Immunologic Significance of CD80/CD86 or Major Histocompatibility Complex-II Expression in Thymic Epithelial Tumors.

Introduction: Unresectable or recurrent thymic epithelial tumors (TETs) have a poor prognosis, and treatment options are limited. This study aimed to investigate the immunologic significance of CD80/CD86 or major histocompatibility complex class II (MHC-II) expression in TETs, as potential predictive biomarkers for immune checkpoint inhibitors (ICIs). Methods: We analyzed CD80, CD86, MHC class I (MHC-I), and MHC-II expression in TETs using immunohistochemistry and investigated their association with T-cell infiltration or ICI efficacy. In addition, we generated CD80- or MHC-II-expressing mouse tumors, evaluated the effects of ICIs, and analyzed tumor-infiltrating lymphocytes. We also performed tumor-rechallenge experiments in vivo. Results: We found that approximately 50% and 30% of TETs had high expression of CD80/CD86 and MHC-II in tumor cells, respectively, and that this expression was related to T-cell infiltration in clinical samples. In mouse models, both CD80 and MHC-II increase the effects of ICIs. In addition, senescent T cells and long-lived memory precursor effector T cells were significantly decreased and increased, respectively, in tumor-infiltrating lymphocytes from CD80-expressing tumors, and rechallenged tumors were completely rejected after the initial eradication of CD80-expressing tumors by programmed cell death protein 1 blockade. Indeed, patients with CD80-high thymic carcinoma had longer progression-free survival with anti-programmed cell death protein 1 monoclonal antibody. Conclusions: Half of the TETs had high expression of CD80/CD86 or MHC-II with high T-cell infiltration. These molecules could potentially increase the effects of ICIs, particularly inducing a durable response. CD80/CD86 and MHC-II can be predictive biomarkers of ICIs in TETs, promoting the development of drugs for such TETs.

Thrombus formation at the stump of the pulmonary vein after lobectomy: a prospective multi-institutional study.

PURPOSE: Recent reports suggest that postoperative cerebral infarction following lung cancer surgery is caused by thrombus formation at the stump of the pulmonary vein and that the risk is highest after left upper lobectomy (LUL). Thrombosis at the stump of the pulmonary vein and the incidence of cerebral infarction was investigated prospectively in patients who underwent lobectomy for lung cancer. METHODS: Lung cancer patients undergoing planned pulmonary lobectomy were enrolled. The endpoint was to confirm if there is a higher incidence of thrombus formation (primary) and a higher incidence of cerebral infarction (secondary) in patients undergoing LUL. We planned to accrue 600 patients. An interim analysis was scheduled for just after the data center received the final clinical review form of the 300th patient. RESULTS: The interim analysis revealed a significant difference in the primary endpoint. In the final analysis, thrombus was identified in 16 of 88 LUL patients (20.5%), and in 4 of 247 patients who underwent other types of lobectomy (1.6%) (p < 0.05). Cerebral infarction was identified in 1 of the LUL patients (1.3%) and in 9 of the other patients (3.6%) (p = 0.318). CONCLUSIONS: Thrombus frequently forms at the stump of the left superior pulmonary vein after LUL. However, our study did not identify a relationship between thrombosis and cerebral infarction.

A randomized controlled phase III trial protocol: perioperative pirfenidone therapy in patients with non-small cell lung cancer combined with idiopathic pulmonary fibrosis to confirm the preventative effect against postoperative acute exacerbation: the PIII-PEOPLE study (NEJ034).

