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Enders K W Ng

Publications and source records attributed to Enders K W Ng.

At least 19 recordsLinked to original sources
PubMed2006

Effects of long-term rofecoxib on gastric intestinal metaplasia: results of a randomized controlled trial.

PURPOSE: Gastric cancer and its premalignant gastric lesion, intestinal metaplasia (IM), frequently express cyclooxygenase-2 (COX-2) at high levels. We tested whether long-term use of specific COX-2 inhibitors regress gastric IM. EXPERIMENTAL DESIGN: This is a double-blind, randomized, placebo-controlled trial. Individuals with confirmed IM and Helicobacter pylori clearance were randomized to receive rofecoxib 25 mg daily or placebo. Endoscopy was done at baseline, at the end of year 1, and at the end of year 2, with multiple biopsies taken from the antrum and corpus. The primary end point was the proportion of subjects with regression of IM. Secondary end points were the severity of other histologic variables and the proportion of subjects with complete regression of IM. RESULTS: Two-hundred and thirteen subjects with confirmed IM were randomized. The proportion of subjects with the regression of IM did not differ significantly between rofecoxib and placebo groups (antrum, 24.5% versus 26.9%; P = 0.74; corpus, 4.3% versus 2.2%; P = 0.68). Patients on rofecoxib (19.1%) and on placebo (16.1%) had no IM detected in the stomach (P = 0.59). There was also no significant difference in the severity of IM between the two treatment groups (P >or= 0.3). CONCLUSIONS: There was no trend to suggest that treatment with rofecoxib for 2 years resulted in the regression of gastric IM. Although our findings cast doubt on the reversibility of gastric IM by COX-2 inhibitor, further studies are needed to establish the role of COX-2 inhibitors in different stages of gastric carcinogenesis.

Adenocarcinoma↗
PubMed2006

Effects of Helicobacter pylori eradication on methylation status of E-cadherin gene in noncancerous stomach.

PURPOSE: Promoter hypermethylation of E-cadherin plays an important role on gastric cancer development. Whereas E-cadherin methylation was frequently detected in the stomach of Helicobacter pylori-infected individuals, we tested whether eradication of H. pylori alters the methylation status of the noncancerous gastric epithelium. EXPERIMENTAL DESIGN: Endoscopic biopsies were taken from the antrum and corpus of H. pylori-infected subjects without gastric cancer. Presence of methylated E-cadherin sequences in the gastric specimens was detected by methylation-specific PCR. Bisulfite DNA sequencing was done to determine the topographical distribution and changes in methylation profiles with H. pylori eradication. RESULTS: Among the 28 H. pylori-infected subjects (median age, 44.5 years), 15 (53.6%) had E-cadherin methylation detected in stomach at baseline. Discordant methylation patterns between the antrum and corpus were noted in six patients. One year after successful H. pylori eradication, there was a significant reduction in the methylation density of the promoter region and exon 1 of the E-cadherin gene as detected by bisulfite DNA sequencing (P < 0.001). CONCLUSION: Promoter methylation in E-cadherin was frequently detected in the stomach of H. pylori-infected individuals. Eradication of H. pylori might possibly reduce the methylation density in E-cadherin gene and the chance of subsequent neoplastic transformation.

Adult↗
PubMed2006

Cholecystectomy or gallbladder in situ after endoscopic sphincterotomy and bile duct stone removal in Chinese patients.

BACKGROUND & AIMS: In patients with stones in their bile ducts and gallbladders, cholecystectomy is generally recommended after endoscopic sphincterotomy and clearance of bile duct stones. However, only approximately 10% of patients with gallbladders left in situ will return with further biliary complications. Expectant management is alternately advocated. In this study, we compared the treatment strategies of laparoscopic cholecystectomy and gallbladders left in situ. METHODS: We randomized patients (>60 years of age) after endoscopic sphincterotomy and clearance of their bile duct stones to receive early laparoscopic cholecystectomy or expectant management. The primary outcome was further biliary complications. Other outcome measures included adverse events after cholecystectomy and late deaths from all causes. RESULTS: One hundred seventy-eight patients entered into the trial (89 in each group); 82 of 89 patients who were randomized to receive laparoscopic cholecystectomy underwent the procedure. Conversion to open surgery was needed in 16 of 82 patients (20%). Postoperative complications occurred in 8 patients (9%). Analysis was by intention to treat. With a median follow-up of approximately 5 years, 6 patients (7%) in the cholecystectomy group returned with further biliary events (cholangitis, n = 5; biliary pain, n = 1). Among those with gallbladders in situ, 21 (24%) returned with further biliary events (cholangitis, n = 13; acute cholecystitis, n = 5; biliary pain, n = 2; and jaundice, n = 1; log rank, P = .001). Late deaths were similar between groups (cholecystectomy, n = 19; gallbladder in situ, n = 11; P = .12). CONCLUSIONS: In the Chinese, cholecystectomy after endoscopic treatment of bile duct stones reduces recurrent biliary events and should be recommended.

