Jiandong Mei

Interleukin-17 and Prostaglandin E2 Are Involved in Formation of an M2 Macrophage-Dominant Microenvironment in Lung Cancer

Introduction: Tumor-associated macrophages (TAMs) are divided into M1 and M2 macrophages. M1 macrophages inhibit tumor growth, whereas M2 macrophages promote tumor growth and metastasis. The aim of this study was to examine the possible causes leading to the formation of an M2-macrophage–dominant tumor microenvironment in non–small-cell lung cancer. Methods: Forty-eight archived lung tumor samples were examined for the expression of interleukin-17 (IL-17) receptors, IL-17 receptor A (IL-17RA) and IL-17 receptor C (IL-17RC), and the number of TAMs using immunohistochemical staining. Twenty fresh lung tumors and matched normal lung tissues were examined for expression of IL-17, cyclooxygenase-2, and prostaglandin E2 (PGE2), using enzyme-linked immunosorbent assay and Western blot analysis. Macrophage-migration assays were performed using fresh lung tumor tissues and IL-17 as chemoattractants. Induction of M2-macrophage differentiation was analyzed using real-time quantitative polymerase chain reaction. Results: TAMs expressed IL-17RA and IL-17RC. Lung tumors expressed higher levels of IL-17, cyclooxygenase-2, and PGE2, compared with normal lung tissues. Lung tumor tissues attracted migration of mouse RAW264.7 macrophages and primary peritoneal macrophages through IL-17, which was mediated by IL-17RA and IL-17RC. IL-17 did not induce either M1- or M2-macrophage differentiation. However, human lung cancer A549 cells strongly induced M2-macrophage differentiation of RAW264.7 macrophages when the two cell lines were cocultured. The inductive factor secreted by A549 cells was identified to be PGE2. Conclusions: IL-17 recruits macrophages, and PGE2 induces M2-macrophage differentiation, hence the increased levels of IL-17 and PGE2 in lung cancer contribute to the formation of an M2-macrophage–dominant tumor microenvironment.

Prognostic impact of tumor-associated macrophage infiltration in non-small cell lung cancer: A systemic review and meta-analysis

Tumor-associated macrophages (TAMs) are important components of cancer microenvironment. In the present study, we searched PubMed, Embase, Cochrane library and Web of Science to perform a meta-analysis of 20 studies including a total of 2,572 non-small cell lung cancer (NSCLC) patients, in order to determine the association between TAMs and NSCLC prognosis. The combined hazard ratio (HR) of 9 studies showed that the density of total CD68+ TAMs in the tumor islet and stroma was not associated with overall survival (OS) of the patients. However, the pooled HR of 4 studies showed that high density of CD68+ TAMs in the tumor islet predicted better OS, while the pooled HR of 6 studies showed that high density of CD68+ TAMs in the tumor stroma was associated with poor OS. A high islet/stroma ratio of CD68+ TAMs was associated with better OS. A high density of M1 TAMs in the tumor islet was associated with better OS, while a high density of M2 TAMs in the tumor stroma predicted poor OS. These findings suggest that, although the density of total CD68+ TAMs is not associated with OS, the localization and M1/M2 polarization of TAMs are potential prognostic predictors of NSCLC.

Video-assisted thoracic surgery for pulmonary sequestration compared with posterolateral thoracotomy.

OBJECTIVES Pulmonary sequestration is a rare congenital malformation of the lungs. This study aims to evaluate the effectiveness of video-assisted thoracic surgery for the treatment of pulmonary sequestration in a larger series compared with posterolateral thoracotomy. METHODS The files of 42 patients with pulmonary sequestration treated via video-assisted thoracic surgery (18 cases) and posterolateral thoracotomy (24 cases) between September 2005 and May 2012 from a single institute were retrospectively reviewed. Data were collected regarding the patient demographics, medical history, preoperative investigations, intraoperative findings, and postoperative course. RESULTS All sequestration lung lesions were found in the lower lobes (31 on the left, 11 on the right), with feeding arteries arising from the thoracic aorta (34 cases) and the abdominal aorta (8 cases). Thirty-nine cases of sequestration were intralobar, and only 3 cases were extralobar. All patients achieved successful resection (including 37 lobectomies, 2 pneumonectomies, and 3 resections of the extralobar lesion). In the video-assisted thoracic surgery group, 1 case was converted to thoracotomy because of an injury to the aberrant artery; 1 case had injury to the left lower pulmonary vein and 1 case had injury to the aberrant artery, which were successfully treated without conversion. No significant differences were found between the 2 groups (video-assisted thoracic surgery vs posterolateral thoracotomy) in terms of the duration of operation, blood loss, amount of chest drainage, duration of chest drainage, length of postoperative hospital stay, and complications. CONCLUSIONS Video-assisted thoracic surgery resection for pulmonary sequestration is feasible, although it should be performed by an experienced surgeon with awareness of the potential risk of severe vascular injury.

