Clinical and pathological predictors of engraftment for patient-derived xenografts in lung adenocarcinoma.

Patient-derived xenografts (PDXs) are increasingly utilized in preclinical drug efficacy studies due to their ability to retain the molecular, histological, and drug response characteristics of patient tumors. This study aimed to investigate the factors influencing the successful engraftment of PDXs. Lung adenocarcinoma PDXs were established using freshly resected tumor tissues obtained through surgery. Radiological data of pulmonary nodules from this PDX cohort were analyzed, categorizing them into solid tumors and tumors with ground-glass opacity (GGO) based on preoperative CT images. Gene mutation status was obtained from next generation sequencing data and MassARRAY panel. A total of 254 resected primary lung adenocarcinomas were utilized for PDX establishment, with successful initial engraftment in 58 cases (22.8 %); stable engraftment defined as at least three serial passages was observed in 43 cases (16.9 %). The stable engraftment rates of PDXs from solid tumors and tumors with GGO were 22.1 % (42 of 190 cases) and 1.6 % (1 of 64 cases), respectively (P < 0.001). Adenocarcinomas with advanced stage, poor differentiation, solid histologic subtype, and KRAS or TP53 gene mutations were associated with stable PDX engraftment. Avoiding tumors with GGO features could enhance the cost-effectiveness of establishing PDX models from early-stage resected lung adenocarcinomas.

Lung cancer detection in perioperative patients' exhaled breath with nanomechanical sensor array.

INTRODUCTION: Breath analysis using a chemical sensor array combined with machine learning algorithms may be applicable for detecting and screening lung cancer. In this study, we examined whether perioperative breath analysis can predict the presence of lung cancer using a Membrane-type Surface stress Sensor (MSS) array and machine learning. METHODS: Patients who underwent lung cancer surgery at an academic medical center, Japan, between November 2018 and November 2019 were included. Exhaled breaths were collected just before surgery and about one month after surgery, and analyzed using an MSS array. The array had 12 channels with various receptor materials and provided 12 waveforms from a single exhaled breath sample. Boxplots of the perioperative changes in the expiratory waveforms of each channel were generated and Mann-Whitney U test were performed. An optimal lung cancer prediction model was created and validated using machine learning. RESULTS: Sixty-six patients were enrolled of whom 57 were included in the analysis. Through the comprehensive analysis of the entire dataset, a prototype model for predicting lung cancer was created from the combination of array five channels. The optimal accuracy, sensitivity, specificity, positive predictive value, and negative predictive value were 0.809, 0.830, 0.807, 0.806, and 0.812, respectively. CONCLUSION: Breath analysis with MSS and machine learning with careful control of both samples and measurement conditions provided a lung cancer prediction model, demonstrating its capacity for non-invasive screening of lung cancer.

Sex-specific emphysematous changes evaluated by a three-dimensional computed tomography volumetric analysis among patients with smoking histories who underwent resection for lung cancer.

PURPOSE: The present study evaluated the sex-specific susceptibility to the development of emphysema in patients with smoking histories who underwent lung cancer surgeries. METHODS: Lung cancer patients with smoking histories who underwent lung resection at the University of Tsukuba Hospital, Japan, were enrolled. Radiologic emphysematous changes were analyzed using three-dimensional computed tomography (3D-CT). The volume proportion of emphysematous lung per unit of smoking and the relationship between emphysematous change and clinicopathologic factors were evaluated. RESULTS: Radiologic emphysematous changes analyzed using 3D-CT per pack-year smoked, defined as the Smoking-Emphysema Index (SEI), were greater in females than males. The difference was more profound in adenocarcinoma patients than in non-adenocarcinoma patients (0.70 ± 2.30 vs. 0.21 ± 0.28, P = 0.037). CONCLUSION: Female lung cancer patients are more susceptible to smoking-induced emphysema than males. The SEI may be an effective indicator for evaluating smoking-induced emphysema.

Three-dimensional analysis reveals a high incidence of lung adenocarcinoma in the upper region.

