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Background/Aims: C to T transition at the matrix metalloproteinase-9 (MMP-9) promoter site -1562 abolishes a binding site of a putative transcription repressor protein to the C allelic promoter. The aim of this study is to elucidate the significance of MMP-9 genotypes in clinicopathological manifestations of gastric cancer. Methodology: We conducted a case-control study based on previously stored peripheral blood samples from 263 gastric cancer patients and 354 controls. MMP-9 genotyping was analyzed by PCR-RFLP method. Stratified analysis, logistic regression and Cox proportional hazards analysis were used to evaluate the associations between polymorphisms and gastric cancer development, invasiveness, and survival. Results: There was significant correlation between female patients with MMP-9 -1562 C/T or T/T genotype and higher risk of gastric cancer (OR=2.12, p=0.02). On stratified analysis, only elderly females with T allele had higher risk of gastric cancer (OR=2.64, p=0.04). On Cox proportional hazards analysis, serosal invasion (adjusted HR=3.47, p<0.001) and lymph node metastasis (adjusted HR=2.31, p=0.003), but not MMP-9 polymorphism, were independent prognostic factors for survival. Conclusions: MMP-9 -1562 promoter polymorphism with T allele may be used as a marker to predict gastric cancer development in female subjects, especially in the elderly.

Background/aims: Operation may result in various kinds of biological responses in patients who undergo surgery. Recent studies revealed cytokine network is greatly involved in the biological response to surgical stress, as sepsis. Extended surgical injuries may result in a deregulated hyperinflammatory response. However, cytokine and adhesion molecule dynamics of the local area and circulatory blood in perioperative period have not been well clarified., Methodology: 18 patients with colorectal cancer undergoing operation were recruited into the study. The patients were without major systemic disease and without postoperative complications. Serum samples were taken before operation (Preop) and on post-operation day 1 (POD1), day 3 (POD3), and day 7 (POD7). Samples from the drain tube (local) were taken on POD 1, 3, and 7. Interleukin-6 (IL-6) and adhesion molecules, including ICAM-1, P-selectin, E-selectin, and L-selectin, in serum and drain fluid were measured using ELISA., Results: Serum IL-6 was lowest at Preop, and elevated and peaked on POD1. IL-6 levels in serum were significantly lower than those in drain fluid on POD1, 3, and 7. Circulatory IL-6 after surgery is speculated to come mainly from the surgical traumatic area. Serum P-selectin elevated after the operation and peaked on POD1. P-selectin in drain fluid also peaked on POD1. P-selectin in serum was significantly higher than that in the drain fluid on POD1, 3, and 7. By contrast to IL-6, circulatory P-selectin may come from sources other than the local area. Serum ICAM-1 diminished from Preop to POD1, and to POD3. ICAM-1 in drain fluid elevated from POD1 to POD3, and also from POD3 to POD7. ICAM-1 in drain fluid was significantly lower than that in serum on POD1 and 3. The operation resulted in a significant decrease in systemic soluble ICAM-1 levels, which may associate the patients wtih post-operative organ failure. Serum and drain fluid E-selectin and L-selectin dynamics exhibited a similar pattern to that of ICAM-1., Discussion: For the first time, we demonstrate that surgery induced distinguished dynamic differences between local and systemic cytokine and adhesion molecule response. Circulating IL-6 and P-selectin incresaed after surgery and peaked on POD1. By contrast, surgery diminished the circulating ICAM-1 and E-selectin. Modulation of cytokine and adhesion molecule responses in the perioperative period, for example with nutritional or anticytokine therapy, may have potential clinical importance.

Background/aims: The roles of urokinase-type plasminogen activator (uPA) expression in tumor occurrence, invasion and prognosis have been established. However, how uPA genetic polymorphisms influence the occurrence and outcome of tumors is not as clear., Methodology: We conducted a case-control study based on previously stored peripheral blood samples from 237 gastric cancer patients and 242 healthy controls. uPA exon 6 and intron 7 genotypes were determined by direct DNA sequencing. Logistic regression analyses and Cox proportional hazards analyses were used to evaluate the associations between polymorphisms and gastric cancer susceptibility, clinicopathological features, and survival., Results: uPA exon 6 C/T and intron 7 T/C polymorphisms did not correlate well with gastric cancer susceptibility. uPA exon 6 T/C and T/T genotypes were associated with venous invasion and lymphatic invasion, but not with stage, serosal invasion or lymph node metastasis. uPA intron 7 T/C polymorphism did not correlate well with invasive phenotype of gastric cancer. On Cox proportional hazards analyses, uPA exon 6 and intron 7 polymorphisms were not independent prognostic factors for survival., Conclusions: uPA exon 6 C/T polymorphism is associated with invasive phenotype of gastric cancer, but not with susceptibility or survival of gastric cancer. uPA intron 7 is a silent polymorphism.

