Hyponatremia unleashes neutrophil extracellular traps elevating life-threatening pulmonary embolism risk.

Neutrophil extracellular traps (NETs), essential for controlling infections, can induce various pathologies when dysregulated. Known triggers for infection-independent NETs release exist, yet a comprehensive understanding of the conditions prompting such responses is lacking. In this study, we identify hyponatremia as an independent inducer of NETs release, a common clinical condition that disrupts sodium/calcium exchange within neutrophils. This disruption leads to an excess of intracellular calcium, subsequent elevation of reactive oxygen species (ROS), and the citrullination of histone H3, culminating in the activation of NETs-release pathways. Notably, under hyponatremic conditions, this mechanism is exacerbated during infectious states, leading to the deposition of NETs in the lungs and increasing the risk of life-threatening pulmonary embolism. Our findings underscore the critical role of sodium and calcium homeostasis in neutrophil functionality and provide insights into the pathogenesis of hyponatremia-associated diseases, highlighting potential therapeutic interventions targeting NETs dynamics.

Postoperative tegafur-uracil for stage I lung adenocarcinoma: first real-world data with an exploratory subgroup analysis.

PURPOSE: The effect of postoperative tegafur-uracil on overall survival (OS) after resection of stage I adenocarcinoma has been shown in clinical trials. The purpose of this study was to investigate whether findings from randomized trials of adjuvant tegafur-uracil are reproducible in a real-world setting. METHODS: A retrospective cohort study was performed using a multi-institutional database that included all patients who underwent complete resection of pathological stage I adenocarcinoma between 2014 and 2016. Survival outcomes for patients managed with and without tegafur-uracil were analyzed using the Kaplan-Meier method and a Cox proportional hazards model for the whole patient cohort and in a selected cohort based on eligibility criteria of a previous randomized trial. Propensity score matching was used to adjust for confounding effects. RESULTS: After propensity score matching, the hazard ratios for OS were 0.57 (95% confidence interval (CI) 0.29-1.14, P = 0.11) in the whole cohort and 0.69 (95% CI 0.32-1.50, P = 0.35) in the selected cohort. CONCLUSIONS: The effects of tegafur-uracil in this retrospective study appear to be consistent with those found in randomized clinical trials. These effects may be maximized in patients aged from 45 to 75 years.

Living-donor lobar lung transplantation for pulmonary Langerhans cell histiocytosis complicated by extensive thrombi in central pulmonary arteries.

BACKGROUND: Pulmonary Langerhans cell histiocytosis (PLCH) is a rare disorder characterized by the proliferation of Langerhans cells along the small airways, which causes nodular and cystic changes in the lung parenchyma. Lung transplantation can be a life-saving option for patients with severe respiratory failure or pulmonary hypertension. Herein, we present a case of successful lung transplantation in a patient with PLCH who developed unusually large thrombi in the central pulmonary artery. CASE PRESENTATION: A 47-year-old woman with 16-year history of PLCH with rapidly developing respiratory failure was admitted to our hospital for the evaluation of a lung transplant. Enhanced computed tomography revealed large thrombi in dilated central pulmonary arteries. Right heart catheterization revealed severe pulmonary hypertension, with a mean pulmonary artery pressure of 48 mmHg. The thrombi shrank markedly after 3 months of anticoagulation therapy. However, the respiratory status of the patient did not improve. We performed bilateral living-donor lobar lung transplantation with thrombectomy under extracorporeal membrane oxygenation for the remaining thrombi in the main pulmonary arteries. The dilated main pulmonary arteries of the recipient required direct plication for size mismatch. The patient survived in good condition for more than 2 years with no recurrence of thrombosis. CONCLUSION: Preoperative anticoagulation therapy for massive thrombi in the pulmonary arteries was effective and led to safe lung transplantation.

Pneumocephalus resulting from traumatic pneumothorax and brachial plexus avulsion.

Background: Traumatic pneumocephalus is commonly encountered after basal skull fractures and rarely associated with blunt chest trauma. Here, we report a case of pneumocephalus caused by traumatic pneumothorax and brachial plexus avulsion. Case Presentation: A 20-year-old male was admitted to our hospital following a motorcycle accident with complete paralysis of the right upper limb. 2 days later, follow-up computed tomography revealed a slight right pneumothorax, pneumomediastinum around the neck, and intracranial air without skull fracture. Air migrates into the subarachnoid space through a dural tear caused by a brachial plexus avulsion. The pneumocephalus immediately improved after the insertion of a chest drain. Conclusion: Pneumothorax combined with brachial plexus avulsion could lead to pneumocephalus. Immediate chest drainage might be the best way to stop the migration of air; however, care should be taken to not worsen cerebrospinal fluid leakage.

