What are the risk factors for postoperative home oxygen therapy in patients with lung cancer?

Background: Home oxygen therapy (HOT) is used to treat chronic respiratory diseases and is sometimes required in patients with lung cancer after radical surgery. We aimed to identify the risk factors for postoperative home-based oxygen therapy in patients with lung cancer. Methods: Patients who underwent surgery for primary lung cancer at Chiba University Hospital between January 2019 and March 2021 were included. Patients who did not undergo complete resection, died in hospital after surgery, or used oxygen therapy preoperatively were excluded. Eligible patients were divided into HOT and non-HOT groups. They were retrospectively analyzed for risk factors for postoperative HOT using medical records in a multivariate analysis. Results: A total of 410 patients were included in this study, 24 (5.9%) of whom required HOT after surgery. The HOT group comprised significantly more men, heavy smokers, and patients with pulmonary comorbidities, low percent forced expiratory volume, percent forced vital capacity, predicted postoperative forced expiratory volume in 1 s, and postoperative pulmonary complications on univariate analysis. In a multivariate analysis, independent risk factors for postoperative HOT were pulmonary comorbidities [odds ratio (OR): 5.94; 95% confidence interval (CI): 1.64-21.5; P=0.002) and postoperative pulmonary complications (OR: 5.39; 95% CI: 2.14-13.5; P<0.001). The postoperative HOT application rate was calculated according to a formula developed for this purpose. Conclusions: Comorbid pulmonary diseases and postoperative pulmonary complications were significantly associated with postoperative HOT in patients with lung cancer.

Impact of central nervous system metastasis after complete resection of lung adenocarcinomas harboring common EGFR mutation - A real-world database study in Japan: The CReGYT-01 EGFR study.

OBJECTIVES: To clarify the impact of central nervous system (CNS) metastasis on performance status (PS) at relapse, on subsequent treatment(s), and on survival of patients with lung adenocarcinoma harboring common epidermal growth factor receptor (EGFR) mutation. METHODS: We conducted the multicenter real-world database study for patients with radical resections for lung adenocarcinomas between 2015 and 2018 at 21 centers in Japan. EGFR mutational status was examined at each center. RESULTS: Of 4181 patients enrolled, 1431 underwent complete anatomical resection for lung adenocarcinoma harboring common EGFR mutations. Three-hundred-and-twenty patients experienced disease relapse, and 78 (24%) had CNS metastasis. CNS metastasis was significantly more frequent in patients with conventional adjuvant chemotherapy than those without (30% vs. 20%, P = 0.036). Adjuvant chemotherapy did not significantly improve relapse-free survival at any pathological stage (adjusted hazard ratio for stage IA2-3, IB, and II-III was 1.363, 1.287, and 1.004, respectively). CNS metastasis did not affect PS at relapse. Subsequent treatment, mainly consisting of EGFR-tyrosine kinase inhibitors (TKIs), could be equally given in patients with or without CNS metastasis (96% vs. 94%). Overall survival after relapse was equivalent between patients with and without CNS metastasis. CONCLUSION: The efficacy of conventional adjuvant chemotherapy may be limited in patients with lung adenocarcinoma harboring EGFR mutations. CNS metastasis is likely to be found in practice before deterioration in PS, and may have little negative impact on compliance with subsequent EGFR-TKIs and survival after relapse. In this era of adjuvant TKI therapy, further prospective observational studies are desirable to elucidate the optimal management of CNS metastasis.

Can modified frailty index predict postoperative complication after lung cancer surgery?

