Chronic atrophic gastritis is a progressive disease: analysis of medical reports from Shanghai (1985-2009)

<p><b>INTRODUCTION</b>We aimed to examine the turnover of chronic atrophic gastritis (CAG) pathologically and endoscopically and explore its potential causes.</p><p><b>METHODS</b>A retrospective analysis was conducted of prospective data collected from 1,592 patients who underwent gastroscopy three times or more during the period 1985-2009 at Renji Hospital, Shanghai, China. Pathological and endoscopic findings were analysed. Data collected included gender, age, length of follow-up period, family history, past medical history, history of Helicobacter (H.) pylori infection, drug history for the use of proton pump inhibitors (PPIs), antacids and non-steroidal anti-inflammatory drugs [NSAIDs], and lifestyle history, including the patients' eating habits.</p><p><b>RESULTS</b>23 (1.44%) patients presented with gastric cancers resulting from CAG and 349 (21.92%) patients had dysplasia. Pathological and endoscopic findings suggested that the proportion of patients with worsening gastric mucosa during the atrophic and intestinal metaplasia (IM) phases was over 35% with increasing age. Gastric mucosa was found to be pathologically aggravated by carbonated drinks and fast food, and pathologically degenerated by H. pylori infection. Smoking deteriorated the gastric mucosa. Side dishes of vegetables may benefit the gastric mucosa even in the atrophic and IM phases.</p><p><b>CONCLUSION</b>Our findings support the consensus that CAG is a progressive disease. Potential factors that were found to affect the state of the gastric mucosa in our patient group were gender, H. pylori infection, use of PPIs or NSAIDs, and intake of vegetable side dishes, spicy food, carbonated drinks and fast food.</p>

Reduced expression of miR-218 and its significance in gastric cancer / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate the expression and function of miR-218 in gastric cancer.</p><p><b>METHODS</b>miR-218 levels were evaluated in 20 non-cardia gastric cancer tissues using TaqMan stem-loop real-time PCR analysis. Pre-miR-218 and anti-miR-218 inhibitor were used to change the miR-218 expression level and examine its effects on cell proliferation, apoptosis, cell cycle and cell invasion.</p><p><b>RESULTS</b>Comparing with the corresponding normal tissues, miR-218 expression was significantly reduced in the gastric cancer tissue (P < 0.01). Forced expression of miR-218 increased apoptosis in AGS cells. The proportion of apoptosis cells induced by transfection of pre-miR-218 was greater than that induced by control (21.6% vs. 10.4%, P = 0.032). Pre-miR-218 resulted in a significantly decreased cell growth activity (P < 0.01) and cell invasion (P < 0.05) of AGS cells compared with that of the control.</p><p><b>CONCLUSION</b>miR-218 expression is reduced in gastric cancer. miR-218 may function as a tumor suppressor in gastric carcinoma.</p>

Epigallocatechin gallate induces apoptosis in human hepatocellular carcinoma HepG2 cells via TGF/Smad signaling pathway / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate the cytotoxic effect of epigallocatechin gallate (EGCG) on human hepatocellular carcinoma cell line HepG2 cells and corresponding changes of TGF-beta1-Smad pathway.</p><p><b>METHODS</b>The cytotoxic effect of EGCG on HepG2 cells was determined by MTT assay. Cell cycle and apoptosis rate were detected by flow cytometry. RT-PCR and luciferase assay were used to verify whether TGF-beta1-Smad signaling pathway is intact in HepG2. The mRNA expression of Smad 2, Smad3, Smad4 and Smad7 was detected by real-time PCR.</p><p><b>RESULTS</b>EGCG induced apoptosis in the HepG2 cells in a time- and concentration-dependent manner. The proportion of G(1) phase cells was increased gradually as the concentration increased. However, the percentage of cells in S phase was decreased gradually. Annexin V/PI assay demonstrated that early apoptosis increased as the concentration increased, and late apoptosis also increased, when treated with high-concentration EGCG. The intact TGF-beta1-Smad pathway was verified by luciferase assay and RT-PCR. There was no significant effect of EGCG on mRNA level of Smad 2, Smad 3, and Smad 4 in HepG2 cells, but downregulated mRNA level of Smad 7.</p><p><b>CONCLUSION</b>EGCG can reduce apoptosis in human hepatocellular carcinoma cell line HepG2 cells. The activation of TGF-beta1-Smad signaling pathway may be involved in its cytotoxicity mechanisms.</p>