Aged↗
PubMed2006

Diagnosis of gastric cancer by serum proteomic fingerprinting.

BACKGROUND & AIMS: Accurate serum biomarkers for gastric cancer currently are lacking. We attempted to identify potential diagnostic serum markers for gastric cancer with the use of the surface-enhanced laser desorption/ionization ProteinChip technology. METHODS: The study was divided into 3 phases: (1) discovery of potential diagnostic markers using sera of gastric cancer patients and controls, (2) development of a diagnostic model, and (3) independent validation of the diagnostic model using a different cohort of gastric cancer and control patients. The serum proteins/peptides were analyzed with 2 types of ProteinChip arrays, IMAC30 arrays loaded with copper (II) ion and CM10 (weak cation exchange) arrays. RESULTS: In the discovery set, peak intensities of 31 surface-enhanced laser desorption/ionization proteomic features were significantly higher in gastric cancer patients. The tumor-specific nature of 6 proteomic features with the mass/charge (m/z) values of 5098, 8592, 8610, 11,468, 11,804, and 50,140 was verified by their lower peak intensities in postoperative sera. After excluding the sodium adduct peak (8610 m/z) of the 8592 m/z protein, the peak intensities of the tumor-specific proteomic features were used to develop a linear regression model for calculating a diagnostic index. The area under the receiver operating characteristic curve of the corresponding diagnostic index was 0.92 (95% confidence interval, 0.85-0.99) in the independent validation set. At a specificity of 95%, the sensitivity for gastric cancer detection was 83%. CONCLUSIONS: A unique serum proteomic fingerprint can be detected in the sera of gastric cancer patients, which may be useful in the noninvasive diagnosis of gastric cancer.

Adult↗
PubMed2006

Helicobacter pylori infection in 1st degree relatives of Chinese gastric cancer patients.

OBJECTIVE: Familial aggregation of gastric cancer has been linked to familial clustering of Helicobacter pylori infection. Patterns and risk factors associated with H. pylori infection were investigated in 1st degree relatives of Chinese gastric cancer patients. MATERIAL AND METHODS: Gastric cancer relatives were invited for screening endoscopy. H. pylori infection was diagnosed by endoscopic and serological methods. RESULTS: Among the 270 cancer relatives examined, 161 (59.6%) were found to be infected with H. pylori. The prevalence of infection in cancer relatives was significantly higher than age- and gender-matched dyspeptic control (45.5%, p=0.0006). The mean age of H. pylori-infected relatives was significantly older than that of non-infected relatives (43.9 versus 38.3 years; p<0.001). The prevalence of H. pylori infection was higher in those with more siblings (p=0.013, chi(2) test for trend). Moreover, individuals whose siblings had stomach cancer were more likely to have H. pylori infection than those with a parental history of cancer (68.2% versus 51.8%, p=0.007). In contrast, the youngest sibling had a significantly lower H. pylori infection rate than other siblings (39.2% versus 64.2%, p=0.001). Using multiple logistic regression, it was found that age >45 years (OR=1.8; 95% CI, 1.02-3.3) and a history of gastric cancer in siblings (OR=1.9; 95% CI, 1.06-3.3) were independent risk factors for H. pylori infection, and that the youngest sibling in the family had a reduced risk (OR=0.45; 95% CI, 0.24-0.84). CONCLUSIONS: This study identifies the patterns and risk factors for H. pylori in gastric cancer relatives, which may shed light on the evolving epidemiology of H. pylori infection in Chinese patients.

Adolescent↗
PubMed2006

H. pylori genotypes and cytokine gene polymorphisms influence the development of gastric intestinal metaplasia in a Chinese population.