PURPOSE: The impact of the modified frailty index (mFI) on postoperative complications after lung cancer surgery was investigated. METHODS: Patients who underwent lung cancer surgery in 2017 were included. 30-day postoperative mortality and morbidity were evaluated according to their Clavien-Dindo classification. mFI values are presented as the sum of values of 11 included items. Logistic regression was used to assess the effect of mFI on postoperative severe complication incidence. RESULTS: Among 190 patients considered, severe postoperative complications (Grade 3 or more) were observed in 30 (16%). No patients died within 30 days of surgery. The incidence of severe complications was 3.6% in patients with mFI of 0, 16.2% in patients with mFI of 1, 23.4% in patients with mFI of 2, and 31.6% in patients with mFI of 3 or more, and was correlated with the grade of mFI. Univariate and multivariate analyses showed that the high mFI was significantly predictive of postoperative complications. Frail patients of mFI ≥ 2 were at 3.0-fold greater risk of severe complications than non-frail patients of mFI 0 or 1. CONCLUSION: mFI was associated with morbidity after lung cancer surgery. Preoperative frailty assessment and appropriate intervention to frail patients would be required to improve postoperative outcomes.

Temporal correlation between postreperfusion complement deposition and severe primary graft dysfunction in lung allografts.

Growing evidence implicates complement in the pathogenesis of primary graft dysfunction (PGD). We hypothesized that early complement activation postreperfusion could predispose to severe PGD grade 3 (PGD-3) at 72 hours, which is associated with worst posttransplant outcomes. Consecutive lung transplant patients (n = 253) from January 2018 through June 2023 underwent timed open allograft biopsies at the end of cold ischemia (internal control) and 30 minutes postreperfusion. PGD-3 at 72 hours occurred in 14% (35/253) of patients; 17% (44/253) revealed positive C4d staining on postreperfusion allograft biopsy, and no biopsy-related complications were encountered. Significantly more patients with PGD-3 at 72 hours had positive C4d staining at 30 minutes postreperfusion compared with those without (51% vs 12%, P < .001). Conversely, patients with positive C4d staining were significantly more likely to develop PGD-3 at 72 hours (41% vs 8%, P < .001) and experienced worse long-term outcomes. In multivariate logistic regression, positive C4d staining remained highly predictive of PGD-3 (odds ratio 7.92, 95% confidence interval 2.97-21.1, P < .001). Hence, early complement deposition in allografts is highly predictive of PGD-3 at 72 hours. Our data support future studies to evaluate the role of complement inhibition in patients with early postreperfusion complement activation to mitigate PGD and improve transplant outcomes.

Single-Center Experience With Lung Transplant Evaluation Referrals of Acute Respiratory Distress Syndrome Patients During the COVID-19 Pandemic: How Do You Make Up For Lost Time?

Transfer of select, medically refractory acute respiratory distress syndrome patients to lung transplant centers requires extensive resources. Here, we report 270 consecutive lung transplant patient referrals to our center for medically refractory ARDS from June 2021 to April 2022, following the implementation of clinical care pathways for intake of these patients. Eighty-seven of 270 patients (32.2%) met screening criteria and were evaluated for transfer within a median of 12 days, during which 38 of 87 patients (43.7%) died and 12 of 87 patients (13.8%) transferred elsewhere. Thirty-seven of 87 patients (42.5%) were accepted for transfer of which 16 of 37 patients (43.2%) successfully transferred to our center with a median transfer waiting period of 12 days. Because of resource constraints, 21 of 37 accepted patients (56.8%) could not be transferred of which 9 of 21 patients (42.9%) died while waiting. Nine of 16 transferred patients (56.2%) eventually underwent lung transplantation with over 80% 6-month survival. ARDS patients referred for transplantation have high risk of mortality and, therefore, require well-described pathways for evaluation and transfer.

Primary graft dysfunction grade correlates with acute kidney injury stage after lung transplantation.