PURPOSE: The lung is a unique organ with a ventilation-perfusion mismatch, which can cause inhomogeneous incidence rates of lung cancer depending on the location in the lung. We aimed to evaluate the incidence of lung adenocarcinoma in each lobe by analyzing the incidence per unit volume, to evaluate the incidence without being affected by differences in the size of each lobe or in the size of the lungs between individuals. METHODS: The number of adenocarcinomas in each lobe was counted. Lung volumes were measured using a three-dimensional computer workstation. The tumor incidence per unit volume was analyzed based on the number of tumors in each lobe. RESULTS: The number of tumors per unit volume was 0.467 in the right upper lobe (RUL), 0.182 in the right middle lobe, 0.209 in the right lower lobe, 0.306 in the left upper segment (LUS), 0.083 in the left lingular segment, and 0.169 in the left lower lobe. The tumor incidence rate of RUL + LUS was 2.269 times that of the other lobes, a value that was significantly higher when using the bootstrap method (p < 0.001). CONCLUSIONS: The incidence of adenocarcinoma per unit volume in both upper lobes was higher than that in other lobes.

Sphericity of lymph nodes using 3D-CT predicts metastasis in lung cancer patients.

BACKGROUND: The presence of mediastinal lymph node metastasis is important because it is related to the treatment and prognosis of lung cancer. Although prevalently used, evaluation of lymph nodes is not always reliable. We introduced sphericity as a criterion for evaluating morphologic differences between metastatic and nonmetastatic nodes. METHODS: We reviewed the cases of 66 patients with N2 disease and of 68 patients with N0-1 disease who underwent lobectomy with mediastinal dissection between January 2012 and December 2021. The sphericity of the dissected station lymph nodes, which represents how close the node is to being a true sphere, was evaluated along with the diameter and volume. Each parameter was obtained and evaluated for ability to predict metastasis. RESULTS: Metastatic lymph nodes had a larger short-axis diameter (average: 8.2 mm vs. 5.4 mm, p < 0.001) and sphericity (average: 0.72 vs. 0.60, p < 0.001) than those of nonmetastatic lymph nodes. Short-axis diameter ≥ 6 mm and sphericity ≥ 0.60 identified metastasis with 76.2% sensitivity and 70.2% specificity (AUC = 0.78, p < 0.001) and 92.1% sensitivity and 53.9% specificity (AUC = 0.78, p < 0.001), respectively. For lymph nodes with a short-axis diameter ≥ 5 mm, sphericity ≥ 0.60 identified metastasis with 84.1% sensitivity and 89.3% specificity. CONCLUSION: By using 3D-CT analysis to examine sphericity, we showed that metastatic lymph nodes became spherical. Our method for predicting lymph node metastasis based on sphericity of lymph nodes with a short-axis diameter ≥ 5 mm could do so with higher sensitivity than the conventional method, and with acceptable specificity.

Assessment of effectiveness and safety of thrombolytic therapy to pulmonary emboli by endobronchial ultrasound-guided transbronchial needle injection.

Objective: Endobronchial ultrasound-guided transbronchial needle injection (EBUS-TBNI) may effectively treat acute pulmonary embolisms (PEs). Here, we assessed the effectiveness of clot dissolution and safety of tissue plasminogen activator (t-PA) injection using EBUS-TBNI in a 1-week survival study of a porcine PE model. Methods: Six pigs with bilateral PEs were used: 3 for t-PA injection using EBUS-TBNI (TBNI group) and 3 for systemic administration of t-PA (systemic group). Once bilateral PEs were created, each 25 mg of t-PA injection using EBUS-TBNI for bilateral PEs (a total of 50 mg t-PA) and 100 mg of t-PA systemic administration was performed on day 1. Hemodynamic parameters, blood tests, and contrast-enhanced computed tomography scans were carried out at several time points. On day 7, pigs were humanely killed to evaluate the residual clot volume in the pulmonary arteries. Results: The average of percent change of residual clot volumes was significantly lower in the TBNI group than in the systemic group (%: systemic group 36.6 ± 22.6 vs TBNI group 9.6 ± 6.1, P < .01) on day 3. Considering the elapsed time, the average decrease of clot volume per hour at pre-t-PA to post t-PA was significantly greater in the TBNI group than in the systemic group (mm3/hour: systemic 68.1 ± 68.1 vs TBNI 256.8 ± 148.1, P < .05). No hemorrhage was observed intracranially, intrathoracically, or intraperitoneally on any contrast-enhanced computed tomography images. Conclusions: This study revealed that t-PA injection using EBUS-TBNI is an effective and safe way to dissolve clots.

