Zhizheng Ge

Predictive role of capsule endoscopy on the insertion route of double-balloon enteroscopy.

BACKGROUND AND STUDY AIMS Double-balloon enteroscopy (DBE) has been suggested to be more efficient if based on the results of screening video capsule endoscopy (VCE). We evaluated the utility of VCE for predicting the best insertion route of DBE for the evaluation and treatment of small-bowel lesions. PATIENTS AND METHODS Results of studies of patients with complete VCE examination of the small bowel and with findings confirmed by DBE are reported. A location index of lesions found on VCE was defined as the time from the pylorus to the lesion as a percentage of the time from the pylorus to the ileocecal valve. Based on our previous retrospective evaluation, a cut-off value of 0.6 was adopted, and the oral or anal approach was selected when the index was < or = 0.6 or > 0.6, respectively. RESULTS Data from 60 patients who underwent both VCE and DBE examinations and in whom the capsule reached the cecum were evaluated. Lesions shown on VCE were all reached by the first DBE procedures (41 orally and 19 anally). Based on the time index cut-off value of 0.6, the accuracy of selecting the insertion route of DBE was 100 %. CONCLUSION DBE is an effective approach for confirming VCE results. In patients with complete small-bowel investigation by VCE, the best insertion route for DBE can be reliably indicated using a time index based on the VCE records.

Derivation and Validation of a Prediction Rule for Estimating Advanced Colorectal Neoplasm Risk in Average-Risk Chinese

No prediction rule is currently available for advanced colorectal neoplasms, defined as invasive cancer, an adenoma of 10 mm or more, a villous adenoma, or an adenoma with high-grade dysplasia, in average-risk Chinese. In this study between 2006 and 2008, a total of 7,541 average-risk Chinese persons aged 40 years or older who had complete colonoscopy were included. The derivation and validation cohorts consisted of 5,229 and 2,312 persons, respectively. A prediction rule was developed from a logistic regression model and then internally and externally validated. The prediction rule comprised 8 variables (age, sex, smoking, diabetes mellitus, green vegetables, pickled food, fried food, and white meat), with scores ranging from 0 to 14. Among the participants with low-risk (≤3) or high-risk (>3) scores in the validation cohort, the risks of advanced neoplasms were 2.6% and 10.0% (P < 0.001), respectively. If colonoscopy was used only for persons with high risk, 80.3% of persons with advanced neoplasms would be detected while the number of colonoscopies would be reduced by 49.2%. The prediction rule had good discrimination (area under the receiver operating characteristic curve = 0.74, 95% confidence interval: 0.70, 0.78) and calibration (P = 0.77) and, thus, provides accurate risk stratification for advanced neoplasms in average-risk Chinese.

The study on the role of inflammatory cells and mediators in post-infectious functional dyspepsia

Abstract Objective. Functional dyspepsia is a common gastrointestinal disorder. The pathogenesis of functional dyspepsia remains unclear. Functional dyspepsia may begin after a bout of gastroenteritis (post-infectious functional dyspepsia) or de novo (nonspecific functional dyspepsia). The aim of this study was to investigate the prevalence and probable mechanisms of post-infectious functional dyspepsia. Material and methods. Functional dyspepsia patients with a history of unsanitary food intake and acute gastroenteritis 6-12 months ago were enrolled. 13C-UBT confirmed absence of H. pylori infection. Controls consisted of healthy nondyspeptic volunteers and patients with nonspecific functional dyspepsia. Gastric biopsies were used for routine histology, immunohistochemistry, electron microscopy, ELISA, HPLC assays and Western blot examination. Results. Eighty-five subjects were entered including 35 with post-infectious functional dyspepsia, 30 with nonspecific functional dyspepsia, and 20 healthy controls. The number of mast cells in post-infectious functional dyspepsia and nonspecific functional dyspepsia were significantly greater than that in healthy controls. The number of enterochromaffin cells (ECs) in post-infectious functional dyspepsia was significantly higher than those in nonspecific functional dyspepsia or in healthy controls. The number of mast cells and ECs increased with the density of chronic inflammatory cells. The release of histamine and 5-hydroxytryptamine from gastric mucosa of post-infectious functional dyspepsia patients was significantly greater than those from nonspecific functional dyspepsia or healthy controls. Tryptase protein expression was higher in post-infectious functional dyspepsia and nonspecific functional dyspepsia than in healthy controls. The histological score of chronic gastric inflammation was greater in post-infectious functional dyspepsia versus patients with nonspecific functional dyspepsia or healthy controls. Electron microscopy showed secreting granules in the cytoplasm of both mast cells and ECs. The number of activated mast cells and Ecs at a distance of < 5 μm of nerve fibers were significantly greater in post-infectious functional dyspepsia versus nonspecific functional dyspepsia or controls. Conclusions. Dyspepsia may occur after an acute onset of gastroenteritis in a part of patients. Potent chemicals derived from mast cells and ECs, including histamine, tryptase and 5-hydroxytryptamine may be involved in the pathogenesis of post-infectious functional dyspepsia.

