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Abstract Background Heartbeat-based cross-sectional area (CSA) changes in the right main pulmonary artery (MPA), which reflects its distensibility associated with pulmonary hypertension, can be measured using dynamic ventilation computed tomography (DVCT) in patients with and without chronic obstructive pulmonary disease (COPD) during respiratory dynamics. We investigated the relationship between MPA distensibility (MPAD) and respiratory function and how heartbeat-based CSA is related to spirometry, mean lung density (MLD), and patient characteristics. Methods We retrospectively analyzed DVCT performed preoperatively in 37 patients (20 female and 17 males) with lung cancer aged 70.6 ± 7.9 years (mean ± standard deviation), 18 with COPD and 19 without. MPA-CSA was separated into respiratory and heartbeat waves by discrete Fourier transformation. For the cardiac pulse-derived waves, CSA change (CSAC) and CSA change ratio (CSACR) were calculated separately during inhalation and exhalation. Spearman rank correlation was computed. Result In the group without COPD as well as all cases, CSACR exhalation was inversely correlated with percent residual lung volume (%RV) and RV/total lung capacity (r = -0.68, p = 0.003 and r = -0.58, p = 0.014). In contrast, in the group with COPD, CSAC inhalation was correlated with MLDmax and MLD change rate (MLDmax/MLDmin) (r = 0.54, p = 0.020 and r = 0.64, p = 0.004) as well as CSAC exhalation and CSACR exhalation. Conclusion In patients with insufficient exhalation, right MPAD during exhalation was decreased. Also, in COPD patients with insufficient exhalation, right MPAD was reduced during inhalation as well as exhalation, which implied that exhalation impairment is a contributing factor to pulmonary hypertension complicated with COPD. Relevance statement Assessment of MPAD in different respiratory phases on DVCT has the potential to be utilized as a non-invasive assessment for pulmonary hypertension due to lung disease and/or hypoxia and elucidation of its pathogenesis. Key points • There are no previous studies analyzing all respiratory phases of right main pulmonary artery distensibility (MPAD). • Patients with exhalation impairment decreased their right MPAD. • Analysis of MPAD on dynamic ventilation computed tomography contributes to understanding the pathogenesis of pulmonary hypertension due to lung disease and/or hypoxia in patients with expiratory impairment. Graphical Abstract

This report details two cases of right upper-lobe lung cancer, of patients aged 62 and 56 years, requiring complex bronchoplasty and thoracoscopic surgeries. In both cases, owing to intraoperative complications, extended thoracotomies were performed to gain access to the right main pulmonary artery. The postoperative courses were uneventful, implying that this approach was safe. Uncomplicated postoperative recoveries underscore the need for adaptable surgical techniques, especially when traditional positioning fails. It emphasizes extending thoracotomy incisions for safer hilar structure access, offering insights for handling similar complex surgeries where standard methods falter.

There have rarely been reports on the neoplastic transformation in other organs during immunotherapy for lung cancer. We report the case of a 71-year-old man who was diagnosed with advanced pulmonary adenocarcinoma and a thyroid tumor. The patient responded to chemoradiotherapy but developed a recurrence of pulmonary metastasis. Therefore, nivolumab was started, and a complete response for pulmonary metastasis was achieved. After 32 nivolumab cycles, he experienced neck pain, and the thyroid tumor grew rapidly. Histological examination revealed anaplastic thyroid carcinoma. Although rare, immunotherapy for lung cancer has the potential to induce neoplastic transformation in other organs.

