotherapy in lung adenocarcinoma.

Tafenoquine and its derivatives as inhibitors for the severe acute respiratory syndrome coronavirus 2.

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has severely affected human lives around the world as well as the global economy. Therefore, effective treatments against COVID-19 are urgently needed. Here, we screened a library containing Food and Drug Administration (FDA)-approved compounds to identify drugs that could target the SARS-CoV-2 main protease (Mpro), which is indispensable for viral protein maturation and regard as an important therapeutic target. We identified antimalarial drug tafenoquine (TFQ), which is approved for radical cure of Plasmodium vivax and malaria prophylaxis, as a top candidate to inhibit Mpro protease activity. The crystal structure of SARS-CoV-2 Mpro in complex with TFQ revealed that TFQ noncovalently bound to and reshaped the substrate-binding pocket of Mpro by altering the loop region (residues 139-144) near the catalytic Cys145, which could block the catalysis of its peptide substrates. We also found that TFQ inhibited human transmembrane protease serine 2 (TMPRSS2). Furthermore, one TFQ derivative, compound 7, showed a better therapeutic index than TFQ on TMPRSS2 and may therefore inhibit the infectibility of SARS-CoV-2, including that of several mutant variants. These results suggest new potential strategies to block infection of SARS-CoV-2 and rising variants.

Discrimination of invasive lung adenocarcinoma from Lung-RADS category 2 nonsolid nodules through visual assessment: a retrospective study.

OBJECTIVES: Invasive adenocarcinomas (IADs) have been identified among nonsolid nodules (NSNs) assigned as Lung Imaging Reporting and Data System (Lung-RADS) category 2. This study used visual assessment for differentiating IADs from noninvasive lesions (NILs) in this category. METHODS: This retrospective study included 222 patients with 242 NSNs, which were resected after preoperative computed tomography (CT)-guided dye localization. Visual assessment was performed by using the lung and bone window (BW) settings to classify NSNs into BW-visible (BWV) and BW-invisible (BWI) NSNs. In addition, nodule size, shape, border, CT attenuation, and location were evaluated and correlated with histopathological results. Logistic regression was performed for multivariate analysis. A p value of < 0.05 was considered statistically significant. RESULTS: A total of 242 NSNs (mean diameter, 7.6 ± 2.8 mm), including 166 (68.6%) BWV and 76 (31.4%) BWI NSNs, were included. IADs accounted for 31% (75) of the nodules. Only 4 (5.3%) IADs were identified in the BWI group and belonged to the lepidic-predominant (n = 3) and acinar-predominant (n = 1) subtypes. In univariate analysis for differentiating IADs from NILs, the nodule size, shape, CT attenuation, and visual classification exhibited statistical significance. Nodule size and visual classification were the significant predictors for IAD in multivariate analysis with logistic regression (p < 0.05). The sensitivity, specificity, positive predictive value, and negative predictive value of visual classification in IAD prediction were 94.7%, 43.1%, 42.8%, and 94.7%, respectively. CONCLUSIONS: The window-based visual classification of NSNs is a simple and objective method to discriminate IADs from NILs. CLINICAL RELEVANCE STATEMENT: The present study shows that using the bone window to classify nonsolid nodules helps discriminate invasive adenocarcinoma from noninvasive lesions. KEY POINTS: • Evidence has shown the presence of lung adenocarcinoma in Lung-RADS category 2 nonsolid nodules. • Nonsolid nodules are classified into the bone window-visible and the bone window-invisible nonsolid nodules, and this classification differentiates invasive adenocarcinoma from noninvasive lesions. • The Lung-RADS category 2 nonsolid nodules are unlikely invasive adenocarcinoma if they show nonvisualization in the bone window.

Efficacy of intraoperative thoracoscopic intercostal nerve blocks in nonintubated and intubated video-assisted thoracic surgery: A randomized study.