Thoracoscopic bronchovascular double sleeve lobectomy for non-small-cell lung cancer

We present our preliminary experience of thoracoscopic bronchovascular double sleeve lobectomy (SL) for non-small-cell lung cancer in the upper lobe involving both the bronchus and the pulmonary artery. From May 2012 to July 2013, 4 patients were selected for this operation, including 3 cases of left upper lobectomy and 1 case of right upper lobectomy. Surgical procedures were performed with four ports for the first patient and three ports for the other patients. Systemic lymph node dissection was finished before removal of the diseased lobe. Thoracoscopic bronchovascular reconstruction was carried out using running Prolene stitches by directly watching a video monitor. The operations were uneventful. Two patients developed postoperative pneumonia with no mortalities. The reconstructed bronchus and artery worked well during postoperative follow-up visits. Though technically difficult, we believe that thoracoscopic bronchovascular SL is feasible if performed by skilled thoracoscopic surgeons in an experienced centre.

Interferon-γ and celecoxib inhibit lung-tumor growth through modulating M2/M1 macrophage ratio in the tumor microenvironment.

Tumor-associated macrophages play an important role in tumor growth and progression. These macrophages are heterogeneous with diverse functions, eg, M1 macrophages inhibit tumor growth, whereas M2 macrophages promote tumor growth. In this study, we found that IFNγ and/or celecoxib (cyclooxygenase-2 inhibitor) treatment consistently inhibited tumor growth in a mouse lung cancer model. IFNγ alone and celecoxib alone increased the percentage of M1 macrophages but decreased the percentage of M2 macrophages in the tumors, and thus the M2/M1 macrophage ratio was reduced to 1.1 and 1.7 by IFNγ alone and celecoxib alone, respectively, compared to the M2/M1 macrophage ratio of 4.4 in the control group. A combination of IFNγ and celecoxib treatment reduced the M2/M1 macrophage ratio to 0.8. Furthermore, IFNγ and/or celecoxib treatment decreased expression of matrix metalloproteinase (MMP)-2, MMP-9, and VEGF, as well as the density of microvessels in the tumors, compared to the control group. This study provides the proof of principle that IFNγ and/or celecoxib treatment may inhibit lung-tumor growth through modulating the M2/M1 macrophage ratio in the tumor microenvironment, suggesting that IFNγ and celecoxib have potential to be further optimized into a new anticancer therapy.

Non-grasping en bloc mediastinal lymph node dissection for video-assisted thoracoscopic lung cancer surgery

BackgroundThis study aims to introduce an optimized method named “non-grasping en bloc mediastinal lymph node dissection (MLND)” through video-assisted thoracoscopic surgery (VATS).MethodsBetween February 2009 and July 2013, 402 patients with clinical stage I non-small cell lung cancer (NSCLC) underwent “non-grasping en bloc MLND” conducted by one surgical team. Target lymph nodes (LNs) were exposed following non-grasping strategy with simple combination of a metal endoscopic suction and an electrocoagulation hook or an ultrasound scalpel. In addition, dissection was performed following a stylized three-dimensional process according to the anatomic features of each station. Clinical and pathological data were prospectively collected and retrospectively reviewed.ResultsThe postoperative morbidity and mortality were 17.4% (70/402) and 0.5% (2/402), respectively. The total number of LNs (N1 + N2) was 16.0 ± 5.9 (range of 5–52), while the number of N2 LNs was 9.5 ± 4.0 (range of 3–23). The incidences of postoperative upstaging from N0 to N1 and N2 disease were 7.7% and 12.2%, respectively.ConclusionsNon-grasping en bloc MLND enables en bloc dissection of mediastinal LNs with comparable morbidity and oncological efficacy while saving troubles of excessive interference of instruments and potential damage to the target LN.