Background: Primary graft dysfunction (PGD) and acute kidney injury (AKI) are major early complications of lung transplantation and are associated with increased mortality. Lung injury after PGD can contribute to renal dysfunction; however, the association between PGD and AKI severity has not been thoroughly investigated. We analyzed the association between PGD grading and AKI staging, and the impact of AKI on subsequent changes to chronic kidney disease (CKD), including glomerular filtration rate (GFR), over time. Methods: This was a retrospective review of a single-center lung transplantation database between January 2018 and June 2022. AKI and GFR categories were classified according to the Kidney Disease: Improving Global Outcomes criteria. Spearman's and Kaplan-Meier tests were used to compare disease severity and assess survival. Results: In a total of 206 patients: 119 (57.8%), 25 (12.1%), 34 (16.5%), and 28 (13.6%) had PGD grades 0, 1, 2, and 3, respectively; 96 (46.6%), 47 (22.8%), 27 (13.1%), and 36 (17.5%) had AKI stages 0, 1, 2, and 3, respectively. Twenty-one of the 28 patients (75.0%) with PGD grade 3 had AKI stage 3. There was a significant correlation between PGD grade and AKI stage (P<0.001). There was also a significant correlation between AKI stage and GFR category of CKD at 3, 6, 9, and 12 months after lung transplantation (all P<0.001). For all AKI stages, GFR categories worsened with postoperative time. Conclusions: PGD grade was significantly correlated with AKI stage, and AKI stage was correlated with GFR categories of CKD.

The effect of chest wall surgery on lung volume: a new evaluation concept.

Background: In the surgical treatment of chest wall tumors requiring large chest wall resection, reconstruction of the chest wall defect is required using various autologous tissues or artificial materials. However, no appropriate method has been reported to evaluate whether each reconstruction is successful or not. Therefore, we performed lung volumetry before and after surgery to evaluate the negative effects of chest wall surgery on lung expansion. Methods: Twenty-three patients with chest wall tumors who underwent surgery were included in this study. Lung volume (LV) before and after surgery was measured using SYNAPSE VINSENT (FUJIFILM, Tokyo, Japan). The rate of change in LV was calculated as the postoperative and preoperative LV of the operative side × preoperative/postoperative LV of the opposite side. The excised chest wall area was calculated as vertical diameter × horizontal diameter of the tissue specimen. Results: Reconstruction methods included rigid reconstruction (a combination of titanium mesh and extended polytetrafluoroethylene sheet) in four patients, non-rigid reconstruction (extended polytetrafluoroethylene sheet only) in 11, no reconstruction in five, and no chest wall resection in three. Changes in LV were generally well preserved, regardless of the resected area. In addition, LVs were well maintained in most patients who underwent chest wall reconstruction. However, in some cases, decreased lung expansion was observed with migration and deflection of the reconstructive material into the thorax due to postoperative lung inflammation and shrinking. Conclusions: Lung volumetry can be used to evaluate the effectiveness of chest wall surgery.

Recipient, donor, and surgical factors leading to primary graft dysfunction after lung transplant.

Background: Primary graft dysfunction is a major cause of early mortality following lung transplantation. The International Society for Heart and Lung Transplantation subdivides it into 4 grades of increasing severity. Methods: A retrospective review of the institutional lung transplant database from March 2018 to September 2021 was performed. Patients were stratified into three groups: primary graft dysfunction grade 0 patients, grade 1 or 2 patients, and grade 3 patients. Recipient, donor, and surgical variables were analyzed by logistic regression analysis to identify risk factors for primary graft dysfunction grade 1 or 2 and grade 3. Results: Primary graft dysfunction grade 1 to 3 occurred in 45.0% of the cohort (n=68) of whom 33.3% (n=23) had primary graft dysfunction grade 3. Longer operative time was more common in primary graft dysfunction grade 1 to 3 patients (P<0.001). The 1-year survival of the patients with primary graft dysfunction grade 3 was lower than the others (grade 0-2 vs. 3, 93.7% vs. 65.2%, P=0.0006). Univariate analysis showed that acute respiratory distress syndrome, operative time, and intraoperative veno-arterial extracorporeal membrane oxygenation use were risk factors for primary graft dysfunction grades 1 or 2 and grade 3. Multivariate analysis identified that intraoperative veno-arterial extracorporeal membrane oxygenation use was an independent risk factor of primary graft dysfunction grade 1 or 2. Patients with an operative time of more than 8.18 hours had significantly higher incidence of primary graft dysfunction grade 3, acute kidney injury, and digital ischemia. Conclusions: The calculated predictors of primary graft dysfunction grade 1 or 2 were similar to those of primary graft dysfunction grade 3.

Early initiation of physical and occupational therapy while on extracorporeal life support improves patients' functional activity.

