Oncological feasibility of segmentectomy for inner-located lung cancer.

Objective: Oncological feasibility of segmentectomy for internal non-small cell lung cancer (NSCLC) has not been assessed adequately. We assessed the oncological feasibility of segmentectomy for inner-located NSCLC by investigating surgical margins and patient prognosis after undergoing the procedure. Methods: Of the 3555 patients who underwent resection for lung cancer between 2013 and 2019 at our institution, 659 patients who underwent segmentectomy for clinical stage 0 to stage1A NSCLC were included in this study. Patients were separated into 2 groups according to whether the tumor was in the inner or outer third of the lung area. Clinical characteristics and prognoses were retrospectively compared between the groups. Results: Of the included 659 cases, 183 (27.8%) were inner-located, and 476 (72.2%) had outer-located NSCLC. The surgical margin was significantly shorter in the inner-located group than in the outer group (median, 16 vs 25 mm; P < .001). The 5-year recurrence-free survival and overall survival probabilities were 91.1%/91.8% (P = .530) and 94.1%/95.6% (P = .345) for inner/outer-located groups, respectively. Multivariate analysis showed that clinical stage IA2 or 3 (P = .043), lymphovascular invasion (P < .001), and surgical margins <20 mm (P = .017) were independent prognostic factors for recurrence-free survival. The location of the inner or outer tumors was not related to the prognosis. Conclusions: For clinical stage 0 to stage1A NSCLC, tumor location in the inner two-thirds of the lung was not associated with prognosis after segmentectomy. Because one of the independent prognostic factors is margin distance, segmentectomy for inner-located NSCLC would be oncologically acceptable when an adequate surgical margin is secured.

Machine Learning to Improve Accuracy of Transcutaneous Bilirubinometry.

INTRODUCTION: This study aimed to develop models for predicting total serum bilirubin by correcting errors of transcutaneous bilirubin using machine learning based on neonatal biomarkers that could affect spectrophotometric measurements of tissue bilirubin. METHODS: This retrospective study included infants born at our hospital (≥36 weeks old, ≥2,000 g) between January 2020 and December 2022. Infants without a phototherapy history were included. Robust linear regression, gradient boosting tree, and neural networks were used for machine learning models. A neural network, inspired by the structure of the human brain, was designed comprising three layers: input, intermediate, and output. RESULTS: Totally, 683 infants were included. The mean (minimum-maximum) gestational age, birth weight, participant age, total serum bilirubin, and transcutaneous bilirubin were 39.0 (36.0-42.0) weeks, 3,004 (2,004-4,484) g, 2.8 (1-6) days of age, 8.50 (2.67-18.12) mg/dL, and 7.8 (1.1-18.1) mg/dL, respectively. The neural network model had a root mean square error of 1.03 mg/dL and a mean absolute error of 0.80 mg/dL in cross-validation data. These values were 0.37 mg/dL and 0.28 mg/dL, smaller compared to transcutaneous bilirubin, respectively. The 95% limit of agreement between the neural network estimation and total serum bilirubin was -2.01 to 2.01 mg/dL. Unnecessary blood draws could be reduced by up to 78%. CONCLUSION: Using machine learning with transcutaneous bilirubin, total serum bilirubin estimation error was reduced by 25%. This integration could increase accuracy, lessen infant discomfort, and simplify procedures, offering a smart alternative to blood draws by accurately estimating phototherapy thresholds.

Is 18F-fluorodeoxyglucose PET recommended for small lung nodules? CT findings of 18F-fluorodeoxyglucose non-avid lung cancer.