Pulmonary cyst newly formed after lobectomy in various underlying lung conditions.

BACKGROUND: It has been recently recognized that pulmonary cyst may develop after pulmonary resection, causing various symptoms. Most previously reported cases were after upper lobectomy in patients with chronic obstructive lung disease (COPD). CASE PRESENTATION: Case 1 was a man in his 70 s with interstitial pneumonia (IP). Right lower lobectomy was performed for metastatic lung tumor using video-assisted thoracoscopic surgery (VATS). On postoperative day (POD) 19, computed tomography (CT) revealed a large cyst at the upper interlobular surface of the middle lobe, with pneumoderma and pneumomediastinum. The cyst was incised, polyglycolic acid (PGA) sheet and fibrin glue were applied, and the cyst was sutured. The sutured line was covered again with PGA sheet and fibrin glue. Case 2 was a man in his 70 s with COPD. Right upper lobectomy for primary lung cancer was performed using VATS. On POD 17, CT revealed a large pulmonary cyst at the apex of S6 and massive air leakage was observed. The same surgical procedure as that used in case 1 was performed. Cases 3 and 4 were healthy donors for living-donor lung transplantation. Two months after the right lower lobectomy in Case 3 and 3 months after the left lower lobectomy in Case 4, the patients had respiratory symptoms such as dyspnea and hemosputum. CT revealed a large cyst on the diaphragmatic surface of the right middle lobe in Case 3 and on the posterior mediastinal surface of the left upper lobe in Case 4. Cyst incision, soft coagulation, and application of PGA sheet with fibrin glue were performed in both cases. CT performed 1 year after surgery showed no development of a pulmonary cyst or air space in these four cases. CONCLUSIONS: Pulmonary cysts newly formed after lobectomy can develop not only in COPD or IP but also in healthy lungs. Our findings suggest that incision of the cyst and application of fibrin glue and PGA sheet with or without suturing the cyst wall is effective for management.

Effect of epoprostenol-induced thrombocytopaenia on lung transplantation for pulmonary arterial hypertension.

OBJECTIVES: Preoperative intravenous epoprostenol therapy can cause thrombocytopaenia, which may increase the risk of perioperative bleeding during lung transplantation. This study aimed to determine whether lung transplantation can be safely performed in patients with epoprostenol-induced thrombocytopaenia. METHODS: From June 2008 to July 2022, we performed 37 lung transplants in patients with pulmonary arterial hypertension (PAH), including idiopathic PAH (n = 26), congenital heart disease-associated PAH (n = 7), pulmonary veno-occlusive disease (n = 3) and peripheral pulmonary artery stenosis (n = 1) at our institution. Of these, 26 patients received intravenous epoprostenol therapy (EPO group), whereas 11 patients were treated with no epoprostenol (no-EPO group). We retrospectively analysed the preoperative and postoperative platelet counts and post-transplant outcomes in each group. RESULTS: Preoperative platelet counts were relatively lower in the EPO group than in the no-EPO group (median EPO: 127 000 vs no-EPO: 176 000/µl). However, blood loss during surgery was similar between the 2 groups (EPO: 2473 ml vs no-EPO: 2615 ml). The platelet counts significantly increased over 1 month after surgery, and both groups showed similar platelet counts (EPO: 298 000 vs no-EPO: 284 000/µl). In-hospital mortality (EPO: 3.9% vs no-EPO: 18.2%) and the 3-year survival rate (EPO: 91.4% vs no-EPO: 80.8%) were similar between the 2 groups. CONCLUSIONS: Patients with PAH treated with intravenous epoprostenol showed relatively lower platelet counts, which improved after lung transplantation with good post-transplant outcomes.

Epidermal growth factor receptor tyrosine kinase inhibitors as first-line treatment for postoperative recurrent EGFR-mutated lung adenocarcinoma: a multi-institutional retrospective study.