PURPOSE: Managing acute respiratory distress syndrome (ARDS) patients on venovenous extracorporeal membrane oxygenation (V-V ECMO), without sedation/neuromuscular blockade to allow physical and occupational therapy (PT/OT) participation, is untraditional. Here, we investigate the impact of early PT/OT initiation on discharge functional activity for ARDS patients managed on V-V ECMO. METHODS: This is a retrospective review of 67 ARDS patients managed with V-V ECMO at a single academic center from February 2018 to June 2021. Data collected included patient characteristics, days of V-V ECMO support, day of PT/OT initiation, and ambulation distance and Activity Measure for Post-Acute Care (AMPAC) Six-Clicks score on day of discharge. RESULTS: Patients with >7 days of V-V ECMO support had decreased ambulation and AMPAC scores compared to those with <7 days (70.5 vs. 162.1, p < 0.01 and 12.3 vs. 16.4, p = 0.01, respectively). PT/OT initiation within 7 days after starting V-V ECMO significantly improved ambulation and AMPAC scores (163.5 vs. 59.5, p < 0.001, and 16.6 vs. 11.8, p < 0.01, respectively). Additionally, in patients with >7 days of V-V ECMO support, those who began PT/OT within 8 days of V-V ECMO cannulation had significantly improved ambulation and AMPAC scores (151.8 vs. 44.2, p < 0.01, and 16.5 vs. 11.0, p < 0.01, respectively). CONCLUSION: Early PT/OT initiation in severe ARDS patients managed on V-V ECMO is associated with improved patient functional activity on day of discharge. Our study further supports the use of V-V ECMO in treatment of severe ARDS without sedation/neuromuscular blockade and specifically demonstrates PT/OT should be started early following V-V ECMO cannulation.

Postreperfusion Pulmonary Artery Pressure Indicates Primary Graft Dysfunction After Lung Transplant.

BACKGROUND: Primary graft dysfunction is a risk factor of early mortality after lung transplant. Models identifying patients at high risk for primary graft dysfunction are limited. We hypothesize high postreperfusion systolic pulmonary artery pressure is a clinical marker for primary graft dysfunction. METHODS: This is a retrospective review of 158 consecutive lung transplants performed at a single academic center from January 2020 through July 2022. Only bilateral lung transplants were included and patients with pretransplant extracorporeal life support were excluded. RESULTS: Primary graft dysfunction occurred in 42.3% (n = 30). Patients with primary graft dysfunction had higher postreperfusion systolic pulmonary artery pressure (41 ± 9.1 mm Hg) than those without (31.5 ± 8.8 mm Hg) (P < .001). Logistic regression showed postreperfusion systolic pulmonary artery pressure is a predictor for primary graft dysfunction (odds ratio 1.14, 95% CI 1.06-1.24, P < .001). Postreperfusion systolic pulmonary artery pressure of 37 mm Hg was optimal for predicting primary graft dysfunction by Youden index. The receiver operating characteristic curve of postreperfusion systolic pulmonary artery pressure at 37 mm Hg (sensitivity 0.77, specificity 0.78, area under the curve 0.81), was superior to the prereperfusion pressure curve at 36 mm Hg (sensitivity 0.77, specificity 0.39, area under the curve 0.57) (P < .01). CONCLUSIONS: Elevated postreperfusion systolic pulmonary artery pressure after lung transplant is predictive of primary graft dysfunction. Postreperfusion systolic pulmonary artery pressure is more indicative of primary graft dysfunction than prereperfusion systolic pulmonary artery pressure. Using postreperfusion systolic pulmonary artery pressure as a positive signal of primary graft dysfunction allows earlier intervention, which could improve outcomes.

A case of primary racemose hemangioma with endobronchial lesions demonstrating recurrent hemoptysis initially treated with bronchial arterial embolization.