OBJECTIVES: To determine the image characteristics associated with low 18F-FDG (18F-fluorodeoxyglucose) avidity among 8-15 mm solid lung cancer. METHODS: Patients satisfying the following criteria were included: underwent surgery between January 2014 and December 2019 for lung cancer, presented 8-15 mm nodule without measurable ground glass component on preoperative CT, and underwent 18F-FDG PET before resection. Image characteristics, including air bronchogram, concave shape, pleural attachment, and background emphysema, were evaluated by two board-certified radiologists. The Mann-Whitney U test was used to compare maximum standardized uptake (SUVmax) values from 18F-FDG PET images. RESULTS: The analysis included 235 patients. The SUVmax values of lesions with air bronchogram and concave shape were significantly lower than the SUVmax values of lesions without these features (median: 1.55 vs 2.56 and 1.66 vs 2.45, both P < .001), whereas lesions arising from emphysematous lungs had significantly higher SUVmax values than lesions arising from non-emphysematous lungs (2.90 vs 1.69, P < .001). No significant differences were detected between lesions attached and not attached to pleura. The interobserver agreement was almost perfect for air bronchograms and background emphysema (κ = 0.882 and 0.927, respectively), and 89.7% of lesions with air bronchograms and arising from non-emphysematous lungs showed SUVmax values below 2.5. CONCLUSIONS: Among 8-15 mm solid lung cancer, the presence of air bronchograms and concave shape and the absence of background emphysema were associated with low 18F-FDG accumulation. ADVANCES IN KNOWLEDGE: 18F-FDG PET can be misleading in differentiating certain type of small solid lung cancer.

Sketch-based semantic retrieval of medical images.

The volume of medical images stored in hospitals is rapidly increasing; however, the utilization of these accumulated medical images remains limited. Existing content-based medical image retrieval (CBMIR) systems typically require example images, leading to practical limitations, such as the lack of customizable, fine-grained image retrieval, the inability to search without example images, and difficulty in retrieving rare cases. In this paper, we introduce a sketch-based medical image retrieval (SBMIR) system that enables users to find images of interest without the need for example images. The key concept is feature decomposition of medical images, which allows the entire feature of a medical image to be decomposed into and reconstructed from normal and abnormal features. Building on this concept, our SBMIR system provides an easy-to-use two-step graphical user interface: users first select a template image to specify a normal feature and then draw a semantic sketch of the disease on the template image to represent an abnormal feature. The system integrates both types of input to construct a query vector and retrieves reference images. For evaluation, ten healthcare professionals participated in a user test using two datasets. Consequently, our SBMIR system enabled users to overcome previous challenges, including image retrieval based on fine-grained image characteristics, image retrieval without example images, and image retrieval for rare cases. Our SBMIR system provides on-demand, customizable medical image retrieval, thereby expanding the utility of medical image databases.

Impact of 18F-FDG PET on TNM Staging and Prognosis in Thymic Epithelial Tumors.

BACKGROUND: Preoperative fluorine-18-fluorodeoxyglucose positron emission tomography (18F-FDG PET) of thymic epithelial tumors (TETs) is well known for identifying malignant-grade TETs; however, its predictive power for determining locally advanced tumors, lymph node (LN) metastasis, and prognosis remains unknown. PATIENTS AND METHODS: We retrospectively evaluated patients with resectable TETs who were preoperatively assessed using 18F-FDG PET from January 2012 to January 2023. The receiver operating characteristic curve was used to evaluate the cutoff value of the maximum standardized uptake value (SUVmax) to predict advanced-stage disease. Recurrence/progression-free survival (RFS/PFS) was analyzed using the Kaplan-Meier method. The staging was classified according to the tumor-node-metastasis system. RESULTS: Our study included 177 patients; 145 (81.9%) had pathological early-stage TET (stage I or II), and 32 (19.1%) had advanced stage (stage III or IV). The area under the curve value for predicting the advanced stage was 0.903, and the cutoff value was 5.6 (sensitivity 81.3%, specificity 84.8%). SUVmax > 5.6 was associated with worse prognosis for RFS/PFS. LN metastasis was preoperatively detected by FDG uptake in 30.8% of patients with pathological LN positivity, whereas LN metastasis was not pathologically detected in patients with SUVmax < 5.9. In patients with advanced-stage TETs, LN recurrence was more frequent in patients who were preoperatively detected by 18F-FDG PET than those who were not (75.0% versus 7.1%). CONCLUSIONS: 18F-FDG PET is a potentially valuable tool for predicting advanced stage and poor prognosis of recurrence in patients with TETs. SUVmax can help thoracic surgeons to guide them in selecting appropriate therapeutic strategies for TETs.

