Myostatin expression in lung cancer induces sarcopenia and promotes cancer progression.

OBJECTIVES: Many studies have demonstrated that sarcopenia among lung cancer predicts poor prognosis due to cancer progression. However, the cytokines that link sarcopenia and lung cancer progression remain unidentified. This study aimed to investigate whether lung cancer producing myostatin, which induces skeletal muscle atrophy, leads to sarcopenia and promotes cancer progression in patients with resected lung cancer. METHODS: Tumor tissues were obtained from 148 patients who underwent curative resection for lung cancer. Tumor cells were stained with myostatin and tumor-associated macrophages (TAM) in the tumor microenvironment were stained with CD68. We assessed the association between myostatin expression and the clinicopathological features. RESULTS: High myostatin expression in lung cancer was significantly associated with low skeletal muscle mass. The 5-year overall survival and relapse-free survival were significantly worse among patients with high myostatin expression than those with low expression. A multivariate analysis showed that TAM count was positively correlated with high myostatin expression. CONCLUSION: Sarcopenia may be induced by myostatin secreted by lung cancer cells. Moreover, myostatin may promote TAM migration into the tumor microenvironment, leading to advance lung cancer. As a result, patients with high myostatin expression had poor prognosis.

Relationship between pulmonary blood flow and volume following lung resection using dynamic perfusion digital radiography.

Background: Surgical intervention for lung resection can cause ventilation-perfusion mismatches and affect gas exchange; however, minimally invasive assessment of blood flow is difficult. This study aimed to evaluate changes in pulmonary blood flow after radical lung cancer surgery using a minimally invasive dynamic digital chest radiography system. Methods: We evaluated 64 patients who underwent radical lobectomies. Postoperative changes in pulmonary blood flow, assessed using dynamic chest radiography-based blood flow ratios (BFRs), were compared with the temporal evolution of both functional lung volumes (FLVs) and estimated lung weight (ELW) derived from computed tomography (CT) volumetry. Results: FLVs on the affected side gradually recovered over time from the lowest value observed 3 months after surgery in all procedures. BFRs on the affected side also showed a gradual recovery from the lowest value 1 month after surgery, except for left upper lobectomies (LULs). In LULs, FLVs and ELWs increased proportionally up to 3 months after surgery, with lung volumes continuing to increase thereafter. The recovery of BFRs differed depending on the resected lobe. Conclusions: A relationship between pulmonary blood flow and FLV was observed in the postoperative period. Despite varying compensatory responses depending on the surgical procedure, FLV recovery coincided with increased pulmonary blood flow.

A comparative analysis of segmentectomy-aswere medicated withinsociated factors influencing bronchial tortuosity in early-stage left upper lung cancer.

BACKGROUND: Several studies of early-stage non-small cell lung cancer (NSCLC) have reported a notable therapeutic effect of segmentectomy. However, the secondary benefits of lung volume preservation remain unclear. This study aimed to investigate the potential benefits of segmentectomy, in terms of its impact on postoperative bronchial change. METHODS: Patients who underwent left-sided upper lobectomy and upper division segmentectomy for pStage 0-IA2 NSCLC, were retrospectively analyzed. Degree of the left main bronchial deviation was measured by the curvature index (CI), determined using computed tomography. Variables, including CI value and postoperative rate of change in CI were compared for postoperative cough management the lobectomy and segmentectomy groups. RESULTS: Sixty-seven patients were reviewed. Thirty-seven and 30 patients underwent lobectomy and segmentectomy, respectively, without any significant differences in baseline and surgical variables. The 5-year overall survival rates in the lobectomy and segmentectomy groups were 86.7 and 95.2%, respectively (p = 0.437). While there was no significant difference in postoperative complications, the rate of change in CI was significantly higher in the lobectomy group than in the segmentectomy group (113 vs. 106%, p = 0.005). In addition, the analysis based on postoperative cough reveals the rate of change in CI to be significantly higher in patients requiring medical treatment (p = 0.005). Conclusions Left upper division segmentectomy provides satisfactory treatment and relief of postoperative bronchial tortuosity. Our study suggests that there is a possibility the mitigation of environmental changes in the thoracic cavity may reduce symptoms, thus contributing to an improved quality of life.

Depletion of tumor-associated macrophages inhibits lung cancer growth and enhances the antitumor effect of cisplatin.

