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ObjectiveTo investigate the incidence of gastric cancer (GC) attributed to gastric intestinal metaplasia (IM), and validate the Operative Link on Gastric Intestinal Metaplasia (OLGIM) for targeted endoscopic surveillance in regions with low-intermediate incidence of GC.MethodsA prospective, longitudinal and multicentre study was carried out in Singapore. The study participants comprised 2980 patients undergoing screening gastroscopy with standardised gastric mucosal sampling, from January 2004 and December 2010, with scheduled surveillance endoscopies at year 3 and 5. Participants were also matched against the National Registry of Diseases Office for missed diagnoses of early gastric neoplasia (EGN).ResultsThere were 21 participants diagnosed with EGN. IM was a significant risk factor for EGN (adjusted-HR 5.36; 95% CI 1.51 to 19.0; pH. pylori. Participants with OLGIM II were also at significant risk of EGN (adjusted-HR 7.34; 95% CI 1.60 to 33.7; p=0.02). A significant smoking history further increases the risk of EGN among patients with OLGIM stages II–IV.ConclusionsWe suggest a risk-stratified approach and recommend that high-risk patients (OLGIM III–IV) have endoscopic surveillance in 2 years, intermediate-risk patients (OLGIM II) in 5 years.

Detection of pre-neoplastic gastric mucosal changes and early gastric cancer (EGC) by white-light endoscopy (WLE) is often difficult. In this study we investigated whether combined autofluorescence imaging (AFI) and narrow band imaging (NBI) can improve detection of pre-neoplastic lesions and early gastric cancer in high-risk patients.Chinese patients who were 50-years-old or above with dyspepsia were examined by both high-resolution WLE and combined AFI followed by NBI (AFI-NBI), consecutively in a prospective randomized cross-over setting, by two experienced endoscopists. The primary outcome was diagnostic ability of the two methods for patients with pre-neoplastic lesions such as intestinal metaplasia (IM) and mucosal atrophy.Sixty-five patients were recruited. One patient with large advanced gastric cancer was found and excluded from the analysis. Among the remaining 64 patients, 38 (59%) had IM; of these, 26 (68%) were correctly identified by AFI-NBI (sensitivity 68%, specificity 23%) and only 13 (34%) by WLE (sensitivity 34%, specificity 65%). AFI-NBI detected more patients with IM than did WLE (p=0.011). Thirty-one patients (48%) had mucosal atrophy. Ten patients (32%) were identified by AFI-NBI (sensitivity 32%, specificity 79%) and four patients (13%) by WLE (sensitivity 13%, specificity 88%) (p=0.100). No dysplasia or EGC was found.AFI-NBI identified significantly more patients with IM than did WLE. Our result warrants further studies to define the role of combined AFI-NBI endoscopy for detection of precancerous conditions.

The present study evaluated the significance of nitric oxide synthase (NOS), cyclooxygenase (COX) expression and p53 status in 55 patients with gastric adenocarcinoma and relationship of these molecular markers to tumor characteristics and metastatic potential. Immunohistochemical technique was used to identify the cellular location and distribution of the enzymes in the specific cells of gastric tumors. In gastric cancer tissue, the expression of inducible enzymes, iNOS and COX-2, increased significantly with increasing tumor stage (P=0.015, P=0.001, respectively), size (P=0.025, P=0.001, respectively) and the presence of metastases (P=0.002, P=0.015, respectively). The expression of constitutive enzymes, ecNOS and COX-1, followed the opposite pattern. COX-1 was significantly reduced in advanced gastric tumors (P=0.007) and tumors larger than 5 cm (P=0.007). Reduced expression of ecNOS was also observed in advanced gastric tumors; however, this did not reach statistical significance. 53% of gastric tumors showed accumulation of p53. This was significantly higher in advanced tumors (P=0.004), larger than 5 cm (P=0.015) with metastases (P

To the Editor:The human exocrine pancreas develops embryologically from the ventral and the dorsal anlagen that evaginate from the primitive foregut during the fifth week of gestation. The dorsal anlage will form the superior part of the head, the body, and the tail of the pancreas, whereas the vent