A Prospective Study on Evaluating the Diagnostic Yield of Video Capsule Endoscopy Followed by Directed Double-Balloon Enteroscopy in Patients with Obscure Gastrointestinal Bleeding

AimsVideo capsule endoscopy (VCE) and double-balloon enteroscopy (DBE) are two novel methods for examining the small bowel and could be complementary to each other. The aim of the present study is to prospectively evaluate the diagnostic yield of VCE followed by a directed DBE in patients with obscure gastrointestinal (GI) bleeding.MethodsPatients with obscure gastrointestinal bleeding for a complete VCE examination were involved in the study. DBE was recommended after a negative or indeterminate finding of VCE. The diagnostic and follow-up data were collected for analysis.ResultsA total of 190 patients with a complete VCE examination were enrolled in the study. The overall positive detection rate for small-bowel disease in the VCE group was 86.8% (165/190), while 63.7% (121/190) patients were definitely diagnosed. Fifty-one patients with indeterminate (44 cases) and negative (seven cases) findings of first VCE underwent DBE procedures. A total of 18 patients with negative VCE findings refused the further examination. DBE demonstrated a positive finding in 66.7% (34/51) patients, 33 from indeterminate group and one from the negative group. Following an unrevealing DBE, at surgical follow-up, three further negative DBE procedures were documented. The overall diagnostic yield was 88.9%, including 121 diagnoses made by VCE alone and 48 by both VCE and DBE (confirmed at surgery or other treatments). The negative predictive value (NPV) and positive predictive value (PPV) of DBE in indeterminate VCE were 81.8 and 100%, respectively.ConclusionsCapsule endoscopy followed by directed double-balloon enteroscopy is a good strategy for investigating the causes of obscure GI bleeding and especially in confirming indeterminate and negative findings from VCE.

Folic Acid Prevents the Initial Occurrence of Sporadic Colorectal Adenoma in Chinese Older than 50 Years of Age: A Randomized Clinical Trial

Colorectal adenoma (CRA) is the precursor lesion of colorectal cancer (CRC). Several agents have been shown to be effective in the chemoprevention of CRA recurrence, but there has been little research on its primary prevention. Participants older than 50 years with no adenomas were recruited for our study and randomized to receive either 1 mg/day folic acid supplement or treatment without folic acid. After 3 years of follow-up, plasma folate and colonoscopy were evaluated. Seven hundred ninety-one participants (91.98%) completed the study. CRA occurred in 64 (14.88%) participants in the folic acid group and 132 (30.70%) in the control group [unadjusted risk ratio (RR), 0.49; 95% confidence interval (CI), 0.37–0.63; P < 0.01]; left-sided adenoma (unadjusted RR, 0.54; 95% CI, 0.38–0.76; P = 0.001) and advanced CRA (unadjusted RR, 0.36; 95% CI, 0.16–0.81; P = 0.01) were most common. There was no significance difference in the occurrence of three or more adenomas (unadjusted RR, 0.70; 95% CI, 0.36–1.77; P = 0.38) or right-sided adenoma (unadjusted RR, 0.55; 95% CI, 0.30–1.00; P = 0.07) between the two groups. Participants with low plasma folate may have a high risk of CRA. In conclusion, primary prevention with 1 mg/day folic acid supplementation could reduce the incidence of CRA, especially left-sided and advanced disease in those with no previous adenomas. People with differing baseline plasma folate levels should be given individualized treatment. Those with low plasma folate should be encouraged to take adequate supplements; plasma folate should be elevated to an effective therapeutic level, which may reduce the incidence of CRA. Cancer Prev Res; 6(7); 744–52. ©2013 AACR.

Assessment of capsule endoscopy scoring index, clinical disease activity, and C‐reactive protein in small bowel Crohn's disease

Small bowel Crohns disease (SBCD) patients are frequently assessed by capsule endoscopy (CE), which enables direct visualization of small bowel mucosal abnormalities; however, the correlations between CE scoring index (CESI), C‐reactive protein (CRP), and disease activity indices remain undefined. We aimed to determine correlations between the CESI, clinical disease activity indices, and CRP in SBCD patients.

Role of vascular endothelial growth factor in angiodysplasia: an interventional study with thalidomide.

Background and Aim:  The pathogenesis of angiodysplasia is still not fully understood and effective therapy is not available. Thalidomide was reported to be effective in the treatment of angiodysplasia, but the mechanisms underlying its activity are, as yet, unknown. We aimed to investigate the expression of vascular endothelial growth factor (VEGF) in angiodysplasia tissues, and the role of hypoxia‐inducible factor‐1α (HIF‐1α) and basic fibroblast growth factor (bFGF) on VEGF expression in human umbilical vein endothelial cells (HUVEC). Additionally, we aimed to study the role of thalidomide in these parameters.