In lung cancer, tumor-associated macrophages (TAMs), especially M2-like TAMs, represent the main tumor progression components in the tumor microenvironment (TME). Therefore, M2-like TAMs may serve as a therapeutic target. The purpose of this study was to investigate the effect of M2-like TAM depletion in the TME on tumor growth and chemotherapy response in lung cancer. The levels of secreted monocyte chemoattractant protein (MCP-1) and prostaglandin E2 (PGE2) in the supernatants of lung cancer cell lines A549 and LLC were evaluated via ELISA. Cell migration assays were performed to assess the recruitment ability of macrophage cell lines THP-1 and J774-1 cells. Differentiation of macrophages was assessed via flow cytometry. Immunohistochemical staining was performed to visualize M2-like TAMs in transplanted lung cancer in mouse. We used the COX-2 inhibitor nimesulide to inhibit the secretion of MCP-1 and PGE2, which promotes macrophage migration and M2-like differentiation. Nimesulide treatment decreased the secretion of MCP-1 and PGE2 from lung cancer cells. Nimesulide treatment suppressed the migration of macrophages by blocking MCP-1. Lung cancer supernatant induced the differentiation of macrophages toward the M2-like phenotype, and nimesulide treatment inhibited M2-like differentiation by blocking MCP-1 and PGE2. In the lung cancer mouse model, treatment with nimesulide depleted M2-like TAMs in the TME and enhanced the tumor inhibitory effect of cisplatin. Our results indicated that blocking the secretion of MCP-1 and PGE2 from tumor cells depleted M2-like TAMs in the TME and the combination therapy with cisplatin considerably suppressed tumor growth in the LLC mouse model.

Reliability of dynamic perfusion digital radiography as an alternative to pulmonary perfusion scintigraphy in predicting postoperative lung function and complications.

Background: Accurate perioperative risk assessment can enhance the perioperative management of patients undergoing radical surgery for lung cancer. In this study, we compared the accuracy of predicting perioperative complications by lung function values, estimated by blood flow ratios (BFRs), to determine whether dynamic perfusion digital radiography (DPDR) could substitute for pulmonary perfusion scintigraphy (PPS). Methods: Patients scheduled for radical surgery for lung cancer who underwent simultaneous dynamic chest radiography (DCR) and lung perfusion scintigraphy were assessed. We confirmed the agreement between two methods in the assessment of the BFR and its predicted postoperative (ppo) value. Besides, the best spirometry thresholds for the risk of perioperative respiratory or cardiovascular complications were calculated from a receiver operating characteristic (ROC) analysis. The imaging methods were compared for sensitivity and specificity. Results: Among the 44 cases enrolled, DPDR and PPS showed high correlations in BFR (r=0.868, P<0.01) and its postoperative value (r=0.975, P<0.01) and between the predicted and measured spirometry values. In both imaging modalities, the estimated postoperative diffusing capacity test for carbon monoxide (DLco) had the best prediction [area under the curve (AUC) >0.7] for respiratory complications within 1 month (with different cut-offs for same target cases). For predicting, respiratory complications within 1-3 months after surgery, these values were similar between two modalities. Furthermore, the ppoDLco values from both imaging methods were excellent indicators of the induction of postoperative long term oxygen therapy, with the AUC greater than 0.8. Conclusions: This study showed that simple and less invasive DPDR can be a good alternative to PPS for predicting postoperative pulmonary function values and the risk of postoperative respiratory complications. This new imaging modality will offer new insights and possible functional analyses of pulmonary circulation.

Cardiac Hemangioma Producing Pericardial Effusion Detected on Thoracoscopic Pericardial Fenestration.

A 76-year-old woman presented with dyspnea. Computed tomography showed massive pericardial effusion, so percutaneous catheter drainage was performed. The usual causes of exudate were ruled out, and no diagnosis was reached. Thoracoscopic pericardial fenestration was performed to obtain a pericardial biopsy specimen and to create a passage allowing longer-term drainage. Observation of the pericardial cavity after the effusion was removed incidentally revealed a tumor measuring 2 cm in diameter located between the left atrial appendage and left pulmonary artery. Surgical resection of the tumor attached to the left atrial appendage was performed. The pathologic diagnosis was hemangioma.

Sarcopenia increases the risk of post-operative recurrence in patients with non-small cell lung cancer.

BACKGROUND: Sarcopenia 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. METHODS: This 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. RESULTS: The 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. CONCLUSION: Sarcopenia is a risk indicator for post-operative recurrence in patients with non-small cell lung cancer.

Does sarcopenia affect postoperative short- and long-term outcomes in patients with lung cancer?-a systematic review and meta-analysis.

