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OBJECTIVES: With the increasing popularity of CT screening, more cases of early-stage lung cancer are being diagnosed. However, 24.5% of stage I non-small-cell lung cancer (NSCLC) patients still experience treatment failure post-surgery. Biomarkers to predict lung cancer patients at high risk of recurrence are needed. MATERIALS AND METHODS: We collected protein mass spectrometry data from the Taiwan Lung Cancer Moonshot Project and performed bioinformatics analysis on proteins with differential expressions between tumor and adjacent normal tissues in 74 stage I lung adenocarcinoma (LUAD) cases, aiming to explore the tumor microenvironment related prognostic biomarkers. Findings were further validated in 6 external cohorts. RESULTS: The analysis of differentially expressed proteins revealed that the most enriched categories of diseases and biological functions were cellular movement, immune cell trafficking, and cancer. Utilizing proteomic profiling of the tumor microenvironment, we identified five prognostic biomarkers (ADAM10, MIF, TEK, THBS2, MAOA). We then developed a risk score model, which independently predicted recurrence-free survival and overall survival in stage I LUAD. Patients with high risk scores experienced worse recurrence-free survival (adjusted hazard ratio = 8.28, p < 0.001) and overall survival (adjusted hazard ratio = 6.88, p = 0.013). Findings had been also validated in the external cohorts. CONCLUSION: The risk score model derived from proteomic profiling of tumor microenvironment can be used to predict recurrence risk and prognosis of stage I LUAD.
Subject(s)
Adenocarcinoma of Lung , Biomarkers, Tumor , Lung Neoplasms , Neoplasm Staging , Proteomics , Tumor Microenvironment , Humans , Prognosis , Lung Neoplasms/pathology , Lung Neoplasms/mortality , Lung Neoplasms/metabolism , Lung Neoplasms/diagnosis , Female , Biomarkers, Tumor/metabolism , Male , Proteomics/methods , Adenocarcinoma of Lung/pathology , Adenocarcinoma of Lung/metabolism , Adenocarcinoma of Lung/mortality , Adenocarcinoma of Lung/diagnosis , Middle Aged , Aged , Neoplasm Recurrence, Local/metabolism , Neoplasm Recurrence, Local/pathology , Taiwan/epidemiology , Computational Biology/methodsABSTRACT
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.
Subject(s)
Cryopreservation , Stents , Tracheal Stenosis , Humans , Male , Tracheal Stenosis/surgery , Tracheal Stenosis/etiology , Adult , Plastic Surgery Procedures/methods , Aorta/surgery , Allografts , Bronchoscopy , Tuberculosis/complications , Tuberculosis/surgery , Quality of LifeABSTRACT
Objectives: Primary spontaneous pneumothorax (PSP) is a common disease in young and thin male. Operation has been regarded as definitive treatment for it. However, the operative methods for those patients are under dispute. This study aims to directly compare the outcomes of uniportal VATS vs. needlescopic VATS in the treatment of PSP, focusing on postoperative pain and safety outcomes. Methods: From July 2013 to December 2017, the patients who underwent video-assisted thoracic surgery for pneumothorax in National Taiwan University Hospital were retrospectively collected. The preoperative condition, surgical results, and postoperative outcomes was analyzed. Results: There were 60 patients undergoing needlescopic VATS and 91 undergoing uniportal VATS during the study period. There was no significant difference between the patients who underwent needlescopic VATS and those who underwent uniportal VATS in their demographic and clinical characteristics. The post-operative pain score was significantly lower in the uniportal VATS group compared to the needlescopic VATS group at day 1 (2.65 ± 1.59 vs. 1.74 ± 1.35, p = 0.001). Conclusion: Uniportal VATS offers an effective, safe alternative for PSP treatment, with benefits including reduced post-operative pain. Our findings support the use of uniportal VATS, supplemented by a wound protector, as a viable option for PSP patients.
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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.