Postnatal longitudinal analysis of serum Nitric oxide and eosinophil counts in extremely preterm infants.

BACKGROUND: Nitric oxide (NO) may be related to the pathogenesis of several morbidities in extremely preterm infants, including late-onset adrenal insufficiency. However, eosinophilia is observed under pathological conditions with adrenal insufficiency. Therefore, this study explored postnatal changes in NO levels and eosinophil counts in extremely preterm infants with and without morbidities. METHODS: Nineteen extremely preterm infants with a median gestational age of 27.0 weeks and median birth weight of 888 g were enrolled in this study. Serum levels of nitrogen oxides (NOx) and peripheral blood eosinophil counts were measured at birth and every 2 weeks thereafter. Morbidities of the study group were diagnosed using a single criterion. RESULTS: Serum NOx levels (mean ± standard deviation) were 22.5 ± 14.9 µmol/L, 51.2 ± 23.7 µmol/L, 42.4 ± 15.2 µmol/L, and 33.8 ± 9.4 µmol/L at birth and 2, 4, and 6 weeks of age, respectively. The serum NOx level at 2 weeks of age was significantly higher than that at birth and 6 weeks of age. Eosinophil counts, which increase with adrenal insufficiency, were measured simultaneously and were 145 ± 199/µL, 613 ± 625/µL, 466 ± 375/µL, and 292 ± 228/µL at birth and 2, 4, and 6 weeks of age, respectively. These values showed that the eosinophil count was significantly higher at 2 weeks of age than at birth and 6 weeks of age. The serum NOx level of infants without chorioamnionitis was significantly increased at 4 weeks of age, and the eosinophil count of infants with necrotizing enterocolitis was significantly increased at 2 weeks of age. No correlation with the NOx level or eosinophil count was observed in infants with late-onset circulatory collapse. CONCLUSION: The postnatal serum NOx level and eosinophil count were significantly correlated with each other and peaked at 2 weeks of age.

Role of fluorine-18-fluorodeoxyglucose positron emission tomography in selecting candidates for a minimally invasive approach for thymic epithelial tumour resection.

OBJECTIVES: We evaluated the potential of preoperative fluorine-18-fluorodeoxyglucose positron emission tomography to predict invasive thymic epithelial tumours in patients with computed tomography-defined clinical stage I thymic epithelial tumours ≤5 cm in size who are generally considered to be candidates for minimally invasive approaches. METHODS: From January 2012 to July 2022, we retrospectively analysed patients who exhibited tumour-node-metastasis (TNM) clinical stage I thymic epithelial tumours with lesion sizes ≤5 cm as determined by computed tomography. All patients underwent fluorine-18-fluorodeoxyglucose positron emission tomography preoperatively. We analysed the association of maximum standardized uptake values with both the World Health Organization histological classification and the TNM staging classification. RESULTS: A total of 107 patients with thymic epithelial tumours (thymomas, 91; thymic carcinomas, 14; carcinoids, 2) were evaluated. Nine patients (8.4%) were pathologically upstaged: TNM pathological stage II in 3 (2.8%), III in 4 (3.7%) and IV in 2 (1.9%). Among these 9 upstaged patients, 5 had thymic carcinoma with stage III/IV, 3 had type B2/B3 thymoma with stage II/III and 1 had type B1 thymoma with stage II. Maximum standardized uptake values were a predictive factor that distinguished pathological stage >I thymic epithelial tumours from pathological stage I [best cut-off value, 4.2; area under the curve = 0.820] and thymic carcinomas from other thymic tumours (best cut-off value, 4.5; area under the curve = 0.882). CONCLUSIONS: Thoracic surgeons should carefully determine the surgical approach for high fluorodeoxyglucose-uptake thymic epithelial tumours and keep in mind the issues associated with thymic carcinoma and potential combined resections of neighbouring structures.

Longitudinal Measurement of Histidine-Rich Glycoprotein Levels in Bronchopulmonary Dysplasia: A Pilot Study.