Background: Radical treatment for non-small cell lung cancer (NSCLC) combined with idiopathic pulmonary fibrosis (IPF) is challenging to plan due to the invasiveness of lung cancer and an acute exacerbation (AE) of IPF that is sometimes lethal. Methods: We intend to conduct the PIII-PEOPLE study (NEJ034), which is a phase III multicenter prospective randomized controlled clinical trial, to validate the effect of perioperative pirfenidone therapy (PPT), involving oral pirfenidone (600 mg) administration for 14 days after registration followed by oral pirfenidone (1,200 mg) for more than 14 days before surgery, with additional oral pirfenidone resumed and continued after surgery. Another group (control) will be allowed to perform any AE preventative treatment, excluding anti-fibrotic agents. Surgery without any preventative measures is also allowed in the control group. The primary endpoint is the IPF exacerbation rate within 30 days postoperatively. The data analysis will be performed in 2023-2024. Discussion: This trial will validate the perioperative AE suppression effect of PPT, and survival benefits including overall, cancer-free, and IP progression free survival due to PPT. It leads to the establishment of an optimized therapeutic strategy for NSCLC combined with IPF. Trial Registration: This trial has been registered at the UMIN Clinical Trials Registry as UMIN000029411 (http://www.umin.ac.jp/ctr/).

Risk-adjusted hazard analysis of survival after pulmonary metastasectomy for uterine malignancies in 319 cases.

Objective: There is little evidence of the outcome of pulmonary metastasectomy for uterine tumors when comparing different histologies. This study aimed to delineate the primary histology that leads to more favorable outcomes after pulmonary metastasectomy. Methods: The database of the Metastatic Lung Tumor Study Group of Japan for 1984 to 2016 was used to analyze the outcomes of patients with gynecologic malignancies who underwent pulmonary metastasectomy. Prognostic factors and long-term outcomes were compared according to the histology of the primary uterine tumors, specifically adenocarcinoma, squamous cell carcinoma, and sarcoma. The adjusted hazard risks according to disease-free intervals (DFIs) and the number and maximum size of resected tumors were also analyzed to delineate the pattern of risk trends. Results: A total of 319 patients were included in the analysis (122 with adenocarcinomas, 113 with squamous cell carcinomas, 46 with sarcomas, and 38 with other types). The 5-year survival rate was 66.5% for the entire cohort, 71.6% for the patients with adenocarcinoma, 61.3% for those with squamous cell carcinoma, and 55.4% for those with sarcoma. Multivariate analyses identified the positive prognostic factors as DFI ≥12 months in adenocarcinoma and sarcoma and the primary site (corpus) of uterine tumors in adenocarcinoma. The nonlinear adjusted hazard risks indicated that a shorter DFI was associated with an elevated risk of death in patients with adenocarcinoma and sarcoma. Conclusions: The survival outcome after pulmonary metastasectomy varies according to primary tumor histology, and the prognostic factors differ among histologic subtypes. Surgical indications should be determined based on the prognostic factors for each histology.

Survival after Lung Metastasectomy from Esophageal Cancer: Results from a Multi-Institutional Database.

To clarify the clinical impact and to identify prognostic predictors of surgical intervention for pulmonary metastasis from esophageal cancer, a registry database analysis was performed. From January 2000 to March 2020, patients who underwent resection of pulmonary metastases from primary esophageal cancer at 18 institutions were registered in a database developed by the Metastatic Lung Tumor Study Group of Japan. An amount of 109 cases were reviewed and examined for the prognostic factors for pulmonary metastasectomy of metastases from esophageal cancer. As a result, five-year overall survival after pulmonary metastasectomy was 34.4% and five-year disease-free survival was 22.1%. The multivariate analysis for overall survival revealed that initial recurrence site, maximum tumor size, and duration from primary tumor treatment to lung surgery were selected as the significant prognostic factors (p = 0.043, p = 0.048, and p = 0.037, respectively). In addition, from the results of the multivariate analysis for disease free survival, number of lung metastases, initial recurrence site, duration from primary tumor treatment to lung surgery, and preoperative chemotherapy for lung metastasis were selected as the significant prognostic factors (p = 0.037, p = 0.008, p = 0.010, and p = 0.020, respectively). In conclusion, eligible patients with pulmonary metastasis from esophageal cancer selected based on the identified prognostic predictors would be good candidates for pulmonary metastasectomy.

Predicting pathological highly invasive lung cancer from preoperative [18F]FDG PET/CT with multiple machine learning models.