Primary racemose hemangioma of the bronchial artery (RHBA) is one of the causes of massive hemoptysis. A 72-year-old woman was admitted to our hospital with recurrent hemoptysis. Bronchoscopy showed an endobronchial lesion, and the angiography of the right bronchial arteries indicated RHBA. Bronchial arterial embolization (BAE) was performed to prevent hemoptysis. Although the endobronchial lesion shrank after the first BAE, the lesion re-increased and caused massive hemoptysis. A thoracoscopic right upper lobectomy was performed, and hemoptysis did not recur. Therefore, in cases of RHBA where there is recurrent hemoptysis and the endobronchial lesions that remain after BAE, additional treatments should be considered.

Antibodies against complement component C5 prevent antibody-mediated rejection after lung transplantation in murine orthotopic models with skin-graft-induced pre-sensitization.

OBJECTIVE: Antibody-mediated rejection (AMR) could induce acute or chronic graft failure during organ transplantation. Several reports have shown that anti-C5 antibodies are effective against AMR after kidney transplantation. However, few reports have assessed the efficacy of anti-C5 antibodies against AMR after lung transplantation. Therefore, this study aimed to evaluate the efficacy of this novel therapy against AMR after lung transplantation. METHODS: BALB/c and C57BL/6 mice were used as donors and recipients. One group was pre-sensitized (PS) by skin transplantation 14 days before lung transplantation. The other group was non-sensitized (NS). Orthotopic left-lung transplantation was performed in both groups. Animals were killed at 2 or 7 days after lung transplantation and evaluated for histopathology, C4d immunostaining, and serum donor-specific antibodies (DSAs) (n = 5 per group). Isograft (IS) models with C57BL/6 mice were used as controls. To evaluate the efficacy of C5 inhibition, other animals, which received similar treatments to those in the PS group, were treated with anti-C5 antibodies, cyclosporine/methylprednisolone, anti-C5 antibodies/cyclosporine/methylprednisolone, or isotype-matched irrelevant control monoclonal antibodies (n = 5 per group). RESULTS: Two days after lung transplantation, the NS group exhibited mild, localized graft-rejection features (rejection score: 0.45 ± 0.08, p = 0.107). The PS group exhibited AMR features with a significantly higher rejection score (2.29 ± 0.42, p = 0.001), C4d vascular-endothelium deposition, and substantial presence of serum DSA. On day 7 after lung transplantation, both groups showed extensive graft alveolar wall destruction, and high acute-rejection scores. Mice receiving anti-C5 antibodies or anti-C5/antibodies/cyclosporine/methylprednisolone demonstrated significantly lower acute-rejection scores (0.63 ± 0.23, p = 0.002; 0.59 ± 0.22, p = 0.001, respectively) than those receiving isotype control antibodies. CONCLUSIONS: Murine orthotopic allograft lung transplant models met the clinical diagnosis and pathogenesis classification criteria of AMR. In these models, anti-C5 antibodies suppressed AMR. Therefore, anti-C5 therapy may be effective against AMR after lung transplantation.

[The Basic Research of Antigen-antibody Reaction in Lung Transplantation].

Lung transplantation has become popular in Japan, showing better survival rate than other countries. However, the results are still not satisfactory compared with other solid organ transplantation. One of the reasons for this might be that knowledge on donor-specific antibodies or antibody-related rejection, which has been attracting attention these days, is less than that of kidney or liver transplantation. Our laboratory has continued basic research in this field using rodent lung transplantation model. We have previously shown that type V collagen is associated in chronic rejection as an autoimmune, and that oral administration of type V collagen induces tolerance. The murine chronic rejection model of the minor antigen mismatch was developed, and involvement of the humoral immunity and role of the complement activation were shown. We are now studying the effects of immune checkpoint molecules, which play a central role in the field of cancer therapy, on rejection after lung transplantation. We are also working to verify the effects of anti-complement drugs and molecular targeted drugs in the future treatment on rejection.

Radiomics is feasible for prediction of spread through air spaces in patients with nonsmall cell lung cancer.

