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.

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.

Selection of Potential Virulence Factors Contributing to Streptococcus suis Serotype 2 Penetration into the Blood-Brain Barrier in an In Vitro Co-Culture Model.

Meningitis caused by Streptococcus suis serotype 2 (S. suis 2) is a great threat to the pig industry and human health. Virulence factors associated with the pathogenesis of meningitis have yet to be clearly defined, even though many potential S. suis 2 virulence factors have been identified. This greatly hinders the progress of S. suis 2 meningitis pathogenesis research. In this study, a co-culture blood-brain barrier (BBB) model was established using primary porcine brain microvascular endothelial cells and astrocytes, and the whole genome library of S. suis 2 was constructed using phage display technology. Finally, a total of 14 potential virulence factors contributing to S. suis 2 adherence to and invasion of the BBB were selected by analyzing the interactions between the phage library and the co-culture model. Twelve of these factors have not been previously reported in meningitis-related research. The data provide valuable insight into the pathogenesis of S. suis 2 meningitis and potential targets for the development of drug therapies.

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.

Capsule endoscopy and single-balloon enteroscopy in small bowel diseases: Competing or complementary?

AIM: To evaluate diagnostic yields of capsule endoscopy (CE) and/or single-balloon enteroscopy (SBE) in patients with suspected small bowel diseases. METHODS: We retrospectively analyzed 700 patients with suspected small bowel diseases from September 2010 to March 2016. CE, SBE, or SBE with prior CE was performed in 401, 353, and 47 patients, respectively. Data from clinical and endoscopy records were collected for analysis. Indications, procedure times, diagnostic yields, and complications were summarized and evaluated. RESULTS: The overall diagnostic yield for the CE group was 57.6%. The diagnostic yield of CE in patients with obscure gastrointestinal bleeding (OGIB) was significantly greater than that in patients with no bleeding (70.5% vs 43.8%, P < 0.01). The overall diagnostic yield of SBE was 69.7%. There was no difference in the diagnostic yield of SBE between patients with OGIB and those with no bleeding (72.5% vs 68.9%, P = 0.534). Forty-seven patients underwent CE prior to SBE. Among them, the diagnostic yield of SBE with positive findings on prior CE was 93.3%. In addition, SBE detected two cases with superficial ulcer and erosive lesions in the small bowel, which were missed by CE. However, one case with lymphoma and two with Crohn's disease were not confirmed by SBE. The rate of capsule retention was 2.0%. There were no significant complications during or after SBE examinations. CONCLUSION: SBE is a safe and effective technique for diagnosing small bowel diseases. SBE with prior CE seemed to improve the diagnostic yield of small bowel diseases.

A severe course of Cronkhite-Canada syndrome and the review of clinical features and therapy in 49 Chinese patients.

We describe a severe case of Cronkhite-Canada syndrome and review the clinical features and therapy in 49 Chinese patients. A 67-year-old man who underwent severe chronic diarrhea had typical clinical manifestations of hyperpigmentation, hair loss, and dystrophic changes in the fingernails. Although sufficient nutrition support and other therapies reported in the literature were provided, the patient died of systemic failure one year later. Cronkhite-Canada syndrome is characterized by generalized gastrointestinal polyps associated with hyperpigmentation, hair loss, and onycholysis. Anemia, positive stool occult blood, serum electrolyte disturbances, and low serum proteins are the main clinical features of patients with Cronkhite-Canada syndrome. Most patients were diagnosed by esophagogastroduodenoscopy and/or colonoscopy, and polyps were found in the entire alimentary tract, except the notable exception of the esophagus. The polyp-like samples of mucosa, hyperplasia, and adenoma were characterized by acute/chronic inflammation. Four cases were complicated with cancer. The treatment of Cronkhite-Canada syndrome includes symptomatic and support therapy, administration of corticosteroids, antibiotics and acid inhibitors, therapeutic endoscopy, and surgery. While the mortality rate was reported as 47.3% (9/19), some patients may live a long life with controlled symptoms.