PURPOSE: The efficacy of sublobar resection of primary lung cancer have been proven in recent years. However, sublobar resection for highly invasive lung cancer increases local recurrence. We developed and validated multiple machine learning models predicting pathological invasiveness of lung cancer based on preoperative [18F]fluorodeoxyglucose (FDG) positron emission tomography (PET) and computed tomography (CT) radiomic features. METHODS: Overall, 873 patients who underwent lobectomy or segmentectomy for primary lung cancer were enrolled. Radiomics features were extracted from preoperative PET/CT images with the PyRadiomics package. Seven machine learning models and an ensemble of all models (ENS) were evaluated after 100 iterations. In addition, the probability of highly invasive lung cancer was calculated in a nested cross-validation to assess the calibration plot and clinical usefulness and to compare to consolidation tumour ratio (CTR) on CT images, one of the generally used diagnostic criteria. RESULTS: In the training set, when PET and CT features were combined, all models achieved an area under the curve (AUC) of ≥ 0.880. In the test set, ENS showed the highest mean AUC of 0.880 and smallest standard deviation of 0.0165, and when the cutoff was 0.5, accuracy of 0.804, F1 of 0.851, precision of 0.821, and recall of 0.885. In the nested cross-validation, the AUC of 0.882 (95% CI: 0.860-0.905) showed a high discriminative ability, and the calibration plot indicated consistency with a Brier score of 0.131. A decision curve analysis showed that the ENS was valid with a threshold probability ranging from 3 to 98%. Accuracy showed an improvement of more than 8% over the CTR. CONCLUSION: The machine learning model based on preoperative [18F]FDG PET/CT images was able to predict pathological highly invasive lung cancer with high discriminative ability and stability. The calibration plot showed good consistency, suggesting its usefulness in quantitative risk assessment.

[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.

PD-1 blockade therapy promotes infiltration of tumor-attacking exhausted T cell clonotypes.

PD-1 blockade exerts clinical efficacy against various types of cancer by reinvigorating T cells that directly attack tumor cells (tumor-specific T cells) in the tumor microenvironment (TME), and tumor-infiltrating lymphocytes (TILs) also comprise nonspecific bystander T cells. Here, using single-cell sequencing, we show that TILs include skewed T cell clonotypes, which are characterized by exhaustion (Tex) or nonexhaustion signatures (Tnon-ex). Among skewed clonotypes, those in the Tex, but not those in the Tnon-ex, cluster respond to autologous tumor cell lines. After PD-1 blockade, non-preexisting tumor-specific clonotypes in the Tex cluster appear in the TME. Tumor-draining lymph nodes (TDLNs) without metastasis harbor a considerable number of such clonotypes, whereas these clonotypes are rarely detected in peripheral blood. We propose that tumor-infiltrating skewed T cell clonotypes with an exhausted phenotype directly attack tumor cells and that PD-1 blockade can promote infiltration of such Tex clonotypes, mainly from TDLNs.

Genetic alterations in squamous cell lung cancer associated with idiopathic pulmonary fibrosis.

Patients with idiopathic pulmonary fibrosis (IPF) are at higher risk of developing lung cancers including squamous cell lung carcinoma (SCC), which typically carries a poor prognosis. Although the molecular basis of cancer development subsequent to IPF has not been fully investigated, we recently reported two epigenetic phenotypes characterized by frequent and infrequent DNA hypermethylation in SCC, and an association of the infrequent hypermethylation phenotype with IPF-associated SCCs. Here, we conducted targeted exon sequencing in SCCs with and without IPF using the Human Lung Cancer Panel to investigate the genetic basis of IPF-associated SCC. SCCs with and without IPF displayed comparable numbers of total mutations (137 ± 22 vs 131 ± 27, P = .5), nonsynonymous mutations (72 ± 14 vs 69 ± 16, P = .5), indels (3.0 ± 3.5 vs 3.0 ± 3.9, P = 1) and synonymous mutations (62 ± 9.1 vs 60 ± 12, P = .5). Signature 1 was the predominant signature in SCCs with and without IPF. SETD2 and NFE2L2 mutations were significantly associated with IPF (44% vs 13%, P = .03 for SETD2; 38% vs 10%, P = .04 for NFE2L2). MYC amplification, assessed by copy number variant analysis, was also significantly associated with IPF (18.8% vs 0%, P = .04). Mutations in TP53 and CDKN2A were observed relatively frequently in SCCs with frequent hypermethylation (P = .02 for TP53 and P = .06 for CDKN2A). Survival analysis revealed that the SETD2 mutation was significantly associated with worse prognosis (P = .04). Collectively, we found frequent involvement of SETD2 and NFE2L2 mutations and MYC amplification in SCCs with IPF, and an association of a SETD2 mutation with poorer prognosis.

