Guilin Peng

Prognostic Significance of Programmed Cell Death 1 (PD-1) or PD-1 Ligand 1 (PD-L1) Expression in Epithelial-Originated Cancer: A Meta-Analysis

AbstractThe expression of programmed cell death 1 (PD-1) and its ligand (PD-L1) has been observed in various epithelial-originated malignancies. However, whether the expression of PD-L1 on tumor cells or the expression of PD-1 on tumor-infiltrating lymphocytes (TILs) is associated with patients’ survival remains controversial.Electronic databases were searched for eligible literatures. Data of hazard ratio (HR) for overall survival (OS) with 95% confidence interval (CI) according to the expression status of PD-L1 or PD-1 evaluated by immunohistochemistry were extracted. The outcomes were synthesized based on random-effects model. Subgroup analyses were proposed.Twenty-nine studies covering 12 types of epithelial-originated malignancies involving 7319 patients (2030/3641 cases for PD-L1 positive/negative, 505/1143 cases for PD-1 positive/negative) with available data of the outcome stratified by PD-L1/PD-1 status were enrolled. Epithelial-originated cancer patients with positive expression of PD-L1 on tumor tissues were associated with significantly poorer OS when compared to those with negative expression of PD-L1 (HR 1.81, 95% CI 1.33–2.46, P < 0.001). Similarly, patients with PD-1 positive expression on TILs had significantly shorter OS than the PD-1 negative group (HR 2.53, 95% CI 1.22–5.21, P = 0.012). In analyses of PD-L1, all subgroups showed consistent trends toward unfavorable prognoses of patients with positive PD-L1 expression, regardless of antibodies and evaluation cutoffs. Subgroup analyses on PD-1 were not available due to limited data.PD-L1 or PD-1 expression status is a significant prognostic factor in epithelial-originated malignancies.

Analysis of feasibility and safety of complete video-assisted thoracoscopic resection of anatomic pulmonary segments under non-intubated anesthesia

OBJECTIVE To explore the feasibility and safety of complete video-assisted thoracoscopic surgery (C-VATS) under non-intubated anesthesia for the resection of anatomic pulmonary segments in the treatment of early lung cancer (T1N0M0), benign lung diseases and lung metastases. METHODS The clinical data of patients undergoing resection of anatomic pulmonary segments using C-VATS under non-intubated anesthesia in the First Affiliated Hospital of Guangzhou Medical University from July 2011 to November 2013 were retrospectively analyzed to evaluate the feasibility and safety of this technique. RESULTS The procedures were successfully completed in 15 patients, including four men and eleven women. The average age was 47 [21-74] years. There were ten patients with adenocarcinoma, one with pulmonary metastases, and four with benign lung lesions. The resected sites included: right upper apical segment, two; right lower dorsal segment, one; right lower basal segment, two; left upper lingular segment, three; left upper apical segment, one; left upper anterior apical segment, two; left upper posterior segment, one; left lower basal segment, one; left upper posterior and apical segments, one; and left upper anterior and apical segments plus wedge resection of the posterior segment, one. One case had intraoperative bleeding, which was controlled with thoracoscopic operation and no blood transfusion was required. No thoracotomy or perioperative death was noted. Two patients had postoperative bleeding without the need for blood transfusions, and were cured and discharged. The pathologic stage for all patients with primary lung cancer was IA. After 4-19 months of follow-up, no tumor recurrence and metastasis was found. The overall mean operative length was 166 minutes (range 65-285 minutes), mean blood loss 75 mL (range 5-1,450 mL), mean postoperative chest drainage 294 mL (range 0-1,165 mL), mean chest drainage time 2 days (range 0-5 days), and mean postoperative hospital stay 5 days (range 3-8 days). CONCLUSIONS Complete video-assisted throacoscopic segmentectomy under anesthesia without endotracheal intubation is a safe and feasible technique that can be used to treat a selected group of IA patients with primary lung cancer, lung metastases and benign diseases.

Evaluation of the efficacy and safety of anti-PD-1 and anti-PD-L1 antibody in the treatment of non-small cell lung cancer (NSCLC): a meta-analysis