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BACKGROUND: The long-term outcome on patients with chronic thromboembolic pulmonary hypertension (CTEPH) has not been ideal after standard medical treatment. However, good outcome for patients with CTEPH after interventions such as pulmonary endarterectomy (PEA) and balloon pulmonary angioplasty (BPA) has been reported recently. The aim of this study was to evaluate the impact of PEA or BPA on long-term outcomes for CTEPH patients in Han-Chinese population. METHODS: This was a multicenter, prospective case-control study. Patients with CTEPH were enrolled between January, 2018 and March, 2020. They were divided into two groups, including intervention (PEA or BPA) and conservative groups. The followed-up period was 26 months after treatment. The endpoints were all-cause mortality and CTEPH mortality. RESULTS: A total of 129 patients were enrolled and assigned to receive PEA/BPA (N = 73), or conservative therapy (N = 56). Overall, the 26-month survival rate of all-cause mortality was significantly higher in intervention group compared to that in conservative group (95.89% vs 80.36%; log-rank p = 0.0164). The similar trend was observed in the 26-month survival rate of CTEPH mortality (97.26% vs 85.71%; log-rank p = 0.0355). Regarding Cox proportional-hazard regression analysis, the hazard ratios (HRs) on patients with CTEPH receiving intervention in the outcome of all-cause mortality and CTEPH mortality were statistically significant (HR = 0.07 and p = 0.0141 in all-cause mortality; HR = 0.11 and p = 0.0461 in CTEPH mortality). CONCLUSION: This multicenter prospective case-control study demonstrated that intervention such as PEA and BPA increased the long-term survival rate for patient with CTEPH significantly. Intervention was an independent factor in long-term outcome for patients with CTEPH, including all-cause mortality and CTEPH mortality.
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Angioplasty, Balloon , Hypertension, Pulmonary , Pulmonary Embolism , Humans , Hypertension, Pulmonary/surgery , Pulmonary Embolism/complications , Pulmonary Embolism/surgery , Case-Control Studies , Chronic Disease , Angioplasty, Balloon/adverse effects , Endarterectomy/adverse effects , Pulmonary Artery/surgeryABSTRACT
OBJECTIVES: Postoperative neurocognitive disorder following thoracoscopic surgery with general anaesthesia may be linked to reduced intraoperative cerebral oxygenation and perioperative inflammation, which can potentially be exacerbated by mechanical ventilation. However, nonintubated thoracoscopic surgery, which utilizes regional anaesthesia and maintains spontaneous breathing, provides a unique model for studying the potential benefits of avoiding mechanical ventilation. This approach allows investigation into the impact on perioperative neurocognitive profiles, inflammatory responses and intraoperative cerebral oxygen levels. METHODS: In total, 110 patients undergoing thoracoscopic surgery were randomly equally assigned to the intubated group and the nonintubated group. Regional cerebral oxygenation was monitored during surgery. Serum neuroinflammatory biomarkers, including interleukin-6 and glial fibrillary acidic protein, were measured at baseline (before surgery) and 24 h after surgery. Postoperative complication severity was compared using the Comprehensive Complication Index. The primary outcome was perioperative changes in neurocognitive test score, which was assessed at baseline, 24 h and 6 months after surgery. RESULTS: Patients in the nonintubated group had higher neurocognitive test scores at 24 h (69.9 ± 10.5 vs 65.3 ± 11.8; P = 0.03) and 6 months (70.6 ± 6.7 vs 65.4 ± 8.1; P < 0.01) after surgery and significantly higher regional cerebral oxygenation over time during one-lung ventilation (P = 0.03). Patients in the intubated group revealed a significantly higher postoperative serum interleukin-6 level (group by time interaction, P = 0.04) and a trend towards a significantly higher serum glial fibrillary acidic protein level (group by time interaction, P = 0.11). Furthermore, patients in the nonintubated group had a significantly lower Comprehensive Complication Index (9.0 ± 8.2 vs 6.1 ± 7.1; P < 0.05). CONCLUSIONS: Nonintubated thoracoscopic surgery was associated with improved postoperative neurocognitive recovery, more stable intraoperative cerebral oxygenation, ameliorated perioperative inflammation and attenuated postoperative complication severity.
Subject(s)
Interleukin-6 , Thoracoscopy , Humans , Glial Fibrillary Acidic Protein , Thoracoscopy/adverse effects , Postoperative Complications , Inflammation , Thoracic Surgery, Video-AssistedABSTRACT
A 21-year-old woman with severe pulmonary hypertension and circulatory collapse was referred to our hospital for possible lung transplantation with extracorporeal membrane oxygenation support. Computed tomography revealed severe stenosis of all 4 pulmonary veins, and fibrosing mediastinitis was suspected. Surgical reconstruction of the pulmonary veins was performed, and extracorporeal membrane oxygenation support was weaned off. After surgery, pulmonary vascular resistance normalized. This successful case demonstrates that surgical pulmonary venous reconstruction is an important treatment for fibrosing mediastinitis induced by pulmonary venous stenosis and pulmonary hypertension.
