Risk Factors for Single and Multiple Recurrences for Endoscopic Retrograde Cholangiopancreatography and Open Choledochotomy in Treating Choledocholithiasis.

Background: There are few studies comparing recurrences between endoscopic retrograde cholangiopancreatography (ERCP) and open choledochotomy (OCT). Aims: To compare the effect of different surgical methods on single and multiple recurrences of choledocholithiasis. Methods: A total of 1255 patients with choledocholithiasis who underwent ERCP or OCT were retrospectively studied. The recurrence of choledocholithiasis was calculated by the Kaplan-Meier method with the log-rank test. Multivariate analyses of recurrent choledocholithiasis were performed by introducing variables with P < 0.20 in univariate analysis into the logistic regression model. Results: A total of 204 (16.7%, 204/1225) patients relapsed. Among the 204 patients, 74.5% relapsed within three years after surgery, of whom 39.7% (81/204) had multiple relapses (≥ 2). The recurrence rate of ERCP (17.2%, 119/692) was higher than that of OCT (15.1%, 85/563), but the difference was not statistically significant. The independent risk factors for a single recurrence of choledocholithiasis were diabetes, stone number ≥ 2, maximum stone diameter ≥ 15 mm, sedentary occupation, the approach of ERCP (EST or EPBD), periampullary diverticulum, primary suture, high-fat diet (postoperative), frequency of weekly vegetable intake (< 4, postoperative), and drinking (postoperative). However, the ERCP approach (EST or EPBD), OCT approach (LCBDE), primary suture, high-fat diet (postoperative), and frequency of weekly vegetable intake (< 4, postoperative) were independent risk factors for multiple recurrences of choledocholithiasis. Conclusion: Patients with choledocholithiasis should be followed up regularly for one to three years after treatment. Stone number ≥ 2, diabetes mellitus, periampullary diverticulum, surgical methods, and lifestyle are all risk factors for the recurrence of choledocholithiasis. ERCP is still the preferred surgical method based on the advantages of low risk of cholangitis recurrence, less hospital stay, minimally invasive surgery, fewer postoperative complications, and easier acceptance by elderly patients. In addition to optimizing the treatment plans, postoperative lifestyle management is also vital.

Histopathological Characteristics and Therapeutic Outcomes of Endoscopic Submucosal Dissection for Gastric High-Grade Intraepithelial Neoplasia.

Background: The endoscopic resection of suspected gastric high-grade intraepithelial neoplasia (HGIN) may incidentally cause the patient to suffer from early gastric cancer (EGC), complicating the subsequent clinical management. Identifying the risk factors for such misstaging may help guide the clinical management. Methods: The information obtained from 123,460 patients, who underwent conventional upper gastrointestinal endoscopy at the First Affiliated Hospital of Nanjing Medical University from January 2010 to December 2015, were retrospectively reviewed. Patients with an initial diagnosis of HGIN underwent endoscopic submucosal dissection (ESD), and received a final diagnosis of EGC. The risk factors for the upgraded pathology and noncurative resection were analyzed. Results: Among the 134 patients initially diagnosed with HGIN, 35 (26.12%) patients were finally diagnosed with EGC after ESD. A lesion size of ≥2 cm (odds ratio [OR] = 5.16, 95% confidence interval [CI] = 2.04-13.05; P < .01), ≤4 biopsies taken (OR = 2.73, 95% CI = 1.15-6.48; P < .05), and the presence of upper gastrointestinal bleeding (UGIB; OR = 15.64, 95% CI = 1.29-189.75; P < .05) were the independent risk factors for upgraded pathology. In addition, patients >65 years old (OR = 0.022, 95% CI = 0.901-6.549; P < .05) or with a lesion size of ≥2 cm (OR = 4.237, 95% CI = 1.650-10.878; P < .01) were more likely to endure the noncurative resection. Conclusion: For suspected gastric HGIN patients, age, lesion size, the number of biopsies, and UGIB should be taken into account before deciding on the ESD.

New genotypes of Helicobacter Pylori VacA d-region identified from global strains.