BACKGROUND: The efficacy of thoracoscopic intercostal nerve blocks (TINBs) for noxious stimulation from video-assisted thoracic surgery (VATS) remains unclear. The efficacy of TINBs may also be different between nonintubated VATS (NIVATS) and intubated VATS (IVATS). We aim to compare the efficacy of TINBs on analgesia and sedation for NIVATS and IVATs intraoperatively. METHODS: Sixty patients randomized to the NIVATS or IVATS group (30 each) received target-controlled propofol and remifentanil infusions, with bispectral index (BIS) maintained at 40-60, and multilevel (T3-T8) TINBs before surgical manipulations. Intraoperative monitoring data, including pulse oximetry, mean arterial pressure (MAP), heart rate, BIS, density spectral arrays (DSAs), and propofol and remifentanil effect-site concentration (Ce) at different time points. A two way ANOVA with post hoc analysis was applied to analyze the differences and interactions of groups and time points. RESULTS: In both groups, DSA monitoring revealed burst suppression and α dropout immediately after the TINBs. The Ce of the propofol infusion had to be reduced within 5 min post-TINBs in both NIVATS (p < 0.001) and IVATS (p = 0.252) groups. The Ce of remifentanil infusion was significantly reduced after TINBs in both groups (p < 0.001), and was significantly lower in NIVATS (p < 0.001) without group interactions. CONCLUSION: The surgeon-performed intraoperative multilevel TINBs allow reduced anesthetic and analgesic requirement for VATS. With lower requirement of remifentanil infusion, NIVATS presents a significantly higher risk of hypotension after TINBs. DSA is beneficial for providing real-time data that facilitate the preemptive management, especially for NIVATS.

Comparisons on the intraoperative desaturation and postoperative outcomes in non-intubated video-assisted thoracic surgery with supraglottic airway devices or high-flow nasal oxygen: A retrospective study.

BACKGROUND: Few studies have compared intraoperative oxygenation and perioperative outcomes between non-intubated video-assisted thoracic surgery (NIVATS) with supraglottic airway devices (SADs) and NIVATS with high flow nasal oxygenation (HFNO). The aim of this retrospective study was to compare the intraoperative desaturation rate and postoperative outcomes between NIVATS with SADs and NIVATS with HFNO. METHODS: Data regarding NIVATS performed for lung cancer from January 2020 to December 2021 were collected. Intraoperative anesthetic results, post-anesthetic adverse effects, and surgical outcomes for patients who received SAD or HFNO were analyzed using propensity score-matched and unmatched analysis. RESULTS: In total, 199 patients with i-gel™ and 95 patients with HFNO were included. Significantly more female patients (91.6 vs. 82.4%, p = 0.0378) and fewer wedge resections (78.9 vs. 85.4%, p = 0.0258) were observed in the HFNO group. Among 250 patients who underwent NIVATS wedge resections under total intravenous anesthesia, those who received HFNO had a significantly higher desaturation event rate (19.8% vs. 7.9% in i-gel™ group; p = 0.0063), lower nadir SPO2 (94.0% vs. 96.1% in i-gel™ group; p = 0.0012), and longer hospitalization (4.0 ± 0.8 vs. 3.6 ± 0.6 in i-gel™ group; p < 0.0001). However, propensity score matching analysis revealed no significant between-group difference in the desaturation rate. A log-rank test revealed that smoking (p = 0.0005) and HFNO (p = 0.0074) were associated with intraoperative desaturation. CONCLUSION: The rate of SAD use in NIVATS was twice the rate of HFNO use, especially for wedge resections. There is uncertain airway patency and limited flow through HFNO during one-lung ventilation, whereas SADs like i-gel™ presented a significantly less intraoperative desaturation rate over time and similar postoperative outcomes.

Application of aortic allograft in trachea transplantation.

BACKGROUND: The use of tracheal implants for tracheal reconstruction remains a challenge in thoracic medicine due to the complex structure of the trachea in mammalian organisms, including smooth muscles, cartilage, mucosa, blood vessels, cilia, and other tissues, and the difficulty in achieving tracheal regeneration using implants from either allografts or synthetic biomaterials. METHODS: This project used the Lee-Sung strain pig, a swine breed local to Taiwan, as the experimental subject. The aorta of the pig was harvested, decellularized to form the scaffold, and transplanted into the trachea of allogeneic pigs together with growth factors. Postoperative physiological function and tissue changes were observed. The postoperative physiological parameters of the LSP were monitored, and they were sacrificed after a certain period to observe the pathological changes in the tracheal epithelial cells and cartilages. RESULTS: Overall, six LSP tracheal transplantations were performed between March 4, 2020, and March 10, 2021. These included aortic patch anastomosis for pig 1 and aortic segmental anastomosis for pigs 2-6. The shortest and longest survival periods were 1 day and 147 days, respectively. Excluding the pig that survived for only 1 day due to a ruptured graft anastomosis, all other subjects survived for over 1 month on average. CONCLUSION: In this study, we grafted a decellularized porcine aorta into a recipient pig with a tracheal defect. We found cryopreservation of the allogeneic aorta transplantation was a feasible and safe method for the management of airway disease, and immunosuppressants were unnecessary during the treatment course.