BACKGROUND Currently, blockade of the programmed cell death 1 (PD-1)/PD-1 ligand 1 (PD-L1) signaling pathway has been proved one of the most promising immunotherapeutic strategies against cancer. Several antibodies have been developed to either block the PD-1 or its ligand PD-L1 are under development. So far, a series of phase I trials on PD-1/PD-L1 antibodies for non-small cell lung cancer (NSCLC) have been completed, without reports of results from phase II studies. Thus, we sought to perform a meta-analysis incorporating all available evidences to evaluate the efficacy and safety of PD-1 or PD-L1 inhibition therapy. METHODS Electronic databases were searched for eligible literatures. Data of objective respond rate (ORR) and rate of adverse effects (AEs) with 95% confidence interval (CI) evaluated by immunohistochemistry (IHC) was extracted. The outcomes were synthesized based on random-effect model. Subgroup analyses were proposed. RESULTS In overall, ORR in the whole population with PD-1 blockage treatment is 22.5% (95% CI: 17.6% to 28.2%). Additionally, the rate of Grade 3-4 AEs is 16.7% (95% CI: 6.5% to 36.8%) and drug-related death rate is 2.5% (95% CI: 1.3% to 4.6%). As for patients with PD-L1 inhibition therapy, an overall ORR is 19.5% (95% CI: 13.2% to 27.7%). A higher rate of Grade 3-4 AEs (31.7%, 95% CI: 14.2% to 56.5%) is observed with a lower drug-related death rate (1.8%, 95% CI: 0.4% to 8.3%). In exploratory analyses of anti-PD-1 agents, we observed that greater ORR was presented in the median-dose cohort (3 mg/kg) than that of both low-dose (1 mg/kg) and high-dose (10 mg/kg) cohort (low-dose vs. median-dose: OR =0.12, P=0.0002; median-dose vs. high-dose: OR =1.47, P=0.18). CONCLUSIONS Anti-PD-1 and anti PD-L1 antibodies showed objective responses in approximately one fourth NSCLC patients with a tolerable adverse-effect profile. In addition, median-dose (3 mg/kg) might be a preferential dosage of anti-PD-1 agents.

Nonintubated thoracoscopic lobectomy plus lymph node dissection following segmentectomy for central type pulmonary masses

Lung cancer is the most common cancer worldwide. In the United States, it causes more cancer-related deaths than the next four causes (breast cancer, prostate cancer, colon cancer, and pancreatic cancer) of cancer-related mortality combined (1). About 30% of people have already progressed to stage III lung cancer and 40% to stage IV at the time they are diagnosed (2). Although chest X-ray and sputum cytology, when applied in health check-ups, can identify some relatively small tumors, they are not able to lower the overall mortality (3). More recently, the low-dose spiral CT scanning reduces the mortality of lung cancer when applied for lung cancer screening (4,5).

Short-Term Outcome of Three-Dimensional Versus Two-Dimensional Video-Assisted Thoracic Surgery for Benign Pulmonary Diseases

BACKGROUND It is unclear whether three-dimensional (3D) video-assisted thoracic surgery (VATS) pulmonary resections are comparable to two-dimensional (2D) VATS pulmonary resections in patients with potentially operable benign pulmonary diseases. METHODS We analyzed the clinical data of patients who underwent 2D and 3D VATS pulmonary resections for benign diseases in our hospital from November 2013 to August 2014. Perioperative factors (estimated blood loss and operative time) and postoperative factors (postoperative hospital length of stay, postoperative complications, and duration of chest tube drainage) were evaluated. RESULTS VATS was performed in 278 patients during the 10-month study period. The 2D VATS system was used in 142 patients (51.08%), and the 3D VATS system was used in 136 (48.92%). Operative time was significantly different between the two groups (p = 0.007). However, no significant differences were found in estimated blood loss (p = 0.75), chest drainage tube placement time (p = 0.852), rate of postoperative complications (p = 0.566), or postoperative hospital length of stay (p = 0.951). CONCLUSIONS The use of 3D VATS appears to facilitate precise execution of surgical techniques in specific operative tasks and, as a result, reduces lung resection performance time in patients with benign pulmonary diseases.

A comparative analysis of lung cancer patients treated with lobectomy via three-dimensional video-assisted thoracoscopic surgery versus two-dimensional resection

BACKGROUND Three-dimensional (3D) vision systems are now available for thoracic surgery. It is unclear whether 3D video-assisted thoracic surgery (VATS) is superior to 2D VATS systems. This study aimed to compare the operative and perioperative data between 2D and 3D VATS lobectomy (VTL) and to identify the actual role of 3D VTL in thoracic surgery. METHODS A two-institutional comparative study was conducted from November 2013 to November 2014 at Liaoning Cancer Hospital & Institute and the First Affiliated Hospital of Guangzhou Medical University, China, of 300 patients with resectable non-small cell lung cancer (NSCLC). Patients were assigned to receive either the 3D VATS (n=150) or 2D VATS (n=150) lobectomy. The operative and perioperative data between 2D VATS and 3D VATS were compared. RESULTS Although there was no significant difference between the two groups regarding the incidence of each single complication, a significantly less operative time was found in the 3D VATS group (145 min) than in the 2D VATS group (176 min) (P=0.006). Postoperative mortality rates in 3D VATS and 2D VATS groups were both 0%.No significant difference was found between groups for estimated blood loss (P=0.893), chest drainage tube placement time (P=0.397), length of hospital stay (P=0.199), number of lymph nodes resected (P=0.397), postoperative complications (P=0.882) and cost of care (P=0.913). CONCLUSIONS Early results of this study demonstrate that the 3D VATS lobectomy procedure can be performed with less operative time. 3D VATS and 2D VATS lobectomy are both safe procedures in first-line surgical treatment of NSCLC.