Background/aims: Proton pump inhibitor-based triple therapy containing immediate-release clarithromycin is an important regimen for the eradication of Helicobacter pylori (H. pylori). However, the efficacy of modified-release clarithromycin for the treatment of H. pylori-associated peptic ulcer disease is still unknown. The aims of the study were to compare the efficacy of modified-release clarithromycin and immediate-release clarithromycin on the rates of ulcer healing and eradication of H. pylori., Methodology: One hundred and sixty-one patients with Helicobacter pylori-associated peptic ulcer were randomized to receive one-week triple therapy with either modified-release clarithromycin 1000mg once daily (AECMR) or immediate-release clarithromycin 500mg twice daily (AECIR) in combination with amoxicillin 1,000mg twice daily (A) and esomeprazole 40mg once daily (E). Post-treatment ulcer healing status and Helicobacter pylori status was determined by endoscopy and 13C urea-breath test at 16 weeks and 8 weeks after completion of triple therapy, respectively., Results: Helicobacter pylori eradication rates were 87.5% and 87.7% for AECMR and AECIR, respectively, in the intent-to-treat analysis. Eradication rates in the per-protocol groups were 90.3% and 91.4% for AECMR and AECIR, respectively. In both the intent-to-treat and per-protocol analyses, the eradication rates were comparable in the AECMR and AECIR groups (p= 1.0 and 1.0, respectively). Ulcer healing rates in the intention-to-treat analysis were 81.3% and 77.8% for AECMR and AECIR, respectively. Ulcer healing rates in the per-protocol analysis were 90.3% and 90.0% for AECMR and AECIR groups, respectively. In both the intention-to-treat and per-protocol analyses, the ulcer healing rates were comparable in the AECMR and AECIR groups (p=0.645 and 0.584, respectively)., Conclusions: Modified-release clarithromycin 1000mg once daily can be used as an alternative to immediate-release clarithromycin 500mg twice daily for the treatment of Helicobacter pylori-associated peptic ulcer disease.

Background/aims: Interindividual differences in degrees and extent of gastritis are responsible for the divergent outcomes after H. pylori infection. Cellular responses in gastric inflammation are mediated by lipopolysaccharide of H. pylori, which activate monocytes to express cytokine expression and growth factors via CD14 and toll-like receptor 4 (TLR4). Whether functional polymorphisms of TLR 4 and CD14 account for H. pylori-related gastric malignancies remains unknown. This study aimed to investigate the contribution of CD14 and TLR4 genotypes to the risk of H. pylori-related gastric malignancies in a Chinese population., Methodology: Genotyping for CD14 (-159C/T) and TLR4 (Asp 299Gly and Thr 399Ile) was performed in 70 patients with gastric mucosa-associated lymphoid tissue lymphoma (MALToma), 204 patients with non-cardia gastric adenocarcinoma (GAC), and 210 unrelated healthy controls. Distribution of genotype and allele frequencies among three groups was compared., Results: The seropositive rate of H. pylori was significantly higher for non-cardia GAC (164/204, 80.4%) and MALToma (66/70, 94.3%) than controls (120/210, 57.5%, p<0.001). A complete absence of Gly or Ile variants was noted for all the studied subjects. The genotype frequencies of CD14 in controls were C/C, 25.7%, C/T, 48.6%, and T/T, 25.7%, and did not deviate from the Hardy-Weinberg equilibrium. The distribution of CD14 genotype did not differ significantly among GAC, MALToma patients, and controls., Conclusions: These data suggest no apparent association of CD14 polymorphisms with H. pylori-related gastric malignancy and provide evidence for race-specific distribution of TLR4 alleles in Chinese population.

Background/aims: H. pylori and NSAIDs are the two most important pathogenic factors in gastric ulcer. NSAIDs and H. pylori share common pathogenic characteristics, but have different effects in modulating COX-2 and local cytokines in gastric ulcer mucosa. This study was designed to explore the influence of COX-2 and local cytokine expressions in gastric ulcer mucosa induced by H. pylori infection and NSAID use., Methodology: Twenty-three patients were recruited. Sixteen subjects were infected with H. pylori. Fifteen patients used NSAIDs. Gastric biopsy specimens were obtained by endoscopy. COX-2 and local cytokine mRNA expressions were assessed by real-time RT-PCR., Results: COX-2 and local cytokines were over-expressed in gastric ulcer and were positively intercorrelated. H. pylori did not alter COX-2 and local cytokine expressions in gastric ulcer, but induced IL-8 and COX-2 in antral mucosa. NSAIDs inhibited COX-2 expression in gastric ulcer, but had no effect on other local cytokines. COX-2 inhibition by NSAIDs in gastric ulcer was compatible with the findings that NSAIDs delayed gastric ulcer healing., Conclusions: H. pylori increased IL-8 and COX-2 in the antral mucosa, but did not influence COX-2 and local cytokines in gastric ulcer. NSAIDs inhibited COX-2 in gastric ulcer and delayed gastric ulcer healing.