OBJECTIVES: The aim of this study was to analyse the long-term survival outcomes and prognostic factors of patients receiving epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) as first-line treatment for postoperative recurrent EGFR-mutated lung adenocarcinoma. METHODS: Using a multi-institutional database, we performed a retrospective chart review to identify all patients who had undergone complete resection of stage I-III EGFR-mutated lung adenocarcinoma at 11 acute care hospitals between 2009 and 2016 and had received first-line EGFR-TKI treatment for postoperative recurrence. Adverse events, progression-free survival (PFS) and overall survival (OS) were investigated. Survival outcomes were assessed using Kaplan-Meier analysis. Cox proportional hazards models were used to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs) for PFS and OS. RESULTS: The study sample comprised 154 patients with a median age of 69. The total numbers of events were 101 for PFS and 60 for OS. The median PFS and OS were 26.1 and 55.4 months, respectively. In the multivariable analysis, EGFR ex 21 L858R mutation (HR: 1.71, 95% CI: 1.15-2.55) and shorter disease-free intervals (HR: 0.98, 95% CI: 0.96-0.99) were significantly associated with shorter PFS. Age (HR: 1.03, 95% CI: 1.00-1.07), smoking history (HR: 2.31, 95% CI: 1.35-3.94) and pathological N2 disease at the initial surgery (HR: 2.30, 95% CI: 1.32-4.00) were significantly associated with shorter OS. CONCLUSIONS: First-line EGFR-TKI treatment was generally associated with favourable survival outcomes in patients with postoperative recurrent EGFR-mutated lung adenocarcinoma. EGFR ex 21 L858R mutation may be an important prognostic factor for shorter PFS.

A novel technique for Endobronchial Watanabe Spigot placement for bronchopleural fistula: a traction method.

Empyema with bronchopleural fistula is a challenging condition that often requires open-window thoracostomy. Bronchial occlusion with Endobronchial Watanabe Spigot is an effective and less invasive procedure to close the fistula; however, delivering a spigot into the target bronchus requires high technical skills. Herein, we report a case of bronchopleural fistula occluded with a spigot using a new 'traction method' in which the spigot is tied as an anchor to a guidewire and pulled into the target bronchus. Our method allows selective and steady placement of the spigot for patients who undergo open-window thoracostomy for the treatment of bronchopleural fistula.

Lymph node dissection in thymic carcinomas and neuroendocrine carcinomas.

OBJECTIVES: Although lymph node (LN) metastases are not uncommon in thymic carcinomas, preoperative LN evaluation, intraoperative lymph node dissection (LND) and postoperative outcomes remain unknown. The aim of this study was to elucidate the characteristics of and outcomes in patients with thymic carcinomas and thymic neuroendocrine carcinomas undergoing LND. METHODS: A retrospective chart review was performed using our multi-institutional database to identify patients who underwent resection and LND for thymic carcinoma or thymic neuroendocrine carcinoma between 1991 and 2018. An enlarged mediastinal LN was defined as having a short-axis diameter >1 cm. We assessed survival outcomes using the Kaplan-Meier analysis. RESULTS: N1-level LND was performed in 41 patients (54.6%), N2-level LND in 14 patients (18.7%) and both-level LND in 16 patients (21.3%). Pathological LN metastasis was detected in 20 patients (26.7%) among the 75 patients undergoing LND. There was a significant difference in the number of LN stations (P = 0.015) and metastasis factor (P = 0.0042) between pathologically LN-positive and pathologically LN-negative patients. The sensitivity of enlarged LNs on preoperative computed tomography was 18.2%. There was a tendency towards worse overall survival of pathologically N2-positive patients, although the difference was not statistically significant (P = 0.15). CONCLUSIONS: Preoperative CT appears to play a limited role in detecting pathological LN metastases. Our findings suggest that the significance of N1- and N2-level LND should be evaluated in prospective studies to optimize the postoperative management of patients with thymic carcinomas and neuroendocrine carcinomas.

Congenital partial pericardial defect confirmed based on spontaneous pneumothorax: A case report and literature review.