Objective: To describe a new transoral technique of cervical oesophagogastric and oesophagojejunal anastomoses using the EEA stapler. Design: Prospective clinical study. Setting: University Hospital, Bratislava, Slovakia. Subjects: Two patients with squamous cell carcinoma of the middle and distal third of the oesophagus. Interventions: Transhiatal subtotal oesophagectomy without thoracotomy, and cervical oesophageal anastomosis by transoral EEA stapling. Main outcome measures: Morbidity and mortality. Results. Transoral stapling was successful in both patients with no anastomotic leaks. The patients were discharged on the 14th and 21st postoperative days, respectively. Conclusions. Transoral stapling of the cervical anastomosis gave good results in two patients. More development and evaluation are needed.

Reliable predictive factors for conversion of laparoscopic cholecystectomy (LC) would be extremely useful in the preparation and planning of admission for patients with symptomatic cholelithiasis. Data from 783 patients in whom LC was attempted in a university clinic from June 1990 to December 1995 were retrospectively analyzed. The aim of this study was to determine preoperative indicators that can be useful for predicting conversion to open cholecystectomy (OC). Conversion was required in 58 (7.4%) patients, of which 48 (83%) were elective and 10 (17%) emergency. Factors evaluated were age, sex, obesity, duration of gallstone disease, co-morbid factors, indication for surgery, previous abdominal surgery, fever, physical examination findings, white blood cell (WBC) count, liver function tests, ultrasound findings, and the experience of the surgeon. Acute cholecystitis, rigidity in the right upper abdomen, fever, thickened gallbladder wall on ultrasonography, elevated alkaline phosphatase (ALP), liver transaminases and the WBC count were significant predictors of conversion in the univariate analysis. Multivariate logistic regression analysis on these significant predictors showed that acute cholecystitis [odds ratio (OR) = 3.12], thickened gallbladder wall on ultrasonography (OR = 3.75), elevated ALP (OR = 2.23), and WBC count (OR = 3.69) were jointly significant.

Background: Adhesion formation between viscera and mesh is almost inevitable following incisional hernia repair with prosthetic mesh. Such adhesions may lead to intestinal obstruction and enterocutaneous fistulae formation and make further laparotomies extremely difficult. Sodium carboxymethylcellulose (SCMC) and Interceed TC7 (oxidized regenerated cellulose) as physical barriers have been shown to be effective in reducing postoperative adhesions. Materials and methods: To evaluate the effects of SCMC and Interceed TC7, we used an incisional hernia model in rats. A ventral abdominal defect (15 × 25 mm) was created in each of 36 male rats which were then divided into three equal groups. In Group I (control) the defect was repaired with polypropylene mesh (PPM) only; in Group II the defect was repaired after a layer of Interceed TC7 was laid over the viscera with Interceed TC7-covered PPM; in Group III the defect was repaired after a layer of SCMC was laid over the viscera with SCMC-coated PPM. Six of the animals from each group were sacrificed at Postoperative Day 7 and the adhesions were scored. The remaining 6 were sacrificed at Day 30 and histological evaluation was made in addition to the adhesion score. Results: Animals in the SCMC-treated group developed significantly less adhesions ( P = 0.0002) compared with control and Interceed TC7-treated groups. However, histological analysis revealed poor fibroblast proliferation with impaired wound healing in the SCMC group. Conclusion: SCMC prevented adhesion formation but seriously impaired wound healing, and Interceed TC7 was ineffective in preventing adhesion in this model.