Background/aims: Helicobacter pylori (H. pylori) infection is a major risk factor of peptic ulcer, gastric cancer, and gastric mucosa-associated lymphoid tissue (MALT) lymphoma. The interplay between H. pylori and host is an important issue for elucidation of pathogenesis of H. pylori-related diseases. We aimed to examine simultaneously dynamic changes of multiple molecular pathways of infection affected by different H. pylori strains by cDNA microarrays., Methodology: To elucidate the cross-talk between H. pylori and gastric epithelial cells, we isolated three different H. pylori strains from patients with gastric cancer (GC), duodenal ulcer (DU), and gastric MALT lymphoma (MA). The bacteria were co-cultured with gastric epithelial cells (AGS) and total RNAs were extracted from AGS cells and used for detection of genes represented in the microarray., Results: Of the 12,814 clones on the microarray, there were 522 genes expressed differently in the three groups. Of the 522 genes, there were 4 genes, 4 genes and 13 genes, either up- or down-regulated more than twofold change, in AGS cells induced specifically by GC, MA, and DU strain, respectively. The GC and DU strains induced more genes involving in carcinogenesis, such as pim-1, jun B, and VEGF., Conclusions: Our data by cDNA microarray suggest bacterial factors may determine the outcomes of H. pylori infection. The expression profiles of cDNA microarray provide clues for diagnosis, treatment, and prevention of H. pylori-related gastroduodenal diseases.

Background/aims: To determine whether there are different causes of acute lower gastrointestinal bleeding and different clinical courses in patients (a) with comorbid illnesses vs. (b) patients with only severe hematochezia., Methodology: From January 2001 to December 2003, 107 hospitalized patients with acute lower gastrointestinal bleeding were evaluated by urgent colonoscopy. Our analyses compared the etiology and clinical characteristics of bleeding in patients with (group A) and without (group B) one or more comorbid illnesses., Results: Group A patients tended to have longer hospital stays, more severe anemic conditions, and more transfusion requirements. The overall mortality rate was 29.5% in group A and 4.3% in group B (p < 0.05). Bleeding-related mortality was not significantly different between groups. Colitis, rectal ulcer, and angiodysplasia were the leading causes of lower gastrointestinal bleeding in group A. Rectal ulcer was a more common cause of bleeding in group A (16.4%) than in group B (2.1%) (p < 0.05), and it resulted in longer hospital stays and more severe anemia and leukocytosis compared to patients with other causes of lower gastrointestinal bleeding., Conclusions: Patients with acute lower gastrointestinal bleeding that starts after hospitalization for other comorbid illnesses have distinctive etiologies and clinical characteristics compared with ordinary patients admitted to the hospital with only bleeding. Rectal ulcer is an important but obscure cause of acute lower gastrointestinal bleeding in elderly patients with significant comorbid diseases.

Background/aims: A new wireless esophageal pH monitoring device, the Bravo system, had been tested in the US with favorable results over conventional systems. However, its clinical application in eastern countries remains limited. The aim of the study was to assess the efficacy of the Bravo system in an Asian population, and compare it with the western results., Methodology: Thirty consecutive patients with clinically evident gastroesophageal reflux disease underwent esophageal pH monitoring by using the Bravo system. The Bravo capsule capable of measuring and transmitting pH data was introduced into the squamocolumnar junction and fixed on the esophageal mucosa through a locking pin. All patients were instructed to carry the receiver for a 48-hour study., Results: Twenty-nine (97%) of the 30 patients were successfully tested. In most cases (26/30, 87%) the capsules were placed without conscious sedation. All patients had successful capsule placement; however, two of them had failed the initial capsule attachment and required a second capsule. All patients had successful 24-hour recordings (30/30, 100%), while the successful 48-hour recording rate was 97% (29/30). A minor mucosal injury caused by inadvertent capsule extraction was the only complication (1/30, 3.3%)., Conclusions: Compared to the western experience, the new wireless pH monitoring system achieved a comparable attaching rate and recording efficacy. Potential complication was rare and self-limited.

Background/aims: Central vein catheters for patients receiving total parenteral nutrition have a high incidence of colonized catheters and catheter-related bloodstream infections. However, the actual incidence and bacterial pattern have not been well studied. This study was undertaken to investigate the difference in bacteriology between colonized catheters and catheter-related bloodstream infections., Methodology: From January 1997 to March 1998, 354 patients receiving total parenteral nutrition were included in this study. The patients ranged in age from 49 to 80 years, 151 women and 203 men. Colonized catheters and catheter-related bloodstream infections were defined., Results: The culture was performed in 249 catheter tips (249 of 614, 40.6%). Sixty tips were found to have organisms. The organisms cultured from colonized catheters were Gram(+) aerobic bacteria (34, 56.7%), fungi (14, 23.3%), and Gram(-) aerobic bacteria (12, 20%). The organisms cultured from catheter-related bloodstream infections were fungi (16, 64%), Gram(-) aerobic bacteria (5, 20%), and Gram(+) aerobic bacteria (4, 16%). Dermatogenic infection in colonized catheters should be stressed, but systemic fungal infection in catheter-related bloodstream infections should be emphasized., Conclusions: A striking difference exists in bacterial species between colonized catheters and catheter-related bloodstream infections. Further studies on different treatment strategy for colonized catheters and catheter-related bloodstream infections should be undertaken. The combined approach of a total parenteral nutrition team, sterile protocols, and early diagnosis of fungemia should be advocated for the total parenteral nutrition patients.