Subject(s)
Hypertension, Pulmonary , Mediastinitis , Pulmonary Veins , Female , Humans , Young Adult , Constriction, Pathologic/complications , Constriction, Pathologic/surgery , Fibrosis , Hypertension, Pulmonary/complications , Hypertension, Pulmonary/surgery , Mediastinitis/complications , Mediastinitis/surgery , Pulmonary Veins/surgery , Pulmonary Veins/pathologyABSTRACT
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.
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Background: The use of nanodiamonds (NDs) and fluorescent nanodiamonds (FNDs) as nonallergenic biocompatible additives in incomplete Freund's adjuvant (IFA) to elicit immune responses in vivo was investigated. Methods: C57BL/6 mice were immunized with chicken egg ovalbumin (OVA) in IFA and also OVA-conjugated NDs (or OVA-conjugated FNDs) in IFA to produce antibodies. OVA-expressing E.G7 lymphoma cells and OVA-negative EL4 cells were inoculated in mice to induce tumor formation. Results: The new formulation significantly enhanced immune responses and thus disease resistance. It exhibited specific therapeutic activities, effectively inhibiting the growth of E.G7 tumor cells in mice over 35 days. Conclusion: The high biocompatibility and multiple functionalities of NDs/FNDs render them applicable as active and trackable vaccine adjuvants and antitumor agents.
Subject(s)
Nanodiamonds , Animals , Mice , Mice, Inbred C57BL , Emulsions , Ovalbumin , Coloring Agents , VaccinationABSTRACT
Background: For uniportal video-assisted thoracoscopic surgery (VATS), which is greatly dependent on satisfactory lung collapse without lung compression from another port, few reports have elucidated the intraoperative efficacy of bronchial blockers (BBs). We hypothesized that operation time would be prolonged if BBs required more intraoperative repositioning during surgical manipulation. We compared the operation times of different surgical procedures performed using BBs with double-lumen tubes (DLTs) in uniportal VATS. Materials and Methods: Patients who underwent intubated uniportal VATS were enrolled retrospectively from March to May 2019. Data on the patient, anesthetic, and surgical factors were collected. Regression analyses were performed to determine the effect of various factors on operation time. Results: 317 patients who underwent uniportal VATS were included. Wedge resection constituted 70.7%, and anatomic resection constituted 29.3% of procedures. BBs were applied for left- and right-side wedge resection (85.6% and 78.7%, respectively) and left- and right-side anatomic resection (74.1% and 56.4%, respectively). The surgical factors significantly affecting operation time were operation procedures (P < .01), number of lymph nodes sampled (P < .001), and size of tumors (P < .01). Conclusions: The efficacy of BBs was comparable to that of DLTs for uniportal VATS wedge resection. With significantly less preference for right-side anatomic resection, the efficacy of DLTs was comparable with that of BBs, which were applied in more than half of right-side uniportal anatomic VATS. We conclude that even in uniportal VATSs, rigid-angled BBs demonstrate comparable efficacy with feasible alternatives.
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Lung , Thoracic Surgery, Video-Assisted , Humans , Thoracic Surgery, Video-Assisted/methods , Retrospective Studies , Lung/surgery , Bronchi , Pneumonectomy/methodsABSTRACT
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.
Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Humans , Lung Neoplasms/surgery , Lung Neoplasms/pathology , Carcinoma, Non-Small-Cell Lung/surgery , Carcinoma, Non-Small-Cell Lung/pathology , Retrospective Studies , Pneumonectomy/methods , Lung/pathology , Thoracic Surgery, Video-Assisted/adverse effects , Thoracic Surgery, Video-Assisted/methodsABSTRACT
OBJECTIVE: To quantitatively assess the pulmonary vasculature using non-contrast computed tomography (CT) in patients with chronic thromboembolic pulmonary hypertension (CTEPH) pre- and post-treatment and correlate CT-based parameters with right heart catheterization (RHC) hemodynamic and clinical parameters. MATERIALS AND METHODS: A total of 30 patients with CTEPH (mean age, 57.9 years; 53% female) who received multimodal treatment, including riociguat for ≥ 16 weeks with or without balloon pulmonary angioplasty and underwent both non-contrast CT for pulmonary vasculature analysis and RHC pre- and post-treatment were included. The radiographic analysis included subpleural perfusion parameters, including blood volume in small vessels with a cross-sectional area ≤ 5 mm² (BV5) and total blood vessel volume (TBV) in the lungs. The RHC parameters included mean pulmonary artery pressure (mPAP), pulmonary vascular resistance (PVR), and cardiac index (CI). Clinical parameters included the World Health Organization (WHO) functional class and 6-minute walking distance (6MWD). RESULTS: The number, area, and density of the subpleural small vessels increased after treatment by 35.7% (P < 0.001), 13.3% (P = 0.028), and 39.3% (P < 0.001), respectively. The blood volume shifted from larger to smaller vessels, as indicated by an 11.3% increase in the BV5/TBV ratio (P = 0.042). The BV5/TBV ratio was negatively correlated with PVR (r = -0.26; P = 0.035) and positively correlated with CI (r = 0.33; P = 0.009). The percent change across treatment in the BV5/TBV ratio correlated with the percent change in mPAP (r = -0.56; P = 0.001), PVR (r = -0.64; P < 0.001), and CI (r = 0.28; P = 0.049). Furthermore, the BV5/TBV ratio was inversely associated with the WHO functional classes I-IV (P = 0.004) and positively associated with 6MWD (P = 0.013). CONCLUSION: Non-contrast CT measures could quantitatively assess changes in the pulmonary vasculature in response to treatment and were correlated with hemodynamic and clinical parameters.
Subject(s)
Angioplasty, Balloon , Hypertension, Pulmonary , Pulmonary Embolism , Humans , Female , Middle Aged , Male , Hypertension, Pulmonary/diagnostic imaging , Hypertension, Pulmonary/therapy , Hypertension, Pulmonary/complications , Pulmonary Embolism/complications , Pulmonary Embolism/diagnostic imaging , Pulmonary Embolism/therapy , Lung , Tomography, X-Ray Computed/methods , Hemodynamics , Angioplasty, Balloon/methods , Chronic Disease , Pulmonary ArteryABSTRACT
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.
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Plastic Surgery Procedures , Trachea , Swine , Animals , Trachea/transplantation , Transplantation, Homologous , Aorta/surgery , Allografts/surgery , MammalsABSTRACT
The clinicopathological presentation of early-stage lung adenocarcinoma patients with epidermal growth factor receptor (EGFR) mutations has been seldom studied. Our study enrolled patients with stage I and II lung adenocarcinoma between January 2014 and December 2017 at the National Taiwan University Hospital. Clinicopathological features and prognosis were retrospectively reviewed and analyzed depending on EGFR mutation status. EGFR mutations were detected in 622 (60%) out of 1034 patients. Compared to the group without EGFR mutations, the group with EGFR mutations had more patients above 65 years of age (p < 0.001), more non-lepidic histological subtypes (p < 0.001), higher CEA levels (p = 0.044), higher grade of pleural (p = 0.02) and lymphovascular (p = 0.001) invasion, higher histological grade (p < 0.001), and a more advanced pathological stage (p = 0.022). In multivariate analysis, there was no significant difference in PFS or OS between the EGFR mutant and wild-type groups. In subtype analysis, the tumors with an L858R mutation had a more lepidic predominant histological type (p = 0.019) and less lymphovascular invasion (p = 0.011). No significant differences in PFS or OS were detected between the exon 19 deletion and L858R mutation groups. In early-stage lung adenocarcinoma, EGFR mutation may be considered as a treatment response predictor for tyrosine kinase inhibitors, instead of a predictor of clinical prognosis.
