Chengchu Zhu

Mutation analysis of the FLCN gene in Chinese patients with sporadic and familial isolated primary spontaneous pneumothorax

Primary spontaneous pneumothorax (PSP) is a common manifestation of Birt–Hogg–Dubé syndrome caused by folliculin gene (FLCN) mutation, which is also found in isolated familial PSP cases. A complete genetic analysis of FLCN was performed in 102 unrelated Chinese patients with isolated PSP and 21 of their family members. Three novel mutations (c.924_926del, c.1611_1631del and c.1740C>T) and a previously reported mutation (c.1733insC) were identified in five familial and five sporadic PSP patients. Of the 21 family members of patients with PSP including 3 previous considered as sporadic, 4 (19%) had history of at least one episode of PSP and 9 (43%) were FLCN mutant carriers without PSP. Seven of the nine (78%) mutant carriers had pulmonary cysts detected by high‐resolution computed tomography (HRCT). Although c.924_926del and c.1611_1631del were found in eight patients from the same geographic district, haplotype analysis demonstrated that they did not share the same affected haplotype, thus excluding common ancestry. This study first demonstrates that FLCN mutation contributes to not only familial but also ‘apparently sporadic’ patients with isolated PSP. It suggests that mutation analysis and HRCT scan may be recommended for first‐degree family members of PSP patients with FLCN mutations, irrespective of their family history status of PSP.

Elevated expression of CCAT2 is associated with poor prognosis in esophageal squamous cell carcinoma

CCAT2, a novel long non‐coding RNAs (lncRNAs), is found to promote the metastasis and invasion of colon, lung, and breast cancers. This study aimed to investigate the level of CCAT2 in esophageal squamous cell carcinoma (ESCC) and to elucidate its clinical significance.

Modified McKeown minimally invasive esophagectomy for esophageal cancer: a 5-year retrospective study of 142 patients in a single institution.

Background To achieve decreased invasiveness and lower morbidity, minimally invasive esophagectomy (MIE) was introduced in 1997 for localized esophageal cancer. The combined thoracoscopic-laparoscopic esophagectomy (left neck anastomosis, defined as the McKeown MIE procedure) has been performed since 2007 at our institution. From 2007 to 2011, our institution subsequently evolved as a high-volume MIE center in China. We aim to share our experience with MIE, and have evaluated the outcomes of 142 patients. Methods We retrospectively reviewed 142 consecutive patients who had presented with esophageal cancer undergoing McKeown MIE from July 2007 to December 2011. The procedure, surgical outcomes, disease-free and overall survival of these cases were assessed. Results The average total procedure time was 270.5±28.1 min. The median operation time for thoracoscopy was 81.5±14.6 min and for laparoscopy was 63.8±9.1 min. The average blood loss associated with thoracoscopy was 123.8±39.2 ml, and for laparoscopic procedures was 49.9±14.3 ml. The median number of lymph nodes retrieved was 22.8. The 30 day mortality rate was 0.7%. Major surgical complications occurred in 24.6% and major non-surgical complications occurred in 18.3% of these patients. The median DFS and OS were 36.0±2.6 months and 43.0±3.4 months respectively. Conclusions Surgical and oncological outcomes following McKeown MIE for esophageal cancer were acceptable and comparable with those of open-McKeown esophagectomy. The procedure was both feasible and safe – properties that can be consolidated by experience.

FLCN intragenic deletions in Chinese familial primary spontaneous pneumothorax

Primary spontaneous pneumothorax (PSP) is a significant clinical problem, affecting tens of thousands patients annually. Germline mutations in the FLCN gene have been implicated in etiology of familial PSP (FPSP). Most of the currently identified FLCN mutations are small indels or point mutations that detected by Sanger sequencing. The aim of this study was to determine large FLCN deletions in PSP families that having no FLCN sequence‐mutations. Multiplex ligation‐dependent probe amplification (MLPA) assays and breakpoint analyses were used to detect and characterize the deletions. Three heterozygous FLCN intragenic deletions were identified in nine unrelated Chinese families including the exons 1–3 deletion in two families, the exons 9–14 deletion in five families and the exon 14 deletion in two families. All deletion breakpoints are located in Alu repeats. A 5.5 Mb disease haplotype shared in the five families with exons 9–14 deletion may date the appearance of this deletion back to approximately 16 generations ago. Evidences for founder effects of the other two deletions were also observed. This report documents the first identification of founder mutations in FLCN, as well as expands mutation spectrum of the gene. Our findings strengthen the view that MLPA analysis for intragenic deletions/duplications, as an important genetic testing complementary to DNA sequencing, should be used for clinical molecular diagnosis in FPSP.