Uniportal versus multiportal nonintubated thoracoscopic anatomical resection for lung cancer: A propensity-matched analysis.

BACKGROUND/PURPOSE: No studies have compared between uniportal and multiportal nonintubated thoracoscopic anatomical resection for non-small cell lung cancer (NSCLC). We aimed to compare short- and long-term postoperative outcomes concerning these two methods. METHODS: Our retrospective dataset comprised patients with NSCLC who underwent uniportal or multiportal nonintubated thoracoscopic anatomical resection between January 2011 and December 2019. The primary outcome was recurrence-free survival. Propensity scores were matched according to age, sex, body mass index, pulmonary function, tumor size, cancer stage, and surgical method. RESULTS: In total, 1130 such patients underwent nonintubated video-assisted thoracoscopic surgery (VATS), and 490 consecutive patients with stage I-III NSCLC underwent nonintubated anatomical resection, including lobectomy and segmentectomy (uniportal, n = 158 [32.3%]; multiportal, n = 331 [67.7%]). The uniportal group had fewer dissected lymph nodes and lymph node stations. In paired group analysis, the uniportal group had shorter operation durations (99.8 vs. 138.2 min; P < 0.001), lower intensive care unit (ICU) admission rates and ICU admission intervals (7.0% vs. 27.8%; P < 0.001), and shorter postoperative hospital stays (4.1 days vs. 5.2 days; P < 0.001). The most common postoperative complication was prolonged air leaks. No surgical mortality was observed. The multiportal group had higher complication rates for grades ≥ II NSCLC; however, this difference was not significant (4.4% vs. 1.3%, respectively; P = 0.09). CONCLUSION: Nonintubated uniportal VATS for anatomical resection had better results for some perioperative outcomes than multiportal VATS. Oncological outcomes such as recurrence-free and overall survival remained uncompromised, despite fewer dissected lymph nodes.

Primary Tumor Resection for Stage IV Non-small-cell Lung Cancer Without Progression After First-Line Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitor Treatment: A Retrospective Case-Control Study.

BACKGROUND: In studies of stage IV epidermal growth factor receptor (EGFR)-mutant nonsmall-cell lung cancer (NSCLC), <10% of patients underwent surgery; thus, the effect of surgery in these patients remains unclear. We investigated whether primary lung tumor resection could improve the survival of patients with stage IV EGFR-mutant NSCLC without progression after first-line EGFR-tyrosine kinase inhibitor (EGFR-TKI) treatment. METHODS: This retrospective case-control study included patients treated with first-line EGFR-TKIs without progression on follow-up imaging. Patients in the surgery group (n = 56) underwent primary tumor resection, followed by TKI maintenance therapy. Patients in the control group (n = 224; matched for age, metastatic status, and Eastern Cooperative Oncology Group performance status) received only TKI maintenance therapy. Local ablative therapy for distant metastasis was allowed in both groups. The primary endpoint was progression-free survival. The secondary endpoints were overall survival, failure patterns, and complications/adverse events. RESULTS: The median time from TKI treatment to surgery was 5.1 months. For the surgery and control groups, the median follow-up periods were 34.0 and 38.5 months, respectively, with a median (95% confidence interval) progression-free survival of 29.6 (18.9-40.3) and 13.0 (11.8-14.2) months, respectively (P < 0.001). Progression occurred in 29/56 (51.8%) and 207/224 (92.4%) patients, respectively. The median overall survival in the surgery group was not reached. The rate of surgical complications of grade ≥2 was 12.5%; complications were treated conservatively. CONCLUSIONS: Primary tumor resection is feasible for patients with EGFR-mutant nonprogressed NSCLC during first-line EGFR-TKI treatment and may improve survival better than maintenance EGFR-TKI therapy alone.

Video-assisted thoracoscopic surgery for primary pulmonary cryptococcosis.