[Surgical Treatment of Metachronous Second Primary Lung Cancer].

Although the incidence of metachronous second primary lung cancer (MSPLC) after curative resection for primary lung cancer may be increasing, appropriate treatment and the outcome are unclear yet. We reviewed the literature and conducted a retrospective chart review of the patients who underwent surgery for MSPLC in our institute. We had 27 surgical cases for MSPLC during 2017 and 2018. The interval from the previous surgery was 59.4±35.2 months. Comparing to the patients who were underwent surgery for first primary lung cancer in the same period, the patients with MSPLC showed significantly older age and lower respiratory function. More than 90% of resected MSPLC were stage 0 orⅠand we selected limited surgery for more than 90% of the MSPLC patients. Maybe due to limited surgery, time for surgical procedure and postoperative complication were significantly less than first primary lung cancer cases. No death or recurrence were observed until one year after surgery for MSPLC. For performing feasible limited surgery to early-stage MSPLC cases, continuous computed tomography surveillance in the late phase after the first primary lung cancer surgery should be important.

A phase I study of loco-regional immunotherapy by transbronchial injection of α-galactosylceramide-pulsed antigen presenting cells in patients with lung cancer.

We conducted a phase I study of the trans-bronchial injection of α-galactosylceramide (αGalCer)-pulsed antigen presenting cells (APCs) to evaluate their safety, immune responses, and anti-tumor activities. Patients with advanced or recurrent non-small cell lung cancer (NSCLC) refractory to standard treatments were eligible. αGalCer-pulsed APCs were administered intratumorally or intranodally by bronchoscopy. Twenty-one patients were enrolled in this study. No severe adverse events related to the cell therapy were observed during this study in any patient. After αGalCer-pulsed APCs were administrated, increased iNKT cell numbers were observed in PBMCs from eight cases, and IFN-γ producing cells were increased in the peripheral blood of 10 cases. Regarding clinical responses, one case exhibited a partial response and eight were classified as stable disease. In the tumor microenvironment, IFN-γ expression was upregulated after treatment in partial response or stable disease cases and TGF-ß was upregulated in progressive disease cases.

A surgical case of synchronous solitary splenic metastasis from lung squamous cell carcinoma: report of a case and review of the literature.

Solitary splenic metastasis is an extremely rare event. We herein report a surgical case of a solitary splenic metastasis from lung cancer. A 78-year-old man presented with abdominal pain. Abdominal computed tomography (CT) showed splenic rupture. Coil embolization to the splenic artery was performed, and the patient's condition improved. Chest CT showed a 5-cm lung mass in the right upper lobe, suggesting lung cancer with splenic metastasis. Transbronchial aspiration cytology showed squamous cell carcinoma of the lung. We diagnosed the patient with lung cancer (cT2bN0M1b [spleen only] stage IVA) and performed splenectomy and right upper lobectomy separately. Both lesions were squamous cell carcinoma and positive for p40. Thus, primary lung squamous cell carcinoma and solitary splenic metastasis were diagnosed. The patient was still alive without recurrence 15 months postoperatively. We herein report a rare case of lung squamous cell carcinoma with solitary splenic metastasis and review the literature.

