• OGD
• early upper gastro-intestinal cancer
• key performance indicators
• quality

Gastroesophageal reflux disease (GERD) is a common chronic disease of the digestive system. In recent years, due to the better understanding of Helicobacter pylori (H. pylori) and the wide clinical application of proton pump inhibitors, the rate of H. pylori infection is declining, while the incidence of GERD is increasing. This phenomenon suggests a possible relationship between H. pylori infection and the incidence of GERD. The pathogenesis of GERD is related to the dysfunction of the protective esophageal barrier, esophageal motility, gastric acidity and gastric emptying, and H. pylori infection may affect these factors to exert an impact on the incidence of GERD.

• Gastroesophageal reflux disease
• Helicobacter pylori
• Atrophic gastritis

The process of carcinogenesis is tightly regulated by antioxidant enzymes and matrix degrading enzymes, namely, matrix metalloproteinases (MMPs). Degradation of extracellular matrix (ECM) proteins like collagen, proteoglycan, laminin, elastin and fibronectin is considered to be the prerequisite for tumor invasion and metastasis. MMPs can degrade essentially all of the ECM components and, most MMPs also substantially contribute to angiogenesis, differentiation, proliferation and apoptosis. Hence, MMPs are important regulators of tumor growth both at the primary site and in distant metastases; thus the enzymes are considered as important targets for cancer therapy. The implications of MMPs in cancers are no longer mysterious; however, the mechanism of action is yet to be explained. Herein, our major interest is to clarify how MMPs are tied up with gastrointestinal cancers. Gastrointestinal cancer is a variety of cancer types, including the cancers of gastrointestinal tract and organs, i.e., esophagus, stomach, biliary system, pancreas, small intestine, large intestine, rectum and anus. The activity of MMPs is regulated by its endogenous inhibitor tissue inhibitor of metalloproteinase (TIMP) which bind MMPs with a 1:1 stoichiometry. In addition, RECK (reversion including cysteine-rich protein with kazal motifs) is a membrane bound glycoprotein that inhibits MMP-2, -9 and -14. Moreover, α2-macroglobulin mediates the uptake of several MMPs thereby inhibit their activity. Cancerous conditions increase intrinsic reactive oxygen species (ROS) through mitochondrial dysfunction leading to altered protease/anti-protease balance. ROS, an index of oxidative stress is also involved in tumorigenesis by activation of different MAP kinase pathways including MMP induction. Oxidative stress is involved in cancer by changing the activity and expression of regulatory proteins especially MMPs. Epidemiological studies have shown that high intake of fruits that rich in antioxidants is associated with a lower cancer incidence. Evidence indicates that some antioxidants inhibit the growth of malignant cells by inducing apoptosis and inhibiting the activity of MMPs. This review is discussed in six subchapters, as follows.

• Gastrointestinal cancer
• Matrix metalloproteinase
• Tissue inhibitor of matrix metalloproteinases
• Reactive oxygen species
• Antioxidants

AIM: To investigate whether P162 enhances radiosensitivity of esophageal carcinoma cell line Eca109 by inhibiting Hedgehog signaling transcription factor Gli-1.

METHODS: Eca109 cells (a total dose of 60 Gy) to induce radioresistant esophageal carcinoma cell line Eca109R. The inhibition of cell proliferation was determined by Cell Counting Kit assay. The expression of Gli-1 was detected by immunohistochemistry and immunofluorescence. HE staining was employed to observe the changes in cell morphology. Western blot was employed to determine the nuclear expression of Gli-1 and dynamic changes of Gli-1 in irradiated Eca109 cells. Apoptosis was determined by flow cytometry. The following four groups were included in the experiments: untreated cells, P162-treated cells, irradiated cells, and P162-treated irradiated cells. Eca109 and Eca109R cells were included in each group.

RESULTS: Eca109R possessing certain radiation resistance displayed lower ability of growth inhibition than Eca109 cells. Nuclear Gli-1 expression was significantly higher in Eca109R cells than in Eca109 cells (0.45 ± 0.01 vs 0.32 ± 0.01, P < 0.0001). On days 2 and 14 after irradiation, the nuclear expression of Gli-1 in Eca109 cells was higher than that in control cells (0.0882 ± 0.011, 0.3560 ± 0.015 vs 0.2552 ± 0.0103, P < 0.05). In both Eca109R and Eca109 cells, the nuclear expression of Gli-1 was reduced after treatment with 20 µmol/L P162 [0.2553 ± 0.011, 0.2578 ± 0.014 (non-irradiation); 0.1324 ± 0.012, 0.0595 ± 0.011(2 d after irradiation); 0.1741 ± 0.013, 0.2397 ± 0.112 (14 d after irradiation), P < 0.0001]. P162 combined with radiotherapy facilitated cells apoptosis.