Association between Fecal Bile Acids and Colorectal Cancer: A Meta-analysis of Observational Studies

PURPOSE: To provide a systematic review with meta-analysis for addressing the relationship between fecal bile acids (FBAs) and colorectal cancer. MATERIALS AND METHODS: Electronic databases were searched for all observational studies that examined the relationship between FBAs and colorectal cancer or adenoma, and calculated weighted mean difference (WMD) and 95% confidence interval (CI). Publication bias was assessed with funnel plot. RESULTS: Twenty case-control or cohort studies were identified. All studies were pooled to assess the relationship between total FBAs and cancer/adenoma of the large bowel, however, no association was seen (WMD 0.61mg/g freeze-dried feces; 95% CI: -0.35-1.57). Significantly increased concentration of chenodeoxycholic acid (CDCA) was seen while pooling to assess the relationship between CDCA and cancer/adenoma of the large bowel (WMD 0.13 mg/g freeze-dried feces; 95% CI: 0.01-0.25), especially for colorectal cancer (WMD 0.28mg/g freeze-dried feces; 95% CI: 0.10-0.46). However, no significant differences in deoxycholic acid (DCA), lithocholic acid (LCA), and primary and secondary bile acids, were seen between patients with cancer and patients with matched controls regardless of fixed and random effects models. CONCLUSION: CDCA might play a role in the etiology of colorectal cancer.

The role of capsule endoscopy combined with double-balloon enteroscopy in diagnosis of small bowel diseases / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The diagnosis of small bowel diseases remains relatively inefficient using traditional imaging techniques. Capsule endoscopy (CE) and double-balloon enteroscopy (DBE) are two novel methods of enteroscopy for examining the entire small bowel. The aim of this study was to evaluate the detection rate and diagnostic accuracy of CE and DBE in patients with suspected small bowel diseases and to investigate the clinical significance of combined use of these two novel modalities.</p><p><b>METHODS</b>Two hundred and eighteen patients were evaluated for suspected small bowel disease, including 116 with obscure gastrointestinal bleeding and 102 with obscure abdominal pain or chronic diarrhea. One hundred and sixty-five out of these patients underwent CE first and 53 patients underwent DBE (under anesthesia with propofol) first. DBE was recommended after negative or equivocal evaluation on CE and vise versa. Introduction of the endoscope during DBE was either orally or anally and the patients were referred for a second procedure using the opposite route several days later when no abnormalities were found on the first procedure. The detection rates, diagnostic accuracy, tolerance and frequency of adverse events of these two modalities were then analyzed.</p><p><b>RESULTS</b>Failure of the procedure was seen in one patient with CE and in two patients with DBE. Sixty-four DBE procedures were carried out in 51 patients; by the oral route in 34 cases, the anal route in 4 and both routes in 13 cases. The overall detection rate of small bowel diseases using CE (72.0%, 118/164) was superior to that with DBE (41.2%, 21/51); chi(2) = 16.1218, P < 0.0001. The diagnostic rate (51.8%, 85/164) was also higher than that with the latter procedure (39.2%, 20/51), but was not significantly different (chi(2) = 2.4771, P > 0.05). Furthermore, the detection rate of small bowel diseases in patients with obscure gastrointestinal bleeding using CE (88.0%, 88/100) was superior to that of DBE (60.0%, 9/15); chi(2) = 7.7457, P = 0.0054. Lesions were detected by DBE in 1 out of 4 patients in whom CE had a negative result. Suspected findings by CE were confirmed by DBE combined with biopsy in 12 out of 15 patients. On the other hand, small bowel lesions were identified by CE in all 3 patients after negative evaluations by DBE. There were no severe complications during or after either of the two procedures.</p><p><b>CONCLUSIONS</b>The detection rate of small bowel diseases by CE is very high. CE should be selected for the initial diagnosis in patients with suspected small bowel diseases, especially in patients with obscure gastrointestinal bleeding. DBE appears to be inferior to CE in the diagnosis of small bowel diseases. However, it was shown that abnormalities could still be identified by DBE in patients with normal images or used to confirm suspected findings from CE. DBE can also serve as a good complementary approach after an initial diagnostic imaging using CE.</p>