BACKGROUND: Lung cancer patients frequently suffer from sarcopenia, and reports on the association of resectable lung cancer and their postoperative outcomes are increasing. Information on whether sarcopenia has any impact on short- and long-term postoperative outcomes in patients surgically treated for non-small cell lung cancer remains insufficient. Furthermore, reports vary regarding the pathological stage, surgical procedure, diagnostic tool of sarcopenia, cut-off value, prognosis, and postoperative complications. We believe that sarcopenia assessment should be included as one of the factors which affect the surgical outcomes of lung cancer. Thus, we conducted a review and meta-analysis to ascertain the association between sarcopenia and postoperative outcomes. METHODS: We performed a systematic literature search in PubMed/MEDLINE. Studies included cases defined sarcopenia, received lung cancer surgery, assessed postoperative complications, and prognosis. The pooled odds ratios for survival and postoperative complications, with 95% confidence intervals, were generated using Review manager 5.3. RESULTS: A total of ten retrospective studies were eligible for this meta-analysis, including a total of 2,643 non-small cell lung cancer patients. All reviews used skeletal muscle mass as a diagnostic tool for sarcopenia. Sarcopenia was associated with worse survival outcomes and increased postoperative complications in patients with resected lung cancer. CONCLUSIONS: Sarcopenia is an independent risk factor for postoperative death and postoperative complications in patients who have undergone surgery. It is necessary to explore the mechanism of sarcopenia and optimal intervention, such as exercise, nutrition, or drug therapy.

Locoregional recurrence via mucus-mediated extension following lung resection for mucinous tumors.

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.

Dynamic perfusion digital radiography for predicting pulmonary function after lung cancer resection.

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.

Feasibility of early removal of chest tube in the operating room for spontaneous pneumothorax: A prospective randomized controlled study.

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 < 0.001), despite their reduced use of rescue drugs. The mean length of post-operative hospital stay was 2.5 days in patients with chest tube, which was significantly longer than that of patients without chest tube (1.2 days; P < 0.001). CONCLUSIONS: Our patient selection and surgical protocols may be feasible and contribute to post-operative pain control.

Airway inflammation and lung function recovery after lobectomy in patients with primary lung cancer.

OBJECTIVE: Fractional exhaled nitric oxide (FeNO), which represents airway inflammation, is an indicator of postoperative complication after lung surgery. However, its effects in the late postoperative period are unknown. The aim of this prospective study was to clarify the impact of FeNO on postoperative lung function in patients with lung cancer. METHODS: We measured preoperative FeNO using NIOX VERO® in patients with primary lung cancer. Patients were divided into two groups according to their potential airway inflammatory status: preoperative FeNO levels below 25 ppb (N group) and above 25 ppb (H group). They were evaluated by spirometry at 3 and 6 months after surgery during follow-up. The relationship between postoperative lung function and preoperative FeNO was evaluated. RESULTS: Between September 2017 and March 2019, 61 participants were enrolled. All of them underwent lobectomy as a curative surgery. There were no significant background variables between the two groups. Postoperative vital capacity (VC) and forced expiratory volume in 1 s (FEV1) in the H group achieved less predictive values than those in the N group, which were not significant. The postoperative VC and FEV1 from 3 to 6 months in the H group were significantly increased as compared to those in the N group (p < 0.001). CONCLUSIONS: Preoperative FeNO is a predictor of delayed lung function recovery 3 months after lobectomy in lung cancer patients. The impact had extended to VC and FEV1. Although this impact is temporary, early postoperative intervention is expected to reduce the adverse effect.

The combination of computed tomography features and circulating tumor cells increases the surgical prediction of visceral pleural invasion in clinical T1N0M0 lung adenocarcinoma.

