Quanpeng Li

Two-year follow-up for 45 patients with achalasia who underwent peroral endoscopic myotomy

OBJECTIVES Achalasia is an oesophageal disorder characterized by abnormalities of peristalsis and impaired swallowing-induced relaxation. The therapeutic approach at present remains palliative. Peroral endoscopic myotomy (POEM) is thought to be less invasive and to maintain the function of the lower oesophageal sphincter postoperatively. However, the effects of POEM still need to be evaluated and understood. METHODS We analysed the outcome for 45 achalasia patients who underwent POEM in our centre, described the details of surgery and evaluated the effects by 4 s integrated relaxation pressure (4s-IRP). All patients were followed up for at least 2 years and were assessed by the dysphagia score, the Eckardt score, oesophageal manometry and the gastro-oesophageal reflux disease (GERD) Q-questionnaire. According to the new Chicago classification of oesophageal motility using high-resolution manometry, the patients were diagnosed and classified into types I, II and III. RESULTS The average age of the patients was 46.32 ± 19.04 years (range 26-72 years), and the ratio of women to men was 1.81. All patients were suffering from dysphagia; more than half of them experienced regurgitation. The data revealed that POEM considerably reduced the 4s-IRP, dysphagia score and Eckardt score postoperatively (all P < 0.05). The patients with type III achalasia had higher values of 4s-IRP than the others (type I, P = 0.025; type II, P = 0.022) before treatment and at 3 months after treatment (type I, P = 0.028; type II, P = 0.047). In type I patients, GERD symptoms were more likely to appear at 24 months after POEM than in type II and III patients (P = 0.001 and P < 0.001, respectively). CONCLUSIONS Peroral endoscopic myotomy provides definite relief of symptoms in these patients with achalasia and offers them long-term therapeutic benefit. Considering the risks of surgery, we believe that POEM is a better choice than surgery for achalasia patients and carries lower risk. However, our study is a preliminary exploration; therefore, larger-scale studies are needed for further research on POEM.

Endoscopic transpancreatic septotomy as a precutting technique for difficult bile duct cannulation

AIM To evaluate the technique of transpancreatic septotomy (TS) for cannulating inaccessible common bile ducts in endoscopic retrograde cholangiopancreatography (ERCP). METHODS Between May 2012 and April 2013, 1074 patients were referred to our department for ERCP. We excluded 15 patients with previous Billroth II gastrectomy, Roux-en-Y anastomosis, duodenal stenosis, or duodenal papilla tumor. Among 1059 patients who underwent ERCP, there were 163 patients with difficult bile duct cannulation. Pancreatic guidewire or pancreatic duct plastic stent assistance allowed for successful ERCP completion in 94 patients. We retrospectively analyzed clinical data from 69 failed patients (36 transpancreatic septotomies and 33 needle-knife sphincterotomies). RESULTS Of the 69 patients who underwent precut papillotomy, common bile duct cannulation was successfully achieved in 67. The success rates in the TS and needle knife sphincterotomy (NKS) groups were 97.2% (35/36) and 96.9% (32/33), respectively, which were not significantly different (P > 0.05). Complications occurred in 11 cases, including acute pancreatitis (n = 6), bleeding (n = 2), and cholangitis (n = 3). The total frequency of complications in the TS group was lower than that in the NKS group (8.3% vs 24.2%, P < 0.05). CONCLUSION Pancreatic guidewire or pancreatic duct plastic stent assistance improves the success rate of selective bile duct cannulation in ERCP. TS and NKS markedly improve the success rate of selective bile duct cannulation in ERCP. TS precut is safer as compared with NKS.

LINC00152: A pivotal oncogenic long non-coding RNA in human cancers

In recent years, increasing evidence has shown the potential role of long non‐coding RNAs (lncRNAs) in multiple cancers. Deregulation of lncRNAs was detected being closely associated with many kinds of tumours where they can act as a tumour suppressor or accelerator. LINC00152 was identified as an oncogene involved in many kinds of cancers, such as gastric cancer, hepatocellular carcinoma, colon cancer, gallbladder cancer and renal cell carcinoma. Moreover, inhibition of LINC00152 can suppress proliferation, migration and invasion of the cancer cells. Increasing evidence has showed that LINC00152 may act as a diagnostic and prognostic biomarker for the above‐mentioned cancers. In our review, we summarize the recent research progress of the expression and role of LINC00152 in various kinds of cancers.