BACKGROUND: Pathogenesis of Helicobacter Pylori (HP) vacuolating toxin A (vacA) depends on polymorphic diversity within the signal (s), middle (m), intermediate (i), deletion (d) and c-regions. These regions show distinct allelic diversity. The s-region, m-region and the c-region (a 15 bp deletion at the 3'-end region of the p55 domain of the vacA gene) exist as 2 types (s1, s2, m1, m2, c1 and c2), while the i-region has 3 allelic types (i1, i2 and i3). The locus of d-region of the vacA gene has also been classified into 2 genotypes, namely d1 and d2. We investigated the "d-region"/"loop region" through bioinformatics, to predict its properties and relation to disease. One thousand two hundred fifty-nine strains from the NCBI nucleotide database and the dryad database with complete vacA sequences were included in the study. The sequences were aligned using BioEdit and analyzed using Lasergene and BLAST. The secondary structure and physicochemical properties of the region were predicted using PredictProtein. RESULTS: We identified 31 highly polymorphic genotypes in the "d-region", with a mean length of 34 amino acids (9 ~ 55 amino acids). We further classified the 31 genotypes into 3 main types, namely K-type (strains starting with the KDKP motif in the "d-region"), Q-type (strains starting with the KNQT motif), and E-type (strains starting with the ESKT motif) respectively. The most common type, K-type, is more prevalent in cancer patients (80.87%) and is associated with the s1i1m1c1 genotypes (P < .01). Incidentally, a new region expressing sequence diversity (2 aa deletion) at the C-terminus of the p55 domain of vacA was identified during bioinformatics analysis. CONCLUSIONS: Prediction of secondary structures shows that the "d-region" adopts a loop conformation and is a disordered region.

Combination of Probiotics and Salvia miltiorrhiza Polysaccharide Alleviates Hepatic Steatosis via Gut Microbiota Modulation and Insulin Resistance Improvement in High Fat-Induced NAFLD Mice.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) increases the risk of hepatocellular carcinoma, which is currently the leading cause of obesity-related cancer deaths in middle-aged men. METHODS: Probiotics with lipid-lowering function were screened from the fecal microbiota of healthy adults. Polysaccharide from different sources was screened for improving insulin resistance. The combination of probiotics and Salvia miltiorrhiza polysaccharide (LBM) was investigated for alleviating hepatic steatosis. RESULTS: First, Bifidobacterium bifidum V (BbV) and Lactobacillus plantarum X (LpX) were obtained from the fecal microbiota of healthy adults. Second, to improve insulin resistance, a Salvia miltiorrhiza Bunge polysaccharide showing good performance in reducing insulin resistance was obtained. The liver total cholesterol (TC) and total triglyceride (TG) levels and the serum levels of free fatty acid, alanine transaminase, aspartate transaminase, low density lipoprotein cholesterol, TG, and TC can be significantly reduced through supplementation with LpX-BbV (LB) in NAFLD mice. Interestingly, the function of the probiotic LB can be enhanced by S. miltiorrhiza Bunge polysaccharide. Furthermore, the gut microbiota was modulated by LpX-BbV+S. miltiorrhiza Bunge polysaccharide (LBM). The lipopolysaccharide concentration of the LBM group was decreased by 73.6% compared to the NAFLD group. Ultimately, the mRNA concentrations of the proinflammatory cytokines (tumor necrosis factor α, interleukin 1ß [IL-1ß], and IL-6) decreased with LB and LBM treatment. CONCLUSION: The results of this this study indicate that the LBM combination can be used as a therapeutic for ameliorating NAFLD via modulating the gut microbiota and improving insulin resistance.

Endoscopic and Histopathology Characteristics in Patients with Esophageal High-Grade Intraepithelial Neoplasia.

