MUC13 promotes lung cancer development and progression by activating ERK signaling.

Mucin 13 (MUC13) is a glycoprotein that is expressed on the cell surface and participates in the tumorigenesis of multiple malignancies, including pancreatic cancer, colorectal cancer and renal cancer. However, to the best of our knowledge, the expression levels and function of MUC13 in lung cancer progression have not yet been demonstrated. Therefore, the present study examined the expression pattern and regulatory role of MUC13 in lung cancer tumorigenesis. The results demonstrated that MUC13 was highly expressed in lung cancer tissues and cell lines compared with that in normal tissues and cell lines. Functionally, knockdown of MUC13 inhibited cell proliferation and enhanced the apoptosis of A549 and NCI-H1650 lung cancer cells. Furthermore, silencing of MUC13 suppressed the migration and invasion of lung cancer cells. Additionally, a xenograft tumor model demonstrated that knockdown of MUC13 delayed the development of the lung cancer xenograft and suppressed the expression of proliferation marker Ki-67 in tumor tissues. Mechanistically, MUC13 activated the ERK signaling pathway by enhancing the phosphorylation of ERK, JNK and p38 in lung cancer tissues compared with that in normal tissues. Knockdown of MUC13 inhibited the phosphorylation of ERK/JNK/p38 in A549 and NCI-H1650 cells. Overall, these findings suggested that MUC13 could act as an oncogenic glycoprotein to accelerate the progression of lung cancer via abnormal activation of the ERK/JNK/p38 signaling pathway and might serve as a therapeutic target for lung cancer treatment.

Hypoxia induces chemoresistance of esophageal cancer cells to cisplatin through regulating the lncRNA-EMS/miR-758-3p/WTAP axis.

Hypoxia contributes significantly to the development of chemoresistance of many malignancies including esophageal cancer (EC). Accumulating studies have indicated that long non-coding RNAs play important roles in chemotherapy resistance. Here, we identified a novel lncRNA-EMS/miR-758-3p/WTAP axis that was involved in hypoxia-mediated chemoresistance to cisplatin in human EC. Hypoxia induced the expressions of lncRNA EMS and WTAP, and reduced the expression of miR-758-3p in EC cell line ECA-109. In addition, the expressions of EMS and WTAP were required for the hypoxia-induced drug resistance to cisplatin in EC cells, while overexpression of miR-758-3p reversed such chemoresistance. The targeting relationships between EMS and miR-758-3p, as well as miR-758-3p and WTAP, were verified by luciferase-based reporter assays and multiple quantitative assays after gene overexpression/knockdown. Moreover, we found significant correlations between tumor expressions of these molecules. Notably, higher levels of EMS/WTAP, or lower levels of miR-758-3p in tumors predicted worse survivals of EC patients. Furthermore, in a xenograft mouse model, targeted knockdown of EMS and WTAP in ECA-109 cells markedly attenuated the resistance of tumors to cisplatin treatments. Our study uncovers a critical lncRNA-EMS/miR-758-3p/WTAP axis in regulating hypoxia-mediated drug resistance to cisplatin in EC.

A modified pleurodesis in treating postoperative chylothorax.

BACKGROUND: To introduce a modified pleurodesis as an effective treatment for refractory chylothorax and to develop a novel insight for its mechanism. METHODS: Patients who underwent thoracic surgery at West China Hospital or its affiliated hospitals between 2010 and 2015 and who subsequently experienced chylothorax that was not resolved by conventional treatment, received daily pleurodesis involving 100 mL 50% glucose and 20 mL 1% lidocaine. The chest tube was clamped after 7 days of pleurodesis, regardless of drainage amount. If no remarkable pulmonary atelectasis was detected within 2 days, the chest tube was removed. All patients were followed up with for at least 3 months after discharge from our hospital. RESULTS: Among the 34 patients, 10 did not experience an increase in the pleural fluid after the chest tube was clamped. Minor effusion increase occurred in 21 patients, while encapsulated effusion occurred in 3. In 23 patients among the latter 24 patients, pleural fluid was gradually absorbed and disappeared spontaneously. One patient suffered chylothorax recurrence after discharge but successfully recovered after the second round of modified pleurodesis. Several patients suffered from electrolyte imbalance, weakness, and dyspnea; all were cured by plasma infusion and other symptomatic treatments. CONCLUSIONS: Being safe and effective for patients with postoperative refractory chylothorax, our modified pleurodesis enhanced the process of chemical pleurodesis and could remove the chest tube right after the extensive adhesion formed instead requiring a wait for drainage decrease. This method can thus shorten the period of hospitalization and reduce fluid loss compared with traditional pleurodesis.