BACKGROUND: The surgical outcome for primary pulmonary cryptococcosis remains unclear. In this study, we investigated the clinical characteristics, treatment, and outcomes of video-assisted thoracoscopic surgery (VATS) for primary pulmonary cryptococcosis. METHODS: We retrospectively reviewed the medical records of 49 patients with confirmed pulmonary cryptococcosis who underwent VATS for pulmonary nodules at the National Taiwan University Hospital between May 2013 and March 2019. Serum cryptococcal antigen (CryAg)-positive and CryAg-negative patients were compared. RESULTS: The diagnosis of pulmonary cryptococcosis was confirmed using histopathology or tissue swab culture. The mean age of the patients was 56.0 ± 12.2 years, and 27 patients (55.1%) were male. Most patients were asymptomatic (67.3%) and admitted following the detection of pulmonary lesions on a computed tomography scan of the chest. A greater proportion of patients in the CryAg-positive group (62.5%) underwent lobectomy compared with those in the CryAg-negative group (7.3%, P < 0.001). Three patients (6.1%) had neurological symptoms (headache or dizziness) and all were serum CryAg-positive. One patient with Cryptococcus gattii developed fluctuating serum CryAg titers after a 12-month antifungal treatment. No relapse occurred in the remaining 48 patients, irrespective of postoperative antifungal treatment. CONCLUSION: In patients with primary pulmonary cryptococcosis, serum CryAg detection rate is low, and VATS was an effective and safe diagnostic and therapeutic tool.

Comparison of perioperative outcomes between intubated and nonintubated thoracoscopic surgery in children.

BACKGROUND/PURPOSE: This study aimed to compare our experiences of nonintubated video-assisted thoracoscopic surgery (VATS) for pneumothorax and lung tumor resections with that of intubated VATS in pediatric patients. METHODS: In total, 17 nonintubated and 64 intubated pediatric VATS were performed between January 2012 and December 2018. Patient characteristics, operation period, comorbidities, precedent lung surgery, diagnosis, type of anesthesia, side and type of procedure, and perioperative outcomes were collected from medical records. Perioperative outcome data included induction time, operation time, postoperative chest tube drainage duration, and length of stay. Simple linear regression and multiple linear regression analyses were used to determine the influence of selected variables on perioperative outcomes. RESULTS: The mean age was 16.2 years in the intubated group and 15.2 years in the nonintubated group. Comorbidities including malignancy and asthma were noted in 9 intubated patients and 6 nonintubated patients. Nonintubated VATS was performed in 9 pneumothorax surgeries and 8 lung tumor resections. Five patients breathed oxygen through a face mask, 3 patients through a high-flow nasal cannula, and 9 patients through a laryngeal mask airway. No patient required tracheal intubation or thoracotomy. No major operative complications were noted in either group. After adjustments for statistically relevant confounders, the multiple regression analysis showed that the nonintubated technique influenced the length of stay, leading to a reduction of 0.75 days. CONCLUSION: Nonintubated VATS is feasible and safe in selected children undergoing bullectomy or wedge resections for lung tumors. The nonintubated approach might enhance postoperative recovery.

Undiagnosed solitary caseating granulomas: Is lung resection surgery a feasible method for diagnosis and treatment?

BACKGROUND: In many patients, low-dose computed tomography (CT) screening for lung cancer reveals asymptomatic pulmonary nodules. Lung resection surgery may be indicated in these patients; however, distinguishing malignancies from benign lesions preoperatively can be challenging. METHODS: From 2013 to 2018, 4181 patients undergoing surgery for pulmonary nodules were reviewed at National Taiwan University Hospital, and 837 were diagnosed with benign pathologies. Only patients with pathological diagnosis as caseating granulomatous inflammation were included, sixty-nine patients were then analyzed for preoperative clinical and imaging characteristics, surgical methods and complications, pathogens, medical treatment and outcomes. Mycobacterial evidence was obtained from the culture of respiratory or surgical specimen. RESULTS: Overall, 68% of the patients were asymptomatic before surgery. More than half of the nodules were in the upper lobes, and all patients underwent video-assisted thoracoscopic surgery (VATS). Some patients (14.5%) developed grade I complications, and the mean postoperative hospital stay was 4 days. The final pathology reports of 20% benign entities postoperatively, and caseating granulomatous inflammation accounted for a significant part. MTB and NTM were cultured from one-fourth of the patients respectively. All patients with confirmed MTB infection received antimycobacterial treatment, while the medical treatment in NTM-infected patients was decided by the infectious disease specialists. The mean follow-up period was 736 days, and no recurrence was found. CONCLUSION: Lung resection surgery is an aggressive but safe and feasible method for diagnosing MTB- or NTM-associated pulmonary nodules, and, potentially, an effective therapeutic tool for patients with undiagnosed MTB- or NTM-associated pulmonary nodules.