Gastrotracheal fistula: Treatment with a covered elf-expanding Y-shaped metallic stent

A 67-year-old man had a sev-ere cough and pulmonary infection for 1 wk before seeking evaluation at our hospital. He had undergone esophagectomy with gastric pull-up and radiotherapy for esophageal cancer 3 years previously. After admission to our hospital, gastroscopy and bronchoscopy revealed a fistulous communication between the posterior tracheal wall near the carina and the upper residual stomach. We measured the diameter of the trachea and bronchus and determined the site and size of the fistula using multislice computed tomography and gastroscopy. A covered self-expanding Y-shaped metallic stent was implanted into the trachea and bronchus. Subsequently, the fistula was closed completely. The patient tolerated the stent well and had good palliation of his symptoms.

The diagnostic/prognostic potential and molecular functions of long non-coding RNAs in the exosomes derived from the bile of human cholangiocarcinoma

Cholangiocarcinoma (CCA) is an aggressive malignancy associated with unfavorable prognosis, and it’s difficult to diagnose and no effective treatments are available. Long non-coding RNAs (lncRNAs) play important roles in tumorigenesis and metastasis. Intact lncRNAs from exosomes have sparked much interest as potential biomarker for the non-invasive analysis of disease. Here, via exosome sequencing on lncRNAs, GO analysis, KEGG pathway and co-expression analysis, receiver operating characteristic curve and survival analyses, we found that, compared with control group, lncRNAs of ENST00000588480.1 and ENST00000517758.1 showed significantly increased expressions in CCA group. Moreover, area under the curve (AUC) was increased to 0.709 when combined the two lncRNAs, they had a sensitivity and specificity of 82.9% and 58.9% respectively. Further, the higher levels of the two lncRNAs showed a significantly increasing trend with the advancement of cancer TNM stages, and prognosticated a poor survival. In addition, KEGG pathway analysis showed that the most significant difference term was “p53 signaling pathway” (KEGG ID: hsa04115, p: 0.001). The altered lncRNAs and their target genes were included to reconstruct a co-expression network. These altered lncRNAs were mainly related to cellular processes, environmental information processing and organismal systems, etc. Collectively, our findings provided the potential roles of lncRNAs of ENST00000588480.1 and ENST00000517758.1 in CCA, and implicated these lncRNAs as potential diagnostic and therapeutic targets for CCA.

NK4 gene therapy inhibits HGF/Met-induced growth of human cholangiocarcinoma cells.

Background and ObjectiveNK4, a competitive antagonist for hepatocyte growth factor (HGF) and the Met receptor, is a bifunctional molecule that acts as an HGF antagonist and an angiogenesis inhibitor. The objective of this study was to investigate the anti-tumor effects of NK4 on the cholangiocarcinoma (CCA) cell line HuCC-T1.MethodsWe assessed the effects of NK4 on proliferation, invasion, migration, and cell cycle progression in mock-transfected HuCC-T1 clones, empty-vector-transfected clones of HuCC-T1 (Hu-Em), and NK4-transfected clones of HuCC-T1 (Hu-NK4), with HuCC-T1 cells serving as the control cells. Correlated with these effects on cellular functions, the mRNA levels of cyclin D1 and cyclin A were monitored using reverse transcription (RT)-PCR and quantitative PCR, and the corresponding protein levels were monitored using Western blotting. In addition, Met phosphorylation and the activity of its important downstream signaling targets protein kinase B (Akt) and glycogen synthase kinase (GSK)-3β were evaluated by Western blotting.ResultsOur data indicate that cell proliferation, invasion, and cell cycle progression of the three types of clones were essentially the same, while these processes were stimulated by HGF in HuCC-T1 and Hu-Em cells, but not in Hu-NK4 cells. Moreover, when stimulated with HGF, the increases in mRNA levels of cyclin D1 and cyclin A were accompanied by corresponding increases in protein levels, and the phosphorylation of Met, Akt, and GSK-3β was upregulated in HuCC-T1 and Hu-Em cells, compared to the levels in the Hu-NK4 cells.ConclusionsThese findings suggest that NK4 gene therapy inhibits HGF/Met-induced growth of human CCA cells by arresting cell cycle progression. It also interferes with Met activation and the downstream phosphatidylinositol-3-kinase/Akt/GSK-3β signaling pathway.