INTRODUCTION: Congenital pericardial defects are rare but can cause fatal complications. Most cases are asymptomatic and incidentally detected during a thoracic surgery or autopsy. We report a case of a partial pericardial defect confirmed based on spontaneous pneumothorax. PRESENTATION OF CASE: A 16-year-old boy with left spontaneous pneumothorax showed pneumopericardium on chest X-ray. Chest computed tomography revealed a partial pericardial defect. Video-assisted thoracoscopic surgery was performed, and a small pericardial defect was confirmed at the level of the upper pulmonary hilum. We did not reconstruct the defect because of the improbability of cardiac herniation. DISCUSSION: Pneumopericardium combined with pneumothorax suggests the existence of a pericardial foramen. Partial pericardial defects could cause cardiac herniation or strangulation, and pneumothorax may worsen the protruding of the heart. Video-assisted thoracic surgery is an effective method to prevent the recurrence of pneumothorax and determine whether reconstruction of the defect is required. CONCLUSION: Video-assisted thoracic surgery should be performed in the case of a pericardial defect combined with pneumothorax.

Hemothorax resulting from an initially masked aortic perforation caused by penetration of the sharp edge of a fractured rib: A case report.

INTRODUCTION: There are multiple causes of hemothorax in blunt chest trauma. However, a traumatic hemothorax with an uncertain cause is potentially life-threatening without treatment, because an undetected and hidden great vessel injury can remain unknown. Delayed diagnosis can lead to death. PRESENTATION OF CASE: A 77-year-old man was transferred to a local hospital, after experiencing a 3-m fall. Contrast CT of the chest revealed a left clavicle fracture, multiple left rib fractures and hemopneumothorax, but no obvious signs of great vessel injury, such as aortic injury. His condition was stable, owing to the chest tube thoracostomy with 800 ml blood output and intravenous fluid. The patient was then transferred to our hospital for further treatment. However, his condition rapidly deteriorated in the ambulance on the way to our hospital, and he needed a blood transfusion. On arrival, he was in shock, with his vital signs compromised due to blood loss. Emergency open thoracotomy was performed to explore the bleeding point and stop hemorrhaging. Intraoperative findings revealed sharp edges of the fractured fourth and fifth left ribs to be protruding into the chest cavity toward the descending aorta and causing an aortic pinhole injury. Ruptured aorta was repaired with a pledget-armed sutures and the sharp fractured ribs were resected. The patient was discharged, uneventfully, 35 days after the operation. CONCLUSION: This case suggests that even if great vessel injury is not detected on contrast CT at admission, it should always be considered especially in a hemothorax case with multiple rib fractures.

Solitary Pulmonary Hematoma Radiographically Indistinguishable from Mediastinal Tumor.

Solitary pulmonary hematoma is a rare consequence of blunt chest trauma. Moreover, there has been no reported case of solitary pulmonary hematoma radiographically diagnosed as a posterior mediastinal tumor. We present the case of a 63-year-old man who was referred for an oval-shaped opacity at the left paraspinal area on a chest X-ray. Chest computed tomography showed a well-circumscribed posterior mediastinal tumor on the left paraspinal lesion with extrapleural sign and callus formation on the left ribs posteriorly (7th to 11th ribs). The tumor was thoracoscopically confirmed to be a subpleural pulmonary tumor of the left lower lobe, and wedge resection was performed. Histological examination confirmed the diagnosis of pulmonary hematoma. On reviewing the callus formation of the ribs, which was suggestive of rib fractures, the pulmonary hematoma was determined to be traumatic in origin. The postoperative course was uneventful. We reviewed a rare case of pathologically proven traumatic solitary pulmonary hematoma. The rarity of this case is enhanced because the hematoma initially appeared to be a posterior mediastinal tumor.

Solitary pulmonary capillary hemangioma presenting with a ground glass opacity: A case report & literature review.

INTRODUCTION: Solitary pulmonary capillary hemangioma (SPCH) is a rare benign lung tumor that clinically resembles early lung cancer and precancerous pulmonary lesions that present with similar imaging manifestations. PRESENTATION OF CASE: The patient was a 54-year-old Japanese man who was referred to Nagara Medical Center with a ground glass opacity (GGO) lesion within the right upper lung that was incidentally detected on computed tomography. After 8 months of follow-up, video-assisted thoracoscopic segmental resection of the right upper lobe was performed with diagnostic and therapeutic intent. Pathologic examination of the resected specimen demonstrated thickening of the alveolar septum caused by the proliferation of capillary vessels. This lesion was positive for CD31 and CD34 and negative for thyroid transcription factor-1 and cytokeratin on immunohistochemical staining. The tumor was diagnosed as SPCH pathologically. DISCUSSION: When radiological examination demonstrates a GGO in the lung, SPCH must be considered as one of the differential diagnoses. For a definitive diagnosis, pathological examination of a surgically resected specimen must be conducted. CONCLUSION: This study describes a case of SPCH and a review of the literature.