A case of primary pulmonary leiomyosarcoma completely resected after neoadjuvant chemotherapy.

BACKGROUND: Primary pulmonary leiomyosarcoma is a rare malignant tumor. We herein report a case of primary pulmonary leiomyosarcoma that was completely resected by surgery after neoadjuvant chemotherapy. CASE PRESENTATION: A 60-year-old man presented with cough. Chest computed tomography showed an 11-cm mass in the right upper lobe of the lung that had invaded the superior vena cava. Endobronchial ultrasound-guided transbronchial needle aspiration revealed leiomyosarcoma of the lung. We considered complete resection of the tumor to be very difficult because of the tumor invasion into the right atrium inflow of the superior vena cava, so we performed chemotherapy using doxorubicin for five cycles. After chemotherapy, the tumor size decreased to 5.6 cm, and we performed right upper lobectomy with combined resection of the superior vena cava. The tumor was completely resected by surgery. The patient is alive without recurrence 17 months postoperatively. CONCLUSIONS: We encountered a case of primary pulmonary leiomyosarcoma that was successfully treated by surgery after neoadjuvant chemotherapy. Doxorubicin monotherapy was effective in this case. Surgery combined with neoadjuvant chemotherapy should be considered for such cases, as a long-term survival can be achieved by complete resection of primary pulmonary leiomyosarcoma.

A strategy for pulmonary resection after contralateral diaphragm plication: a surgical case report.

BACKGROUND: Pulmonary carcinoma patients with low pulmonary function cannot be treated surgically because of the high risk of complications. Diaphragmatic eventration is a disease characterized by diaphragmatic paralysis and dyspnea. Here, we report a surgical case of multiple pulmonary carcinomas with contralateral diaphragmatic eventration. CASE PRESENTATION: The patient was a 75-year-old woman with multiple metachronous right lung carcinomas complicated by left diaphragmatic eventration. When she was 70 years old, a right upper lobectomy and right S6b wedge resection were performed for double lung carcinomas. Five years later, two new lung tumors in her right lower lobe and left diaphragmatic eventration were identified, but resection was thought to be impossible because of her low pulmonary function. We performed video-assisted thoracoscopic surgery (VATS) plication with carbon dioxide (CO2) insufflation for the left diaphragmatic eventration, and her pulmonary function improved. Subsequently, we performed a right S6 wedge resection and right S9 segmentectomy for the double lung tumors with no complications. The tumors were diagnosed as double primary carcinomas. CONCLUSIONS: Our case presented with low pulmonary function and right multiple lung carcinomas with left diaphragmatic eventration. VATS plication for the left diaphragmatic eventration achieved improvement in her pulmonary function, and right pulmonary resection for the lung carcinomas was performed. VATS plication can expand the choice of treatments in such cases.

Bronchoscopic assessment of bronchial anastomosis by visualizing local circulation status-index of hemoglobin (IHb) imaging.

BACKGROUND: Healing of airway anastomosis is largely affected by local circulation. Index of hemoglobin (IHb) imaging is a color enhancement technique that clarifies local circulation in the gastrointestinal endoscopic field. In this study, we investigated the relationship between bronchoscopic assessment of bronchial anastomosis using IHb mode and occurrence of anastomosis-related complications. METHODS: IHb was calculated by logarithmic transformation for each pixel of the electronic endoscopic images and expressed by colors of red, green, and blue. The distribution of each color area was automatically calculated by the summation of pixels. A preliminary experiment spraying vasodilator on swine was performed to confirm the relationship between bronchial mucosal circulation and the IHb image. Forty consecutive patients who underwent bronchoplasty were divided into retrospective training and prospective validation cohorts, and anastomosis-related complications and IHb images were analyzed. RESULTS: The IHb images immediately and accurately reflected the mucosal changes in the animal experiment. Among 25 cases in the retrospective training cohort, 6 cases experienced complications, with significantly lower red and higher blue values in IHb observed (P=0.03 and P=0.01, respectively). A receiver operating characteristic (ROC) curve for IHb red and blue distributions revealed the thresholds to differentiate cases with complications as 89.2 and 109.0, respectively. An analysis of the prospective validation cohort revealed that IHb blue on POD 7 was a potentially reliable predictor of complications, with 60.0% sensitivity and 90.0% specificity. CONCLUSIONS: IHb mode of bronchoscopy may be useful for assessing the local circulatory condition of bronchoplasty, which can predict anastomosis-related morbidity.