LRG1 modulates epithelial-mesenchymal transition and angiogenesis in colorectal cancer via HIF-1α activation

BackgroundLeucine-rich-alpha-2-glycoprotein 1 (LRG1) has been reported to be involved in several tumors, whether it participates in colorectal cancer (CRC) progression remains unclear. Here, we investigated the biological function and underlying molecular mechanisms of LRG1 in CRC.MethodsThe mRNA and protein levels of LRG1 were assessed in CRC tissues through RT-PCR and immunohistochemistry, respectively. HCT116 and SW480 cells were treated with LRG1 siRNA, control siRNA, or recombinant LRG1. Transwell invasion assays and wound healing assays were performed to evaluate the invasion and migration of CRC cells. Epithelial-to-mesenchymal transition (EMT) markers of E-cadherin, VDR, N-cadherin, α-SMA, Vimentin and Twist1 were detected by RT-PCR and western blot. Enzyme-linked immunosorbent assay was used to measure the secretion level of VEGF-A. Conditioned medium from CRC cells was collected for endothelial cell migration, tube formation and aortic ring sprouting assays.ResultsLRG1 was overexpressed in CRC tissues and associated with cancer aggressiveness. LRG1 was further found to induce the EMT process, as well as CRC cell migration and invasion capacity. In addition, LRG1 promoted VEGF-A expression in CRC cells and contributed to tumor angiogenesis. Furthermore, HIF-1α could be induced by LRG1 in a concentration- and time-dependent manner, which was responsible for LRG1-induced VEGF-A expression and EMT.ConclusionsThe present study suggests that LRG1 plays a crucial role in the progression of CRC by regulating HIF-1α expression, thereby may be a promising therapeutic target of CRC.

A pilot study of endoscopic spray cryotherapy by pressurized carbon dioxide gas for Barrett's esophagus.

BACKGROUND AND STUDY AIMS Endoscopic spray cryoablation is a novel approach for the treatment of Barretts esophagus. However, few studies have reported its efficacy, especially with the use of carbon dioxide (CO (2)). The aim of the current study was to evaluate the short term efficacy and complications using CO (2) in endoscopic cryoablation of Barretts esophagus. METHODS Patients diagnosed with Barretts esophagus underwent monthly stepwise cryoablation with pressurized CO (2) gas, with follow-up esophageal biopsies until complete histological reversal was achieved. Responses were analyzed with an intention-to-treat analysis according to complete response for intestinal metaplasia (CR-IM), which was defined as the elimination of all intestinal metaplasia including specialized intestinal metaplasia (SIM), subsquamous SIM, and dysplasia with intestinal metaplasia in the biopsies under narrow-band imaging (NBI). RESULTS In total, 22 patients were enrolled, 20 of whom completed the treatment. Two patients declined further ablation after the first cryotherapy session. A total of 44 sessions were performed; a median of 2 sessions per patient (range 1 - 3 sessions) were needed to complete the ablation of Barretts esophagus. No severe complications occurred. Follow-up endoscopies were performed in 20 patients (90.9 %). Two patients (9.1 %) were lost to follow-up. Median follow-up was 10 months (range 6 - 18 months). After cryotherapy, 20 patients (90.9 %) reached CR-IM of Barretts esophagus. Patients underwent a median number of 3 follow-up endoscopies (range 2 - 4) with biopsies. At 6 months, recurrence was evident in three patients (13.6 % of the overall population, 15.0 % of the CR-IM population). One of the three patients developed intestinal metaplasia but no dysplastic change and the other two developed subsquamous SIM. CONCLUSIONS The pressurized CO (2) spray cryotherapy is a relatively effective and safe endoscopic treatment for Barretts esophagus.

Water Exchange Method Significantly Improves Adenoma Detection Rate: A Multicenter, Randomized Controlled Trial.

Objectives:Adenoma detection rate (ADR) is a key colonoscopy quality indicator in Western clinical literature. Our low ADR prompted us to assess novel methods to improve performance. Western retrospective reports suggested that water exchange (WE) could increase ADR. However, most of these studies used pain score or intubation rate as the primary outcome. Here we test the hypothesis that WE significantly increases ADR among Chinese colonoscopists and design a prospective randomized controlled trial using ADR as our primary outcome.Methods:This prospective, randomized controlled trial was performed at six centers in China. Screening, surveillance, and diagnostic cases were randomized to be examined by WE or traditional air insufflation (AI) method. The primary outcome was ADR.Results:From April 2014 to July 2015, 3,303 patients were randomized to WE (n=1,653) and AI (n=1,650). The baseline characteristics were comparable. Overall ADR was 18.3% (WE) and 13.4% (AI) (relative risk 1.45, 95% confidential interval: 1.20–1.75, P<0.001). ADR in screening patients using AI was 25.8% (male) and 15.7% (female). ADR in screening patients aged >50 years old was 29.4% (WE) and 22.9% (AI) (relative risk 1.09, 95% confidential interval: 1.00–1.19, P=0.040). The increase by WE was reproducibly observed in all indication categories, and significant in screening and diagnostic cases. The limitation imposed by the unblinded investigators was mitigated by comparable inspection times in cases without polyps, similar adenoma per positive colonoscopy, and reproducible enhancement of ADR and adenoma per colonoscopy by WE across all eight investigators.Conclusions:This prospective study confirms Western retrospective data that WE significantly improves ADR among Chinese colonoscopists. WE may be superior to AI for screening colonoscopy in China. Colonoscopists elsewhere with low ADR might consider evaluating WE for performance improvement.