Clinical application of wireless capsule endoscopy in pediatric and adolescent patients / 中华儿科杂志

<p><b>OBJECTIVE</b>Capsule endoscopy (CE) has been demonstrated to be safe and well tolerated in adults. However, its value in pediatric patients has not been well studied. The present study aimed to evaluate the safety and effectiveness of CE in pediatric patients with suspicious small bowel disorders.</p><p><b>METHODS</b>Fifteen children and adolescents (less than 18 years) were referred to our study for suspected small bowel diseases from Aug. 2002 to May 2005. They aged from 3 to 18 years. Among them, 5 patients were less than 10 years old. The range of weight was from 17 to 83 kg and height was from 49 to 176 cm. Clinical indications included obscure gastrointestinal bleeding (n = 12) and abdominal pain (n = 3). All the patients had normal results on upper and lower gastrointestinal examinations before they underwent CE. The procedures for capsule placement, gastric transit time, small bowel transit time, the average time of the elimination of the capsule, capsule findings, and complications were recorded.</p><p><b>RESULTS</b>All the patients described that the capsule was easy to swallow except 3 youngest children. Finally the capsule was delivered via gastroscopy with overtube for these three children under intravenous anesthesia. No capsule retention occurred during the study. Median recording time was (464 +/- 40) min. In 5 patients, the capsule did not pass the ileal valve by the end of the recording time. Median gastric transit time was (85 +/- 90) min. Median small bowel transit time was (283 +/- 106) min. The average time of the elimination of the capsule was (34.3 +/- 21.8) h. The detective yield of CE was 80%. These positive findings included Crohn's disease (5), hemangioma (2), angiodysplasia (2), Meckel diverticulum (1), polyp (1), and granulomatous lesions (1).</p><p><b>CONCLUSION</b>CE was performed safely in pediatric patients after ingestion or endoscopic placement of the capsule. The high yield of abnormal findings was comparable to those of adult patients.</p>

Experimental study on anti-neoplastic activity of epigallocatechin-3-gallate to digestive tract carcinomas / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Epigallocatechin-3-gallate (EGCG) has been demonstrated to have anti-neoplastic activity, but the effective concentration of EGCG and its possible mechanisms are uncertain. The study on the killing effects of EGCG on different digestive tract cancer cell lines can find target sites of its anti-neoplastic effect and provide a theoretical basis for its clinical application in the treatment of cancers.</p><p><b>METHODS</b>Methyl thiazolyl tetrazolium (MTT) analysis was made to detect the differential sensitivities of eight digestive tract cancer cell lines to EGCG. The effect of EGCG on cell cycle distribution of sensitive cancer cell line was measured by flow cytometry. By polymerase chain reaction (PCR)-enzyme linked immunosorbent assay (ELISA) protocol, the influence of EGCG on telomerase activity of sensitive cancer cell line was also investigated. RT-PCR method was employed to detect the influence of EGCG on the expressions of hTERT, c-myc, p53 and mad1 genes in sensitive cancer cell line.</p><p><b>RESULTS</b>EGCG exhibited dose-dependent killing effects on all eight digestive tract cancer cell lines. The 50% inhibitory concentration (IC50) of SW1116, MKN45, BGC823, SGC7901, AGS, MKN28, HGC27 and LoVo cells were 51.7 micromol/L, 55.9 micromol/L, 68.5 micromol/L, 79.1 micromol/L, 83.8 micromol/L, 119.8 micromol/L, 183.2 micromol/L and 194.6 micromol/L, respectively. There were no apparent changes in cell cycle distribution of sensitive cancer cell line MKN45 48 hours after incubating with three different concentrations of EGCG compared with the controls. It was found that EGCG could suppress the telomerase activity of MKN45 cells, and the effects were dose- and time-dependent. After EGCG administration, the expression of hTERT and c-myc genes in MKN45 cells was decreased, that of the mad1 gene increased, and that of the p53 gene unchanged.</p><p><b>CONCLUSIONS</b>EGCG has dose-dependent killing effects on different digestive tract cancer cell lines. Administration of EGCG has no obvious effect on cell cycle distribution of sensitive cancer cell line MKN45. The anti-neoplastic activity of EGCG might be due to the inhibition of telomerase activity by means of its influence on hTERT and the up-stream regulation genes.</p>