Confocal laser endomicroscopy (CLE) may be used to diagnose gastric cancer and intestinal metaplasia, but the impact of CLE experience on the accuracy of confocal diagnosis of gastric cancer and intestinal metaplasia is not clear.To establish the sensitivity, specificity, and intragroup interobserver agreement of CLE image interpretation by 3 experienced (group 1) and 3 inexperienced (group 2) CLE endoscopists for diagnosing gastric intestinal metaplasia (GIM) and adenocarcinoma.Blinded review of CLE images for the diagnosis of gastric cancer or intestinal metaplasia.Tertiary care hospital.CLE images obtained ex vivo from gastrectomy specimens with proven gastric cancer and CLE images obtained in vivo from Chinese subjects older than 50 years of age by using matched biopsy specimens as reference standards.Sensitivity, specificity, and intragroup interobserver agreement of CLE image interpretation.Interpretation of in vivo images by group 1 was associated with higher sensitivity (95.2% vs 61.9%, P = .039) and higher specificity (93.3% vs 62.2%, P.001) for GIM than interpretation by group 2. The agreement between interpretation by group 1 and histology for GIM was higher than that for group 2 (κ = 0.864 vs 0.217). The sensitivity (93.3% for group 1 vs 86.7% for group 2, P = 1.000) and specificity (87.7% for group 1 vs 80.7% for group 2, P = .344) of interpretation of ex vivo CLE images for the diagnosis of gastric adenocarcinoma was similar for groups 1 and 2.Single-center study.Experience in CLE was associated with greater accuracy in the diagnosis of intestinal metaplasia.

Identification of Individuals at High Risk of Gastric Cancer for Targeted Endoscopic Screening Zhu Feng, Li Lin Lim, Calvin J. Koh, David E. Ong, Lee Guan Lim, Khek-Yu Ho, Chia Chung-King, Christopher J. Khor, Choon Jin Ooi, Kwong Ming Fock, Jimmy B. So, Wee Chian Lim, Khoon-Lin Ling, Tiing Leong Ang, Andrew S. Wong, Jaideepraj Rao, Andrea Rajnakova, Ming Teh, Manuel Salto-Tellez, Supriya Srivastava, Yik Ying Teo, Khay Guan Yeoh

Loss of RUNX3 expression is suggested to be causally related to gastric cancer as 45% to 60% of gastric cancers do not express RUNX3 mainly due to hypermethylation of the RUNX3 promoter. Here, we examined for other defects in the properties of RUNX3 in gastric cancers that express RUNX3. Ninety-seven gastric cancer tumor specimens and 21 gastric cancer cell lines were examined by immunohistochemistry using novel anti-RUNX3 monoclonal antibodies. In normal gastric mucosa, RUNX3 was expressed most strongly in the nuclei of chief cells as well as in surface epithelial cells. In chief cells, a significant portion of the protein was also found in the cytoplasm. RUNX3 was not detectable in 43 of 97 (44%) cases of gastric cancers tested and a further 38% showed exclusive cytoplasmic localization, whereas only 18% showed nuclear localization. Evidence is presented suggesting that transforming growth factor-β is an inducer of nuclear translocation of RUNX3, and RUNX3 in the cytoplasm of cancer cells is inactive as a tumor suppressor. RUNX3 was found to be inactive in 82% of gastric cancers through either gene silencing or protein mislocalization to the cytoplasm. In addition to the deregulation of mechanisms controlling gene expression, there would also seem to be at least one other mechanism controlling nuclear translocation of RUNX3 that is impaired frequently in gastric cancer.

Duodenal diverticula, discovered incidentally in patients during endoscopic retrograde cholangiopancreatography, are usually asymptomatic, but can be the source of significant morbidity. The aim of this study was to evaluate the indications for endoscopic retrograde cholangiopancreatography, the course of this procedure and complications after this procedure in patients with periampullary diverticulum.Clinical, laboratory, ultrasonographic, and endoscopic retrograde cholangiopancreatography data of 626 patients from a single endoscopy center were retrospectively analyzed.The periampullary diverticulum was identified in 72 patients (11.5%). The difficulty in cannulation of papilla of Vater was encountered in 57 patients (79.2%) with diverticulum compared to 54 patients (9.7%) without diverticulum (P0.001). Cannulation of common bile duct was successful in 592 patients (94.6%). Cannulation of common bile duct failed in 8 patients (11.1%) with diverticulum compared to 26 patients (4.7%) without diverticulum (P = 0.046). Patients without diverticulum (n = 168, 31.9%) had two-times more often dilated common bile ductor = 6 mm without stone on ultrasound compared to patients with diverticulum (n = 12, 17.6%) (P = 0.017). Patients with diverticulum presented 1.8-times more often with retained stone in the common bile duct than patients without diverticulum (16.7% vs. 9.7%). 17.3% of patients developed post-endoscopic retrograde cholangiopancreatography complications, which did not significantly differ in both groups. However, the patients who presented with retained common bile duct stones had higher post-endoscopic retrograde cholangiopancreatography complications (P = 0.011).Cannulation of the common bile duct is more difficult in patients with periampullary diverticulum and requires more skills. Periampullary diverticulum is also associated with higher risk of retained stones in the common bile duct which may lead to higher post-endoscopic retrograde cholangiopancreatography complication rate.