Glasses-free three-dimensional endoscopic bronchoplasty, arterioplasty, and angioplasty of the superior vena cava for the radical treatment of right middle upper lung cancer

The role of video-assisted thoracoscopic surgery (VATS) radical resection in the treatment of lung cancer has widely recognized. Studies have demonstrated that the thoracoscopic radical treatment of lung cancer can achieve similar long-term survival as that of conventional open surgeries; meanwhile, it can be applied for bronchial sleeve resection that is more challenging for most thoracic surgeons. Bronchial sleeve pneumonectomy can avoid total pneumonectomy when removing tumors, and therefore it can lower the surgery-associated mortality and improve the long-term survival by maximizing the preservation of lung function. Thus, it has become a standard procedure for central-type lung cancer. We have completed a glasses-free three-dimensional (3D) complete thoracoscopic surgery in a patient with central-type lung cancer in his right lung. During the surgery, we found the tumor had invaded the right pulmonary trunk, right main bronchus, and lateral wall of superior vena cava.

MAP kinase-interacting serine/threonine kinase 2 promotes proliferation, metastasis, and predicts poor prognosis in non-small cell lung cancer

We hypothesized that MAP kinase-interacting serine/threonine kinase 2 (MNK2) may contribute to non-small cell lung cancer (NSCLC) development, and serve as a new therapeutic target. Immunohistochemical staining evaluated the correlation between MNK2 expression and clinicopathological features in 367 NSCLC cancer tissues. We determined the effects of MNK2 silencing in NSCLC cell lines in vitro and in vivo. RT-PCR and western blotting was used to examine the impact of MNK2 on ERK and AKT pathways. MNK2 was overexpressed in NSCLC cell lines and tumor tissues. Patients with MNK2 overexpression had lower OS rates (P < 0.001). High expression of MNK2 was correlated with lymph node metastasis (P = 0.008). MNK2 functioned as an independent prognostic factor for poor survival in patients with NSCLC (P = 0.003). MNK2 down-regulation inhibited proliferation, migration and invasion in vitro (P < 0.001), and reduced tumor growth and invasion in nude mice (P < 0.05). MNK2 enhanced phosphorylation of eIF4E, a downstream target of ERK and AKT pathways, which promoted NSCLC proliferation and invasion. We conclude that MNK2 overexpression in NSCLC is associated with proliferation, migration, invasion, and lower survival rates in patients via the phosphorylated eIF4E-mediated signaling pathway.

Non-intubated combined with video-assisted thoracoscopic in carinal reconstruction

Carinal reconstruction is a difficult technique combined with video-assisted thoracoscopic surgery (VATS). It has a high requirement on the operators skills in operating thoracoscope and meanwhile requires the close cooperation from anesthesiologists. Tracheal intubation and ventilator-assisted ventilation are key steps to ensure the success of surgery. However, tracheal intubation itself may influence the exposure of surgical field and increase the difficulty of anastomosis. In close cooperation of anesthesiologists, we did not perform tracheal intubation; rather, we carried out non-intubated complete VATS carinal reconstruction in a patient with adenoid cystic carcinoma (ACC) of the lower trachea. The awake complete VATS carinal reconstruction was successfully performed. The anastomosis lasted about 36 hours, and the whole surgical procedure lasted 230 min. The intraoperative blood loss was about 80 mL. The patient recovered well 100 min after surgery. A semi-solid diet began 6 hours following the surgery. This non-intubated anesthesia method makes the surgery easier, especially during the anastomosis of stumps. It is feasible and safe to apply this anesthesia technique in carinal reconstruction.

Prognosis and status of lymph node involvement in patients with adenocarcinoma in situ and minimally invasive adenocarcinoma-a systematic literature review and pooled-data analysis.

BACKGROUND Adenocarcinoma in situ (AIS) and minimally invasive adenocarcinoma (MIA) have been brought up that substitute for bronchioloalveolar carcinoma (BAC), according to the new classification of lung adenocarcinoma. There has been increasing opinions that argues for the adjustment of lymph node disposition in patients with such early stage tumors. Therefore, we sought to overview the prognosis and status of lymph node involvement in AIS/MIA patients. METHODS PubMed, Springer and Ovid databases were searched for relevant studies. Data was extracted and results summarized to demonstrate the disposition of lymph nodes in AIS/MIA. RESULTS Twenty-three studies consisting of 6,137 lung adenocarcinoma were included. AIS/MIA accounted for 821 of the total 6,137. All included patients received curative surgery. After a review of the summarized data we found that only one patient (with MIA) had N1 node metastasis, N2 disease was not found in any of the included patients. In concordance with this, studies that reported 5-year disease free survival (5-year DFS) have almost 100% rate. CONCLUSIONS Our findings indicated that patients with AIS/MIA have good survival prognosis after surgical resection, and that recurrence and lymph node metastasis in these patients is rare. Therefore, we strongly encouraged further studies to determine the role of different lymph node disposition strategies.