Anatomic evaluation of Pancoast tumors using three-dimensional models for surgical strategy development.

OBJECTIVE: Pancoast tumor resection planning requires precise interpretation of 2-dimensional images. We hypothesized that patient-specific 3-dimensional reconstructions, providing intuitive views of anatomy, would enable superior anatomic assessment. METHODS: Cross-sectional images from 9 patients with representative Pancoast tumors, selected from an institutional database, were randomly assigned to presentation as 2-dimensional images, 3-dimensional virtual reconstruction, or 3-dimensional physical reconstruction. Thoracic surgeons (n = 15) completed questionnaires on the tumor extent and a zone-based algorithmic surgical approach for each patient. Responses were compared with surgical pathology, documented surgical approach, and the optimal "zone-specific" approach. A 5-point Likert scale assessed participants' opinions regarding data presentation and potential benefits of patient-specific 3-dimensional models. RESULTS: Identification of tumor invasion of segmented neurovascular structures was more accurate with 3-dimensional physical reconstruction (2-dimensional 65.56%, 3-dimensional virtual reconstruction 58.52%, 3-dimensional physical reconstruction 87.50%, P < .001); there was no difference for unsegmented structures. Classification of assessed zonal invasion was better with 3-dimensional physical reconstruction (2-dimensional 67.41%, 3-dimensional virtual reconstruction 77.04%, 3-dimensional physical reconstruction 86.67%; P = .001). However, selected surgical approaches were often discordant from documented (2-dimensional 23.81%, 3-dimensional virtual reconstruction 42.86%, 3-dimensional physical reconstruction 45.24%, P = .084) and "zone-specific" approaches (2-dimensional 33.33%, 3-dimensional virtual reconstruction 42.86%, 3-dimensional physical reconstruction 45.24%, P = .501). All surgeons agreed that 3-dimensional virtual reconstruction and 3-dimensional physical reconstruction benefit surgical planning. Most surgeons (14/15) agreed that 3-dimensional virtual reconstruction and 3-dimensional physical reconstruction would facilitate patient and interdisciplinary communication. Finally, most surgeons (14/15) agreed that 3-dimensional virtual reconstruction and 3-dimensional physical reconstruction's benefits outweighed potential delays in care for model construction. CONCLUSIONS: Although a consistent effect on surgical strategy was not identified, patient-specific 3-dimensional Pancoast tumor models provided accurate and user-friendly overviews of critical thoracic structures with perceived benefits for surgeons' clinical practices.

Repeated photodynamic therapy mediates the abscopal effect through multiple innate and adaptive immune responses with and without immune checkpoint therapy.

In combination with immune checkpoint inhibitors, photodynamic therapy can induce robust immune responses capable of preventing local tumor recurrence and delaying the growth of distant, untreated disease (ie. the abscopal effect). Previously, we found that repeated photodynamic therapy (R-PDT) using porphyrin lipoprotein (PLP) as a photosensitizer, without the addition of an immune checkpoint inhibitor, can induce the abscopal effect. To understand why PLP mediated R-PDT alone can induce the abscopal effect, and how the addition of an immune checkpoint inhibitor can further strengthen the abscopal effect, we investigated the broader immune mechanisms facilitated by R-PDT and combination R-PDT + anti-PD-1 monoclonal antibody (αPD-1) in a highly aggressive, subcutaneous AE17-OVA mesothelioma dual tumor-bearing C57BL/6 mice. We found a 46.64-fold and 61.33-fold increase in interleukin-6 (IL-6) after R-PDT and combination R-PDT + αPD-1 relative to PBS respectively, suggesting broad innate immune activation. There was a greater propensity for antigen presentation in the spleen and distal, non-irradiated tumor draining lymph nodes, as dendritic cells and macrophages had increased expression of MHC class II, CD80, and CD86, after R-PDT and combination R-PDT + αPD-1. Concurrently, there was a shift in the proportions of CD4+ T cell subsets in the spleen, and an increase in the frequency of CD8+ T cells in the distal, non-irradiated tumor draining lymph nodes. While R-PDT had an acceptable safety profile, combination R-PDT + αPD-1 induced 1.26-fold higher serum potassium and 1.33-fold phosphorus, suggestive of mild laboratory tumor lysis syndrome. Histology revealed an absence of gross inflammation in critical organs after R-PDT and combination R-PDT + αPD-1 relative to PBS-treated mice. Taken together, our findings shed light on how the abscopal effect can be induced by PDT and strengthened by combination R-PDT + αPD-1, and suggests minimal toxicities after R-PDT.