Abstract Epidermal growth factor receptor (EGFR)-mutated (mt) lung adenocarcinoma (LA) is refractory to immune checkpoint inhibitors (ICIs). However, the mechanisms have not been fully elucidated. CD8+ T cell infiltration was significantly lower in EGFR-mt than in EGFR-wild-type LA, which was associated with suppression of chemokine expression. Since this T cell-deserted tumor microenvironment may lead to the refractoriness of ICIs against EGFR-mt LA, we investigated the mechanism by focusing on the regulation of chemokine expression. The expression of C-X-C motif ligand (CXCL) 9, 10 and 11, which constitute a gene cluster on chromosome 4, was suppressed under EGFR signaling. The assay for transposase-accessible chromatin with high-throughput sequencing (ATAC-seq) revealed open chromatin peaks near this gene cluster following EGFR-tyrosine kinase inhibitor (TKI) treatment. The histone deacetylase (HDAC) inhibitor recovered the expression of CXCL9, 10 and 11 in EGFR-mt LA. Nuclear HDAC activity, as well as histone H3 deacetylation, were dependent on oncogenic EGFR signaling. Furthermore, the Cleavage Under Targets and Tagmentation (CUT & Tag) assay revealed a histone H3K27 acetylation peak at 15 kb upstream of CXCL11 after treatment with EGFR-TKI, which corresponded to one of the open chromatin peaks detected by ATAC-seq. The data suggest that EGFR-HDAC axis mediates silencing of the chemokine gene cluster through chromatin conformational change, which might be relevant to the ICI resistance by creating T cell-deserted tumor microenvironment. Targeting this axis may develop a new therapeutic strategy to overcome the ICI resistance of EGFR-mt LA.

Abstract p16 has been used as a surrogate marker for human papillomavirus (HPV)‐related tumours. However, it remains unclear whether p16 is also a potential marker for pulmonary tumours. Herein, we report the case of an 80‐year‐old woman with a history of papillary squamous cell carcinoma of the uterine cervix, presenting with a left pulmonary tumour. A bronchoscopic biopsy revealed squamous cell carcinoma with a papillary pattern, which did not rule out pulmonary metastasis from the cervix. Immunohistochemical staining revealed that the cervical tumour was positive for p16, whereas the pulmonary tumour was negative and was effectively diagnosed as primary pulmonary carcinoma.

Abstract A 64‐year‐old man presented to the emergency department with a chief complaint of epigastric pain that improved with vomiting. He was initially treated for gastrointestinal disease, but computed tomography (CT) showed a mediastinal haematoma and contrast‐enhanced CT and bronchial arteriography showed a bronchial aneurysm. Bronchial artery aneurysm is a rare but potentially life‐threatening condition that can lead to haemorrhagic shock if it ruptures. Patients with bronchial aneurysms may present with symptoms similar to that of gastrointestinal diseases owing to increased pressure in the mediastinum caused by mediastinal haematoma.

Abstract Background Clinically, locoregional recurrences following mucinous tumor resection are often experienced. However, it remains unclear whether mucinous tumors directly affect local recurrence or not, and if so, the mechanism is not known. Therefore, we investigated whether mucinous tumors are associated with locoregional recurrence after pulmonary resection and whether mucus extension is a risk factor for locoregional recurrence. Methods The data of 152 patients who underwent pulmonary resection for metastases were reviewed. When mucus was partially or wholly present in the tumor based on macro- or microscopic identification, we assigned the tumor as mucinous. In mucinous tumors, when mucus was identified within the air spaces in the normal lung parenchyma, beyond the edge of the tumor, we assigned the tumor as positive for “mucus extension.” Results The 5-year cumulative incidence of locoregional recurrence in patients with mucinous tumors was 48.1%, which was significantly higher than that observed in those with non-mucinous tumors (14.9%). Within the mucinous tumor, the presence of mucus extension beyond the tumor edge was an independent risk factor for locoregional recurrence after pulmonary resection (hazard ratio, 5.52; P = 0.019). Conclusions During the resection of mucinous cancer, surgeons should maintain sufficient distance from the tumor edge to prevent locoregional recurrences.