Video‐assisted thoracoscopic surgery versus posterolateral thoracotomy lobectomy: A more patient‐friendly approach on postoperative pain, pulmonary function and shoulder function

We evaluated the physiological benefits following video‐assisted thoracoscopic surgery (VATS) lobectomy or posterolateral thoracotomy (PLT) lobectomy for lung cancer patients. One hundred and three patients were included in this study, who underwent either a VATS approach (n= 51) or a PLT approach (n= 52) lobectomy for clinical stage I lung cancer. Pain scores were measured preoperatively and on postoperative day (POD) one, three, seven, 30, and 90, by using a visual analog scale. Pulmonary function and shoulder function were measured preoperatively and on POD seven, 30 and 90 by using a portable spirometer and by the American Shoulder and Elbow Surgeons (ASES) standardized shoulder assessment form, respectively. Postoperative pain was experienced less in the VATS group than in the PLT group on POD one, three, seven, 30, and 90 (P= 0.060, 0.055, 0.000, 0.000, 0.000, respectively). Analgesic requirements were significantly less in the VATS group than in the PLT group during hospital stay (90.2 ± 60.8 mg vs. 119.2 ± 70.8 mg, P= 0.028). The pain score returned to the preoperative reference level on POD seven in the VATS group, but not until POD 30 in the PLT group. The recovery of forced vital capacity (FVC) was statistically better in the VATS group on POD seven, postoperative month (POM) one, and POM three (P= 0.000, 0.000, 0.002, respectively). The recovery of forced expiratory volume in 1 second (FEV1) was better in the VATS group, but the differences were not significant. The shoulder function in the VATS group was significantly well preserved on POD seven, 30 and 90, compared with the PLT group. Lobectomy by the VATS approach generates less pain, and preserves better pulmonary function and shoulder function in the early postoperative phase.

Surgical treatment of primary mediastinal myelolipoma

OBJECTIVES Primary mediastinal myelolipoma (PMM) is a rare benign tumour composed of haematopoietic tissue and mature adipose tissue. Here, we report the largest series aiming to investigate the outcomes of surgical treatment for patients with PMM. METHODS We retrospectively reviewed the data of 12 patients operated in a single institute during the period between April 2008 and December 2014. RESULTS There were 7 female and 5 male patients between 54 and 73 years old (median age, 64 years). Among them, 11 patients underwent unilateral (n = 10) or bilateral (n = 1) mass resection via video-assisted thoracic surgery (VATS), and 1 patient underwent a planned open thoracotomy due to a large tumour volume. The VATS operating time ranged from 20 to 65 min (median, 30 min) and intraoperative blood loss ranged from 20 to 60 ml (median, 30 ml). The open thoracotomy operating time was 120 min, and the blood loss was 1000 ml; thus, the patient received blood transfusion (2 units of RBCs). No operative mortalities or major postoperative complications were observed. All patients experienced a regular follow-up ranging from 2 to 80 months with a median follow-up of 18 months. No recurrence was observed at the time of evaluation. CONCLUSIONS Surgical treatment is recommended for the diagnosis and treatment of PMM, while VATS is a safe and feasible option in most cases.

A rare large tracheal glomus tumor with postoperative haematemesis

Glomus tumors are uncommon benign tumors which usually arise from the distal portion of the digits. A tracheal glomus tumor with large size is extremely rare. We present a case of a large tracheal glomus tumor that was resected using posterolateral thoracotomy and successful primary reconstruction of the trachea was achieved. Severe haematemesis happened after the patient was discharged. An emergency exploratory thoracotomy was performed but no signs of anastomotic bleeding were observed, while intraoperative gastroscopy revealed plenty of blood and blood clots in the patients stomach. Medical treatments targeting hemorrhage of upper digestive tract were given and the patient finally recovered.

A ruptured pulmonary arteriovenous fistula

IGURE 1. A, Chest computed tomography scan shows a massive left pleura sterisks). B-D, Pulmonary angiography and 3-dimensional reconstruction con onary artery and the pulmonary vein in the left lower lung (arrows and arrow rom the Department of Thoracic Surgery, West China Hospital, Sichuan University, Chengdu, China; and Department of Thoracic Surgery, Affiliated Hospital of Guizhou Medical University, Guiyang, China. isclosures: Authors have nothing to disclose with regard to commercial support. eceived for publication April 13, 2015; accepted for publication May 9, 2015; available ahead of print June 2, 2015. ddress for reprints: Lunxu Liu, MD, PhD, No 37, Guoxue Alley, Chengdu, Sichuan 610041, China (E-mail: lunxu_liu@aliyun.com). Thorac Cardiovasc Surg 2015;150:716-7 22-5223/