BACKGROUND/AIMS: To correlate the endoscopic characteristics with the histopathology of specimens of esophageal high-grade intraepithelial neoplasia obtained by endoscopic submucosal dissection (ESD). METHODS: This was a retrospective study developed from January 2010 to December 2015. The study included 169 patients who underwent ESD and were diagnosed with esophageal high-grade intraepithelial neoplasia according to endoscopic forceps biopsy, Lugol staining, endoscopic ultrasonography, computed tomography, and Narrow-Band Imaging. The demographic, endoscopic, and histopathologic characteristics were analyzed. RESULTS: A total of 19 cases (11.2%) had a change in diagnosis after histopathology exam and 16 (9.5%) needed a change in established treatment. An increase in the severity of disease was correlated with a lesion size > 2 cm, less than 4 samples in biopsy, and depressed or excavated patterns (p < 0.05). One hundred forty patients (82.8%) underwent curative resection. Lesions with leukoplakia (p < 0.001) and negative Lugol staining (p = 0.028) were independent risk factor for non-curative resection. CONCLUSION: This study confirms that lesion size > 2 cm, depressed and excavated patterns, and ≤4 biopsy samples are independent risk factors for histological grade changes compared to pre-endoscopic treatment diagnosis. Similarly, leukoplakia and no Lugol staining of lesions are independent risk factors for non-curative resection.

Hiwi overexpression does not affect proliferation, migration or apoptosis of liver cancer cells in vitro or in vivo.

Piwi like RNA-mediated gene silencing 1 (Hiwi) is a human homolog of the Piwi gene family that has been reported to be upregulated in hepatocellular carcinoma (HCC). The present study aimed to investigate the role of Hiwi in the initiation and development of HCC in vitro and in vivo. Adenovirus-mediated Hiwi overexpression was established in primary murine hepatocytes and SMMC7721 HCC cells. Cell viability and proliferation were assessed using MTT and EdU assays, respectively. Cell migration was measured using a scratch migration assay. The cell cycle was assessed using flow cytometry, and the expression of genes associated with the epithelial mesenchymal transition (EMT) was assessed using reverse transcription-quantitative polymerase chain reaction. SMMC7721 cells that stably express Hiwi were also generated and injected subcutaneously into the nude mice, and tumor growth was examined. Recombinant adenovirus encoding green fluorescent protein or Hiwi was delivered by injection into the tail vein, and its effect on murine hepatocyte gene expression was studied. The present study revealed that the overexpression of Hiwi did not affect the proliferation or migration of liver cancer cells and failed to suppress perifosine- or doxorubicin-induced apoptosis in vitro. The tumors of mice that were injected with Hiwi-expressing SMMC7721 cells were not significantly larger compared with mice that were injected with control SMMC7721 cells. Hiwi overexpression did not noticeably alter the expression of genes involved in EMT, either in vitro or in vivo. The results of the present study indicate that although expression of Hiwi is associated with HCC development and progression in the clinic, it does not act as an oncogene in liver cancer cells.

Risk factors for intestinal metaplasia in a southeastern Chinese population: an analysis of 28,745 cases.

PURPOSE: To identify risk factors for intestinal metaplasia in a southeastern Chinese population. METHODS: Subjects who underwent upper GI endoscopy and endoscopic biopsy in the First Affiliated Hospital of Nanjing Medical University from 2008 to 2013 were included into this study. Various demographic, geographic, clinical and pathological data were analyzed separately to identify risk factors for intestinal metaplasia. RESULTS: The incidence of intestinal metaplasia differed significantly in 17 municipal areas ranging from 16.79 to 38.56% and was positively correlated with the age range of 40-70 years, male gender, gastric ulcer, bile reflux, Helicobacter pylori infection, atrophic gastritis, dysplasia, gastric cancer, degree of chronic and acute inflammation, and gross domestic product per capita (P < 0.01). Multivariate linear regression analysis indicated that only gross domestic product per capita revealed a significant difference in the incidence of intestinal metaplasia among all factors mentioned. CONCLUSION: This study confirms age, male gender, gastric ulcer, bile reflux, H. pylori infection, severe degree of chronic and acute inflammation to be the risk factors for intestinal metaplasia. We speculate that the gross domestic product per capita of different areas may be a potential independent risk factor impacting the incidence of intestinal metaplasia.