Tumor spread through air spaces (STAS) in non-small-cell lung cancer (NSCLC) is known to influence a poor patient outcome, even in patients presenting with early-stage disease. However, the pre-operative diagnosis of STAS remains challenging. With the progress of radiomics-based analyses several attempts have been made to predict STAS based on radiological findings. In the present study, patients with NSCLC which is located peripherally and tumors ≤ 2 cm in size on computed tomography (CT) that were potential candidates for sublobar resection were enrolled in this study. The radiologic features of the targeted tumors on thin-section CT were extracted using the PyRadiomics v3.0 software package, and a predictive model for STAS was built using the t-test and XGBoost. Thirty-five out of 226 patients had a STAS histology. The predictive model of STAS indicated an area under the receiver-operator characteristic curve (AUC) of 0.77. There was no significant difference in the overall survival (OS) for lobectomy between the predicted-STAS (+) and (-) groups (p = 0.19), but an unfavorable OS for sublobar resection was indicated in the predicted-STAS (+) group (p < 0.01). These results suggest that radiomics with machine-learning helped to develop a favorable model of STAS (+) NSCLC, which might be useful for the proper selection of candidates who should undergo sublobar resection.

Left superior segmentectomy for a patient with displaced anomalous apicoposterior branches of the pulmonary vein and bronchus: a case report.

BACKGROUND: Knowledge of anatomical abnormalities and variations in pulmonary vessels and bronchi is critical for patients requiring a lung segmentectomy. To the best of our knowledge, this is the first case of a tumor existing in the lower lobe in conjunction with a displaced B1+2 in which the B1+2 was not accidentally cut during surgery. CASE PRESENTATION: A 71-year-old woman was referred to our hospital after a part-solid lung cancer was found in the superior segment of her left lung on chest computed tomography. Preoperative three-dimensional computed tomography revealed a displaced anomalous left B1+2 arising from the left main bronchus and anomalous V1+2 returning to the inferior pulmonary vein. We identified these anomalies during surgery and performed a left superior segmentectomy. After an unremarkable recovery, the patient was discharged from the hospital on the eighth day postoperative. CONCLUSIONS: We used a three-dimensional construction system during the preoperative planning of the pulmonary segmentectomy to better understand the bronchovascular structures. When performing surgery where anatomical abnormalities are present, there is the possibility of misidentification. Using the three-dimensional construction system, it was possible to perform safer surgery, as the surgeons were able to preoperatively prepare for any abnormalities.

CD1d expression in glioblastoma is a promising target for NKT cell-based cancer immunotherapy.

Glioblastoma is the most common and aggressive type of brain tumor with high recurrence and fatality rates. Although various therapeutic strategies have been explored, there is currently no effective treatment for glioblastoma. Recently, the number of immunotherapeutic strategies has been tested for malignant brain tumors. Invariant natural killer T (iNKT) cells play an important role in anti-tumor immunity. To address if iNKT cells can target glioblastoma to exert anti-tumor activity, we assessed the expression of CD1d, an antigen-presenting molecule for iNKT cells, on glioblastoma cells. Glioblastoma cells from 10 of 15 patients expressed CD1d, and CD1d-positive glioblastoma cells pulsed with glycolipid ligand induced iNKT cell-mediated cytotoxicity in vitro. Although CD1d expression was low on glioblastoma stem-like cells, retinoic acid, which is the most common differentiating agent, upregulated CD1d expression in these cells and induced iNKT cell-mediated cytotoxicity. Moreover, intracranial administration of human iNKT cells induced tumor regression of CD1d-positive glioblastoma in orthotopic xenografts in NOD/Shi-scid IL-2RγKO (NOG) mice. Thus, CD1d expression represents a novel target for NKT cell-based immunotherapy for glioblastoma patients.

Risk factors of postoperative recurrence of primary spontaneous pneumothorax.