Histidine-rich glycoprotein (HRG) has been reported to inhibit signaling leading to the release of high mobility group box 1 protein, a damage-associated molecular pattern. The present study aimed to determine the longitudinal change in HRG levels in extremely preterm infants and assess whether complications such as bronchopulmonary dysplasia (BPD) were associated with differences in HRG levels. In this multicenter, prospective, observational study, we measured serum HRG levels every 2 weeks from birth to 8 weeks of age. Serum HRG was measured using an enzyme-linked immunosorbent assay. We included 19 extremely preterm infants in the study and 74 samples were analyzed. The median gestational age was 26.0 weeks, and the median birth weight was 858 g. Serum HRG levels showed a significant upward trend after birth (p < 0.001); median HRG concentrations at birth and at 2, 4, 6, and 8 weeks of age were 1.07, 1.11, 2.86, 6.05, and 7.49 µg/mL, respectively. Onset of BPD was not associated with differences in serum HRG levels. Further, the serum HRG levels increased significantly after birth in extremely preterm infants.

Radiological precursor lesions of lung squamous cell carcinoma: Early progression patterns and divergent volume doubling time between hilar and peripheral zones.

OBJECTIVES: This study investigated the early progression patterns of lung squamous cell carcinoma (SqCC) on computed tomography (CT) images. MATERIALS AND METHODS: In total, 65 patients with SqCC who underwent surgical resection and two CT scans separated by an interval of at least 6 months were enrolled. We categorized the findings of the initial and at-diagnosis CT images into five patterns as previously reported. The volume doubling time (VDT) was calculated for measurable lesions. RESULTS: A single nodule pattern on CT images at-diagnosis was most common in 56 (86.2 %) patients, in line with practical clinical findings. However, the patterns were diverse in the initial images, with 28 (43.1 %) patients displaying atypical findings, including multiple nodules (3.1 %), endobronchial lesions (20.0 %), subsolid nodules (10.8 %), and cyst wall thickening (9.2 %). All endobronchial lesions were located in the central/middle zone of the lung field, whereas lesions presented as multiple nodules, subsolid nodules, and cyst wall thickening were predominantly observed in the peripheral zone. The differences in the developed zones were reflected in the median VDT, and the tumors with an initial endobronchial pattern had a significantly shorter VDT than those with a subsolid nodule pattern (median: 140 days vs 276 days, p < 0.001). CONCLUSIONS: Lung SqCC initiated with various CT image patterns, although most tumors ultimately developed a single nodule pattern by diagnosis. The initial CT image patterns differed between the hilar and peripheral zones, suggesting a difference in the progression scheme, which was also supported by differences in VDT.

Prediction model for nonopiate-induced neonatal abstinence syndrome.

BACKGROUND: Neonatal abstinence syndrome (NAS) induced by opiate use is common worldwide. Psychiatric drugs are a more common cause of NAS in Japan but infants of mothers taking psychiatric medications do not always develop NAS. The purpose of this study was to develop a practical model for predicting the onset of nonopiate-induced NAS, using variables available at birth. METHODS: In this diagnostic study, prediction models were developed using multivariable logistic regression with retrospective data collected at our hospital between 2010 and 2019. The NAS diagnosis was based on the Isobe score, and maternal medications were converted to dose equivalents. RESULTS: A total of 164 maternal and infant dyads met the inclusion criteria; 91 were included in the analysis, of whom 29 infants (32%) were diagnosed with NAS. Final models were created with and without the drug indices. The model without the drug indices consisted of neonatal head circumference in z-scores and Apgar scores at 5 min < 9, and the model with the drug indices included these, as well as antipsychotics and hypnotics indices. The C-statistics were 0.747 (95% CI: 0.638-0.856), and 0.795 (95% CI: 0.683-0.907), respectively, indicating that the models possessed good predictive accuracy for NAS onset. CONCLUSIONS: This study developed models that predicted nonopiate-induced NAS accurately. They may be further improved through the use of drug indices.

Nivolumab-induced radiation recall pneumonitis in non-small-cell lung cancer patients with thoracic radiation therapy.