Outcomes of Video-Assisted Thoracic Surgical Decortication in 274 Patients with Tuberculous Empyema

OBJECTIVE The present work aimed to retrospectively assess the outcomes associated with decortication by video-assisted thoracic surgery (VATS) in patients with tuberculous empyema. METHODS Patients (n = 274) who underwent decortication by VATS for surgical management of pleural empyema between January 2000 to 2010 were included. Pre-, intra-, and postoperative characteristics were observed for all patients, which were followed up for 12 months to evaluate surgical outcomes such as postoperative complications and disease recurrence. RESULTS No patients required conversion to thoracotomy, and no death or postoperative bleeding was reported. The mean operation time was 104.5 ± 20.4 min, with 271.5 ± 41.3 ml intraoperative blood loss and median length of hospital stay of 7.2 ± 3 .4 days. Of the 274 patients, 262 were followed up for 12 months; 26 (9.9%) patients showed complications, including incomplete lung re-expansion (11 patients) and persistent air leak (6 patients). While early disease recurrence was observed in 3 (1.1%) patients after surgery, late recurrence was reported for 6 (2.3%) individuals. Interestingly, the complication rate was much higher in patients with chronic empyema (15/34, 44.1%) than in subjects with acute empyema (11/228, 4.8%). CONCLUSIONS Decortication by VATS decreases postsurgical complications, and results in decreased disease recurrence. This study demonstrated improved outcomes by decortication by VATS, even in patients with stage III tuberculous empyema.

[Expression and its clinical significance of eIF4E in non-small cell lung cancer].

BACKGROUND AND OBJECTIVE precious studies proven that the overexpression of eukaryotic translation initiation factor 4E (eIF4E) in a variety of solid tumors has linked with malignant tumorigenesis, invasion and metastasis. The aim of this work is to explore the expression of eIF4E and its clinical significance in non-small cell lung cancer (NSCLC) through immunohistochemical method. METHODS seventy NSCLC specimens were constructed into tissue microarray, simultaneously took 19 cases adjacent tissues and 20 cases normal lung tissue as control, all performed using immunohistochemistry (Envision). RESULTS eIF4E expression in NSCLC was significantly higher than that in adjacent tissues and normal lung tissues, statistically significant difference between the groups. The eIF4E positive expression in lymph node metastasis group was significantly higher than that in no-lymph node metastasis. eIF4E protein positive expression of WD/MD cancer tissue was significantly lower than those in PD/ND cancer tissue. There were no significant differences of positive expression of eIF4E with the tumor diameter, age, smoking status, gender of NSCLC patients (P > 0.05). CONCLUSIONS there were highly over expression rate of eIF4E, and closely correlated with lymphnode metastasis in NSCLC, which implies that the eIF4E expression may be related to tumorgenesis, invasion and metastasis of lung cancer. eIF4E may be a new marker for lung cancer and objective indicators assessing the development of lung cancer.

Association of polymorphisms in translesion synthesis genes with prognosis of advanced non‐small‐cell lung cancer patients treated with platinum‐based chemotherapy

Translesion synthesis (TLS) polymerases enable cells to bypass or overcome DNA damage during DNA replication and contributes to genomic instability and cancer. Inhibition of the expression of TLS genes enhances the sensitivity of cancer cells to cisplatin. This study aimed to investigate the relationship between single nucleotide polymorphisms (SNPs) in the TLS genes and clinical outcome of advanced non‐small‐cell lung cancer (NSCLC) patients treated with platinum‐based chemotherapy.