Background/aims: COX-2 (Cyclooxygenase-2) is the inducible isoform of cyclooxygenase in response to cytokines, mitogens, and growth factors and may induce carcinogenesis through the mechanisms of inhibiting apoptosis, increasing cell proliferation, and enhancing angiogenesis. This study aimed to clarify the relationship of COX-2 and p53, a well-known tumor suppressor gene, in gastric carcinoma., Methodology: Immunohistochemical staining of nuclear p53 protein and cytoplasmic COX-2 protein were utilized on tumor tissue sections from 65 surgical specimens. Their correlation was further analyzed according to pathologic characteristics., Results: There were 47% (16/34) of high COX-2 expression in the high p53 immunoreactivity group but only 19% (6/31) of high COX-2 expression in the low p53 immunoreactivity group. COX-2 overexpression significantly correlated with the accumulation of nuclear p53 protein in general (p = 0.035). Analysis based on different pathologic characteristics revealed that COX-2 correlates with p53 in subsets of advanced, cardiac, and H. pylori (-) gastric carcinomas (p = 0.027, 0.048, 0.036, respectively). But the relationship does not differ between Lauren's intestinal- and diffuse-type gastric carcinomas., Conclusions: Our work provides evidence linking COX-2 and p53 in gastric carcinogenesis, but the mechanism how they interact to promote tumorigenesis remains to be elucidated.

Background/aims: Interleukin-1 beta (IL-1 beta) plays an important role in gastric inflammation and physiology. Functional polymorphisms of IL-1 beta gene have been related to different risks of gastric cancer and duodenal ulcer but their role in gastric ulcer remains unknown. In this study, we investigate a plausible association between gastric ulcer and the polymorphisms in the IL-1 beta and IL-1 receptor antagonist (IL-1RN) genes. The relationships among the cytokine genotyping, other environmental risks such as Helicobacter pylori infection and smoking, and clinical characteristics of gastric ulcer were also determined., Methodology: Peripheral blood DNAs from 120 unrelated Taiwan Chinese patients with gastric ulcer and 238 ethnically matched healthy controls were genotyped for the promoter (position -31 and -511) and Taq I polymorphism (position +3954) in the IL-1 beta gene and the variable number of tandem repeats polymorphisms in intron 2 of the IL-1RN gene. The status of Helicobacter pylori infection was determined by serology., Results: The seropositive rate of Helicobacter pylori (95/120 vs. 134/238, OR: 2.95, 95%CI 1.77-4.91), habitual smoking (67/120 vs. 82/238, OR: 2.40, 95%CI 1.54-3.77) and blood group O (63/120 vs. 98/238, OR: 1.55, 95%CI 1.0-2.41) were significantly higher in patients with gastric ulcer than controls. The distributions of allele frequencies of IL-1 beta (-31 C/T or -511 C/T or +3954) and IL-1RN were similar between patients with gastric ulcer and controls. No significant differences were observed, including those analyzed after stratification of the infected population and by the ulcer subgroup., Conclusions: Our data suggested that Helicobacter pylori infection, cigarette smoking, and blood group O are risk factors of gastric ulcer and IL-1 beta or IL-1RN polymorphisms do not influence susceptibility to gastric ulcer in a Taiwanese population.

Background/aims: Tumor angiogenesis is associated with disease stage in gastric carcinoma. The tumor suppressor p53 was recently reported to regulate angiogenesis. We investigated the relationship between nuclear p53 accumulation and tumor vascularity in gastric carcinoma., Methodology: Patients with gastric carcinoma undergoing surgery were randomly enrolled. Nuclear p53 expression assessed by immunohistochemistry on tumor sections was categorized as higher and lower groups. Tumor vascularity was assessed by counting microvessel density on anti-CD34 stained sections. Tumor vascularity between different p53 expressions was compared based on the different clinicopathologic characteristics., Results: Twenty-three patients had gastric carcinoma with higher nuclear p53 expression and 42 with lower nuclear p53 expression. Vascularity in higher p53 group (54.3 +/- 35.3) was significantly higher than that in lower p53 group (32.1 +/- 29.9) (p = 0.009). Further analysis showed that higher nuclear p53 immunoreactivity was associated with significantly higher vascularity in the advanced gastric carcinoma group (p = 0.023), the intestinal type group (p = 0.003), the non-cardiac group (p = 0.019), and the H. pylori-negative group (p = 0.014)., Conclusions: The present study demonstrated that nuclear p53 protein expression positively associates vascularity in gastric carcinoma although their relationship varies in the different clinicopathologic subsets.