BACKGROUND: Visceral pleural invasion (VPI) is a clinical manifestation associated with a poor prognosis, and diagnosing it preoperatively is highly imperative for successful sublobar resection of these peripheral tumors. We evaluated the roles of computed tomography (CT) features and circulating tumor cells (CTCs) for improving VPI detection in patients with clinical T1N0M0 invasive lung adenocarcinoma. METHODS: Three hundred and ninety-one patients were reviewed retrospectively in this study, of which 234 presented with a pleural tag or pleural contact on CT images. CTCs positive for the foliate receptors were enriched and analyzed prior to surgery. Logistic regression analyses were performed to assess the association of CT features and CTCs with VPI, and the receiver operating characteristic (ROC) curve was generated to compare the predictive power of these variables. RESULTS: Patients mostly underwent either segmentectomies (18.9%) or lobectomies (79.0%). Only 49 of the 234 patients with pleural involvement on CT showed pathologically confirmed VPI. Multivariate logistic regression analysis revealed that CTC level ≥10.42 FU/3 mL was a significant VPI risk factor for invasive adenocarcinoma cases ≤30 mm [adjusted odds ratio (OR) =4.62, 95% confidence interval (CI): 2.05-10.44, P<0.001]. Based on CT features, subgroup analyses showed that the solid portion size was a statistically significant independent predictor of VPI for these peripheral nodules with pleural tag, while the solid portion length of the interface was an independent predictor of pleural contact. The receiver operating curve analyses showed that the combination of CTC and CT features were highly predictive of VPI [area under the curve (AUC) =0.921 for pleural contact and 0.862 for the pleural tag, respectively]. CONCLUSIONS: CTC, combined with CT features of pleural tag or pleural contact, could significantly improve VPI detection in invasive lung adenocarcinomas at clinical T1N0M0 stage prior to the patient's surgery.

Survival and prognostic factors in patients undergoing extended pulmonary metastasectomy.

Extended pulmonary metastasectomy has become feasible in patients with extrapulmonary metastases and multiple or bilateral pulmonary metastases. Even peritoneal dissemination is considered to be curable in modern medicine. Therefore, it is necessary to analyze the prognosis of patients undergoing complete pulmonary metastasectomy. A total of 80 patients who underwent pulmonary resection for lung metastases were retrospectively analyzed. The eligibility criteria for the present study were as follows: i) the primary tumor was controlled; ii) if extrapulmonary metastases (including peritoneal dissemination) existed, these were controlled by local treatment or such treatment was planned; iii) the one to three months follow-up computed tomography (CT) following the first assessment revealed no increase of pulmonary metastatic disease; iv) pulmonary metastases could be resected completely. The overall 5- and 10-year survival rates were 71.7 and 41.5%, respectively. Applying the extended criteria for surgery, the present study demonstrated that pulmonary metastasectomy resulted in a good patient prognosis.

Right sleeve pneumonectomy for local recurrent lung cancer following right sleeve upper lobectomy with bronchoplasty: a case report.

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.

Cytoreductive Surgery and Hyperthermic Chemotherapy for Intrathoracic Pseudomyxoma Peritonei.

Dissemination of pseudomyxoma peritonei into the thoracic cavity is rare and carries a poor prognosis. Optimal treatment has not been defined. In our institution, patients have received cytoreductive surgery with hyperthermic intrathoracic chemotherapy, which demonstrated a good prognosis. A 51-year-old woman was referred to our hospital with right intrathoracic dissemination of pseudomyxoma peritonei. We performed parietal and mediastinal pleurectomy and simple resection of all visible tumors on the diaphragm and visceral pleura, followed by hyperthermic intrathoracic chemotherapy with 20 mg mitomycin at 42°C to 43°C. The patient had no evidence of disease progression in the thoracic cavity 1 year after surgery.

Clinical efficacy of osimertinib for a patient with ileus due to peritoneal carcinomatosis.

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.

Sarcopenia predicts poor postoperative outcome in elderly patients with lung cancer.

PURPOSE: Sarcopenia gradually progress with age; hence, it is necessary to define sarcopenia to predict postoperative outcomes in elderly patients with lung cancer. The purpose of this study is to propose a definition of sarcopenia in elderly patients with lung cancer, and to demonstrate the post operative outcomes. METHODS: Using computed tomography scans, the cross-sectional area (cm2) of the psoas muscle at the third lumbar vertebral level was measured. The psoas area was normalized for height. The psoas muscle mass index was calculated as total psoas muscle area at L3 level/height2 (cm2/m2). RESULTS: A total of 173 patients aged > 75 years of age received lobectomy for non-small cell lung cancer in our hospital. We defined sarcopenia as the psoas muscle mass index under 3.70 cm2/m2 in males and 2.50 cm2/m2 in females, based on the morbidity rate. The postoperative complication rate was significantly higher in patients with sarcopenia (62.5%) than in those without sarcopenia (22.7%). The 5-year survival rate was 26.5% in patients with sarcopenia, and 66.3% in patients without sarcopenia. CONCLUSIONS: In elderly lung cancer patients, sarcopenia was observed to be a high risk for morbidity and predicted poor prognosis.