Baofu Chen

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.

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.

[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.

Characteristics of lymph node metastasis in resected adenosquamous lung cancer

Abstract The aim of this study was to retrospectively analyze the clinical data of resected adenosquamous lung cancer (ASLC) and to explore the influencing factors and clinicopathological characteristics of the metastasis lymph nodes. A total of 1156 consecutive patients with surgically resected lung cancer from January 2009 to June 2014 were studied. Fifty-four previously diagnosed ASLC patients were re-evaluated by experienced pathologists. IHC and H&E staining were employed to examine the primary focus and metastasis lymph nodes. The relationship between lymph node metastasis and clinicopathological characteristics of ASLC patients was then analyzed and the pathological type of metastasis lymph node was also determined. Forty-nine cases of typical ASLC were included in the study. Of the 49 ASLC patients, 26 cases presented lymph node metastasis. Lymph node metastasis was not associated with gender, smoking, tumor distribution, histological type of primary focus, and preoperative CEA level, but was associated with age ≥ 65 (P < .05) and tumor size ≥ 3 cm (P < .05). Lymph node metastasis adenocarcinoma was the main type in ASLC patients, and was related to the age and tumor size of the primary focus. Further large sample studies are necessary to identify influencing factors and clinicopathological characteristics of metastasis lymph nodes.

Promoter methylation is not associated with FLCN irregulation in lung cyst lesions of primary spontaneous pneumothorax

Germline mutations in FLCN are responsible for ~10% of patients with primary spontaneous pneumothorax (PSP), characterized by multiple lung cysts in the middle/lower lobes and recurrent pneumothorax. These clinical features are also observed in a substantial portion of patients with sporadic PSP exhibiting no FLCN coding mutations. To assess the potential underlying mechanisms, 71 patients with PSP were selected, including 69 sporadic and 2 familial cases, who bared FLCN mutation‑like lung cysts, however, harbored no FLCN protein‑altering mutations. Notably, in a significant proportion of the patients, FLCN irregulation was observed at the transcript and protein levels. Genetic analyses of the cis‑regulatory region of FLCN were performed by sequencing and multiplex ligation‑dependent probe amplification assay. No inheritable DNA defect was detected, with the exception of a heterozygous deletion spanning the FLCN promoter, which was identified in a family with PSP. This mutation caused a reduction in the expression of FLCN in the lung cysts. Pedigree analysis demonstrated that haploinsufficiency of FLCN was pathogenic. To determine whether epigenetic mechanisms may be involved in the irregulation of FLCN, the promoter methylation status was measured in the remainder of the patients. No evidence of FLCN promoter methylation was demonstrated. The present study suggested that FLCN irregulation in lung cysts of PSP is not associated with promoter methylation.