The role of previous thoracic radiation therapy as a risk factor of immune-related pneumonitis is unclear. Furthermore, some patients develop radiation recall pneumonitis, which is characterized by a radiation pneumonitis-like imaging pattern with consolidation progressing within a previous radiation field. In this multicenter retrospective study, we analyzed the relationship of previous thoracic radiation therapy with immune-related pneumonitis and the characteristics of radiation recall pneumonitis. The medical records of patients with non-small-cell lung cancer who had received nivolumab between December 2015 and March 2017 at five institutions were retrospectively reviewed. Incidence, imaging patterns, clinical course, and risk factors of immune-related pneumonitis and radiation recall pneumonitis were evaluated. A total of 669 patients were evaluated, and the incidences of all-grade and grade 3 or higher immune-related pneumonitis were 8.8% and 2.6%, respectively. The incidences of immune-related pneumonitis were 13.2% (34/257) and 6.1% (25/412) in patients with and those without previous thoracic radiation therapy, respectively. A history of previous thoracic radiation therapy was associated with immune-related pneumonitis (odds ratio, 2.11; 95% confidence interval, 1.21-3.69 in multivariate analysis). Among the patients with previous thoracic radiation therapy, 6.2% (16/257) showed radiation recall pattern. This study found an increased risk of nivolumab-induced immune-related pneumonitis associated with a history of thoracic radiation therapy. Radiation recall pattern was one of the major patterns of immune-related pneumonitis among the patients with previous thoracic radiation therapy. Incidence, risk factors, and clinical outcome of radiation recall pneumonitis were elucidated.

Consistency and prognostic value of preoperative staging and postoperative pathological staging using 18F-FDG PET/MRI in patients with non-small cell lung cancer.

OBJECTIVE: In recent years, positron emission tomography/magnetic resonance imaging (PET/MRI) has been clinically used as a method to diagnose non-small cell lung cancer (NSCLC). This study aimed to evaluate the concordance of staging and prognostic ability of NSCLC patients using thin-slice computed tomography (CT) and 18F-fluorodeoxyglucose (FDG) PET/MRI. METHODS: This retrospective study was performed on consecutive NSCLC patients who underwent both diagnostic CT and 18F-FDG PET/MRI before surgery between November 2015 and May 2019. The cTNM staging yielded from PET/MRI was compared with CT and pathological staging, and concordance was investigated, defining pathological findings as reference. To assess the prognostic value of disease-free survival (DFS) and overall survival (OS), we dichotomized the typical prognostic factors and TNM classification staging (Stage I vs. Stage II or higher). Kaplan-Meier curves derived by the log-rank test were generated, and univariate and multivariate analyses were performed to identify the factors associated with DFS and OS. RESULTS: A total of 82 subjects were included; PET/MRI staging was more consistent (59 of 82) with pathological staging than with CT staging. There was a total of 21 cases of CT and 11 cases of PET/MRI that were judged as cStage I, but were actually pStage II or pStage III. CT tended to judge pN1 or pN2 as cN0 compared to PET/MRI. There was a significant difference between NSCLC patients with Stage I and Stage II or higher by PET/MRI staging as well as prognosis prediction of DFS by pathological staging (P < 0.001). In univariate analysis, PET/MRI, CT, and pathological staging (Stage I or lower vs. Stage II or higher) all showed significant differences as prognostic factors of recurrence or metastases. In multivariate analysis, pathological staging was the only independent factor for recurrence (P = 0.009), and preoperative PET/MRI staging was a predictor of patient survival (P = 0.013). CONCLUSIONS: In NSCLC, pathologic staging was better at predicting recurrence, and preoperative PET/MRI staging was better at predicting survival. Preoperative staging by PET/MRI was superior to CT in diagnosing hilar and mediastinal lymph-node metastases, which contributed to the high concordance with pathologic staging.

Invasive Mucinous Adenocarcinoma of the Lung With a Mural Nodule-like Lesion.