Background/aims: Argon plasma coagulation is an innovative non-touch electrocoagulation technique. A broad spectrum of indications has been proposed for argon plasma coagulation since its introduction into endoscopy in 1991. The aim of this study is to evaluate the efficacy of utilizing argon plasma coagulation in the endoscopic hemostasis of non-ulcer, non-variceal gastrointestinal bleeding in Taiwan., Methodology: A total of 26 consecutive patients (15 men, 11 women; mean age: 67.6 years) underwent argon plasma coagulation treatment between May 1999 and August 2000. Causes of bleeding included angiodysplasia in 3, tumor bleeding in 8, radiation colitis in 11, watermelon stomach in 1, Osler-Weber-Rendu syndrome in 1, and post-intervention in 2. Argon plasma coagulation was performed in 2 patients with bleeders in the esophagus, 10 in the stomach, 1 in the stomach and duodenum, and 13 in the colon., Results: A total of 38 sessions of application in 26 patients were performed. Successful endoscopic argon plasma coagulation treatment was achieved in 21 (80.8%) patients. Neither complication nor mortality related to argon plasma coagulation was observed in these 26 patients., Conclusions: Argon plasma coagulation is a safe, efficacious, and low-cost hemostatic modality for non-ulcer, non-variceal gastrointestinal bleeding. It is mandatory to establish a comparative trial with other treatment modalities with a longer follow-up in the future.

Background/aims: Helicobacter pylori (H. pylori) infection has a causative relationship with various gastrointestinal disorders. 13C-urea breath test and H. pylori stool antigen test are two valuable noninvasive tests for detecting H. pylori infection. Since the bacterial load of H. pylori in the stomach and the resulting severity of gastritis are important in validating the status of H. pylori infection, we would like to investigate the relative diagnostic accuracy of 13C-urea breath test and H. pylori stool antigen test with respect to the severity of gastritis., Methodology: The H. pylori statuses of 62 consecutive patients were evaluated by five tests, i.e., culture, histology, biopsy urease test, 13C-urea breath test, and H. pylori stool antigen test. Gastritis was graded by the updated Sydney system. H. pylori status was defined as positive when the culture was positive or the concordance of positivity of two of the other four tests., Results: Thirty-five patients (56%) were H. pylori positive. The accuracy of H. pylori stool antigen test and 13C-urea breath test were 92.6% and 100%, respectively. There was a positive correlation between the level of delta 13CO2 of the 13C-urea breath test and the optical density value of enzyme immunoassay of the H. pylori stool antigen test (Rho = 0.758, P < 0.001). Both the level of delta 13CO2 of 13C-UBT and the optical density value of enzyme immunoassay of the H. pylori stool antigen test correlated well with the separate score of the density of H. pylori (P < 0.001, each) and the inflammatory activity (each P < 0.001)., Conclusions: Both the 13C-urea breath test and H. pylori stool antigen test are effective non-invasive methods to detect the status of H. pylori infection with respect to correlation with the density of H. pylori and inflammatory activity of gastritis.

Background/aims: To elucidate the relationship among disparate ulcer risk factors in 3 subtypes of gastric ulcer., Methodology: One hundred and fifty-nine age-matched controls, 30 patients with ulcer craters in the gastric body (GU-I), 55 with coexistent gastroduodenal ulcer (GU-II), and 69 with ulcer craters in the prepyloric region (GU-III) were examined for potential risk factors. These included cigarette smoking, nonsteroidal anti-inflammatory drug use, Helicobacter pylori infection, gender and ABO blood group. Using multiple logistic regression analysis, Odds ratios of relevant risk factors associated with different subtypes of gastric ulcer were reported., Results: Among all gastric ulcer subsets, cigarette smoking, nonsteroidal anti-inflammatory drugs use and H. pylori infection were independent ulcer risk factors. For GU-I, smoking (OR: 3.98; 95% CI: 1.44-11.0) and nonsteroidal anti-inflammatory drugs use (OR: 4.33; 95% CI: 1.10-17.1) raised the likelihood of ulceration. For GU-II and GU-III, smoking, nonsteroidal anti-inflammatory drug use and H. pylori infection were identified as risk factors. H. pylori infection carried the strongest association with gastroduodenal ulcer (OR: 9.29; 95% CI: 3.11-27.7) in GU-II, and nonsteroidal anti-inflammatory drug use generated the highest possibility of GU-III (OR: 11.3; 95% CI: 3.49-36.5). Nonsteroidal anti-inflammatory drug use also markedly raised the likelihood of multiple gastric ulcers (OR: 17.0; 95% CI: 4.21-68.9)., Conclusions: Stratification analysis showed differential influences of risk factors on separate subtypes of gastric ulcer. These data support the hypothesis that peptic ulcer disease is heterogeneous in etiology and pathogenesis.