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BACKGROUND: No published studies to date have evaluated the detailed pathologic and genetic features of lung adenocarcinoma after epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) therapy and salvage surgery. We aimed to evaluate the pathologic and genetic changes of tumors in patients with advanced lung adenocarcinoma treated with EGFR TKI therapy and salvage surgery. METHODS: This study retrospectively collected data from 29 advanced lung adenocarcinoma patients who underwent EGFR TKI therapy, followed by salvage operation, between January 2010 and December 2018. All patients had partial response or stable disease without evidence of progressive disease. Next-generation sequencing was used to determine whether acquired resistant mutations in morphologically treatment-sensitive and morphologically treatment-resistant regions of tumor existed. RESULTS: There were 3, 22, and 4 patients with clinical stage IIIB, IVA, and IVB, respectively. After a mean TKI treatment duration of 134 days, 27 patients had partial response, 2 had stable disease, and 27.6% of patients were downstaged before salvage surgery. All patients had residual viable tumor cells in their tumor bed; 5 patients (17.2%) had a major pathologic response. Acquired T790M mutations (n = 4), histologic transformations (n = 2), and acquired T790M mutation with histologic transformation (n = 1) were identified in the morphologically treatment-resistant regions of tumors. The 3-year overall survival was 75.9%. CONCLUSIONS: The presence of morphologically treatment-resistant tumor regions with acquired T790M mutations and histologic transformations demonstrate the existence of resistant subclones in TKI-treated tumors before disease progression. Salvage surgery performed in selected patients before disease progression may improve survival by removing TKI-resistant subclones.
Subject(s)
Adenocarcinoma of Lung , Lung Neoplasms , Humans , Lung Neoplasms/drug therapy , Lung Neoplasms/genetics , Lung Neoplasms/surgery , Retrospective Studies , ErbB Receptors/genetics , Mutation , Protein Kinase Inhibitors/therapeutic use , Adenocarcinoma of Lung/drug therapy , Adenocarcinoma of Lung/genetics , Adenocarcinoma of Lung/surgery , Disease ProgressionABSTRACT
It remains a challenge to preoperatively forecast whether lung pure ground-glass nodules (pGGNs) have invasive components. We aimed to construct a radiomic model using tumor characteristics to predict the histologic subtype associated with pGGNs. We retrospectively reviewed clinicopathologic features of pGGNs resected in 338 patients with lung adenocarcinoma between 2011-2016 at a single institution. A radiomic prediction model based on forward sequential selection and logistic regression was constructed to differentiate adenocarcinoma in situ (AIS)/minimally invasive adenocarcinoma (MIA) from invasive adenocarcinoma. The study cohort included 133 (39.4%), 128 (37.9%), and 77 (22.8%) patients with AIS, MIA, and invasive adenocarcinoma (acinar 55.8%, lepidic 33.8%, papillary 10.4%), respectively. The majority (83.7%) underwent sublobar resection. There were no nodal metastases or tumor recurrence during a mean follow-up period of 78 months. Three radiomic features-cluster shade, homogeneity, and run-length variance-were identified as predictors of histologic subtype and were selected to construct a prediction model to classify the AIS/MIA and invasive adenocarcinoma groups. The model achieved accuracy, sensitivity, specificity, and AUC of 70.6%, 75.0%, 70.0%, and 0.7676, respectively. Applying the developed radiomic feature model to predict the histologic subtypes of pGGNs observed on CT scans can help clinically in the treatment selection process.
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Background: Preoperative two-dimensional manual measurement of pulmonary artery diameter in a single-cut axial view computed tomography (CT) image is a commonly used non-invasive prediction method for pulmonary hypertension. However, the accuracy may be unreliable. Thus, this study aimed to evaluate the correlation of short-term surgical outcomes and pulmonary artery/aorta (PA/Ao) diameter ratio measured by automated three-dimensional (3D) segmentation in lung cancer patients who underwent thoracoscopic lobectomy. Materials and methods: We included 383 consecutive lung cancer patients with thin-slice CT images who underwent lobectomy at a single institute between January 1, 2011 and December 31, 2019. Automated 3D segmentation models were used for 3D vascular reconstruction and measurement of the average diameters of Ao and PA. Propensity-score matching incorporating age, Charlson comorbidity index, and lobectomy performed by uniportal VATS was used to compare clinical outcomes in patients with PA/Ao ratio ≥1 and those <1. Results: Our segmentation method measured 29 (7.57%) patients with a PA/Ao ratio ≥1. After propensity-score matching, a higher overall postoperative complication classified by the Clavien-Dindo classification (p = 0.016) were noted in patients with 3D PA/Ao diameter ratio ≥1 than those of <1. By multivariate logistic regression, patients with a 3D PA/Ao ratio ≥ 1 (p = 0.013) and tumor diameter > 3 cm (p = 0.002) both significantly predict the incidence of postoperative complications. Conclusions: Pulmonary artery/aorta diameter ratio ≥ 1 measured by automated 3D segmentation may predict postoperative complications in lung cancer patients who underwent lobectomy.