Thoracoscopic Wedge Resection Versus Segmentectomy for cT1N0 Lung Adenocarcinoma.

BACKGROUND: The choice between wedge resection and segmentectomy as a sublobar resection method for patients with cT1N0 lung cancer remains debatable. This study aimed to evaluate the clinical outcomes after wedge resection and segmentectomy for patients with cT1N0 lung adenocarcinoma. METHODS: The study enrolled 1002 consecutive patients with cT1N0 lung adenocarcinoma who underwent sublobar resection at the authors' institution between 2011 and 2017. A propensity score-matching analysis was used to compared the clinical outcomes between the wedge resection and segmentectomy groups. RESULTS: Wedge resection was performed for 810 patients (80.8%), and segmentectomy was performed for 192 patients (19.2%). Wedge resection resulted in better perioperative outcomes than segmentectomy. The multivariate analysis showed that the significant risk factors for poor disease-free survival (DFS) were elevated preoperative serum carcinoembryonic antigen levels, total tumor diameter greater than 2 cm, and a consolidation-to-tumor (C/T) ratio higher than 50%. After propensity-matching, no differences in overall survival or DFS were noted between the two matched groups. However, subgroup analysis showed that segmentectomy was associated with better DFS than wedge resection (p = 0.039) for the patients with a tumor diameter greater than 2 cm and a C/T ratio higher than 50%. CONCLUSION: Segmentectomy is the appropriate surgical method for sublobar resection in cT1N0 lung adenocarcinoma patients with a tumor diameter greater than 2 cm and a C/T ratio higher than 50%. Wedge resection may be a safe and feasible sublobar resection method for patients with a tumor diameter of 2 cm or smaller or a C/T ratio of 50% or lower.

Detecting small pulmonary nodules with spiral ultrashort echo time sequences in 1.5 T MRI.

OBJECTIVE: This study investigated ultrashort echo time (UTE) sequences in 1.5 T magnetic resonance imaging (MRI) for small lung nodule detection. MATERIALS AND METHODS: A total of 120 patients with 165 small lung nodules before video-associated thoracoscopic resection were enrolled. MRI sequences included conventional volumetric interpolated breath-hold examination (VIBE, scan time 16 s), spiral UTE (TE 0.05 ms) with free-breathing (scan time 3.5-5 min), and breath-hold sequences (scan time 20 s). Chest CT provided a standard reference for nodule size and morphology. Nodule detection sensitivity was evaluated on a lobe-by-lobe basis. RESULTS: The nodule detection rate was significantly higher in spiral UTE free-breathing (> 78%, p < 0.05) and breath-hold sequences (> 75%, p < 0.05) compared with conventional VIBE (> 55%), reaching 100% when nodule size was > 16 mm, and reaching 95% when nodules were in solid morphology, regardless of size. The inter-sequence reliability between free-breathing and breath-hold spiral UTE was good (κ > 0.80). Inter-reader agreement was also high (κ > 0.77) for spiral UTE sequences. Nodule size measurements were consistent between CT and spiral UTE MRI, with a minimal bias up to 0.2 mm. DISCUSSION: Spiral UTE sequences detect small lung nodules that warrant surgery, offers realistic scan times for clinical work, and could be implemented as part of routine lung MRI.

Recurrence rate and risk factors for recurrence after thoracoscopic surgery for primary spontaneous pneumothorax: A nationwide population-based study.

PURPOSE: This large-scale nationwide population-based study aimed to determine the recurrence rate and risk factors for recurrence after video-assisted thoracoscopic surgery (VATS) for primary spontaneous pneumothorax (PSP). METHODS: This retrospective study used data from the Taiwan National Health Insurance Database to identify individuals who underwent VATS for PSP from 2007 to 2014. All patients were followed up until December 31, 2017. Study variables included demographic characteristics, intensive care unit admission, lung resection status, use of non-steroidal anti-inflammatory drugs (NSAIDs), and hospital level. The primary outcome was 1-year recurrence, and the secondary outcomes were the 1-year rate of reintervention for recurrence and overall recurrence rate. RESULTS: During the study period, 6654 patients underwent VATS for PSP (average age: 23.2 years, 89.1% male), including 910 patients (13.7%) who experienced recurrence within 1 year and 531 patients (8.0%) who required reintervention within 1 year. The overall recurrence rate was 24.8%, with an average follow-up time of 6.7 years. Age ≤18 years and the use of NSAIDs, especially ketorolac, were significant risk factors for 1-year recurrence and overall recurrence. Younger age was a risk factor for 1-year reintervention. In subgroup analysis, NSAID use was a significant risk factor for 1-year recurrence, 1-year reintervention, and overall recurrence in pediatric patients but not in adult patients. CONCLUSIONS: In Taiwan, the 1-year recurrence rate was 13.7% after VATS for PSP. Younger age and the use of NSAIDs, especially ketorolac, were significant risk factors for short- and long-term recurrence after VATS for PSP.