Background/aims: Gastrointestinal tumors with microsatellite instability represent a replication error-positive phenotype. BAT-26, a repeat of 26 deoxyadenosine localized in intron 5 of hMSH2 gene, has been reported as a reliable indicator of replication error phenotype in colorectal cancers. This study investigated whether BAT-26 is a useful marker for a mutator phenotype with distinct clinicopathologic features in gastric cancer., Methodology: One hundred and nineteen gastric cancer tissues and matched non-tumor tissue were examined by polymerase chain reactions with electrophoresis for 9 dinucleotide microsatellites and BAT-26, and frameshift mutations of transforming growth factor-beta type II receptor. The relation between BAT-26 alterations and relevant clinicopathological or genetic parameters were analyzed., Results: Gastric cancer with BAT-26 alterations was highly correlated with multiple microsatellite alterations (> or = 3 loci) and frameshift mutations of transforming growth factor-beta type II receptor, and predominantly showed antral location, intestinal histologic subtype, advanced stage, a higher rate of Helicobacter pylori infection, a better postoperative survival and less lymph node metastasis., Conclusions: These results show testing of BAT-26 alterations is a convenient and rapid screening method for identifying a subset of gastric cancer with a mutator phenotype and better prognosis.

Background/aims: Peroral cholangioscopy with a mother-baby scope system has been introduced for two decades. The paper presents the experience of peroral cholangioscopy at a university hospital in Taiwan where the prevalence of hepatocellular carcinoma and choledocholithiasis was high., Methodology: A total of 27 sessions of peroral cholangioscopy were performed in 26 patients during a period of 4 years. Of them, 20 patients were for diagnosis and the rest 6 for removing the retained biliary stones., Results: The overall successful rate was 96.3%. The post-procedure complication rate was 11.5% with 2 cholangitis and 1 gram-negative septicemia. There were a total of 19 successful diagnostic sessions. These resulted in definite histological diagnosis in 5 patients and more precise diagnoses subsequently confirmed by surgery in 5 patients. In the remaining 9 patients with tentative diagnoses, 5 confirmed their diagnoses but 4 patients changed their diagnoses after peroral cholangioscopy. By this procedure, hepatocellular carcinoma and choledocholithiasis can be well identified and differentiated., Conclusions: Peroral cholangioscopy is a safe and valuable modality in diagnosing and treating difficult biliary tract disease when handled with care. It is particularly useful in an endemic area with high prevalence of hepatocellular carcinoma and choledocholithiasis.

Acute abdomen due to perforation of one of the hollow organs is one of the major challenges for clinicians. Traditionally, pneumoperitoneum shown on X-ray film taken of the decubitus view or in the standing position, is the major key to making a diagnosis of perforation. However, free air is not shown on X-ray film in about one third of cases and sometimes, a standing X-ray cannot be taken in weak patients or for various reasons. In such conditions, abdominal ultrasonography (US) plays a complementary role. Free air is usually detected between the anterior surface of the liver and the anterior abdominal wall by US. However, if free air is not detected on an erect X-ray or not demonstrated over the anterior surface of the liver by US, the diagnosis of perforation of the hollow organ will be difficult. We treated a patient with perforation of a small intestinal lymphoma, which presented as free air over the left flank area by US rather than the anterior surface of liver as is usually the case. Moreover, we located the perforated site pre-operatively by US, which detected focal thickening of a segment of small intestine with intramural slits. Lymphoma of the jejunum with perforation was finally diagnosed after surgery. The value of US is justified in such a condition.

Background/aims: To evaluate the clinicopathological features of lymphoepithelioma-like carcinoma of stomach in Taiwan., Methodology: Of 379 patients with gastric adenocarcinoma, from 1993 to 1996, 6 of them with lymphoepithelioma-like carcinoma of stomach were retrospectively studied., Results: Five patients were females and one patient was male. Their age ranged from 51-75 years with a mean age of 61.5 years. Endoscopically, 2 patients were initially diagnosed as early gastric cancer and the other 4 were diagnosed as advanced gastric cancer. Three patients had tumors located in the lower third of the stomach, while the other three tumors were located in the middle and upper third. Two tumors invaded into the serosal layer and the other four lesions were confined at submucosal and muscular layers. Using the in situ hybridization method, all 6 patients (100%) had positive nuclear Epstein-Barr virus-encoded small RNA signals in the tumor cells but not in the surrounding lymphoid stroma and non-neoplastic gastric mucosa. Helicobacter pylori was found in 4 (66.7%) of the cases. The mean follow-up period of the 6 patients was 27 months. Five patients were free of the disease. Lymph node involvement and mesenteric implantation was noted in one patient in which cancer recurred 1 year after gastrectomy., Conclusions: Lymphoepithelioma-like carcinoma of stomach in this study revealed a female predominance, preferential localization in the proximal part of the stomach, better prognosis, and a high association with Epstein-Barr virus infection.