Downward trend in the prevalence of Helicobacter pylori infections and corresponding frequent upper gastrointestinal diseases profile changes in Southeastern China between 2003 and 2012.

This present study aims to determine trends in the prevalence of H. pylori infections in Southeastern China between 2003 and 2012, and investigate corresponding changes in the prevalence of upper gastrointestinal diseases. This retrospective study screened 196,442 patients with a mean age of 47.49 ± 14.47 years (age range 5-100 years) in Southeastern China, and a total of 134,812 cases of an endoscopy-referral patient population with digestive symptoms between 2003 and 2012 were enrolled. Based on esophago-gastro-duodenoscopy and pathology, patients diagnosed with chronic gastritis, peptic ulcer, gastric cancer or reflux esophagitis were included in this study. Basic demographic and clinical characteristics such as H. pylori infection status and endoscopic findings were collected and analyzed. Among the 134,812 subjects, mean prevalence of H. pylori infection was 31.97 %; which demonstrated a linear downward trend from 42.40 to 23.82 % (P < 0.001) at an annual rate of 2 % from 2003 to 2012. Similarly, the prevalence of duodenal and gastric ulcer rapidly decreased from 12.65 to 6.57 % and from 7.51 to 3.78 %, respectively; while the prevalence of gastric cancer (from 3.76 to 2.34 %) did not significantly change in the same time period. In contrast, the prevalence of reflux esophagitis increased from 6.19 to 12.80 %. The progressively decreasing prevalence of H. pylori infections from 2003 to 2012 in Southeastern China appears to be linked with the decline of related upper gastrointestinal diseases and increase of some gastrointestinal motility diseases.

Anatomical predilection of intestinal metaplasia based on 78,335 endoscopic cases.

BACKGROUND/AIMS: Gastric intestinal metaplasia (IM) is an important risk factor for intestinal-type gastric carcinoma, and successful treatment critically depends on its timely detection. In order to guide appropriate endoscopic surveillance, objective knowledge on the anatomical predilection of intestinal metaplasia development is urgently needed. MATERIALS AND METHODS: A total of 78,335 cases who underwent gastroduodenoscopy from 2008 to 2013 in Jiangsu and Anhui provinces in China, were studied. Demographic and clinical characteristics, as well as biopsy location and histological results, were analyzed. RESULTS: This study revealed that intestinal metaplasia incidence was 28.5% in angulus, 20.24% in lesser curvature of the antrum, and 25.48% in corpus; and all these were significantly higher than those observed in other sites (P < 0.01). Histological grading of intestinal metaplasia in the lesser curvature of the antrum and angulus was generally worse than the grading observed in the greater curvature of the antrum. For Helicobacter pylori-positive patients, acute inflammation was more severe in the lesser curvature of the antrum compared with the greater curvature. In the H. Pylori-negative group, both acute and chronic inflammations were more severe in the lesser curvature of the antrum. CONCLUSIONS: The angulus, lesser curvature in the antrum, and corpus are most prone to the development of intestinal metaplasia. Inflammation is most severe in the lesser curvature of the antrum, which corresponds to a higher predilection to develop intestinal metaplasia at this site. The lesser curvature of the antrum and corpus require the most attention during endoscopic biopsy surveillance.

[Prevention of restenosis with a new modified fully-covered retrievable esophageal stent].