Long-term outcomes after nonintubated versus intubated thoracoscopic lobectomy for clinical stage I non-small cell lung cancer: A propensity-matched analysis.

BACKGROUND: Nonintubated thoracoscopic lobectomy has been described as a feasible surgical treatment for early-stage lung cancer since 2011. Despite promising perioperative results, studies on tumor recurrence and long-term survival are very limited. This study was aimed to compare outcomes after thoracoscopic lobectomy with versus without intubation for stage I non-small cell lung cancer. METHODS: A retrospective data set including 115 and 155 patients who underwent nonintubated and intubated thoracoscopic lobectomy, respectively, between January 2011 and December 2013 was used to identify matched nonintubated and intubated cohorts (n = 97 per group) using a propensity score matching algorithm that accounted for confounding effects of preoperative patient variables. Primary outcome variables included freedom from recurrence and overall survival. Factors affecting survival were assessed using Cox regression analysis and Kaplan-Meier survival estimates. RESULTS: No perioperative mortality occurred in both groups. At an average follow-up of 74 months, comparing nonintubated thoracoscopic lobectomy with intubated procedure, no differences were observed in recurrence rates (14.4% vs. 25.8%, respectively; p = .057). Furthermore, no significant differences were noted in overall survival (97.9% vs. 93.8%, respectively; p = .144). Nonintubated thoracoscopic lobectomy was not found to be an independent predictor of recurrence (hazard ratio, .53; 95% confidence interval [CI], .28-1.02) or overall survival (hazard ratio, .33; 95% CI, .07-1.61). CONCLUSION: In this propensity-matched comparison, nonintubated thoracoscopic lobectomy was not associated with an increased risk for recurrence and overall survival during the 5-year follow-up. However, more randomized trials should be conducted for further validation of these results.

A retrospective study of clinicopathologic and molecular features of inoperable early-stage non-small cell lung cancer treated with stereotactic ablative radiotherapy.

BACKGROUND/PURPOSE: Stereotactic ablative radiotherapy (SABR) is the treatment of choice for medically inoperable, early-stage non-small cell lung cancer (ES-NSCLC). The influence of oncogenic driver alterations and comorbidities are not well known. Here we present treatment outcomes based on clinicopathologic features and molecular profiles. METHODS: We retrospectively analyzed patients treated with SABR for inoperable ES-NSCLC. Molecular features of oncogenic driver alterations included EGFR, ALK, and ROS1. Comorbidities were assessed using the age-adjusted Charlson Comorbidity Index (ACCI). Survival was calculated using the Kaplan-Meier method. The Cox regression model was performed for univariate and multivariate analyses of prognostic factors. Competing risk analysis was used to evaluate the cumulative incidence of disease progression. RESULTS: From 2008 to 2020, 100 patients (median age: 82 years) were enrolled. The majority of patients were male (64%), ever-smokers (60%), and had adenocarcinoma (65%). With a median follow-up of 21.5 months, the median overall survival (OS) and real-world progression-free survival were 37.7 and 25.1 months, respectively. The competing-risk-adjusted 3-year cumulative incidences of local, regional, and disseminated failure were 8.2%, 14.5%, and 31.2%, respectively. An ACCI ≥7 was independently associated with inferior OS (hazard ratio [HR] 2.45, p = 0.03). Tumor size ≥4 cm (HR 4.16, p < 0.001) was the most important independent prognostic factor predicting real-world progression. EGFR mutation status had no impact on the outcomes. CONCLUSION: SABR provides excellent local control in ES-NSCLC, although disseminated failures remains a major concern. ACCI is the best indicator for OS, while tumor sizes ≥4 cm predicts poor disease control.