Association Between Formalin Fixation Time and Programmed Cell Death Ligand 1 Expression in Patients With Non-Small Cell Lung Cancer.

BACKGROUND/AIM: The expression of programmed cell death ligand 1 (PD-L1) determined by immunohistochemistry (IHC) may be associated with tissue formalin fixation time in non-small cell lung cancer (NSCLC) samples. We investigated the association between the PD-L1 expression and formalin fixation time, and clarified the optimal duration of fixation for accurate PD-L1 evaluation. MATERIALS AND METHODS: We collected 55 tumor specimens from resected NSCLC patients. The samples were halved and immediately fixed in 10% buffered formalin for 12-24 h (normal fixation), or 96-120 h (prolonged fixation). Each specimen was stained using two assay systems (22C3 and SP263) for PD-L1. RESULTS: The mean PD-L1 tumor proportion score was not significantly different between normal and prolonged fixation groups for either 22C3 or SP263 (normal fixation: 18.8%; prolonged fixation: 16.3%, p=0.277; normal fixation: 16.2%; prolonged fixation: 17.6%, p=0.560, respectively). CONCLUSION: Formalin fixation duration for up to 120 h does not affect PD-L1 IHC expression. PD-L1 tumor proportion score of tumor specimens can be evaluated by IHC even if these have been fixed in formalin outside the recommended duration in clinical practice.

Salvage Pulmonary Operations Following Stereotactic Body Radiotherapy for Small Primary and Metastatic Lung Tumors: Evaluation of the Operative Procedures.

Stereotactic body radiotherapy is an alternative treatment option for small-sized, primary lung cancers and pulmonary metastatic diseases. In the case of local relapse after stereotactic body radiotherapy, salvage pulmonary resection is considered cautiously. However, no study has described the difficulty of the salvage operations. This study aimed to assess the difficulty associated with salvage operative procedures. Eight patients who developed local relapse after stereotactic body radiotherapy and had undergone salvage pulmonary operations were enrolled in this study (stereotactic body radiotherapy group). Additionally, 439 patients who underwent video-assisted thoracoscopic lobectomy without previous stereotactic body radiotherapy were enrolled as the standard operative control group (non-stereotactic body radiotherapy group). In the stereotactic body radiotherapy group, 1 of the 8 patients had undergone lobectomy with composite resection of the third and fourth ribs. Of the 8 patients, 6 had undergone video-assisted thoracoscopic lobectomy and 1 had been inoperable because of rapid tumor progression. The operation time and the incision length of the utility port were apt to be longer in the stereotactic body radiotherapy group than in the non-stereotactic body radiotherapy group. On the contrary, the duration of drain placement and the length of hospital stay after the operation were not different. Thus, the salvage pulmonary operations were performed in the usual video-assisted thoracoscopic lobectomy approach, but slightly complicated than the standard video-assisted thoracoscopic lobectomy. Although to decide the indication of salvage operation might be difficult, it could be a feasible treatment option in local relapse after stereotactic body radiotherapy.

Comparison of PD-L1 Assays in Non-small Cell Lung Cancer: 22C3 pharmDx and SP263.

BACKGROUND/AIM: While the PD-L1 22C3 pharmDx assay is an FDA-approved diagnostic assay for pembrolizumab use, not every pathology laboratory has the Dako Autostainer to use this assay. Since Ventana BenchMark platforms are more common, the Ventana SP263 assay can be used to inform treatment decisions involving nivolumab and pembrolizumab in non-small cell lung cancer (NSCLC). However, some studies have shown discordant results between the two assays. This study aimed was to compare PD-L1 expression using these two assays. MATERIALS AND METHODS: A total of 100 samples from consecutive cases of resected NSCLC were tested using the two PD-L1 assays. RESULTS: The agreement rates of the two assays were 88-97% at various cut-offs. There was no significant difference between 22C3 and SP263 in tumour proportion score (p=0.455). CONCLUSION: The SP263 assay can be used in the place of the 22C3 assay for PD-L1 testing, for guiding therapy with PD-1 axis inhibitors in NSCLC.