Preclinical feasibility of bronchoscopic fluorescence-guided lung sentinel lymph node mapping.

OBJECTIVE: Lung sentinel lymph node mapping, where peritumorally injected material is tracked through the lymphatics, aims to find the first potential sites of nodal metastasis. We sought to evaluate the preclinical feasibility of bronchoscopic fluorescence-guided sentinel lymph node mapping. METHODS: Healthy Yorkshire pigs were used; sentinel lymph node mapping was performed with indocyanine green. The primary fluorescence imaging method was an ultrathin composite fiberscope placed in the bronchoscope working channel. Secondary methods used a fluorescence thoracoscope placed in the trachea (rigid bronchoscopy) and pretracheal fascial plane (mediastinoscopy) to validate ultrathin composite fiberscope settings for sentinel lymph node detection. A tracheostomy was created, and the pig was placed in a lateral decubitus position. Transbronchial intraparenchymal indocyanine green injection was performed primarily in the right lower lobe. Ultrathin composite fiberscope and rigid bronchoscopy were performed with (n = 6) or without (n = 2) mediastinoscopy, with the former group guiding dose and ultrathin composite fiberscope optimization. Fluorescent targets were interrogated by endobronchial ultrasound before ultrathin composite fiberscope-guided transbronchial needle aspiration. Specimen fluorescence was documented before creating cytological smears. Pigs were killed postprocedure for nodal dissection. RESULTS: A total of 100 µL of 10 mg/mL indocyanine green generated strong transbronchial fluorescence with low risk of indocyanine green contamination. Fluorescence was detectable by 10 minutes postinjection. There was concordance among ultrathin composite fiberscope, rigid bronchoscopy, and mediastinoscopy. Except for 1 pig with airway contamination, ultrathin composite fiberscope-guided endobronchial ultrasound transbronchial needle aspiration obtained fluorescent material in all pigs. Specimen fluorescence was associated with specimen adequacy. CONCLUSIONS: Bronchoscopic fluorescence-guided sentinel lymph node mapping was feasible, with specimen fluorescence providing real-time feedback on sentinel lymph node biopsy success. If translated to clinical practice, attention must be paid to minimizing indocyanine green leakage.

Effect of pulmonary training for community-dwelling frail older adults with chronic stroke: A randomized controlled pilot trial.

Background: Decreased pulmonary function and poor deglutition are a major risk factor for poststroke aspiration pneumonia. We analyzed the benefits of pulmonary training on pulmonary function, deglutition, and quality of life (QOL) in community-dwelling, frail elderly people with chronic stroke. Method: This study was designed as an open, randomized, controlled pilot trial. The participants, who were frail older adults with a history of stroke, were randomized to 2 rehabilitation groups: intervention group (n = 15) and control (n = 15). All participants (65-94 years) attended twelve 20-min sessions twice a week for 6 weeks of either standard rehabilitation (control group) or standard rehabilitation with pulmonary training including home pulmonary exercise (intervention group). The main outcome measures were pulmonary function (%MIP), deglutition (DRACE), and QOL (SF8ï½¥PCS), while secondary outcomes were muscle strength (grip and abdominal), thorax flexibility, 6-min walk distance, and activities in daily living. All outcomes were measured both prior to training and after the 12 sessions. Results: The intervention group showed significant improvement in %MIP (95% CI, 2.9-31.6; p < 0.01), DRACE (95% CI, -4.1-0.1; p < 0.01), and SF8ï½¥PCS (95% CI, 2.5-7.2; p < 0.01) compared with controls. There were no cognitive function decline and higher brain dysfunction. Conclusions: These results suggest that the addition of pulmonary training including home pulmonary exercise to a standard rehabilitation program could improve pulmonary function, deglutition, and QOL in frail elderly people with chronic stroke.

Efficacy of Alaska Pollock Gelatin Sealant for Pulmonary Air Leakage in Porcine Models.