Non-intubated video-assisted thoracoscopic surgery under loco-regional anaesthesia for thoracic surgery: a meta-analysis.

OBJECTIVES: The short-term feasibility and safety of non-intubated video-assisted thoracoscopic surgery under loco-regional anaesthesia for thoracic surgery remains unknown. Therefore, we conducted a meta-analysis to provide evidence for the short-term efficacy and safety profile of non-intubated video-assisted thoracoscopic surgery under loco-regional anaesthesia for thoracic surgery. METHODS: We performed a systematic literature search in PubMed, Embase, Cochrane Library databases and Google Scholar, as well as American Society of Clinical Oncology to identify relevant studies comparing non-intubated video-assisted thoracoscopic surgery under loco-regional anaesthesia with conventionally intubated video-assisted thoracoscopic surgery under general anaesthesia, dated up to 31 August 2015. Data concerning global in-operating room time, hospital stays, rate of postoperative complications and perioperative mortality were extracted and analysed. We conducted a meta-analysis of the overall results and two subgroup analyses based on study design (a meta-analysis of randomized controlled trials and a second meta-analysis of observational studies). RESULTS: Four randomized controlled trials and six observational studies with a total of 1283 patients were included. We found that in the overall analysis, patients treated with non-intubated video-assisted thoracoscopic surgery under loco-regional anaesthesia achieved significantly shorter global in-operating room time [weighted mean difference = -41.96; 95% confidence interval (CI) = (-57.26, -26.67); P < 0.001] and hospital stays [weighted mean difference = -1.24; 95% CI = (-1.46, -1.02); P < 0.001] as well as a lower rate of postoperative complications [relative risk = 0.55; 95% CI = (0.40, 0.74); P < 0.001] than patients treated with intubated video-assisted thoracoscopic surgery under general anaesthesia. Subgroup meta-analyses based on study design achieved the same outcomes as overall analysis. In our meta-analysis, no perioperative mortality was observed in patients treated with non-intubated video-assisted thoracoscopic surgery under loco-regional anaesthesia. CONCLUSIONS: Non-intubated video-assisted thoracoscopic surgery under loco-regional anaesthesia for thoracic surgery proved to be feasible and safe. Future multicentre and well-designed randomized controlled trials with longer follow-up are needed to confirm and update the findings of our study, as well as the long-term efficacy of non-intubated video-assisted thoracoscopic surgery under loco-regional anaesthesia.

Mutations of C-reactive protein (CRP) -286 SNP, APC and p53 in colorectal cancer: implication for a CRP-Wnt crosstalk.

C-reactive protein (CRP) is an established marker of inflammation with pattern-recognition receptor-like activities. Despite the close association of the serum level of CRP with the risk and prognosis of several types of cancer, it remains elusive whether CRP contributes directly to tumorigenesis or just represents a bystander marker. We have recently identified recurrent mutations at the SNP position -286 (rs3091244) in the promoter of CRP gene in several tumor types, instead suggesting that locally produced CRP is a potential driver of tumorigenesis. However, it is unknown whether the -286 site is the sole SNP position of CRP gene targeted for mutation and whether there is any association between CRP SNP mutations and other frequently mutated genes in tumors. Herein, we have examined the genotypes of three common CRP non-coding SNPs (rs7553007, rs1205, rs3093077) in tumor/normal sample pairs of 5 cancer types (n = 141). No recurrent somatic mutations are found at these SNP positions, indicating that the -286 SNP mutations are preferentially selected during the development of cancer. Further analysis reveals that the -286 SNP mutations of CRP tend to co-occur with mutated APC particularly in rectal cancer (p = 0.04; n = 67). By contrast, mutations of CRP and p53 or K-ras appear to be unrelated. There results thus underscore the functional importance of the -286 mutation of CRP in tumorigenesis and imply an interaction between CRP and Wnt signaling pathway.

Early recurrence and death after esophagectomy in patients with esophageal squamous cell carcinoma.