Molecular Nodal Staging Using miRNA Expression in Lung Cancer Patients by Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration.

BACKGROUND: The limited negative predictive value of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) has often been discussed. OBJECTIVE: The aim of this study was to identify a highly sensitive molecular biomarker for lymph node staging by EBUS-TBNA. METHODS: Five microRNAs (miRNAs) (miR-200a, miR-200b, miR-200c, miR-141, and let-7e) were selected as biomarker candidates for the detection of nodal metastasis in a miRNA expression analysis. After having established a cutoff level of expression for each marker to differentiate malignant from benign lymph nodes among surgically dissected lymph nodes, the cutoff level was applied to snap-frozen EBUS-TBNA samples. Archived formalin-fixed paraffin- embedded (FFPE) samples rebiopsied by EBUS-TBNA after induction chemoradiotherapy were also analyzed. RESULTS: The expression of all candidate miRNAs was significantly higher in metastatic lymph nodes than in benign ones (p < 0.05) among the surgical samples. miR-200c showed the highest diagnostic yield, with a sensitivity of 95.4% and a specificity of 100%. When the cutoff value for miR-200c was applied to the snap-frozen EBUS-TBNA samples, the sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy were 97.4, 81.8, 95.0, 90.0, and 94.0%, respectively. For restaging FFPE EBUS- TBNA samples, the sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy were 100, 60.0, 80.0, 100, and 84.6%, respectively. Among the restaged samples, 4 malignant lymph nodes were false negative by EBUS-TBNA, but they were accurately identified by miR-200c. CONCLUSIONS: miR-200c can be used as a highly sensitive molecular staging biomarker that will enhance nodal staging of lung cancer.

Successful diagnosis of an occult fallopian tube carcinoma detected from the diaphragm metastasis.

We herein reported a rare case of an occult fallopian tube carcinoma first detected from the diaphragm metastasis. An 83-year-old woman who had a 30-mm tumor on the right diaphragm underwent radical resection. Pathologically, the tumor was diagnosed as a high-grade serous adenocarcinoma, suggesting metastasis from the pelvic visceral carcinoma. Although the primary site could not be detected by imaging examinations, laparoscopy revealed multiple peritoneal disseminations; therefore, total hysterectomy was performed. Finally, microscopic tumor invasion into the right fimbriae of the fallopian tube was found. A precise and detailed pathological and immunohistochemical examinations of the resected metastatic diaphragm tumor helped us obtain a proper diagnosis of the primary lesion and treat the patient appropriately. Since it is difficult to diagnose diaphragm tumors before surgery based on the anatomy, surgical options have played an important role in their treatment and diagnosis clinically.

Pathological diagnosis of pulmonary large cell neuroendocrine carcinoma by endobronchial ultrasound-guided transbronchial needle aspiration.