BACKGROUND: Postoperative prolonged air leakage is a frequent complication after lung resection. We have developed a new sealant based on a hydrophobically modified Alaska pollock-derived gelatin (ApGltn) sealant. The purpose of this study was to evaluate the adhesive strength of the ApGltn sealant in comparison with a fibrin sealant using a new spray system in ex vivo and in vivo models. METHODS: Pleural defects in ex vivo and in vivo porcine models were created, to which the ApGltn sealant or the fibrin sealant was applied. The pressure resistance was assessed with a stepwise increase in airway pressure to confirm air leakage from the sealing site. Tissue samples covered with each sealant were obtained for histologic assessment. RESULTS: In the ex vivo experiment, the leak pressures of the ApGltn sealant were significantly greater than those of the fibrin sealant (102.94 ± 15.6 cm H2O and 28.37 ± 5.1 cm H2O, respectively) (P < .01). In the in vivo experiment, the leak pressures of the ApGltn sealant were also significantly greater than those of the fibrin sealant (68.82 ± 18.04 cm H2O and 43.33 ± 7.13 cm H2O, respectively) (P = .043). The histologic examination confirmed that the ApGltn sealant adhered tightly to both the pleura and the surface of the pleural defect. CONCLUSIONS: The ApGltn sealant has sufficiently high adhesive quality in ex vivo and in vivo porcine lungs, which could be considered suitable and effective for use in the prevention of air leakage from the lungs.

Predicting Respiratory Complications Following Lobectomy Using Quantitative CT Measures of Emphysema.

PURPOSE: In performing surgery for lung cancer, emphysema is a risk factor related to postoperative respiratory complications (PRC). However, few studies have addressed the risk of radiological emphysematous volume affecting PRC. The aim of this study was to investigate the relationship between emphysematous volume as measured on 3-dimensional computed tomography and PRC. PATIENTS AND METHODS: We reviewed 342 lung cancer patients undergoing lobectomy between 2013 and 2018. The percentage of low attenuation area (LAA%) was defined as the percentage of the lung area showing attenuation of -950 Hounsfield units or lower. Preoperative factors including age, sex, body mass index, smoking index, respiratory function, tumour histology, and LAA% were evaluated. PRC included pneumonia, atelectasis, prolonged air leakage, empyema, hypoxia, ischemic bronchitis, bronchopleural fistula, and exacerbation of interstitial pneumonia. Uni- and multivariable analyses were performed to investigate the relationship between independent clinical variables and postoperative adverse events. RESULTS: Median LAA% was 5.0% (range, 0-40%) and PRC was observed in 50 patients (14.6%). Patients who presented with PRC showed significantly high LAA% compared to those without complications (median: 8.1% vs 3.8%; p < 0.001). Based on univariable analysis, age, sex, smoking index, percentage of forced expiratory volume in 1 s (FEV1.0%), histology, and LAA% were significant predictors for PRC. Multivariable analysis revealed higher LAA% as a significant risk factor for PRC (odds ratio = 1.040; 95% confidence interval, 1.001-1.080; p = 0.046). CONCLUSION: In addition to respiratory function with spirometry, LAA% can be used as a predictor of PRC.

Risk factors of middle lobe bronchus kinking following right upper lobectomy.

BACKGROUND: The incidence rate of kinking of the middle lobe bronchus following right upper lobectomy is higher compared to that with residual lung bronchus following other lobectomies. Bronchial kinking was presumed to be caused by the displacement of the residual lung lobes, but its etiology is unclear. Moreover, prevention methods and effective treatments have not yet been established. The purpose of this study was to investigate the risk factors and etiology of middle lobe bronchus kinking and discuss prevention methods. METHODS: Patients who underwent right upper lobectomy in our hospital were retrospectively evaluated. Patient clinical characteristics, lung function, and lung lobe volume, surgical procedure were analyzed in association with the incidence of middle lobe bronchus kinking. The association between the displacement of residual lung lobes after operation and the incidence of middle lobe bronchus kinking was analyzed to assess the etiology. RESULTS: A total of 175 patients were enrolled in the risk analysis. Middle lobe bronchus kinking was observed in 5 patients (2.9%). The low percentage of forced expiratory volume percentage in 1 second (P=0.021), the low volume ratio of the right middle lobe (RML) to the right thoracic cavity (RTC) (P=0.016), and the low volume ratio of RML to right upper lobe (RML/RUL) (P=0.006) were significant risk factors of middle lobe bronchus kinking. In the patients who underwent CT at 6 months after surgery, the degree of the cranial displacement of RML was associated with the incidence of middle lobe bronchus kinking (P=0.025). CONCLUSIONS: The risk of middle lobe bronchus kinking could be assessed preoperatively by calculating the volume ratio of RML/RTC and RML/RUL. The displacement of RML could be associated with the incidence of middle lobe bronchus kinking.

