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Pancreatic ductal adenocarcinoma has been reported to carry a rate mutation high in codon 12 of the K-ras oncogene. To avoid the pitfalls of conventional methods of tissue dissection that might affect the sensitivity and specificity of detecting K-ras mutation, laser capture microdissection (LCM) technique was used. Pancreatic adenocarcinoma tissues were obtained from 15 patients who underwent Whipple's procedure. Selected tissues procured by LCM were analyzed by direct sequencing after polymerase chain reaction amplification of K-ras sequences at codon 12. K-ras mutation was noted in nine patients. All mutations showed G to A substitution at codon 12. The mutational pattern (GGT to GAT) is similar in both western and eastern reports. LCM is a feasible method to effectively obtain pure tumor cells from a surgical specimen. It remains to be determined whether this low mutation rate is a result of relatively early stage of disease or different carcinogenesis in different geographic regions.

Background & Aims: The association of Epstein-Barr virus (EBV) and gastric carcinomas (GCs) has been shown to vary among different populations and certain histological subtypes. Few studies have addressed the status of Helicobacter pylori infection and genetic alterations in these EBV-positive or -negative GCs., Methods: Eleven gastric lymphoepithelioma-like carcinomas (LELCs) and 139 cases of common non-LELCs were evaluated for the presence of EBV DNA using polymerase chain reaction (PCR) and RNA in situ hybridization. H. pylori infection was determined by anti-H. pylori immunoglobulin G in preoperative sera. Immunostaining for p53, c-erbB-2, and E-cadherin was performed. Microsatellite instability was analyzed by PCR using 10 primers., Results: EBV was detected in 11 (100%) LELCs and in 19 (13.7%) of 139 common GCs. Compared with EBV-negative GCs, gastric LELCs tended to have a relatively higher frequency of proximal location, diffuse histological subtype, p53 overexpression, and reduced E-cadherin expression but a lower frequency of lymph node metastasis, previous H. pylori infection, and c-erbB-2 overexpression. In contrast, no significant difference of clinicopathologic and genetic profiles was observed between EBV-positive non-LELC GCs and EBV-negative GCs. No correlation of microsatellite instability was found among these 3 subsets of GCs., Conclusions: Dissecting clinicopathologic characteristics and infection status of EBV and H. pylori provide additional evidence of etiological and genetic heterogeneity for GC. Distinct clinicopathologic and genetic pathways exist in gastric LELCs, in which EBV may play a more important role than H. pylori infection.

Background: It has been suggested that p53 plays an important part in gastric carcinogenesis but the data remain inconclusive., Methods: Alteration of the tumour suppressor gene p53 was prospectively investigated by immunohistochemistry in 168 primary gastric cancers., Results: Positive staining, indicative of gene mutations, was detected in 34 tumours (20.2 per cent). No correlation was observed between expression of p53 and various clinicopathological factors, including age, sex, tumour site, gross type, tumour size, depth of invasion, lymph node metastases, distant metastases, and tumour node metastasis stage. However, p53 overexpression was different between intestinal and diffuse type gastric cancer. Survival analysis revealed a significant survival disadvantage of p53 expression in diffuse type gastric cancer (P=0.039) but not in the intestinal type. Multivariate analysis of all 168 patients revealed that independent predictors of recurrent disease included age, invasion depth and nodal involvement but not p53 expression., Conclusion: The presence of p53 overexpression may identify a subset of more aggressive tumours with a poor prognosis in diffuse type gastric cancer.

The clinicopathologic features of 221 patients with intestinal-type (IT) gastric cancer were compared retrospectively with those of 290 diffuse type (DT). Intestinal type was characterized by an older mean age (65.0 +/- 10.8 years vs. 56.2 +/- 13 years), a higher male-female ratio (2.56 vs. 1.06), predominance of blood group O (46.2% vs. 31.1%), and frequent habitual smoking (50.7% vs. 31.4%) and drinking (28.5% vs. 17.6%) than did DT. In contrast, DT had a higher frequency of positive history of parent or sibling with gastric cancer (9.3% vs. 4.1%) and blood group A (40.3% vs. 27.6%) than did IT. The distinguishing histologic features of DT included more Borrmann type IV (13.1% vs. 1.3%) but less Borrmann type I (1% vs. 7.2%), more frequent involvement of middle third (26.9% vs. 15.9%) and whole stomach (4.1% vs. 0%), and more peritoneal seeding (15.5% vs. 9%), lymph node metastasis (67.2% vs. 51%), and nerve permeation (34.1% vs. 24.4%), but less Helicobacter pylori infection (55.9% vs. 69.2%) when compared with those of IT. There was no difference in depth of tumor invasion, venous permeation, duodenal involvement, and postoperative survival between IT and DT. These distinct clinicopathologic features between IT and DT in Taiwan suggest the presence of a different pathogenic process for these two histologic subtypes of gastric cancer.