Abstract Background Accurate prediction of postoperative pulmonary function is important for ensuring the safety of patients undergoing radical resection for lung cancer. Dynamic perfusion digital radiography is an excellent and easy imaging method for detecting blood flow in the lung compared with the less-convenient conventional lung perfusion scintigraphy. As such, the present study aimed to confirm whether dynamic perfusion digital radiography can be evaluated in comparison with pulmonary perfusion scintigraphy in predicting early postoperative pulmonary function and complications. Methods Dynamic perfusion digital radiography and spirometry were performed before and 1 and 3 months after radical resection for lung cancer. Correlation coefficients between blood flow ratios calculated using dynamic perfusion digital radiography and pulmonary perfusion scintigraphy were then confirmed in the same cases. In all patients who underwent dynamic perfusion digital radiography, the correlation predicted values calculated from the blood flow ratio, and measured values were examined. Furthermore, ppo%FEV1 or ppo%DLco values, which indicated the risk for perioperative complications, were examined. Results A total of 52 participants who satisfied the inclusion criteria were analyzed. Blood flow ratios measured using pulmonary perfusion scintigraphy and dynamic perfusion digital radiography showed excellent correlation and acceptable predictive accuracy. Correlation coefficients between predicted FEV1 values obtained from dynamic perfusion digital radiography or pulmonary perfusion scintigraphy and actual measured values were similar. All patients who underwent dynamic perfusion digital radiography showed excellent correlation between predicted values and those measured using spirometry. A significant difference in ppo%DLco was observed for respiratory complications but not cardiovascular complications. Conclusions Our study demonstrated that dynamic perfusion digital radiography can be a suitable alternative to pulmonary perfusion scintigraphy given its ability for predicting postoperative values and the risk for postoperative respiratory complications. Furthermore, it seemed to be an excellent modality because of its advantages, such as simplicity, low cost, and ease in obtaining in-depth respiratory functional information. Trial registration Registered at UMIN on October 25, 2017. https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr_his_list.cgi?recptno=R000033957 Registration number: UMIN000029716

Background/Objective: Chest drainage tube after surgery causes pain and prolonged length of hospital stay. Especially, young patients tend to experience greater postoperative pain than elderly patients. Therefore, we needed to discuss the indication of chest tube placement. The purpose of this study was to demonstrate the safety and advantages of post-operative management without drainage tube placement, by comparing cases with and without drainage tube placement. Methods: Patients who underwent bullectomy for spontaneous pneumothorax were enrolled in this prospective randomized controlled study and randomized into two groups: group with a post-operative chest tube and group without a chest tube. Surgery and post-operative management were performed according to our protocol. Results: Among the 42 patients, pneumothorax occurred in 1 patient with a chest tube a day after tube removal. Patients without chest tube had significantly lower post-operative pain (P = 0.107∼P

Abstract Background Salvage surgery has been frequently performed, increasing the opportunity to actively perform surgery for recurrence after a function-preserving operation. However, re-operation after airway reconstruction surgery on the proximal side and the effect of prior treatment, such as radiotherapy and/or chemotherapy, make the operation more difficult. In addition, cases of sleeve pneumonectomy after sleeve lobectomy with bronchoplasty are uncommon. Case presentation A 71-year-old lung cancer patient underwent right upper sleeve lobectomy with bronchoplasty combined with perioperative chemotherapy in 2007. A new undiagnosed right hilar mass that appeared 9 years post-operation showed a temporary response to radiotherapy but progressed thereafter. Sleeve pneumonectomy was completed 14 months after radiotherapy by the following procedures: dividing the right pulmonary artery at the proximal site under median sternotomy and then reconstructing the bronchus by telescoping the left main bronchus into the distal trachea after pneumonectomy under posterolateral thoracotomy. Conclusions Sleeve pneumonectomy for recurrent lung cancer could be safely performed under good vision using a two-stage approach as salvage surgery, even in high-risk patients who received various treatments and proximal airway reconstruction.

Abstract We report a patient of stage IV lung adenocarcinoma who developed ileus due to peritoneal carcinomatosis. We placed an ileus tube and started an oral intake of osimertinib. Within one month, the tumor had shrunk, and the ileus was controlled.

Spontaneous hemothorax is less common. We report the case of an 83-year-old woman with spontaneous hemothorax caused by lung cancer with nontuberculous mycobacteriosis. She presented with chest pain and hemoptysis. Computed tomography revealed a tumor in the right middle lobe with middle syndrome and pleural effusion. Hemothorax was confirmed, and the right middle lobe was resected to control bleeding. The lung tumor invaded the mediastinal tissue, and tumor rupture was observed. Histological examination revealed pulmonary spindle cell carcinoma and epithelioid granulomas with caseous necrosis. Rapid tumor growth and mediastinal invasion could have led to intratumoral hemorrhage and tumor rupture.