Consolidation volume and integration of computed tomography values on three-dimensional computed tomography may predict pathological invasiveness in early lung adenocarcinoma.

PURPOSE: To investigate the relationship between three-dimensional computed tomography (3D-CT) findings and pathological invasiveness in lung adenocarcinoma. METHODS: We retrospectively evaluated 95 patients who underwent surgical resection of lung adenocarcinoma of ≤ 20 mm. The diameters, volumes, and CT values of tumor consolidation were analyzed. We defined the modified CT value by setting air as 0 and water as 1000 and assumed a correlation with pathological invasiveness. Pre-invasive lesions and minimally invasive adenocarcinomas were classified as non-invasive adenocarcinoma. We compared the clinico-radiological features with pathological invasiveness. Receiver operator characteristic (ROC) curves and recurrence-free survival curves were constructed. RESULTS: Twenty-six non-invasive adenocarcinomas and 69 invasive adenocarcinomas were evaluated. The multivariate analysis revealed that the consolidation volume and the integration of modified CT values were the most important predictors of pathological invasion. The area under the ROC curve and the cut-off values of the consolidation volume were 0.868 and 75 mm3, respectively. The area under the ROC curve and the cut-off values of the integration of modified CT values were 0.871 and 80,000, respectively. There was no recurrence in cases with values below the cut-off across all parameters. CONCLUSION: The consolidation volume and integration of modified CT values were shown to be highly predictive of pathological invasiveness.

Factors related to physical and mental components of quality of life in the community-dwelling frail older persons.

[Purpose] The aim of this study was to investigate factors associated with changes in both the physical and mental components of quality of life (QOL) in of community-dwelling frail older persons in long-term care and to clarify which aspects are important to maintaining physical and mental components of QOL. [Participants and Methods] In this 1 year follow-up cohort study, participants were older persons from a single day care rehabilitation center in Japan. The Medical Outcome Study 8-Item Short-Form Health Survey (MOS-SF8), which gives both physical component summary (PCS) and mental component summary (MCS) scores, was used as the main QOL assessment. Participants were divided according to their level of QOL maintenance according to changes in PCS and MCS scores over the study period, and the variables were compared between the groups. [Results] PCS domain was significantly associated with forced vital capacity and the MCS domain was significantly associated with the Geriatric Depression Scale and Dysphagia Risk Assessment for the Community-Dwelling Elderly Test. [Conclusion] Depression, reduced pulmonary function, and reduced deglutition ability were independently related to low QOL. Assessment of these factors could be beneficial for maintaining the physical and mental components of QOL in community-dwelling frail older persons in long-term care.

Successful use of extracorporeal membrane oxygenation for airway-obstructing lung adenocarcinoma.

Endobronchial-invasive lung cancers are generally diagnosed at advanced stages and may require emergency treatment for airway obstruction. Stent implantation is a common intervention for such obstructed airways but certain subsets of patients cannot receive adequate treatment without respiratory support. Veno-venous extracorporeal membrane oxygenation (ECMO) is a salvage therapy for respiratory failure but its usefulness in managing patients with advanced lung cancer remains unclear given the poor prognosis. In recent years, molecular targeted agents for patients with driver mutations offer rapid responses and may be administered even while under critical care. In this report, we describe the case of 39-year-old female who presented to our emergency department with severe respiratory distress. A computed tomography scan revealed a large mediastinal tumor invading the tracheal carina causing severe stenosis of the left main bronchus and right main pulmonary artery. ECMO support was required as the respiratory condition remained unstable despite high pressure ventilation. Under ECMO support, the patient underwent bronchial stent implantation and was successfully weaned off ECMO. The tumor was histologically diagnosed as pulmonary adenocarcinoma with anaplastic lymphoma kinase gene rearrangement. Treatment with a tyrosine kinase inhibitor, alectinib, induced a marked tumor reduction within a short period. The patient recovered well and is now in remission one year later. This case indicates that intensive respiratory support with ECMO may become a bridge through the critical period for selected patients with respiratory failure secondary to advanced lung cancer. KEY POINTS: SIGNIFICANT FINDINGS OF THIS STUDY: ECMO was important to maintain oxygenation during airway intervention for acute respiratory failure due to critical lung adenocarcinoma with ALK gene rearrangement. WHAT THIS STUDY ADDS: With the development of targeted therapies and the improvement in therapeutic bronchoscopy, intensive respiratory support with ECMO may be helpful especially in selected lung cancer patients with oncogenic driver mutations.