Background/aims: To access the reliability of a newly developed test, the Helicobacter pylori (H. pylori) stool antigen (HpSA) test was used for detection of H. pylori infection., Methodology: Stool specimens were collected from 33 consecutive patients (19 males and 14 females, age range: 16-73 years, mean: 49 years) who received upper gastrointestinal endoscopic examination for gastrointestinal symptoms. The H. pylori status was evaluated based on six different tests: culture, histology, biopsy urease test, 13C-urea breath test (13C-UBT), serology, and HpSA test. A commercial kit using an enzyme-linked immunosorbent assay examined HpSA in the stool. H. pylori status was defined as positive when the culture was positive or concordance of three of the other four tests (histology, biopsy urease test, 13C-UBT, and serology) was positive., Results: Twenty patients were diagnosed as H. pylori-positive. The HpSA test was positive in 19 patients and negative in 14 patients. The sensitivity and specificity were 95.0% and 100%, respectively. The overall accuracy rate was 96.3%., Conclusions: The HpSA test is a new, simple, non-invasive method for accurate diagnosis of H. pylori infection.

Lymphangioma is an uncommon tumor. Lymphangiomatosis, a benign tumor consisting of a cluster of dilated lymphatic channels, is very unusual. Most lymphangiomatoses are found in the neck and head area. Less than 5% are diagnosed intraabdominally and they are very infrequently encountered in the retroperitoneal area. Herein, we report a rare case of a 32 year-old woman who had disseminated intra-abdominal and retroperitoneal cystic lymphangiomatosis, which presented as acute abdomen. She received exploratory laparotomy due to the suspicion of malignancy, which was finally confirmed as cystic lymphangiomatosis. The clinical manifestations, imaging features, and management of this patient are discussed and compared with previous literature.

Background/aims: Dysphagia and odynophagia are common problems with significant morbidity in acquired immunodeficiency syndrome (AIDS) patients. Endoscopy in AIDS patients with esophageal symptoms is valuable for diagnosis, but the timing and necessity of routine endoscopy remains controversial., Methodology: We retrospectively studied 40 AIDS patients undergoing upper gastrointestinal endoscopy. Among them, 25 patients were enroled with dysphagia and/or odynophagia and were put on empirical fluconazole treatment before endoscopic evaluation., Results: Fourteen (56%) of 25 patients improved after fluconazole treatment, while 11 patients had persistent symptoms. Among the 14 patients with symptomatic improvement, 7 were found to have esophageal candidiasis which improved after continuation of fluconazole for 1-2 more weeks. The other 7 patients had a normal endoscopic appearance. In contrast, among 11 patients with persistent symptoms, there were 3 patients with azole-resistant candidiasis, 3 with cytomegalovirus esophagitis, 1 with herpes simplex virus esophagitis with candidiasis, 1 with Kaposi's sarcoma, and 3 with idiopathic esophageal ulcer. They were successfully treated with Amphotericin B, Ganciclovir, Acyclovior, and oral steroids, except for the patient with Kaposi's sarcoma., Conclusions: Routine endoscopy may not necessarily be indicated in every AIDS patient with dysphagia or odynophagia. Empirical fluconazole treatment can improve symptoms in 50% of patients. It is only indicated when patients have persistent symptoms after empirical treatment. With endoscopic examination, etiologic agents other than common candidiasis can be determined and the patients can thus be put on specific treatment.

Background/aims: Both intestinal metaplasia (IM) and Helicobacter pylori (H. pylori) infection have been linked to gastric carcinogenesis in an age-dependent manner. However, their relationship remains ill defined, especially with respect to age., Methodology: Three hundred and two asymptomatic subjects (167 males and 135 females; mean age 44.3+/-11.1 years) underwent complete endoscopic examination and biopsy at the antrum and the corpus. H. pylori infection was diagnosed according to histopathology and serology, while IM was determined by histopathology., Results: Eighty-four patients (27.8%) had IM, while 185 patients (61.3%) were seropositive to H. pylori. The frequency of IM was higher in patients with gastric ulcer (9/14, 64.3%) than in those with minimal change (68/229, 29.7%) or duodenal ulcer (7/59, 11.9%), both p<0.01. Patients with IM had a higher mean age (49.5+/-14.1 vs. 42.3+/-9.0, p<0.01) and a higher H. pylori prevalence than those without IM (61/84, 72.6% vs. 124/218, 56.9%, p<0.01). The concordance rate of H. pylori infection between histopathologic and serologic diagnosis was lower in patients with IM (67/84, 79.8%) than those without (196/218, 89.9%, p<0.05). Using logistic regression analyses, the development of IM was noted to be independently related to both H. pylori infection (odds ratio=1.97, 95% confidence interval: 1.1(3.53)) and age (odds ratio = 1.93, 95% confidence interval: 1.51(2.47))., Conclusions: These data suggest that age and H. pylori infection are independent risk factors for the development of IM. Furthermore, H. pylori infection may have been underestimated in patients with IM because of the use of a single method of detection.

A 73 year-old female patient suffered from anemia and a palpable abdominal mass. Abdominal ultrasonography and magnetic resonance imaging revealed a lesion with papillary excrescences at the pancreatic tail. Endoscopic retrograde cholangiopancreatography showed a normal pancreatic duct, but a small submucosal tumor was found in the stomach incidentally. Laparotomy disclosed an exophytic tumor arising from the submucosal layer of the stomach. Pathology revealed a gastric leiomyosarcoma with remarkable liquefaction and cystic change. Gastric leiomyosarcoma can be so necrotic as to be mistaken for a cystic tumor. It is critically important to differentiate the peripancreatic cystic lesion because the treatment strategy is totally different.