Background and aims: Chronic bowel disturbances resembling irritable bowel syndrome (IBS) develop in approximately 25% of patients after an episode of infectious diarrhoea. Although we have previously shown that psychosocial factors operating at the time of, or prior to, the acute illness appear to predict the development of post-infectious IBS (PI-IBS), our finding of an increased inflammatory cell number in the rectum persisting for at least three months after the acute infection suggested that there is also an organic component involved in the development of PI-IBS. To evaluate this further, we measured expressions of interleukin 1β (IL-1β) and its receptor antagonist (IL-1ra) in these patients to provide additional evidence that the pathogenesis of PI-IBS is underpinned by an inflammatory process. Methods: Sequential rectal biopsy samples were prospectively obtained during and three months after acute gastroenteritis, from eight patients who developed post-infectious IBS (INF-IBS) and seven patients who returned to normal bowel habits after acute gastroenteritis (infection controls, INF-CON). Eighteen healthy volunteers who had not suffered from gastroenteritis in the preceding two years served as normal controls (NOR-CON). IL-1β and IL-1ra gene expressions were assayed by reverse transcriptase-polymerase chain reaction, and their levels of expression were quantitated by optical densitometry after electrophoresis on agarose gel. Results: INF-IBS patients exhibited significantly greater expression of IL-1β mRNA in rectal biopsies than INF-CON patients both during and three months after acute gastroenteritis. Moreover, IL-1β mRNA expression had increased in biopsies taken from INF-IBS patients at three months after the acute infection but no consistent change was observed in INF-CON patients. IL-1β mRNA expression of INF-IBS patients at three months post gastroenteritis was significantly greater than NOR-CON whereas that of INF-CON patients was not significantly different from NOR-CON. Despite these differential changes in IL-1β mRNA expression, no significant changes were observed in IL-1ra mRNA expression among the three groups. Conclusions: These findings indicate that those patients who develop IBS post infection exhibit greater IL-1β mRNA expression, both during and after the infection, compared with individuals who do not develop PI-IBS. We conclude that such patients may be susceptible to inflammatory stimuli, and that inflammation may play a role in the pathogenesis of PI-IBS.

Background: Nucleoside analogues such as lamivudine for chronic hepatitis B have an excellent safety profile while patients are on therapy but reactivation flares occur in 19–50% of patients after stopping therapy, some of whom develop liver decompensation. Aims: To describe and report three cases who developed fatal hepatitis B reactivation after stopping nucleoside analogue therapy. Subjects and results: Three patients are described who developed hepatitis B reactivation and liver decompensation after stopping therapy. One of the three patients was participating in a famciclovir trial and the other two were receiving lamivudine therapy for active hepatitis B infection. All three patients had documented hepatitis B flares, and all had hepatitis B virus DNA detected at that time. All patients developed decompensated liver disease despite one patient having had a prior liver biopsy showing absence of cirrhosis. Reintroduction of lamivudine therapy failed to halt progression of liver decompensation even after hepatitis B virus DNA had been demonstrated to be absent. Sequencing for lamivudine resistant mutants in two cases where serum was available failed to show evidence of mutations associated with lamivudine resistance. Conclusion: Hepatitis B virus reactivation, leading to decompensation and death, are possible complications of treatment withdrawal and patients should be monitored closely if therapy is ceased.