BACKGROUND: The aim of this retrospective study is to analyze recurrence and death within 1 year after esophagectomy in patients with esophageal carcinoma. METHODS: The records of 533 consecutive patients with esophageal squamous cell carcinoma who underwent surgery from January 2002 to January 2005 were reviewed. Patients who died of recurrence within 1 year after operation (group A) were compared with patients who survived more than 5 years without any recurrence (group B). Their clinicopathologic characteristics were evaluated by univariate and multivariate analyses. RESULTS: The overall 1-year and 5-year survival rates for the entire cohort were 76.1% and 32.3%, respectively, with the follow-up rate of 93.4%. Of the 119 patients who died within 1 year after the esophagectomy, local recurrence or distant metastasis or both were documented in 62 patients (52.1%). The radicality of resection, size of tumor, radicality of resection, grade of differentiation, depth of invasion, status of lymph node metastasis, number of lymph node metastases, and marginal status were shown by univariate analysis to be the significant prognostic factors. By multivariate analysis, they were also the independent prognostic factors, except for the size of tumor and the radicality of resection. CONCLUSIONS: More than half of early death in esophageal squamous cell carcinoma patients after esophagectomy were still tumor recurrence related, especially hematogeneous spreading. The grade of differentiation, depth of invasion, lymph node metastasis, number of lymph node metastases, and marginal status are valuable prognostic factors in predicting early death.

[Long-term result of total versus partial fundoplication following esophagomyotomy for primary esophageal motor disorders].

OBJECTIVE: To compare the long-term results of total and partial fundoplication on esophagus myotomy. METHODS: From January 1978 to October 1998, 64 patients with achalasia or diffuse esophageal spasm underwent esophagomyotomy and antireflux operation via left thoracotomy. Twenty-one patients underwent Nissen total fundoplication (Nissen group) and 43 patients underwent Belsey Marker IV partial fundoplication (Belsey group). Clinical, radiologic, radionuclide transit, manometric, 24-hour pH monitoring and endoscopic assessments were performed before and after the operation. RESULTS: There was no operative death and major complications for either group. At over 6 years follow-up and compared to Belsey group, patients in Nissen group revealed a higher frequency of dysphagia (P = 0.025) and more radionuclide material retention (P = 0.044). Both operative procedures reduced the lower esophageal sphincter pressure gradient. However, in Nissen group, the esophageal diameter observed on radiology was significantly increased from 3.9 cm preoperatively to 5.5 cm postoperatively (P = 0.012), while it kept the same for Belsey group (from 5.4 to 5.3 cm, P = 0.695). Reoperation in order to relieve the recurrent dysphagia and esophageal obstruction was performed on 8 patients in Nissen group and 1 in Belsey group (P < 0.01). CONCLUSION: When treating achalasia or diffuse esophageal spasm by esophageal myotomy and an antireflux operation, a total fundoplication is not appropriate, whereas a partial fundoplication provides proper antireflux effect without significant esophageal emptying difficulty.

[Analysis of lymph node metastasis in the thoracic esophageal squamous cell carcinoma].

OBJECTIVE: To assess the metastatic frequency in different groups of lymph nodes and its influencing factors of the thoracic esophageal squamous cell carcinoma (ESCC) in order to determine the extent of lymphadenectomy during esophagectomy. METHODS: The clinical data of 730 patients with ESCC who underwent esophagectomy and lymphadenectomy were analyzed retrospectively. RESULTS: Of 730 patients, 166 had metastasis to the para-esophageal lymph nodes (22.7%), 90 to the left gastric artery lymph nodes (12.3%), 67 to the lymph nodes around gastric cardia, and 15 to the subcrinal lymph nodes (2.1%). Univariate analysis showed that metastasis to the subcrinal lymph node was positively correlated with the length and differentiation of tumor (P < 0.05), but it was not correlated with any the above parameters when analyzed by multivariate analysis. The metastasis to the para-esophageal lymph node was positively correlated with the length, invasion depth and differentiation of tumor by univariate and multivariate analysis (P < 0.05). The metastasis to the lymph nodes around gastric cardia and metastasis to left gastric artery lymph nodes were positively correlated with the position and invasion depth of tumor by univariate and multivariate analysis (P < 0.05). CONCLUSION: Lymph nodes of the para-esophagus, gastric cardia and left gastric artery usually have high frequency to harber mestastasis, therefore, it was suggested that the lymph nodes in these groups should be dissected during esophagectormy with two-field lymphadenectomy for thoracic esophageal squamous cell carcinoma. Whereas for those patients with the lesion < 3 cm in length or with tumor invasion confined within the esophageal wall or with a lesion located at the upper or lower third of the thoracic esophagus, the subcrinal lymph nodes may not be necessarily dissected.