Invasive mucinous adenocarcinoma (IMA) of the lung shares some clinicopathological features with mucinous carcinoma of other organs, such as the ovary. Sarcoma-like lesions, called mural nodules, have been reported in the cystic walls of ovarian mucinous tumors. In this study, we analyzed 213 surgically resected cases of IMA of the lung to determine whether similar mural nodule-like lesions were present. We considered abrupt discrete lesions composed of dedifferentiated tumor cells as mural nodule-like lesions. Of 213 IMAs, we identified 11 tumors with mural nodule-like lesions that were histologically categorized into three subtypes similar to those in the ovary. The sarcomatoid and anaplastic carcinoma-like nodules were composed of spindle cell proliferations and polygonal undifferentiated carcinoma, respectively. Sarcoma-like lesions mimicked sarcomatoid nodules, but the spindle cell proliferations were considered a fibroblastic reaction to the scattered, isolated clusters of tumor cells. Molecular analysis of the components of differentiated IMAs and mural nodule-like lesions revealed a clonal relationship, suggesting a spectrum of tumors with different histology. Clinicopathologically, an older age, the male sex, and smokers were significantly associated with IMAs with mural nodule-like lesions. Notably, patient outcomes were unaffected by the presence or absence of these lesions. Our findings demonstrated that IMA of the lung rarely develops mural nodule-like lesions (11 of 213, 5%). Despite a histological impression of clinical aggressiveness, there was no clear trend in patient outcomes, suggesting that pathologists should avoid overstating this mural nodule-like lesion.

Aggressive histological component in subsolid lung adenocarcinoma: priority for resection without delay.

INTRODUCTION: This study explored the predictors of a histological aggressive component in ground glass opacity-containing lung adenocarcinoma. METHODS: Of the 2388 patients who underwent resection for lung cancer at our institute between 2017 and 2020, we collected data on the 501 patients with ground glass opacity-containing adenocarcinoma with a total diameter of ≤2 cm. Using a historical cohort, we identified histological aggressive components that were related to a poor prognosis in early-stage adenocarcinoma. A multivariable analysis was conducted to identify predictors for the presence of a histological aggressive component. RESULTS: Lymphovascular invasion and predominant micropapillary or solid patterns were identified as histological aggressive components by a prognostic analysis using a historical cohort. Of the 501 patients included, 36 (7.2%) had at least one histological aggressive component. A multivariate analysis showed that a consolidation/tumour ratio > 0.5 (P < 0.01), maximum standardized uptake value on positron emission tomography ≥1.5 (P = 0.01) and smoking index >20 pack-years (P = 0.01) were predictors of the presence of a histological aggressive component. A total of 98% of cases without any of the above factors did not have a histological aggressive component. CONCLUSIONS: Approximately 7% of ground glass opacity-containing small adenocarcinomas contained histological aggressive component. A consolidation/tumour ratio > 0.5, maximum standardized uptake value ≥ 1.5 and smoking index >20 pack-years were predictors for such cases. These predictors may be useful for screening patients with a potentially high risk of a poor prognosis and for prioritizing resection without delay.

Clinicopathologic and Genotypic Features of Lung Adenocarcinoma Characterized by the International Association for the Study of Lung Cancer Grading System.

INTRODUCTION: The new grading system proposed by the Pathology Committee of the International Association for the Study of Lung Cancer in 2020 was based on the combination of the histologically predominant subtype and high-grade component. Because the predominant subtypes are associated with characteristic subsets, unique subsets can be identified by this grading system. METHODS: We analyzed the clinicopathologic, genotypic, and prognostic features of a cohort of 781 consecutive patients with invasive nonmucinous adenocarcinoma of the lung. RESULTS: Grade 3 tumors were associated with younger age, male sex, a higher smoking dose, and aggressive features (tumor size, lymph node metastasis, stage, lymphovascular invasion, and pleural invasion). Recurrence-free survival and 3-year overall survival were well-stratified according to tumor grade, and the differences were confirmed with multivariate analysis using the Cox proportional hazard model. Radiologically, most grade 3 tumors exhibit a solid nodular pattern on computed tomography images and a high maximum standardized uptake value with positron emission tomography. Genotypically, 43% of the grade 3 adenocarcinomas lacked any driver mutations, although one of the driver mutations was detected in 79% of grade 1 or 2 tumors. Patient age, positive smoking history, solid nodule on computed tomography image, and higher maximum standardized uptake value were identified as significant preoperative predictive factors of grade 3 tumors, with a prediction rate greater than 90%. CONCLUSIONS: Besides stratifying the patient outcomes, the new grading system characterized unique clinicopathologic subsets and this study suggested that grade 3 tumors could be predicted using the preoperative variables.