Capsule endoscopy and push enteroscopy in the diagnosis of obscure gastrointestinal bleeding / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>In obscure gastrointestinal (GI) bleeding, it is often difficult to detect the bleeding sites located in the small bowel with conventional radiological, scintigraphic or angiographic techniques. Push enteroscopy and capsule endoscopy are currently considered to be the most effective diagnostic procedures. The aim of this study was to compare the detection rates between capsule endoscopy and push enteroscopy.</p><p><b>METHODS</b>From May 2002 through January 2003, we prospectively examined by capsule endoscopy 39 patients with suspected small bowel diseases, in particular GI bleeding of unknown origin in Renji Hospital. Among them, 32 complained of obscure recurrent GI bleeding. Between January 1993 and October 1996, we used push enteroscopy on 36 patients who suffered from unexplained GI bleeding. All patients had prior normal results on gastroscopy, colonoscopy, small bowel barium radiography, scintigraphy and/or angiography.</p><p><b>RESULTS</b>M2A capsule endoscopy disclosed abnormal small bowel findings in 26 (82%) out of 32 patients. Twenty-one of them had significant pathological findings explaining their clinical disorders. Diagnostic yield was therefore 66% (21 of 32 patients). Definite bleeding sites diagnosed by capsule endoscopy in 21 patients included angiodysplasia (8), inflammatory small-bowel (5), small-bowel polyps (4), gastrointestinal stromal tumour (2), carcinoid tumour and lipoma (1), and hemorrhagic gastritis (1). Push enteroscopy detected the definite sources of bleeding in 9 (25%) of the 36 patients. Patients with definite bleeding sources included angiodysplasias (2), leiomyosarcoma (2), leiomyoma (1), lymphoma (1), Crohn's disease (1), small-bowel polyps (1) and adenocarcinoma of ampulla (1). Suspected bleeding sources were shown by push enteroscopy in two additional patients (6%), and in other five patients (16%) by capsule endoscopy.</p><p><b>CONCLUSIONS</b>The present study of patients with obscure GI bleeding showed that capsule endoscopy significantly superior to push enteroscopy in detecting GI bleeding (P < 0.001). Capsule endoscopy is safe and painless, and should become the initial diagnostic choice for patients with obscure GI bleeding.</p>

5-Aza-2'-deoxycitydine induces demethylation and up-regulates transcription of p16INK4A gene in human gastric cancer cell lines / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>To investigate the effects of DNA methylation on the expression of tumor-associated genes and the cell cycle in human gastric cancer cells.</p><p><b>METHODS</b>Two gastric cancer cell lines (MKN-45 and HGC-27) were treated with DNA methyltransferase (DNMT) inhibitor, 5-aza-2'-deoxycytidine (5-aza-dC). The expressions of p16INK4A, p21WAF1, p53, p73, c-Ha-ras and c-myc genes mRNA were detected by using reverse transcription PCR (RT-PCR). DNA methylation status of p16INK4A gene promoter was assayed by bisulfite modification and sequencing. The cell cycle was analyzed by using flow cytometry (FCM).</p><p><b>RESULTS</b>5-aza-dC induced the demethylation of p16INK4A gene promoter. The expression of p16INK4A mRNA was obviously up-regulated by treatment with 10 micro mol/L (MKN-45 cells) or 5 micro mol/L (HGC-27 cells) of 5-aza-dC for 24 hours. However, 5-aza-dC treatment failed to regulate the expressions of p21WAF1, p53, p73, c-Ha-ras and c-myc genes in MKN-45 and HGC-27 cells. Furthermore, 5-aza-dC induced the cell cycle arrest in G1 phase in HGC-27 cell, but not in MKN-45 cell.</p><p><b>CONCLUSIONS</b>DNA methylation regulates the transcription of p16INK4A but not p21WAF1 and proto-oncogenes in human gastric cancer cell lines MKN-45 and HGC-27.</p>