CONCLUSION: Nuclear Gli-1 expression is related to radioresistance of esophageal cancer cells. P162 enhances radiosensitivity of Eca109 cell possibly by inhibiting Gli-1 expression and promoting apoptosis.

• Esophageal carcinoma cell
• Hedgehog
• Gli-1
• P162
• Radioresistance

AIM: To evaluate the effects of combined thoracoscopic-laparoscopic esophagectomy (TLE) versus open esophagectomy (OE) in the management of esophageal cancer.

METHODS: Eligible studies were identified from electronic databases including Medline, Embase, OVID, Cochrane Library, Springerlink, CNKI, WanFang Data and VIP. We screened the retrieved literature according to the inclusion and exclusion criteria and performed a Meta-analysis with the software RevMan 5.2 after identification of the relevant data.

RESULTS: A total of 1448 patients from 14 studies were included for the analysis, including 735 patients who underwent TLE and 713 patients who underwent OE. TLE was associated with less blood loss, fewer respiratory complications and shorter length of hospital stay. However, TLE had longer operative time. There was no significant difference in the incidence of anastomotic leak or the number of lymph nodes harvested (P > 0.05 for both) between the two groups.

CONCLUSION: TLE for esophageal cancer offers results as good as or better than those with open esophagectomy. TLE is associated with reduced perioperative complications and shortened length of hospital stay.

• Esophageal cancer
• Esophagectomy
• Thoracoscopy
• Laparoscopy
• Meta-analysis

AIM: To investigate a classification of endocytoscopy (ECS) images in Barrett’s esophagus (BE) and evaluate its diagnostic performance and interobserver variability.

METHODS: ECS was applied to surveillance endoscopic mucosal resection (EMR) specimens of BE ex-vivo. The mucosal surface of specimen was stained with 1% methylene blue and surveyed with a catheter-type endocytoscope. We selected still images that were most representative of the endoscopically suspect lesion and matched with the final histopathological diagnosis to accomplish accurate correlation. The diagnostic performance and inter-observer variability of the new classification scheme were assessed in a blinded fashion by physicians with expertise in both BE and ECS and inexperienced physicians with no prior exposure to ECS.

RESULTS: Three staff physicians and 22 gastroenterology fellows classified eight randomly assigned unknown still ECS pictures (two images per each classification) into one of four histopathologic categories as follows: (1) BEC1-squamous epithelium; (2) BEC2-BE without dysplasia; (3) BEC3-BE with dysplasia; and (4) BEC4-esophageal adenocarcinoma (EAC) in BE. Accuracy of diagnosis in staff physicians and clinical fellows were, respectively, 100% and 99.4% for BEC1, 95.8% and 83.0% for BEC2, 91.7% and 83.0% for BEC3, and 95.8% and 98.3% for BEC4. Interobserver agreement of the faculty physicians and fellows in classifying each category were 0.932 and 0.897, respectively.

CONCLUSION: This is the first study to investigate classification system of ECS in BE. This ex-vivo pilot study demonstrated acceptable diagnostic accuracy and excellent interobserver agreement.

• Endocytoscopy
• Barrett’s esophagus
• Dysplasia
• Esophageal adenocarcinoma
• Interobserver agreement

• Adenocarcinoma/pathology
• Adenocarcinoma/surgery
• Barrett Esophagus/classification
• Barrett Esophagus/pathology
• Barrett Esophagus/surgery
• Clinical Competence
• Esophageal Neoplasms/pathology
• Esophageal Neoplasms/surgery
• Esophagoscopy/methods
• Esophagus/pathology
• Esophagus/surgery
• Humans
• Image Enhancement
• Mucous Membrane/pathology
• Observer Variation
• Pilot Projects
• Predictive Value of Tests
• Reproducibility of Results
• Staining and Labeling
• Video Recording

AIM: To assess esophageal motility after esophageal endoscopic submucosal dissection (ESD).

METHODS: Twelve patients (6 men and 6 women) aged 53-64 years (mean age, 58 years) who underwent regular examination 3-12 mo after esophageal ESD for neoplasms of the esophageal body were included in this study. The ESD procedure was performed under deep sedation using a combination of propofol and fentanyl, and involved a submucosal injection to lift the lesion and use of a dual-knife and an insulated-tip knife to create a circumferential incision around the lesion extending into the submucosa. Esophageal motility was examined using a high-resolution manometry system. Dysphagia was graded using a five-point scale according to the Mellow and Pinkas scoring system. Patient symptoms and the results of esophageal manometry were then analyzed.