BACKGROUND: Cytokine gene polymorphisms and Helicobacter pylori (HP) genotypes have been linked to gastric cancer development in Western countries. We determined the role of host cytokine polymorphisms and bacterial virulent factors in the development of gastric intestinal metaplasia (IM) in a Chinese population with a high background gastric cancer incidence. METHODS: Three hundred two HP-infected noncancer individuals living in Shandong province of China with available DNA were studied. Polymorphisms in different loci of inflammatory cytokines Interleukin IL-1B, IL-1RN, Interleukin IL-8, IL-10, IL-18, tumor necrosis factor-A (TNF-A), and Transforming growth factor (TGF-B), were determined by allelic discriminating TaqMan polymerase chain reaction (PCR) or a variable number of tandem repeats. Presence of HP virulence factors in cagA, vacA, and babA2 were determined by PCR. Baseline gastric biopsies were assessed for the presence of IM. RESULTS: Among HP-infected subjects, carriers of the IL-1B-511 T allele were associated with a modestly greater prevalence of IM (adjusted OR 2.0, 95% CI 1.0-3.7). There was no association between the presence of IM and polymorphisms in other inflammatory cytokines. Although most subjects from this region harbored the virulent HP strains, carriage of the vacA m1 strain was associated with a significantly higher prevalence of IM (adjusted OR 1.8, 1.1-3.0). The presence of both host (IL-1B-511 T) and HP (vacA m1) genotypes further increased the risk of IM (OR 5.7, 2.0-16) when compared with individuals with the low-risk genotype. CONCLUSION: The carriage of proinflammatory IL-1B-511 and HP vacA m1 genotypes was associated with the development of gastric IM in the Chinese.

China↗
PubMed2005

Cell death induced by Pteris semipinnata L. is associated with p53 and oxidant stress in gastric cancer cells.

In this study, we demonstrated that Ent-11alpha-hydroxy-15-oxo-kaur-16-en-19-oic-acid (5F) had stronger cytotoxicity against MKN-45, a gastric cancer cell line bearing wild-type p53 than MKN-28, another gastric cancer cell line containing missense mutation in p53. The rapid increase of ROS level was involved in the mechanism of cytotoxicity. Classical features of apoptosis induced by 5F were observed in MKN-45 cells only or more significant in MKN-45 cells than MKN-28 cells. Translocation of Bax from cytosol to mitochondria, reduction of delta psi m and DNA fragmentation were induced by 5F in the p53-dependent manner. We conclude that the expression of Bax and its downstream molecules requires the presentation of a wild-type p53 in the cells treated by 5F.

Apoptosis↗
PubMed2005

Premedication with orally administered midazolam in adults undergoing diagnostic upper endoscopy: a double-blind placebo-controlled randomized trial.

BACKGROUND: A double-blind placebo-controlled randomized trial was conducted to investigate the safety and the efficacy of orally administered midazolam as premedication for patients undergoing elective EGD. METHODS: A total of 130 patients were randomized to receive either 7.5 mg of midazolam orally (n = 65) or a placebo (n = 65) as premedication. Outcomes measures included the anxiety score (visual analog scale) during EGD, overall tolerance, extent of amnesia, overall satisfaction, patient willingness to repeat the procedure, recovery time, and hemodynamic changes after medication. RESULTS: The median (interquartile range) anxiety score during the procedure in the midazolam group was significantly lower than that in the control group (2.0 [0-4.9] vs. 3.8 [2.1-7.95], p < 0.001). A significantly greater number of patients in the midazolam group graded overall tolerance as "excellent or good" (70.8% vs. 49.2%, p = 0.012) and reported a partial to complete amnesia response (52.3% vs. 32.3%, p = 0.02) when compared with the control group. Patients in the midazolam group were more willing to repeat the procedure if necessary (89.2% vs. 69.2%, p = 0.005). The median (interquartile range) recovery time was significantly longer in the midazolam group than in the control group (5 [5-15] minutes vs. 5 [5-10] minutes, p = 0.014). There were no statistically significant differences in satisfaction score and hemodynamic changes between groups. CONCLUSIONS: Premedication by oral administration of midazolam is a safe and an effective method of sedation that significantly reduces anxiety and improves overall tolerance for patients undergoing EGD.