"Real" Tumor-Spread Through Air Spaces of Lung Adenocarcinoma Presented Intrapulmonary Metastases Through Bronchiole Air Spaces: A Case Report.

Here, we report a rare case of lung adenocarcinoma with intrapulmonary metastases that have "spread through air spaces" (STAS) by means of the alveoli and bronchioles. The peripheral intrapulmonary metastases were exhibiting pure ground-glass nodules along the bronchioles on computed tomography. The primary pathologic diagnosis was micropapillary adenocarcinoma with prominent tumor STAS. Histopathologic examination revealed that the cancer cells in the bronchioles around the primary tumor revealed micropapillary clusters on the mucosal surface or in the air spaces and reached peripheral intrapulmonary metastatic nodules. Notably, no vascular and stromal invasion was observed. The pathologic findings suggest that cancer cells are viable in the airspace of the bronchioles and alveoli and may support the significance of STAS as a pattern of airborne metastasis.

Incidence and prognostic factors in severe drug-induced interstitial lung disease caused by antineoplastic drug therapy in the real world.

PURPOSE: Investigate the frequency and prognostic factors of severe drug-induced interstitial lung disease (DILD) caused by antineoplastic drugs regardless of cancer types or type of drugs. METHODS: From 2014 to 2018, we reviewed patients with a history of antineoplastic agents administration in the real-world database of our hospital's electronic medical record and extracted patients who experienced "severe" DILD, requiring hospitalization with treatment or developed during hospitalization and required treatment. We collected patients' backgrounds, clinical and radiological features, laboratory data, treatment, and survival outcomes. RESULTS: 19,132 cancer patients received antineoplastic drug therapy during the study period, and 120 (0.62%) experienced severe DILD. The incidence of severe DILD in patients with thoracic cancer was highest among the patients included in this analysis (2.52% vs. 0.34% other cancers). Diffuse alveolar damage (DAD) pattern on CT was associated with higher mortality in patients with severe DILD compared with non-DAD pattern (hazard ratio [HR], 11.24; 95% CI, 4.82-26.2). Multivariate analysis revealed that the DAD pattern at diagnosis as severe DILD (HR, 3.59; 95% CI, 1.17-11.03), concurrent/previous interstitial lung disease (HR, 3.20; 95% CI, 1.27-8.10), and ECOG performance status of 2-4 (HR, 3.81; 95% CI, 1.10-13.17) were independent risk factors for mortality in patients with severe DILD. CONCLUSIONS: The frequency of severe DILD was highest in patients with thoracic cancer. The DAD pattern was associated with a poor outcome. From the perspective of DILD, special attention should be paid when administering antineoplastic agents to patients with thoracic cancer.

Visualization of patterns of lymph node metastases in non-small cell lung cancer using network analysis.

Objective: We aimed to visualize complicated patterns of lymph node metastases in surgically resected non-small cell lung cancer by applying a data mining technique. Methods: In this retrospective study, 783 patients underwent lobectomy or pneumonectomy with systematic mediastinal lymph node dissection for non-small cell lung cancer between January 2010 and December 2018. Surgically resected lymph nodes were classified according to the International Association for the Study of Lung Cancer lymph node map. Network analysis generated patterns of lymph node metastases from stations 1 to 14, and the degree of connection between 2 lymph node stations was assessed. Results: The median number of lymph nodes examined per patient was 20, and the pathological N category was pN0 in 428 cases, pN1 in 132, pN2 in 221, and pN3 in 2. N1 lymph node stations had strong associations with superior mediastinal lymph node stations for patients with primary tumors in the upper lobes and with station 7 for the lower lobes. There was also a connection from the N1 lymph node stations to superior mediastinal lymph node stations in the lower lobes. In the right middle lobe, an even distribution from station 12m toward stations 2R, 4R, and 7 was noted. We released an interactive web application to visualize these data: http://www.canexapp.com. Conclusions: Lymph node metastasis patterns differed according to the lobe bearing the tumor. Our results support the need for clinical trials to further investigate selective mediastinal lymph node dissection.