NK4 regulates 5-fluorouracil sensitivity in cholangiocarcinoma cells by modulating the intrinsic apoptosis pathway

The aim of the present study was to investigate the role of NK4, an antagonist for hepatocyte growth factor (HGF) and the Met receptor, in regulating the response of cholangiocarcinoma (CCA) cells to 5-fluorouracil (5-FU). We established the CCA cell line, HuCC-T1, to produce abundant NK4 (Hu-NK4). Cell proliferation, cell cycle distribution, apoptosis, 5-FU metabolism and intracellular signaling were examined. There were no significant differences in the mRNA levels of thymidylate synthase, thymidine phosphorylase and dihydropyrimidine dehydrogenase between the mock-transfected control Hu-Em cells and Hu-NK4 cells, suggesting that NK4 expression does not alter 5-FU metabolism. Moreover, cell cycle analysis showed that 5-FU treatment caused a decrease in the proportion of cells in the G2/M phase while NK4 gene expression had little effect on the cell cycle distribution. However, 5-FU-induced apoptosis was significantly increased in the Hu-NK4 cells when compared to that in the Hu-Em cells. Further investigation revealed that NK4 gene expression enhanced 5-FU-induced caspase-3 and caspase-9 activation, and that the apoptosis of cells was associated with modulation of expression of the Bcl-2 family members. Furthermore, western blot analysis revealed that both NK4 and 5-FU were inhibitors for HGF-induced phosphorylation of Met, but they may be independent factors. Collectively, these results suggest that following 5-FU treatment in CCA cell lines, NK4 was involved in apoptosis induction through the intrinsic mitochondrial pathway. This indicates that NK4 may be an important mediator of 5-FU-induced cell death. Moreover, downregulation of NK4 in response to 5-FU may represent an intrinsic mechanism of resistance to this anticancer drug.

Endoscopic retrieval of 28 foreign bodies in a 100-year-old female after attempted suicide

Foreign body ingestion is a common emergency situation in children with one or a few objects having been ingested. Here we report our experience using endoscopic retrieval in a female centenarian with dyspnea and foreign bodies in the esophagus. She attempted suicide by swallowing 26 coins and two other foreign bodies. A gastroscope was used to remove all foreign bodies in the lower esophagus. In total, 26 coins, one ferrous ring and one cylindrical plastic object were retrieved. To our knowledge, this is the first clinical report on retrieval of so many foreign bodies in a single case.

Long non-coding RNA PVT1 promotes cell proliferation and migration by silencing ANGPTL4 expression in cholangiocarcinoma

Cholangiocarcinoma (CCA) is the most common biliary tract malignancy, with a low survival rate and limited treatment options. Long non-coding RNAs (lncRNAs) have recently been verified to have significant regulatory functions in many kinds of human cancers. It was discovered in this study that the lncRNA PVT1, whose expression is significantly elevated in CCA, could be a molecular marker of CCA. Experiments indicated that PVT1 knockdown greatly inhibited cell migration and proliferation in vitro and in vivo. According to RNA sequencing (RNA-seq) analysis, PVT1 knockdown dramatically influenced target genes associated with cell angiogenesis, cell proliferation, and the apoptotic process. RNA immunoprecipitation (RIP) analysis demonstrated that, by binding to epigenetic modification complexes (PRC2), PVT1 could adjust the histone methylation of the promoter of ANGPTL4 (angiopoietin-like 4) and, thus, promote cell growth, migration, and apoptosis progression. The data verified the significant functions of PVT1 in CCA oncogenesis, and they suggested that PVT1 could be a target for CCA intervention.

Epigenetic silencing of tumor suppressor gene CDKN1A by oncogenic long non-coding RNA SNHG1 in cholangiocarcinoma.

Cholangiocarcinoma (CCA) is the as the most frequently observed biliary tract malignancy, which has low survival rate in addition to constrained treatment options; nevertheless, the fundamental molecular phenomenon underlying malignant progression of CCA is quite ambiguous. Recently long non-coding RNAs (lncRNAs) have been found to have significant regulatory functions in several human cancers. Herein, we have figured out that lncRNA SNHG1, with substantially enhanced expression in CCA, is capable of acting as the oncogenic molecule of CCA. As revealed by our data, SNHG1 knockdown extensively inhibited CCA cell migration as well as proliferation in vitro and in vivo. In addition, in accordance with the findings of the RNA-Seq analysis, SNHG1 knockdown exhibited a significant impact on the target genes that were linked to cell migration and regulation of cell proliferation, in addition to the apoptotic phenomenon. In a mechanistic manner, we also showed that SNHG1 bound to the histone methyltransferase enhancer of the zeste homolog 2 (EZH2, which is regarded as the catalytic subunit of the polycomb repressive complex 2 (PRC2), which is an extremely conserved protein complex regulating gene expression with the help of methylating lysine 27 on histone H3), specifying the histone alteration pattern on the target genes, including CDKN1A, and, as a result, altered the CCA cell biology. These data verified a major function of the epigenetic regulation of SNHG1 in CCA oncogenesis, in addition to its likely function as a target for CCA interruption.