Long-term result of total versus partial fundoplication after esophagomyotomy for primary esophageal motor disorders.

BACKGROUND: The selection of the type of fundoplication or the necessity for an added fundoplication after esophagomyotomy (Heller's operation) for the treatment of achalasia remains controversial. The present retrospective study was designed to compare the long-term results of total and partial fundoplication on the myotomized esophagus. METHODS: Between 1978 and 1998, a total of 64 consecutive patients with achalasia or diffuse esophageal spasm underwent esophagomyotomy and an antireflux operation via a left thoracotomy approach. Twenty-one had a total fundoplication (Nissen Group) during the period 1978-1983. After 1984 and until 1998, the remaining 43 patients were treated with addition of a Belsey Mark IV partial fundoplication (Belsey Group) to protect the myotomized esophagus. Clinical, radiologic, radionuclide transit, manometric, 24-h pH monitoring, and endoscopic assessments were obtained before and after the operation. RESULTS: There were no operative deaths or major complications in either group. After 6 years of follow-up the Belsey group was compared to the Nissen group. A higher frequency of dysphagia (7/18 versus 3/31; p=0.025), more barium stasis (9/13 versus 10/27; p=0.056), and increased radionuclide material retention (52.4% versus 29.2%; p=0.044) were observed in the Nissen group. These findings were confirmed by endoscopy, which showed increased esophageal lumen dilation (10/15 versus 8/26; p=0.026) and more frequent food retention (11/15 versus 6/26; p=0.002). Functionally, both operations successfully reduced the lower esophageal sphincter pressure gradient (from 23.8 to 7.7 mmHg for the Nissen group, and from 27.4 to 8.2 mmHg for the Belsey group; p=0.656). In the Nissen group, the esophageal diameter observed on radiology increased from 3.9 cm preoperatively to 5.5 cm postoperatively (p=0.012), whereas it remained identical for the Belsey group (ranging from 5.4 cm to 5.3 cm; p=0.695). Reoperation to relieve recurrent dysphagia and esophageal retention was necessary in 8 patients from the Nissen group and in 1 patient from the Belsey group (p<0.001). CONCLUSIONS: When treating achalasia or diffuse esophageal spasm by esophageal myotomy and an antireflux operation, a total fundoplication adds too much resistance to allow esophageal emptying and is considered as inappropriate. A partial fundoplication provides proper antireflux effects without causing significant esophageal emptying difficulties.

Clinical application of layered anastomosis during esophagogastrostomy.

The aim of this study was to compare the operative results in regard to reducing anastomotic leakage and stricture formation using a newly designed layered manual esophagogastric anastomosis versus a stapler esophagogastrostomy versus the conventional hand-sewn whole-layer anastomosis after resection for esophageal or gastric cardiac carcinoma. From January 2004 to September 2006, a total of 1024 patients with esophageal or gastric cardia carcinoma underwent a layered esophagogastric anastomosis with the assistance of a three-leaf clipper in a single university medical center. The mucosal layers of the esophagus and stomach were sutured continuously with 4/0 Vicryl plus antibacterial suture (polyglyconate). From May 2002 to December 2003, there were also 170 patients and 69 patients who underwent stapler and conventional whole-layer anastomosis, respectively; they served as control groups. The results were analyzed retrospectively. The operative mortality rate was 0.7% in the layered group compared to 5.9% and 7.2% for the stapler group and the whole-layer group (p < 0.01), The anastomotic leakage rates were 0%, 3.5%, and 5.8% for the layered group, stapler group, and whole-layer group, respectively (p < 0.01). All patients were followed postoperatively. Six patients in the layered group (0.6%) developed mild stricture formation compared to 16 patients in stapled group (9.9%) and 5 patients in the conventional whole-layer group (7.8%) (p < 0.01). The application of layered esophagogastric anastomosis could reduce the incidence of anastomotic leakage and stricture after esophagectomy compared with the stapler and whole-layer manual anastomoses. It is easy to apply and could be used as an alternative for esophagogastric anastomosis after resection for esophageal or cardiac carcinoma.