Detection of circulating tumor cells in patients with lung cancer using metallic micro-cavity array filter: A pilot study.

We have developed a metallic micro-cavity array filter and an automated detection system for capturing circulating tumor cells (CTCs). In this single institutional pilot study, we assessed the ability of this device to detect CTCs in patients with lung cancer at each stage. Patients diagnosed with lung cancer, undergoing planned surgery for lung cancer, or suspected of having lung cancer were recruited (40 recruited and 2 excluded). Blood samples were obtained from the patients and 3 ml whole blood was applied to the device without any preparation. The captured cells were stained to differentiate the nucleus, and determine cytokeratin and CD45 expression. Subsequently, two operators blinded to clinical information counted the number of CTCs. Sample collection was performed at the time of recruitment, before treatment and ~3 months after initial blood collection. CTC counts at recruitment were 1.4±0.4, 1.8±1.2, 1.3±0.6 and 7.4±5.1 (mean ± SE) in clinical stages I, II, III and IV, respectively. No significant difference was observed among the stages. These data indicated the ability of this device to detect CTCs at early or non-metastatic stages of lung cancer. Further research on a larger scale is needed for a more accurate assessment of the device, and research on the utility of captured cells remains a future challenge.

Rolipram plus Sivelestat inhibits bone marrow-derived leukocytic lung recruitment after cardiopulmonary bypass in a primate model.

Cardiopulmonary bypass (CPB) recovery is complicated by lung inflammation from bone marrow (BM)-derived polymorphonuclear leukocytes (PMNs) and monocytes (MO). Although Sivelestat reduces inflammatory mediators and Rolipram inhibits PMN and MO activation, any kinetic effects to improve CPB recovery in vivo are unknown. We hypothesized that intraoperative co-administration of these compounds would reduce CPB-induced lung inflammation through downregulation of PMN and MO recruitment. A 2-h CPB was surgically established in cynomolgus monkeys (n = 13), and BM leukocyte release and lung recruitment were monitored postoperatively by flow cytometry with 5'-bromo-2'-deoxyuridine (BrdU) and cytokine ELISA. Either Sivelestat, Sivelestat plus Rolipram, or saline (control) was administered intraoperatively and both peripheral and perfusion sampling courses revealed BrdU-labeled cells representative of activated leukocyte infiltration. Levels of cytokines CD11b and CD18 were leukocytic activation markers. Sivelestat plus Rolipram attenuated increases in CPB-associated circulating band cells, prolonged BM-transit time (PMN: 121.0 ± 3.7 to 96.2 ± 4.3 h [control], p = 0.012; MO: 84.4 ± 4.1 to 61.4 ± 3.0 h [control], p = 0.003), and reduced their alveolar appearance. CD11b-mediated PMN and MO changes during CPB and the post-surgical increases of Interleukin (IL)-6 and IL-8 in the bronchoalveolar lavage fluid were suppressed. Sivelestat alone increased PMN transit time to 115.8 ± 6.6 h, but monocytes were unaffected. Therefore, Rolipram has additive inhibitory effects with Sivelestat on the CPB-induced activation and release of BM-derived PMNs and MO and their recruitment to the lungs. Co-administration of these compounds could, therefore, hold value for preventing CPB-induced lung injury.

[Outcome of Surgical Treatment of Locally Advanced Lung Cancer after Induction Chemoradiotherapy].