RESULTS: Of the 12 patients enrolled, 1 patient had grade 2 dysphagia, 1 patient had grade 1 dysphagia, and 3 patients complained of sporadic dysphagia. Ineffective esophageal motility was observed in 5 of 6 patients with above semi-circumference of resection extension. Of these 5 patients, 1 patient complained of grade 2 dysphagia (with esophageal stricture), one patient complained of grade 1 dysphagia, and 3 patients complained of sporadic dysphagia. Normal esophageal body manometry was observed in all 6 patients with below semi-circumference of resection extension. The 6 patients with normal esophageal motility did not complain of dysphagia.

CONCLUSION: Extensive esophageal ESD may cause esophageal dysmotility in some patients, and might also have an influence on dysphagia although without esophageal stricture.

• Esophageal neoplasm
• Endoscopic submucosal dissection
• Dysphagia
• Ineffective esophageal motility
• Esophageal manometry

• Dissection/adverse effects
• Esophageal Motility Disorders/diagnosis
• Esophageal Motility Disorders/etiology
• Esophageal Motility Disorders/physiopathology
• Esophageal Neoplasms/physiopathology
• Esophageal Neoplasms/surgery
• Esophagectomy/adverse effects
• Esophagectomy/methods
• Esophagoscopy/adverse effects
• Esophagus/physiopathology
• Esophagus/surgery
• Female
• Gastrointestinal Motility
• Humans
• Male
• Manometry
• Middle Aged
• Risk Factors
• Severity of Illness Index
• Time Factors
• Treatment Outcome

AIM: To investigate the feasibility and safety of the treatment of an upper gastrointestinal (GI) submucosal tumor with endoscopic submucosal dissection (ESD).

METHODS: A total of 20 patients with esophageal and gastric submucosal tumors emerged from the muscular layer identified by endoscopic ultrasonography were collected from January 2009 to June 2010. Extramural or dumbbell-like lesions were excluded by an enhanced computerized tomography (CT) scan. All patients had intravenous anesthesia with propofol and then underwent the ESD procedure to resect these submucosal tumors. The incision was closed by clips as much as possible to decrease complications, such as bleeding or perforation, after resection of the tumor. All the specimens were collected and evaluated by hematoxylin, eosin and immunohistochemical staining, with antibodies against CD117, CD34, desmin, α-smooth muscle actin and vimentin to identify the characteristics of the tumors. Fletch’s criteria was used to evaluate the risk of gastrointestinal stromal tumors (GISTs). All patients underwent a follow-up endoscopy at 3, 6 and 12 mo and CT scan at 6 and 12 mo.

RESULTS: The study group consisted of 5 men and 15 women aged 45-73 years, with a mean age of 60.2 years. Three tumors were located in the esophagus, 9 in the gastric corpus, 4 in the gastric fundus, 3 lesions in the gastric antrum and 1 in the gastric angulus. Apart from the one case in the gastric angulus which was abandoned due to being deeply located in the serosa, 94.7% (18/19) achieved complete gross dissection by ESD with operation duration of 60.52 ± 30.32 min. The average maximum diameter of tumor was 14.8 ± 7.6 mm, with a range of 6 to 30 mm, and another lesion was ligated by an endoscopic ligator after most of the lesion was dissected. After pathological and immunohistochemical analysis, 12 tumors were identified as a GI stromal tumor and 6 were leiomyoma. Mitotic count of all 12 GIST lesions was fewer than 5 per 50 HPF and all lesions were at very low (9/12, 75.0%) or low risk (3/12, 25.0%) according to Fletch’s criteria. Procedure complications mainly included perforation and GI bleeding; perforation occurred in 1 patient and conservative treatment succeeded by a suturing clip and no post-operative GI bleeding occurred. All patients were followed up for 6.5 ± 1.8 mo (range, 3-12 mo) by endoscopy and abdominal CT. Local recurrence and metastasis did not occur in any patient.

CONCLUSION: ESD shows promise as a safe and feasible technique to resect esophageal and gastric submucosal tumors and the incidence of complications was very low. Clinical studies with more subjects and longer follow-up are needed to confirm its treatment value.

• Endoscopic submucosal dissection
• Stromal tumors
• Leiomyoma
• Upper gastrointestinal tract