[Corrigendum] Knockdown of eukaryotic translation initiation factor 4E suppresses cell growth and invasion, and induces apoptosis and cell cycle arrest in a human lung adenocarcinoma cell line

Eukaryotic translation initiation factor 4E (eIF4E) was shown to be upregulated in malignant human tumors. To assess the effect of downregulation of eIF4E on the prolifera- tion and invasiveness of a human lung adenocarcinoma cell line, a short hairpin (sh)RNA targeting eIF4E was constructed and transfected into A549 human lung adenocarcinoma cells. The expression of eIF4E was determined by reverse tran- scription-quantitative polymerase chain reaction and western blotting. Cell viability was assessed using a Cell Counting kit-8, and apoptosis levels and cell cycle distribution were assessed by flow cytometry. Invasiveness was assessed using Transwell chambers. Transfection of the A549 cells with eIF4E targeting shRNA reduced the mRNA and protein expression levels of eIF4E by >70% 48 and 72 h following transfection, and eIF4E targeting shRNA-transfected cells were significantly less viable compared with the cells transfected with scrambled shRNA. The rate of apoptosis was also significantly increased, significantly more cells were in the G 0/G1 phase and fewer were in the S phase, indicating cell cycle arrest. The fraction of transfected cells migrating across Transwell inserts were also reduced. In conclusion, inhibition of eIF4E suppressed cell growth and invasion, induced apoptosis and cell cycle arrest, suggesting that eIF4E may be a potential therapeutic target in lung adenocarcinoma.

Left atrial concomitant surgical ablation for treatment of atrial fibrillation in cardiac surgery: A meta-analysis of randomized controlled trials

Introduction Surgical ablation is a generally established treatment for patients with atrial fibrillation undergoing concomitant cardiac surgery. Left atrial (LA) lesion set for ablation is a simplified procedure suggested to reduce the surgery time and morbidity after procedure. The present meta-analysis aims to explore the outcomes of left atrial lesion set versus no ablative treatment in patients with AF undergoing cardiac surgery. Methods A literature research was performed in six database from their inception to July 2017, identifying all relevant randomized controlled trials (RCTs) comparing left atrial lesion set versus no ablative treatment in AF patient undergoing cardiac surgery. Data were extracted and analyzed according to predefined clinical endpoints. Results Eleven relevant RCTs were included for analysis in the present study. The prevalence of sinus rhythm in ablation group was significantly higher at discharge, 6-month and 1-year follow-up period. The morbidity including 30 day mortality, late all-cause mortality, reoperation for bleeding, permanent pacemaker implantation and neurological events were of no significant difference between two groups. Conclusions The result of our meta-analysis demonstrates that left atrial lesion set is an effective and safe surgical ablation strategy for AF patients undergoing concomitant cardiac surgery.

Inter-relationship among myasthenia gravis, WHO histology, and Masaoka clinical stage and effect on surgical methods in patients with thymoma: a retrospective cohort study

Background The aim of study is to analyze the inter-relationship among WHO histology, myasthenia gravis (MG) and Masaoka stage and to assess the feasibility of thoracoscopic surgery in thymoma patients. Methods Data from 142 consecutive thymoma patients from January 2009 to March 2016 were retrospectively reviewed in our institution. Histological classification and clinical staging were assessed by WHO histology criteria and Masaoka stage. We investigated the clinical characteristics, inter-relationship among WHO histology, MG and Masaoka stage, and compared the feasibility and safety of thoracoscopic thymectomy by comparison of open thymectomy. Results Among 142 patients, the incidence of MG was 29.6%. Compared with A and AB-type thymomas, a higher prevalence of advance clinical stage was in B1 to C-type thymomas (37/63 vs. 9/43, P<0.001), and there was an increased trend of Masaoka stage from A to C-type thymomas (P<0.001). The incidence of MG was significantly higher in AB, B1 and B2-type thymomas than other type thymomas (23/63 vs. 6/44, P=0.009) and in early Masaoka clinical stage than advanced Masaoka clinical stage (29/80 vs. 12/59, P=0.042). Thoracoscopic surgery could significantly decrease blood loss in patients with (104.06±137.36 vs. 350.91±560.79 mL, P=0.001) or without MG (91.90±77.70 vs. 266.32±292.60 mL, P=0.02), with comparable complications. Additionally, thoracoscopic surgery could achieve an equal effect on the remission of MG with open surgery (7/11 vs. 10/14, P=1.000), and Masaoka stage was significantly associated with the remission of MG after thymectomy. Conclusions Our study suggests that WHO histology, MG, and Masaoka stage interrelate with one another, and Masaoka stage is an important prognostic factor in remission of MG after thymectomy in thymoma patients. Thoracoscopic thymectomy could achieve an equal efficacy to open thymectomy and should be recommended as a routine surgery for patients with early Masaoka stage.