Tumor grade-associated genomic mutations in Chinese patients with non-small cell lung cancer.

Background: Lung cancer is the most prevalent cancer worldwide and accounts for approximately 20% of cancer-related death in China every year. High-grade lung cancer poses a significant threat to patients, and developing a novel treatment for these patients requires an understanding of its underlying mechanism. Methods: Chinese patients with lung cancer were enrolled. The tumor samples were collected by surgery or puncture and applied for next-generation sequencing. A panel of pan-cancer genes was targeted, and the sequencing depth was set to over 1,000 to improve the sensitivity of detecting mutations. Short-length mutations (substitution, insertion, and deletion), copy number variation, and gene fusion were called. Gene mutations were compared between low-grade, middle-grade, and high-grade tumors using Fisher's exact test. The enriched pathways in each grade of tumors were also inferred. Results: The study included 173 Chinese patients with non-small cell lung cancer, of whom 98 (56.6%) patients were female and 75 (43.4%) were male, with a mean age of 56.8 years. All patients were microsatellite stable; 66.4% were at the early stages (Stages 0, I, and II) with a tumor mutational burden of approximately 2.5 (confidence interval = [0, 48.3]). Compared to low-grade tumors, high-grade tumors had a significantly higher percentage of mutations in TP53 (75.9% vs 34.4%, p = 1.86e-3) and PIK3CA (24.1% vs. 0%, p = 3.58e-3). Pathway analysis found that high-grade tumors were enriched with mutations in bacterial invasion of epithelial cells (31% vs. 0%, p = 5.8e-4), Epstein-Barr virus infection (79.3% vs. 37.5%, p = 1.72e-3), and the Wnt signaling pathway (75.9% vs. 34.4%, p = 1.91e-3). High-grade tumors had a significantly higher tumor mutational burden than low-grade tumors (p-value = 0.0017). However, actionable mutations with high-level evidence were lower in high-grade tumors. Conclusion: Patients with high-grade tumors from lung cancer may be more affected by bacteria and Epstein-Barr virus than low-grade tumors. High-grade tumors were specially mutated in TP53 and PIK3CA and may benefit more from immunotherapy. Further research on the underlying mechanism of high-grade lung cancer is necessary to develop new therapeutic options. Lung cancer, tumor grade, genomic mutations, Epstein-Barr virus, pathway analysis.

[Surgical treatment of primary malignant tumors of the trachea and main bronchus].

OBJECTIVE: To explore the clinical experience of surgical treatment of primary malignant tumors of the trachea and main bronchus. METHODS: The clinicopathological data of 18 patients with primary malignant tumors of the trachea and main bronchus surgically treated from February 1994 to August 2007 were reviewed retrospectively. The surgical management included sleeve tracheal resection in 8 cases, lower trachea and carina resection with carina reconstruction in 4 cases, local enucleation of the tumor in 4 cases, left or right carino-pneumonectomy and carina reconstruction in 2 cases, and resection of the tracheal or bronchial tumor and reconstruction of the airway under cardiopulmonary bypass in 6 cases. RESULTS: Among the 18 cases, there were 7 adenoid cystic carcinomas, 9 squamous cell carcinomas, 1 lymphoepithelial-like carcinoma and 1 follicular non-Hodgkin lymphoma. All the cases recovered well except one who died of endotracheal bleeding and asphyxia at the 10(th) postoperative day. CONCLUSION: Surgical resection is the most effective treatment for primary malignant tumors of the trachea and main bronchus. The selection of operation modes should be individualized according to patients' condition. Both complete resection and safety should be taken into consideration simultaneously.

[Experimental study of myocardial protective effect of cardiac arrest versus beating heart during open heart surgery].

OBJECTIVE: To investigate the myocardial protective effects of beating heart versus heart arrest in goats undergoing open heart surgery with cardiopulmonary bypass (CPB). METHODS: Eighteen healthy and homologous goats were randomly divided into three groups: groupI (n=6), with intermittent cold crystalloid cardioplegia; group II (n=6), with continuous warm blood cardioplegia; group III (n=6), with beating heart. Animals in group II and group III were operated with mild hypothermic CPB. The changes in malondialdehyde (MDA) in the myocardium of the right ventricles and atrial natriuretic peptide (ANP) in venous blood were measured respectively. The myocardial tissues were examined for ultrastructural changes. RESULTS: In group I, contents of MDA and ANP rose significantly during CPB, especially when blood was reperfused routinely. While in group II and group III, the levels were lower than those in group I at the same time points. There was no difference in the values between group II and group III. Ultrastructural changes were distinctly seen in group I, while they were mild in group II and group III. CONCLUSION: Continuous warm blood cardioplegia to keep the heart beating during operation can prevent ischemia-reperfusion injury and protect heart better.