Administration, Oral↗
PubMed2005

Optimum duration of prophylactic antibiotics in acute non-perforated appendicitis.

BACKGROUND: The effect of extended prophylactic antibiotic therapy on postoperative infective complications such as wound infection and intra-abdominal abscess for non-perforated appendicitis is poorly defined. METHODS: In a randomized controlled trial of 269 patients aged 15-70 years with non-perforated appendicitis undergoing open appendicectomy; 92 received single dose preoperative (group A), 94 received three-dose (group B) and 83 received 5-day perioperative (group C) regimens of cefuroxime and metronidazole. Postoperative infective complication was the primary endpoint. Secondary outcomes included length of hospital stay and complications related to antibiotic therapy. RESULTS: The rate of postoperative infective complication was not significantly different among the groups (6.5% group A, 6.4% group B, 3.6% group C). The duration of antibiotic therapy had no significant effect on the length of hospital stay. Complications related to antibiotic treatment were significantly more common for 5-day perioperative antibiotic group (C) compared with single dose preoperative antibiotic group (A) (P = 0.048). CONCLUSION: Single dose of preoperative antibiotics is adequate for prevention of postoperative infective complications in patients with non-perforated appendicitis undergoing open appendicectomy. Prolonging the use of antibiotics can lead to unnecessary antibiotic related complications.

Adolescent↗
PubMed2005

Premedication with intravenous ketorolac trometamol (Toradol) in colonoscopy: a randomized controlled trial.

OBJECTIVE: We conducted a prospective double-blinded placebo-controlled randomized trial to investigate the effect of ketorolac trometamol (KT) administered intravenously as premedication in colonoscopy. METHODS: One hundred and forty patients undergoing colonoscopy were randomized to receive either 60 mg of KT (KT group (KTG), n=70) or placebo (normal saline group (NSG), n=70) intravenously as premedication 30 min prior to procedure. Patient-controlled sedation (PCS) was used as the mode of sedation. Outcome measures included patient self-assessed pain score in a 10-cm unscaled visual analog scale (VAS), endoscopist assessment of patient pain score in VAS, patient's willingness to repeat colonoscopy, administered and demanded doses of PCS, patient satisfaction score in VAS, and hemodynamic changes during and after the procedure. RESULTS: The mean patient self-assessed pain score (SD) during procedure was significantly lower in KTG than NSG: 5.08 (2.74) vs 6.62 (2.45); p=0.001. The mean endoscopist assessment of patient pain score (SD) was significantly lower in KTG than NSG as well: 3.99 (2.80) vs 5.28 (2.71); p=0.006. More patients in KTG were willing to repeat procedure as compared with NSG (80.0%vs 57.1%; p=0.004). No significant difference was found in the administered and demanded doses of PCS, mean satisfactory scores and hemodynamic changes in both groups. No serious complication related to intravenous (IV) KT was noted. CONCLUSIONS: Premedication with IV KT (Toradol) improves pain control during colonoscopy with no associated serious complications.

Academic Medical Centers↗
PubMed2005

Risk factors associated with the development of intestinal metaplasia in first-degree relatives of gastric cancer patients.

Family relatives of gastric cancer patients have a higher risk of gastric cancer and premalignant gastric lesions. We sought to determine the risk factors associated with the presence of intestinal metaplasia in a large cohort of gastric cancer relatives. First-degree relatives of gastric cancer patients were invited for screening gastroscopy. Endoscopic gastric biopsies were obtained from the antrum and corpus. Gastric biopsies were analyzed for Helicobacter pylori infection, severity of inflammation, and presence of intestinal metaplasia. Stepwise logistic regressions were used to identify for risk factors associated with presence of intestinal metaplasia in cancer relatives. Two hundred seventy cancer relatives underwent screening endoscopy (median age, 42; 47% male and 48% siblings). Among them, 161 (59.6%) were H. pylori positive and 81 (30%) had confirmed intestinal metaplasia. The following factors were found to be associated with the presence of intestinal metaplasia: age, male sex, H. pylori infection, birth order, alcohol use, siblings with stomach cancer, childhood living conditions, and water supply. Individuals with intestinal metaplasia had more severe acute and chronic inflammation in the antrum and corpus (P < 0.003). With multiple logistic regression, H. pylori infection [odds ratio (OR), 3.23], male gender (OR, 2.09), age (OR, 1.07), and a history of gastric cancer in siblings (OR, 1.91) were independent factors associated with the development of intestinal metaplasia in cancer relatives. In conclusion, we have identified risk factors associated with gastric intestinal metaplasia in stomach cancer relatives, which may be useful in the understanding of gastric carcinogenesis in these high-risk individuals.