The role of nitric oxide (NO) in tumorigenesis is multifactorial. NO can participate in the complicated process of carcinogenesis by mediating DNA damage in early phases of tumorigenesis, as well as support tumor progression through the induction of angiogenesis and suppression of the immune response. This paper addresses the effects of NO on transcriptional regulation following DNA damage and cyclooxygenase expression in the multistep process of tumorigenesis.

Mr C, a 68-year-old Chinese male with diabetes mellitus, previous stroke and ischaemic cardiomyopathy on clopidogrel, presented with haematochezia. Colonoscopy showed a sigmoid ulcer, which was treated endoscopically. Histology of the biopsy from the ulcer revealed non-specific changes. However, he presented with recurrent bleeding from this non-healing sigmoid ulcer. A review of the histologic specimen revealed CMV intranuclear inclusion bodies. He was treated with intravenous ganciclovir, with no further hematochezia.

The present study investigated the expression and distribution of three isoforms of nitric oxide synthase (NOS) in different anatomical regions of the human stomach and in gastric neoplastic tissues by immunohistochemistry using specific antibodies. Intracellular localization of individual isoenzymes of NOS was detected in normal gastric mucosa. Gastric cancer tissues had a marked reduction of all three NOS isoforms expression. The expression of the endothelial NOS, neuronal NOS and inducible NOS in the tumor tissue was significantly lower than in normal gastric mucosa (P = 0.01, P = 0.02, P < 0.01, respectively). In the tumor tissue the expression of inducible NOS was significantly lower than the expression of both constitutive forms of NOS (P < 0.01). There was a tendency to higher expression of both constitutive forms of NOS in earlier stages T2 of the tumor compared to advanced T4 tumor. In contrast, the expression of inducible NOS was higher than in the advanced T4 tumor than in the earlier stages T2 of the tumor. The mapping of the expression of endothelial NOS, neuronal NOS and inducible NOS in human stomach showed higher expression of NOS isoforms in the distal third than in the proximal third of the stomach (P = 0.03, P = 0.04, P = 0.01, respectively). We conclude that there is greater expression of NOS in the stomach corpus and in antrum than in the proximal third of the normal human stomach mirroring the anatomical predilection of common pathological changes in this part of the human stomach. Furthermore, there was loss of the expression of individual isoenzymes in gastric neoplasms.

Background: To determine the predictive factors of synchronous common bile duct (CBD) stones, data from 878 consecutive patients who underwent cholecystectomy in a university clinic from June 1991 to June 1996 were retrospectively analyzed. Methods: Based on clinical, biochemical, and ultrasonographic criteria, 194 patients were selected for ERCP, 180 preoperative and 14 postoperative. Results: Cannulation of CBD was successful in 192 (99%) patients. Stones were identified in 62 (32%) patients and sphincterotomy was performed in 56 (90%). Duct clearance was achieved in 43 (77%) cases. There was a high predictive value for the presence of CBD stones in patients with cholangitis, present jaundice, and dilated CBD with evidence of stones on ultrasound (75%, 72%, and 67% respectively). A dilated CBD without stone on ultrasound and elevated liver enzymes had less than 40% positive predictive value. History of previous jaundice, pancreatitis, previously raised liver enzymes, and present pancreatitis was predictive in less than 20% of the cases. Univariate analyses revealed that clinical findings of cholangitis and obstructive jaundice, elevated liver enzymes (previous and present), and ultrasonographic findings of stones in a dilated CBD were significant positive predictors. Subanalysis of each elevated liver enzyme revealed that alanine transaminase, aspartate transaminase, alkaline phosphatase, and gamma glutamyl transpeptidase were significant predictors. Both elevated conjugated and total bilirubins were also significant predictors for CBD stones. Conclusion: Multivariate logistic regression analysis on these significant predictors showed that cholangitis (odds ratio [OR]: 10.5), dilated CBD with evidence of stones on ultrasound (OR: 7.4), elevated aspartate transaminase (OR: 2.9), and conjugated bilirubin (OR: 5.3) were jointly significant. The likelihood of having stones in the duct without any of these predictors was 7%, but 99% when all the predictors were positive.