OBJECTIVE: The outcome of surgical treatment of non-small-cell lung cancer after induction chemoradiotherapy was investigated. SUBJECTS: The subjects were 74 patients with non-small-cell lung cancer who received induction chemoradiotherapy( ICRT) between 1998 and 2016. ICRT was administered to pT3 lung cancer invading the chest wall(20 patients), pT4 lung cancer invading the adjacent organ(22 patients), and cN2 lung cancer(32 patients). cN2 was confirmed by mediastinoscopy(13 patients) and endobronchial ultrasound-guided transbronchial needle aspiration(EBUS-TBNA)(19 patients). RESULTS: Sixty-eight and 6 patients were male and female, respectively, and the mean age was 59.6 years old. The histologic type was adenocarcinoma in 43 patients, squamous cell carcinoma in 24, adenosquamous carcinoma in 5, and others in 2. In chemotherapy, 2 or more anticancer drugs including platinum agent were administered. The radiation dosage was 36 Gy in 1 patient, 40 Gy in 43, 50 Gy in 28, and 60 Gy in 2. The effect of ICRT was complete response( CR) in 1 patient, partial response( PR) in 40, and stable disease (SD) in 33 (CR+PR:55.4%). The surgical procedure was lobectomy in 60 patients, pneumonectomy in 10, bilobectomy in 3, and segmentectomy in 1. Tracheobronchoplasty was performed in 9 patients, and combined resection of the vertebral body, left atrium, carina, superior vena cava, aorta, and brachiocephalic subclavian artery was performed in 7, 5, 4, 3, 3, and 3 patients, respectively. Regarding postoperative complications, empyema developed in 5 patients, acute respiratory distress syndrome(ARDS)in 3, pneumonia in 3, tracheobronchial dehiscence in 2, postoperative hemorrhage in 1, atrial fibrillation in 1, and others in 5. Postoperative complication rate was 27.0%, and operative death occurred due to postoperative hemorrhage in 1 patient. Complete resection was achieved in 69 patients(93.2%). Regarding the histological effect of ICRT, Ef.1/2/3 = 32/28/14(Ef.2-3:56.7%), and down stage was achieved in 24 patients (32.4%). The 5-year survival rate of all 74 patients was 51.0%, median survival time (MST)was 62.7 months, and the recurrence-free survival rate was 47.3%. Recurrence occurred in 28 patients (40.6%)with complete resection and the recurrence was distant metastasis in 20 of them. Regarding the outcome by the effect of ICRT, the 5-year survival rates of patients who achieved CR+PR/SD, Ef.2-3/Ef.0-1, and down stage/non-down stage were 66.0%/34.3%(p=0.009), 73.2%/20.1%(p=0.001), and 83.7%/44.0%(p=0.02), respectively, showing that the outcomes of patients who achieved CR/PR, Ef.2-3, and down stage were significantly favorable. CONCLUSION: The morbidity and mortality rates of patients who underwent surgery after ICRT were 27 and 1.4%, respectively. More than half of the patients achieved CR-PR and Ef.2-3, 1/3 of the cases were down staged, and the outcomes of these patients were significantly favorable. Surgery after ICRT may improve the treatment outcome of patients with locally advanced lung cancer.

Three-dimensional computed tomographic volumetry precisely predicts the postoperative pulmonary function.

PURPOSE: It is important to accurately predict the patient's postoperative pulmonary function. The aim of this study was to compare the accuracy of predictions of the postoperative residual pulmonary function obtained with three-dimensional computed tomographic (3D-CT) volumetry with that of predictions obtained with the conventional segment-counting method. METHODS: Fifty-three patients scheduled to undergo lung cancer resection, pulmonary function tests, and computed tomography were enrolled in this study. The postoperative residual pulmonary function was predicted based on the segment-counting and 3D-CT volumetry methods. The predicted postoperative values were compared with the results of postoperative pulmonary function tests. RESULTS: Regarding the linear correlation coefficients between the predicted postoperative values and the measured values, those obtained using the 3D-CT volumetry method tended to be higher than those acquired using the segment-counting method. In addition, the variations between the predicted and measured values were smaller with the 3D-CT volumetry method than with the segment-counting method. These results were more obvious in COPD patients than in non-COPD patients. CONCLUSIONS: Our findings suggested that the 3D-CT volumetry was able to predict the residual pulmonary function more accurately than the segment-counting method, especially in patients with COPD. This method might lead to the selection of appropriate candidates for surgery among patients with a marginal pulmonary function.