OBJECTIVE: To observe and evaluate the effectiveness of a new modified fully-covered retrievable esophageal stent in preventing restenosis at the proximal end of the stent. METHODS: From January 2008 to October 2011, 380 consecutive patients who underwent placement of a conventional stent or a new modified stent for benign or malignant dysphagia were divided into two groups: conventional stent group 193 patients (male 137, female 56) and modified stent group 187 patients (male 125, female 62). The granulation formation and restenosis rate one month after stenting were evaluated. Data such as patient demographics, outcomes and complications were collected. The results were statistically analyzed by Student t test, chi-squared test, Fisher's exact probability or rank sum test. A P-value less than 0.05 was considered statistically significant. RESULTS: All stents were successfully implanted. They were highly effective in palliating dysphagia. The dysphagia score decreased from 3 (1) to 0 (1) in conventional stent group (P < 0.01), and that from 4 (1) to 0 (1) in modified stent group (P < 0.01). The modified stent group were superior to the conventional stent group in severe granulation formation rate (0 vs 4.7% (9/193), P = 0.004) and restenosis rate (2.7% (5/187) vs 7.3% (14/193), P = 0.041) within one month after stenting, and the modified stent was easier to retrieve. Postoperative remission rate of dysphagia, and complications such as chest pain, bleeding, perforation, stent migration had no statistical differences between the two groups (all P > 0.05). CONCLUSIONS: The new modified fully-covered retrievable esophageal stent can significantly reduce granulation formation at the proximal end of the stent. Using of this stent seems to be a better choice in treating patient of dysphagia, with lower restenosis rate and easier to retrieve.

Coordinate increase of telomerase activity and c-Myc expression in Helicobacter pylori-associated gastric diseases.

AIM: To detect the telomerase activity and c-Myc expression in gastric diseases and to examine the relation between these values and Helicobacter pylori (H pylori) as a risk factor for gastric cancer. METHODS: One hundred and seventy-one gastric samples were studied to detect telomerase activity using a telomerase polymerase chain reaction enzyme linked immunosorbent assay (PCR-ELISA), and c-Myc expression using immunohistochemistry. RESULTS: The telomerase activity and c-Myc expression were higher in cancers (87.69% and 61.54%) than in noncancerous tissues. They were higher in chronic atrophic gastritis with severe intestinal metaplasia (52.38% and 47.62%) than in chronic atrophic gastritis with mild intestinal metaplasia (13.33% and 16.67%). In chronic atrophic gastritis with severe intestinal metaplasia, the telomerase activity and c-Myc expression were higher in cases with H pylori infection (67.86% and 67.86%) than in those without infection (21.43% and 7.14%). c-Myc expression was higher in gastric cancer with H pylori infection (77.27%) than in that without infection (28.57%). The telomerase activity and c-Myc expression were coordinately up-regulated in H pylori infected gastric cancer and chronic atrophic gastritis with severe intestinal metaplasia. CONCLUSION: H pylori infection may influence both telomerase activity and c-Myc expression in gastric diseases, especially in chronic atrophic gastritis.

[Coordinated expression of c-Myc and telomerase activity in Helicobacter pylori infected gastric diseases].

OBJECTIVE: To detect the telomerase activity and c-Myc expression in gastric diseases and to examine the relation between these values and Helicobacter pylori (Hp) as a risk factor for gastric cancer. METHODS: 171 gastric samples were studied to detect telomerase activity with telomerase polymerase chain reaction enzyme linked immunosorbent assay and c-Myc expression using immunohistochemistry. RESULTS: Telomerase activity and c-Myc expression were higher in cancers (87.7% and 61.5%) than in noncancerous tissues. Telomerase activity and c-Myc expression were higher in chronic atrophic gastritis with moderate or severe intestinal metaplasia (52.4% and 47.6%) than in chronic atrophic gastritis with mild intestinal metaplasia (13.3% and 16.7%). In chronic atrophic gastritis with moderate or severe intestinal metaplasia, telomerase activity and c-Myc expression were higher in cases with Hp infection (67.9% and 67.9%) than in these without infection (21.4% and 7.1%). c-Myc expression was higher in gastric cancer with Hp infection (77.3%) than that without infection (28.6%). Telomerase activity and c-Myc expression were coordinately up-regulated in Hp infected gastric cancer and chronic atrophic gastritis with moderate or severe intestinal metaplasia. CONCLUSIONS: Hp infection may influence both c-Myc expression and telomerase activity in gastric diseases, especially in chronic atrophic gastritis. c-Myc and telomerase co-expressed in gastric cancer and chronic atrophic gastritis with moderate or severe intestinal metaplasia.