Both insulin-like growth factor II (IGF2) and H19 gene are located on chromosome 11p15.5 in close vicinity to each other, and are imprinted on different parental alleles. Although the exact mechanism remains unclear, loss of imprinting (LOI) leading to the biallelic expression of IGF2 and H19 genes has recently been reported in a variety of tumors. To study the role of IGF2 and H19 genes in gastric carcinogenesis, the LOI and loss of heterozygosity (LOH) status of these two genes were determined in 70 patients with gastric cancer. Among them, 30 patients were heterozygous for IGF2, 28 patients were heterozygous for H19, and 42 patients were heterozygous for either IGF2 or H19 gene. Among the 30 patients who were heterozygous for IGF2, one exhibited LOH (1/30, 3.3%) and 10 exhibited LOI (10/29, 34.5%). None of the 28 patients heterozygous for H19 gene had either LOH or LOI. LOI of IGF2 was more frequently found in the diffuse type (8/15, 53.3%) than the intestinal type (2/14, 14.3%, P < 0.05) gastric cancer. Five out of the six tumors with LOI of IGF2 exhibited overexpression of mRNA, but no obvious alterations of expression of H19 were noted by Northern hybridization. These data suggest that LOI leading to overexpression of IGF2 plays an important role in carcinogenesis of diffuse type gastric cancer.

The status of genetic instability was determined with seven microsatellite markers from 40 patients with primary gastric adenocarcinoma. For those cases with microsatellite instability, alterations of hMSH2 were further investigated by direct sequencing of reverse transcription-polymerase chain reaction products. Twelve (30%) of 40 patients were found to have microsatellite instability. Among them, one patient (1/6, 16.7%) was early gastric cancer and 11 (11/34, 32.4%) were advanced gastric cancer. There were seven patients with diffuse type (7/18, 38.7%), while five (5/22, 22.7%) were intestinal type tumors. The entire coding region of the hMSH2 gene in these 12 affected individuals was amplified and sequenced. Only a 41-year-old female patient with diffuse type advanced gastric cancer showed a GCT to TCT missense mutation at codon 207 with predicted protein change from alanine to serine. Our results indicate that genetic instability plays an important role in gastric tumorigenesis and alterations of the hMSH2 gene are related to only a small portion of sporadic gastric adenocarcinoma with microsatellite instability.

Non-invasive diagnosis of gastric adenocarcinoma (GAC) is usually difficult due to the low sensitivity and specificity of serologic markers,including pepsinogens and gastrin. For the improvement of the diagnostic values of these markers, a "recursive partitioning and amalgamation" algorithm was employed to construct a decision protocol. A total of 636 subjects including 161 healthy subjects, 163 patients with GAC, 196 with gastric ulcer and 116 with duodenal ulcer were enrolled. Serum levels of gastrin, pepsinogen I, pepsinogen II, and the ratio of pepsinogen I / pepsinogen II were determined for each of the subjects. The proposed "decision tree" classifies subjects into five subgroups with different risks of GAC and peptic ulcer, based on the information of age, serum pepsinogen and gastrin levels. Using this novel analysis system, an expected probability of GAC or ulcers could be obtained. Patients with an age > 62 years and a serum level of pepsinogen I < or = 33 ng/ml were strongly indicated for further confirmatory tests of GAC. This treestructured analysis is also helpful in clarifying the interactions between various serologic markers and demographic factors.

To study the molecular mechanism of gastric carcinogenesis, the frequencies of microsatellite instability were evaluated with seven dinucleotide repeat loci in 59 patients with gastric carcinoma. Microsatellite instability at two or more loci was found in 41.5% (17/41) of advanced gastric carcinoma, 21.4% (3/14) of early gastric carcinoma, but not in remnant gastric carcinoma (0/4), with an overall frequency of 33.9% (20/59). Diffuse gastric carcinoma had a similar prevalence (32.1%, 9/28) to intestinal gastric carcinoma (40.7%, 11/27). The frequency of microsatellite instability in gastric carcinoma was not significantly different with respect to age, sex and Helicobacter pylori infection. Microsatellite instability tended to occur more frequently in cancers of the cardia (62.5%, 5/8) compared with cancers of other stomach regions (31.9%, 15/47), but the difference was not statistically significant. These data suggest that microsatellite instability occurs in early gastric carcinoma and its occurrence increases during tumour progression. Furthermore, its frequency was independent of age, gender, histological types and Helicobacter pylori infection.

This study was carried out to develop a scoring system for the diagnosis of gastric adenocarcinoma (GAC). A total of 686 subjects, 150 patients with GAC, 182 with gastric ulcer, 127 with duodenal ulcer, and 227 subjects with negative findings, were enrolled. Analysis of the likelihood ratio (LR) showed that patients with advanced age, ulcer in the stomach, low serum levels of pepsinogen I (PGI), low PGI x gastrin values, and low PGI/gastrin ratio were likely to have GAC. Of these indicators, the serum PGI level had the greatest weight, with a LR of 7.59 for the group with a level < 30 ng/ml. A scoring system combining serum PGI level, Helicobacter pylori seropositivity, and gastric ulcer status was derived, using a logistic regression model. This scoring system was found to be better than any one-parameter criterion for diagnosing GAC after evaluation by the area under the receiver operating characteristic curve (0.84; 95% confidence interval, 0.81-0.88) or by specificity-fixed sensitivity (sensitivity 0.82 at specificity 0.72, sensitivity 0.87 at specificity 0.66, sensitivity 0.96 at specificity 0.44). This scoring system may be potentially useful as a new model for the noninvasive diagnosis of GAC in the future.