BACKGROUND: Pulmonary large cell neuroendocrine carcinoma (LCNEC) is a relatively rare subtype of lung malignancy. According to revised 2015 World Health Organization (WHO) criteria for the pathological diagnosis of LCNEC, neuroendocrine markers must be examined by immunohistochemistry. In this study, we reevaluated endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) samples of patients previously diagnosed with LCNEC using the revised WHO criteria. METHODS: Clinical tissue samples that had been obtained by EBUS-TBNA between January 2004 and December 2011, and that had been pathologically diagnosed as LCNEC according to the previous criteria, were reevaluated according to the revised WHO criteria. RESULTS: The records of 471 lung cancer patients with mediastinal or hilar lymph node metastasis diagnosed by EBUS-TBNA were analyzed. Thirteen patients were diagnosed with LCNEC; one of which was diagnosed based on cytology alone because the histological material was insufficient for a histological examination. Among the 12 cases in which a histological examination was performed, nine were diagnosed with possible LCNEC based on neuroendocrine marker positivity, while three were diagnosed with suspected LCNEC because they did not meet the immunostaining criteria. The patient who was cytologically diagnosed was found to have non-small cell carcinoma with neuroendocrine morphology. CONCLUSION: LCNEC could be pathologically diagnosed based on 2015 WHO criteria using EBUS-TBNA samples.

Mini grasping basket forceps for endobronchial foreign body removal in pediatric patients.

BACKGROUND: Appropriate device selection is crucial for endobronchial foreign body removal using a bronchoscope. In pediatric patients, bronchoscopy requires the use of a thin device due to the narrow access to the airway, limiting the range of useful endobronchial devices. We herein review our experience in endobronchial foreign body removal with a focus on the type of bronchoscope and the instruments used in comparison with the literature, and investigate the utility of mini grasping basket forceps (FG-55D, Olympus® ; and Zero Tip™ , Airway Retrieval Basket, Boston Scientific). METHODS: Between April 2008 and April 2016, foreign bodies were removed from the airway of 12 pediatric patients by bronchoscopy. These cases are reviewed in this study. The clinical presentation, location and characteristics of the foreign bodies, and the type of bronchoscope and instruments used were analyzed. RESULTS: A consecutive series of 12 pediatric patients was retrospectively reviewed, and the therapeutic characteristics investigated. Nuts were the most frequently observed foreign body. Seven of the 12 pediatric patients required an ultrathin bronchoscope (diameter, 2.8 mm) for foreign body removal. Only one patient required a rigid scope in addition to flexible bronchoscopy. The most frequently used instrument was a mini grasping basket forceps (n = 7; 58%), which was used with a 1.2 mm instrument channel (n = 4; 33%). CONCLUSIONS: The use of a mini grasping basket forceps in combination with an ultrathin flexible bronchoscope was useful for removing smooth, soft materials such as a nuts or beans in pediatric cases.

Concordant pattern of radiologic, morphologic, and genomic changes during compensatory lung growth.

BACKGROUND: Although compensatory lung growth (CLG) after lung resection has been reported in various mammalian species, it has generally been thought that the lung cannot regenerate in adult humans. We recently developed a method for evaluating lung weight using a radiologic analysis and demonstrated that the lung was heavier than expected in adult humans after pulmonary resection. In this study, we serially evaluated the morphologic, radiologic, and genomic status during CLG in pneumonectomized mice. METHODS: The serial changes in morphology and gene expression of the remnant right lung after left pneumonectomy were examined in adult male mice. The alveolar density was determined by the mean linear intercept, and the weight was estimated using the Hounsfield value and volumetric data from micro-computed tomography. The parameters were obtained on days 3, 7, and 30 after left pneumonectomy or thoracotomy only (sham control). RESULTS: After left pneumonectomy, the right lung became significantly progressively larger in volume and weight on postoperative days 3, 7, and 30 in comparison to the sham controls (P < 0.01). The estimated weight also significantly increased in association with the real volume on postoperative days 3, 7, and 30 (P < 0.01). The cardiac lobe markedly increased in size. During the observation period, the alveolar density was always lower in the pneumonectomized mice than in controls. A microarray analysis revealed that multiple genes related to proliferation (but not specific alveolar development) were initially upregulated until postoperative day 7 and then returned to normal after 1 mo. The morphologic and genomic changes were more evident in the cardiac lobe than in the upper lobe during the observation period. CONCLUSIONS: The morphologic, radiologic, and genomic changes during CLG were related to each other in pneumonectomized mice. The present study revealed an association between the radiologically estimated weight and other parameters, indicating a marked CLG reaction of the cardiac lobe.