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Purpose: Liver transplantation (LT) is the definite curative treatment for hepatocellular carcinoma (HCC), but recurrence can occur even under stringent criteria. "Delayed" HCC recurrence (>3 years after LT) is not common. Here, we present the clinical features of patients who developed delayed HCC recurrence after LT. Patients and Methods: We reviewed the data of eligible patients from February 1999 to December 2020 from medical records. Results: From among 195 (17%) HCC patients who received LT, 34 experienced HCC recurrence, with 5 (15%) delayed recurrence. These five explant tumors were staged T1b-T2, graded II-III, with two vascular invasion and four beyond the Milan criteria. The median time to recurrence was 6.1 years, with the longest interval being nearly 18 years. Recurrence patterns included two extrahepatic, one intrahepatic, and two mixed extrahepatic and intrahepatic recurrences. A drastic increase in serum alpha-fetoprotein levels was observed in four cases 1 year before recurrence. Management of recurrence included locoregional (surgssical resection in three, radiotherapy in three, transarterial chemoembolization in one, radiofrequency ablation in one) and systemic sorafenib use in three. Two patients died within 12-18 months, one died within 18-24 months, and two are still alive until the end of the study, with respective 13.5- and 16.5-month survival. Conclusion: Delayed HCC recurrence could occur over 10 years. Therefore, continual surveillance for recurrence is justified, but biomarkers and intervals or intensities specific for delayed recurrence are not validated, which warrants further validation to facilitate personalized medical care.
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Background: Lung cancer is one of the most devastating cancers. Low-dose computed tomography (LDCT) can detect lung cancer at an early stage of the disease when a minimally invasive surgical procedure using video-assisted thoracoscopic surgery is the best strategy. Herein, we discuss the treatment of deep lung tumors between segments or lesions located near the margin of a segment. Patients and Methods: This was a retrospective study conducted from January 2013 to January 2020 using the National Taiwan University Hospital data bank. We included early-stage non-small cell lung cancer (NSCLC) patients who underwent lung surgery and screened out those who received CT-guided localization for extended segmentectomy. Outcome measurements were safety margin, complication rate, and postoperative course. Results: During the study period, 68 patients with early-stage NSCLC received CT-guided localization followed by extended segmentectomy. The mean surgery time was 92.1 ± 30.3 min, and the mean blood loss was 32.8 mL. Mean drainage time was 2.3 ± 1 days, and the total hospital stay was 4.9 ± 1.1 days. Pathological reports showed tumor-free resection margins >2 cm. Sixty-one patients had adenocarcinoma at stage IA and two patients at stage IB. One patient had squamous cell carcinoma at stage IA. Conclusion: CT-guided localization followed by extended segmentectomy allows lung volume preservation with clean safety margins and good clinical outcomes.
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BACKGROUND: Lung transplantation is a therapeutic option for patients with end-stage lung disease. However, the increase in organ demand has surpassed the number of donors, with many patients unable to outlive the long waiting period. This study aimed to assess mortality and its risk factors in patients on the waiting list for lung transplantation in a single medical centre. METHODS: All evaluated clinical and laboratory data of the patients with end-stage lung disease assessed for lung transplantation between February 2005 and November 2018 in National Taiwan University Hospital were recorded in the waiting list database. The patients in this study were divided into two groups: survival and death groups. RESULTS: Between February 2005 and November 2018, 169 patients were enrolled in the waiting list. Thirty-one patients were alive and waiting for the chance of lung transplantation, 56 underwent lung transplantation, and 82 died while waiting. The mean age of all patients was 43.7 years, and 91 were women. The mean body mass index (BMI) was 20.3. The most common blood type was type O. All patients were in New York Heart Association (NYHA) class III or IV. After analysis of the two groups, lower BMI presented as a mortality factor. CONCLUSION: This is the first Taiwanese study to describe the mortality factors in patients waiting for lung transplantation. The main factors influencing the survival of these patients were lower BMI, NYHA class IV, and diseases which cause end-stage lung diseases (infection and pulmonary fibrosis).