The association between Helicobacter pylori (H. pylori) and gastric adenocarcinoma remains controversial. However, the prevalence of H. pylori infection in gastric adenocarcinoma varies with the method of detection used, eg, serology, histology, culture, and polymerase chain reaction. However, studies on gastric adenocarcinoma by these methods remain inconclusive. We compared the results of serology, histology, and polymerase chain reaction for detection of H. pylori infection in 12 patients with gastric adenocarcinoma to investigate the actual status of H. pylori infection in gastric adenocarcinoma. IgG antibodies to H. pylori were examined in the sera, and histology and polymerase chain reaction were used for identification of H. pylori on the resected gastric tissues of 12 patients with gastric adenocarcinoma. Among them. H. pylori infection was verified by serology in eight, polymerase chain reaction in seven, and histology in five. In all positive cases, H. pylori was identified only in the non-tumorous part of the gastric tissue. In all four seronegative patients, H. pylori was not present in any of the tissues examined by histology and polymerase chain reaction. We conclude that: 1) polymerase chain reaction is more sensitive than histology; 2) a good correlation between serology and polymerase chain reaction is found; and 3) H. pylori infection is absent in a proportion of patients with gastric adenocarcinoma identified by these methods.

The association between gastric adenocarcinoma and Helicobacter pylori infection remains controversial. A seroprevalence study of Helicobacter pylori infection in 143 patients with gastric adenocarcinoma and a control group of 823 subjects randomly selected from four areas in Taiwan, was carried out to elucidate the association. The overall seropositivity of Helicobacter pylori in gastric adenocarcinoma patients (62.9%) was higher than in controls (54.4%), but the difference was not statistically significant (p > 0.05). The seropositivity of early gastric adenocarcinoma (61.5%) was not significantly different from that of advanced gastric adenocarcinoma (63.2%). Various demographic factors such as sex, blood type, cigarette smoking, tumor histology and location were not associated with the seroprevalence of Helicobacter pylori. The age-specific seroprevalence of Helicobacter pylori tended to be higher in younger patients and decreased after the age of 60 years in gastric adenocarcinoma, in contrast to a stepwise increase of seropositivity in controls. This suggests that Helicobacter pylori infection in early life may be a contributory factor in gastric carcinogenesis.

To investigate the association of Helicobacter pylori and gastric ulcer and adenocarcinoma, IgG antibodies against H. pylori were examined in 823 randomly selected subjects, 92 healthy volunteers, 117 patients with gastric ulcer, and 148 with gastric adenocarcinomas in Taiwan, where the prevalence of gastric adenocarcinoma is high. The seropositivity of this population in Taiwan was 54.4%. Gastric ulcer patients had a higher seropositivity (83.8%) than healthy volunteers (62.0%) and gastric adenocarcinoma patients (62.2%) (P < 0.001). Gender difference, blood type, and habit of smoking were not associated with the seroprevalence in any study groups. Gastric ulcer coexistent with duodenal ulcer had a higher seropositivity (94.7%) (P < 0.05). The seropositivity of H. pylori in gastric adenocarcinoma patients was higher than in healthy volunteers only in younger age and was not associated with histologic type, invasion, and location of major tumors. The results reemphasize the association of H. pylori infection with gastric ulcer but not with gastric adenocarcinoma in Taiwan.

The discrepancy between Eastern and Western countries exists regarding the time trends of Barrett's esophagus (BE)/adenocarcinoma. We aimed to elucidate this issue through a retrospective review of the endoscopic and pathological diagnoses of gastroesophageal reflux disease (GERD) over time in a Chinese population. All records were analyzed from 2000 to 2007. Records included demographic data, clinical indication for endoscopy, and endoscopic findings. The total number of endoscopic procedures increased over time. The indications for referral endoscopy secondary to GERD increased from 366 cases (4.9%) in the beginning of the study to 1439 cases (14.1%) at the end. Concomitant GERD symptoms did not significantly change (range, 13–15.1%) in screening endoscopic studies. Endoscopic detection of erosive esophagitis increased in referral populations from 1546 (20.7%) to 5207 cases (51%) and by screening endoscopy from 791 (14.5%) to 1983 cases (23.5%). The prevalence of nonerosive reflux disease and BE did not change over time. BE-associated dysplasia and adenocarcinoma were rare. The detection of Los Angeles class A disease increased with time in referral endoscopy cases with a focus on erosive esophagitis composition. The endoscopic demand for GERD investigation and the GERD endoscopic diagnosis increased in our population. The results were related to a higher prevalence of low-grade erosive disease diagnosed. The incidence of BE-associated dysplasia and adenocarcinoma has been the same and the increased screening did not detect more cancers. [ABSTRACT FROM AUTHOR]