An 86-year-old man, who had undergone pleurodesis several times for intractable pneumothorax due to severe emphysema was referred to our department in order to treat for recurrent pneumothorax. Computed tomography after chest tube drainage revealed incomplete re-expansion right lung and giant cyst. Because the air leakage continued, we performed surgery.Thoracotomy revealed extensive intrathoracic adhesions due to chemical pleurodesis with OK-432.There was a fistula at the base of the giant cyst in the upper right lobe, which was firmly adhered to the superior vena cava and other mediastinal organs. It was not feasible to staple the lesion cyst, and covering the fistula was ineffective. Therefore, we tried to suture the fragile bulla manually to close the fistula. Adhesion was peeled off carefully to relieve tension of the bulla from mediastinum. The thin wall was folded and reinforced with polytetrafluoroethylene pledget, and then this thickened tissue was sutured to the lung with U-stitches to close the fistula. After the operation, pneumothorax improved. He was discharged without complications.

BackgroundSarcopenia is among the most prevalent and serious cancer-related symptom, and is strongly correlated with a poor prognosis. Moreover, it reportedly predicts poor prognosis after surgery in patients with lung cancer. However, it is unclear whether sarcopenia directly affects post-operative recurrence. The purpose of this study was to evaluate whether sarcopenia can be a risk indicator for post-operative recurrence, and whether it suppresses anti-tumor immunity, in a cohort of patients with resected non-small cell lung cancer.MethodsThis study retrospectively reviewed the data of 256 consecutive patients who underwent curative lobectomy and lymph node dissection for non-small cell lung cancer at our institution. The psoas muscle mass index was calculated as the total psoas muscle area at the third lumbar vertebral level/height2 (cm2/m2). Sarcopenia was defined by a psoas muscle mass index of under 5.03 cm2/m2 and 3.17 cm2/m2 in male and female patients, respectively. Post-operative prognosis and cumulative incidence of recurrence rates were calculated.ResultsThe 5-year overall survival and disease-free survival rates post-surgery were 59.5% and 38.6%, respectively, in patients with sarcopenia versus 81.1% and 72.1%, respectively, in patients without sarcopenia (p < 0.001). The 5-year cumulative incidence of recurrence rate in patients with sarcopenia was significantly higher than those without sarcopenia (49.9% versus 22.4%, respectively) in every pathological stage. Pathological stages II and III (hazard ratio, 3.36; p = 0.004), histological type (hazard ratio, 2.31; p = 0.025), and sarcopenia (hazard ratio, 2.52; p = 0.001) were independent risk factors for post-operative recurrence according to multivariate analysis.ConclusionSarcopenia is a risk indicator for post-operative recurrence in patients with non-small cell lung cancer.

Abstract Background A displaced bronchus is a rare disorder of the left upper lobe. Displaced bronchi are often accompanied by an anomaly of a pulmonary artery, but rarely of a pulmonary vein. Case presentation We here present a patient with primary lung cancer and simultaneous migration abnormalities of the pulmonary artery and vein in a displaced bronchus of the left upper lobe. Previous reports and our findings indicate that anomalies of the pulmonary artery and vein combined with a displaced bronchus of the left upper lobe have the following characteristics: (1) the left main pulmonary artery does not cross the dorsal side of the displaced bronchus; (2) V1 + 2 returns to the inferior pulmonary vein; and (3) there is an accessory fissure (aberrant fissure) in the segments dominated by the displaced bronchus. Conclusions Prevention of intraoperative damage during procedures for a displaced bronchus and pulmonary arteriovenous anomalies requires careful preoperative evaluation and surgical technique with particular attention to the above-listed characteristics.

Combined subsegmentectomy (CSS) is procedure as diagnostic purpose adding sufficient surgical margin. Compared to other procedure, CSS is not common, with the surgical results also being controversial. We analyzed the patients who had undergoing CSS in the right upper lobe for ground glass opacity (GGO) -dominant nodules. Between April 2011 and March 2017, we experienced 7 cases underwent CSS. In all cases, three subsegments resection and lymph node dissection using Video-Assisted Thoracic Surgery (VATS) was performed. The mean radiological tumor size was 1.4 (1.1–1.9) cm and the mean consolidation/tumor ratios was 19 (0–33) %. Pathological diagnosis was all t1a-pIA1 adenocarcinoma in all cases, curative resection was obtained with sufficient margin. There were no serious postoperative complications or death within 90 days after treatment. Unfortunately, one patient died of pneumonia 28 months after surgery, but there was no recurrence and other delayed adverse events (follow up period was mean 42.8 months). We conclude that CSS had effects on both tumor control and preservation of the residual lungs with tolerable complications. Keywords: Non-small cell lung cancer, Lung adenocarcinoma, Surgery, Subsegmentectomy, CSS