BACKGROUND: Spontaneous pneumothorax is common in relatively young, healthy patients. The risk factors for postoperative recurrence after correction are not fully understood. METHODS: We retrospectively reviewed the records of patients who underwent surgery for spontaneous pneumothorax between January 2006 and October 2017. We assessed the possible factors causing postoperative recurrence using univariate and multivariate analyses. We then used the inverse probability of treatment-weighted method to correct for confounding factors. RESULTS: Postoperative recurrence was observed in 41 of 233 patients (17.6%). A significant association with recurrence was noted for primary spontaneous pneumothorax (PSP), never smokers, thoracoscopic surgery, patients younger than 30 years, operative time less than 100 minutes, and surgery by a resident surgeon. Patients younger than 30 years of age had a 5-year recurrence-free probability of 46.3%. On multivariate analysis, patients younger than 30 years was an independent risk factor for recurrence. The confounding factors for recurrence of PSP included patients younger than 30 years, surgery by a resident surgeon, and thoracoscopic surgery. After adjusting for confounders, patients younger than 30 years was the only factor associated with recurrence (P=0.015). Patients who underwent bulla ligation with pleural reinforcement using an absorbable polyglycolic acid (PGA) sheet had a 4% recurrence rate and a 5-year recurrence-free probability of 90.0%. CONCLUSIONS: Patients younger than 30 years of age is a significant factor for postoperative recurrence in patients with PSP. Surgeons may attempt to prevent postoperative recurrence by devising the operative method and pleural reinforcement methods.

Is needle biopsy a risk factor of pleural recurrence after surgery for non-small cell lung cancer?

BACKGROUND: Tumor seeding, whereby malignant cells are deposited along the needle tract, is considered to be a potential hazard of needle biopsies. The aim of this study is to elucidate the relationship between needle biopsies for lung tumor, such as a preoperative computed tomography-guided needle biopsy (PCTGNB) or an intraoperative fine-needle aspiration biopsy (IFNAB), and ipsilateral pleural recurrence (PR) after lung cancer surgery. METHODS: Between 2008 and 2017, 1,047 patients with non-small cell lung cancer (NSCLC) underwent curative lung resection in our institution. They were divided into two groups: those in whom the first recurrent site was the ipsilateral pleural cavity (PR group) and the others (control group). Risk factors of PR were investigated retrospectively. RESULTS: Recurrence was observed in 191 patients (18.2%), 25 of whom were categorized to the PR group (17 malignant effusion, 10 dissemination). Pathological tumor [2-4], lymph nodes [1-2], pleural, lymphatic and vascular invasion (each ≥1) factors and patients who underwent PCTGNB were more frequently observed in the PR group than in the control group (each P<0.01) whereas the proportion of patients who underwent IFNAB was not significant. A multivariate analysis identified pathological lymph node factor and the frequency of PCTGNB as independent risk factors for PR with hazard ratios of 7.33 (95% CI, 2.93-19.8; P<0.01) and 6.92 (95% CI, 2.25-17.8; P<0.01), respectively. CONCLUSIONS: PCTGNB is a risk factor of PR but IFNAB is not. Indications for PCTGNB should be carefully determined.

Differential gene analysis during the development of obliterative bronchiolitis in a murine orthotopic lung transplantation model: A comprehensive transcriptome-based analysis.

BACKGROUND: Obliterative bronchiolitis (OB) is a known issue during minor histocompatibility antigen (mHA) disparity during lung transplantation. This study evaluated gene expression in a murine orthotropic lung transplantation model using microarray analysis. METHODS: Left lungs from C57BL/10(H-2b) donor mice were transplanted into mHA-mismatched C57BL/6(H-2b) recipient mice. Three groups (OB, non-OB, and sham controls) were confirmed pathologically and analyzed. Gene expression changes in the lung grafts were determined by microarray and immunohistochemical staining, and genes were verified by quantitative PCR in the lungs and mediastinal lymph nodes (LNs). RESULTS: A total of 1343 genes were upregulated in the OB lungs compared to the sham group. Significant upregulation was observed for genes related to innate, e.g. Tlr2 and CCL3 and adaptive immunity, e.g. H2-ab1 and Il-21. Positive labeling for MHC class II antigen was observed in the bronchial epithelium of OB accompanied with B cells. We found increased Tlr2, Ccl3, H2-ab1, Il-21, Ighg3, Ifng, and Pdcd1 mRNA expression in the OB lung, and increased Il-21, Ighg3, and Pdcd1 expression in the OB LNs. CONCLUSIONS: Adaptive and innate immune reactions were involved in OB after lung transplantation, and genetic examination of related genes could be used for detection of OB.