Adenocarcinoma↗
PubMed2005

Endoscopic therapy for oesophageal cancer.

Transthoracic surgery for oesophageal cancer is associated with a high incidence of respiratory complications. Recent development of minimally invasive oesophagectomy by the use of video-assisted thoracoscopic approach may have a potential to minimize morbidity and mortality. While results from earlier series were equivocal, recent reports have shown an encouraging trend. This article serves to review the recent literature evidence in relation to the surgical approach, safety, efficacy and potential problems of such a highly complex minimally invasive operation.

Endoscopy, Gastrointestinal↗
PubMed2005

Promoter hypermethylation of Death-associated protein-kinase gene associated with advance stage gastric cancer.

Death-associated protein kinase (DAP-kinase) is a serine/threonine kinase and a positive mediator of apoptosis. Down-regulation of DAP-kinase was associated with increased metastatic potential of tumors. Gene promoter hypermethylation could lead to down-regulation of DAP-kinase. We aimed to investigate the frequency of gene promoter methylation of DAP-kinase in gastric carcinoma (GCA) and assessed its association with clinicopathological features. One hundred and seven cases of gastric carcinoma were examined. The relevant clinical and pathological features, including survival data were reviewed. Methylation status was assessed by methylation-specific PCR (MSP). Seventy-four cases (69.2%) of GCA demonstrated promoter methylation of DAP-kinase. Methylation of DAP-kinase was observed in intestinal, diffuse and mixed type of GCA. It also occurred in similar frequency among antral, body and cardiac gastric cancer. No association between methylation status and age or gender was demonstrated. However, the methylated cases correlated with the presence of nodal metastasis (p=0.041), advance stage of disease (p=0.029) and a poorer event-free survival (log-rank test p=0.0141). DAP-kinase promoter methylation as a potential prognostic marker for gastric cancer patients deserved further evaluation.

Apoptosis Regulatory Proteins↗
PubMed2004

Upregulation of heme oxygenase-1 and p21 confers resistance to apoptosis in human gastric cancer cells.

Both heme oxygenase-1 (HO-1) and p21(WAF1/Cip1) (p21) are involved in the pathogenesis of human cancer and their functions are closely associated with apoptosis. However, how these two molecules regulate apoptosis in human gastric cancer is unknown. In this study, we studied how HO-1 and p21 were regulated in two gastric cancer cell lines, MKN-45 with wild p53 and MKN-28 with mutant p53. The cells were treated with hemin and cadmium to induce HO-1. The result showed that HO-1 protein was significantly induced by hemin and cadmium in both cells tested. Following the HO-1 expression, p21 level was also markedly induced. The cells with increased HO-1 and p21 showed obviously resistantance to apoptotic stimuli. The levels of HO-1 and p21 induced were significantly inhibited by p38 mitogen-activated protein kinase (p38 MAPK) inhibitor (SB203580) and extracellular-regulated kinase (ERK) inhibitor (PD098059). Parallel to decreased HO-1 and p21 expression, the kinase inhibitors also significantly attenuated the resistance of the cells to apoptosis. The elevated HO-1 and p21 was further found to be associated with increase activity of the nuclear NF-kappaB and the inhibition of NF-kappaB led to the block of their induction. The elevated HO-1 and p21 were also demonstrated to be related to increased cellular inhibitor of caspase inbitory protein-2 (c-IAP2) and decreased caspapse-3 activity. It was noted that the above changes observed were not different between MKN-45 and MKN-28 cells, suggesting the functions of HO-1 and p21 were irrespective of the status of p53. In conclusion, we demonstrate that the resistance to apoptosis in gastric cancer cells with elevated HO-1 and p21 is independent of p53 status in a p38 MAPK- and ERK-mediated pathway with elevated c-IAP2 and decreased caspase-3 activity and that this pathway is sensitive to the inhibition of NF-kappaB.

Apoptosis↗