Abstract Background The interaction of vascular endothelial growth factor-C (VEGF-C)/VEGF-D/VEGF receptor-3 is considered to be a major driver of lymphangiogenesis, however the mechanism of this process remains unclear. We aimed to investigate the possible lymphangiogenic significance of synaptonemal complex protein 3 (SCP3) in non-small cell lung cancer (NSCLC). Methods The expression of SCP3, VEGF-C, and VEGF-D were measured and examined a correlation between SCP3 and VEGF-C or VEGF-D in various human lung cancer cell lines. Subsequently, we assessed SCP3, VEGF-A, VEGF-B, VEGF-C, and VEGF-D expression in archival tumor tissues from 89 NSCLC patients with lymph node (LN) metastasis by combined immunohistochemistry with quantitative digital image analysis. Results Positive correlations between SCP3 and VEGF-C expression (R 2 = 0.743) and VEGF-D expression (R 2 = 0.932) were detected in various human lung cancer cell lines. The high expression of SCP3, VEGF-A, VEGF-B, VEGF-C, and VEGF-D were detected in 24 (27.0%), 22 (24.7%), 27 (30.3%), 27 (30.3%), and 24 cases (27.0%), respectively. Notably, SCP3 positively correlated with VEGF-C and VEGF-D expression (for both, P

Background: A pulmonary tumor is occasionally detected on a chest computed tomography (CT) scan before cardiovascular surgery. Purpose: In this study, we examined clinical courses of patients who had undergone the simultaneous resection of a pulmonary tumor following cardiovascular surgery. Methods: From 2008 to 2013, 18 patients (13 men and 5 women) with a median age of 69.8 years underwent the wedge pulmonary resection for a lung tumor through a median thoracotomy following cardiovascular surgery in our hospital. Cardiovascular surgeries consisted of off-pump coronary artery bypass grafting (CABG) in six patients, aortic valve replacement and/or mitral valve plasty in 10 patients, total arch replacement in 10 patients and descending aorta replacement in 10 patients. Results: No complications associated with pulmonary resections were observed. Pathological examination revealed that 15 patients (83.3%) were diagnosed with lung cancers including 13 adenocarcinomas and two squamous cell carcinomas, with the clinical stages of 1A in 13 patients, 2A in one patient and 2B in one patient. Among them, five patients received the radical pulmonary resection subsequently, whereas 10 patients were unable to receive it due to their poor cardiopulmonary function. Kaplan-Meier analysis of patients with lung cancer revealed that the 5-year survival rate and progression-free survival (PFS) rate after 3 years from the surgery were 46.2% and 73.8%, respectively. Conclusion: The simultaneous resection of pulmonary tumor following cardiovascular surgery is safely performed, and is useful for the pathological diagnosis of the tumor. Further studies are warranted, however, this procedure may contribute to controlling the progression of lung cancer in patients with cardiovascular disease with comorbidities.

Delirium is a common post-surgical complication, but few studies have examined postoperative delirium following lung cancer surgery. The purpose of this study was to clarify the risk factors of postoperative delirium, to construct a useful scoring system, and to clarify the relationship between delirium and prognosis after lung cancer surgery. We retrospectively analyzed data from 570 patients who underwent surgery for primary lung cancer. Logistic regression analysis was used to determine the effects of various factors on the onset of delirium. Kaplan-Meier analysis was performed to determine the relationship between delirium and prognosis. Postoperative delirium occurred in 6.7% of the patients. Three risk factors were identified, and the risk scores were determined as follows: 2×(cerebrovascular disease history) + 1×(squamous cell carcinoma) + 1×(age older than 75 years). Scores 0-1 denoted low risk, 2 denoted intermediate risk, and 3-4 denoted high risk. Additionally, we found that patients who developed delirium had significantly shorter overall survival. However, there was no difference in the frequency between cancer-related death and non-cancer related death when comparing the delirium and non-delirium groups. We identified the risk factors, i.e., cerebrovascular disease history, squamous cell carcinoma, and age older than 75 years, that determine the onset of delirium after lung cancer surgery and constructed a useful scoring system. In addition, although the prognosis of the delirium group was poor, the factor that determines prognosis may not be cancer per se but vulnerability in the patient background.

Background: Airway stenosis after bronchial tuberculosis may reduce the patient's activities of daily living owing to various respiratory symptoms. Thus, it is necessary to treat the condition. Various treatment modalities, such as balloon dilatation, are attempted in cases where radical surgical resection is difficult to perform; however, the best treatment method remains unknown. Although balloon dilatation is relatively easy to perform and effective, there are not many cases reporting successful treatment of tracheal stenosis as compared to that of bronchial stenosis. Case presentation: We report a case involving a 63-year-old man who presented with dyspnea on effort and stridor for 6 months. He was diagnosed with bronchotracheal stenosis due to endobronchial tuberculosis. A chest computed tomography scan showed thickening of the tracheal lumen and deformation of the tracheal cartilage from the annular cartilage to the middle trachea, and severe stenosis in the left main bronchus. Good patency of the trachea and the left main bronchus was obtained after two rounds of balloon dilatation with laser cauterization, which resulted in improvement of symptoms over a relatively long period. Conclusions: Our study shows that balloon dilatation combined with laser cauterization can be easily repeated and may be effective for treatment of patients with bronchotracheal stenosis, wherein radical treatment cannot be performed. Keywords: Balloon dilatation, Endobronchial tuberculosis, Tracheal stenosis

Traumatic hemothorax is usually caused by thoracic organ damage. Cases of atypical bleeding sources may be difficult to diagnose. Here we present two surgical cases of vertebral fracture that caused hemothorax. Case 1: an 81-year-old man was admitted to our hospital after a fall. Computed tomography showed right hemothorax without rib fractures. He suddenly developed shock and intrathoracic hemorrhage. Thoracotomy revealed the bleeding source as a transverse laceration in T7. Case 2: an 83-year-old woman fell on her back and was admitted. Computed tomography indicated an L1 vertebral fracture. A few days later, she suddenly developed a right hemothorax. An intrathoracic hemorrhage was sustained after transcatheter embolization. Thoracotomy revealed a diaphragmatic rupture. Total cross-fracture of the vertebral body solely caused the hemothorax. If bleeding source is unclear in elderly patients, this etiology should be considered. We saved both patients by performing spinal fusion surgery at the appropriate time.

Background: The dendritic cell (DC)-based vaccine targeting the highly immunogenic tumor antigen, MUC1, has been promising for a cancer immunotherapy; however, predictive biomarkers for beneficial clinical responses of the vaccine remain to be determined. Methods: DCs loaded with MUC1-derived peptide were subcutaneously administered to patients with MUC1-positive non-small cell lung cancer (NSCLC) that was refractory to standard anticancer therapies, every 2 weeks. The effectiveness and tolerability of the vaccine were evaluated, and predictive biomarkers of clinical responses were explored. Results: Between August 2005 and May 2015, 40 patients received the vaccines. The median survival time (MST) after the initial vaccination was 7.4 months, and the 1-year survival rate was 25.0%. The MST for patients who received more than six vaccinations was 9.5 months, and the 1-year survival rate was 39.3%. In this cohort, patients who experienced immune-related adverse events, including skin reactions at the vaccination site and fever, had significantly longer survival times compared with patients without those immune-related adverse events (12.6 versus 6.7 months, p = 0.042). Longer survival times were also observed in patients whose peripheral white blood cells contained >20.0% lymphocytes (12.6 versus 4.5 months; p = 0.014). MUC1-specific cytotoxic immune responses were achieved in all of seven patients analyzed who received six vaccinations. Conclusion: The MUC1-targeted DC-based vaccine induced an antitumor immune response that promoted prolonged survival of patients with refractory NSCLC. The occurrence of immune-related adverse events and having a higher percentage of peripheral lymphocytes were predictive biomarkers of a beneficial clinical response during cancer immunotherapy for NSCLC.