Background/aims: The frequent association of gastric atrophy and intestinal metaplasia in gastric cancer (GC) might preclude serologic detection of Helicobacter pylori (H. pylori) infection in GC. By using polymerase chain reaction (PCR) for detection, we would like to determine whether there exists a subset of genuinely H. pylori-negative GC patients, and whether they have distinct clinicopathologic features or not., Methodology: IgG antibodies against H. pylori were determined by ELISA in sera, and H. pylori DNA was detected by PCR in resected gastric specimens from 160 GC patients. Clinicopathologic characteristics were then compared among group A: seropositive, group B: seronegative but PCR-positive, and group C: seronegative and PCR-negative., Results: Among 160 patients, 105 (65.6%) were classified as group A, 25 (15.6%) as group B, and 30 (18.8%) as group C. Group B patients were older and had more infiltrative tumor growth than group A. Group C had a significantly higher frequency of female predominance, and their cancers were of a more cardiac location and of the diffuse histologic subtype than those of groups A and B., Conclusions: A significant portion (15.6%) was negative to ELISA but positive to PCR, suggesting that older ages and infiltrative tumor growth might preclude serologic detection of H. pylori infection by impairing humoral responses. Although the majority (81.2%) has a strong association with H. pylori infection, an H. pylori-negative subset indeed exists and has distinct clinicopathologic features, supporting that causes other than H. pylori infection are involved in GC carcinogenesis.

Background/aims: Anomalous pancreaticobiliary ductal union (APBDU) has been proposed as a risk factor of gallbladder cancer. To clarify the frequency and the subtype distribution of APBDU in patients with gallbladder cancer and adenomyomatosis, a retrospective study was performed., Methodology: The radiograms of endoscopic retrograde cholangiopancreaticography of 680 patients with well-documented biliary and pancreatic ducts from April 1992 to November 1996 were reviewed. The length of the common channel and insertion of the pancreatic duct and the bile duct were identified and recorded., Results: Gallbladder cancer and adenomyomatosis were identified in 8 and 12 patients, respectively. Patients with gallbladder cancer were significantly older (mean age: 66.5 years, p<0.01) than those with gallbladder adenomyomatosis (mean age: 42.7 years). APBDU was noted in 59 (8.7%) of 680 cases with complete pancreaticobiliary radiograms. Among them, 5 of 8 patients with gallbladder cancer coexisted with APBDU. Four (80%) belonged to the P-B type. Six of 12 patients with gallbladder adenomyomatosis had APBDU. Five (83.3%) belonged to P-B type., Conclusions: Patients with gallbladder cancer and adenomyomatosis were frequently associated with APBDU. The close relationship and similar distribution of the P-B type of APBDU in both diseases suggest an etiologic association in various gallbladder diseases.

Background/aims: Reduced expression of E-cadherin leading to loss of cellular adhesion is crucial for cancer invasion and metastasis. The aim of this study is to investigate the role of E-cadherin in gastric tumorigenesis., Methodology: Immunohistochemical expression of E-cadherin was analyzed and correlated with clinicopathological characteristics of 122 patients with gastric cancer., Results: Reduced E-cadherin expression was noted in 71 tumors (58.2%), while all normal epithelium showed a normal expression. Correlation of E-cadherin status to histological subtypes and growth patterns revealed a significantly higher frequency of reduced expression in diffuse type (46/60, 76.7%), advanced tumors (48/68, 70.6%) and stage III/IV (39/53, 73.6%) than that in intestinal type (25/62, 40.3%, p<0.0001), early tumors (23/54, 42.6%, p<0.005) and stage I/II (32/69, 46.4%, p<0.005) respectively. Moreover, abnormal expression was more frequent in tumors with positive lymph node metastasis (45/62, 72.6%), peritoneum seeding (10/11, 90.9%) and venous permeation (27/37, 73%) than that in tumors without lymph node metastasis (26/60, 43.3%, p<0.005), peritoneum seeding (61/111, 55.0%, p<0.05) and venous permeation (44/85, 51.8%, p<0.05). There is no statistical difference between E-cadherin expression and the status of perineural invasion or H. pylori infection. Analysis of survival for patients demonstrated that reduced E-cadherin expression was correlated with poor prognosis., Conclusions: These data indicate that impaired expression of E-cadherin is an important characteristic of gastric cancer and contributes to histogenesis, tumor growth, metastasis and poor survival.

Background/aims: Conflicting results concerning the relationships between abnormal expression of p53 and c-erbB-2 and biologic behavior of gastric cancer are noted. Therefore, overexpression of p53 and c-erbB-2 in relation to the following aspects of gastric cancer: tumor histopathology, Helicobacter pylori infection, and prognosis are explored., Materials and Methods: Expression of p53 and c-erbB-2 by immunohistochemistry was correlated with histopathology, H. pylori infection and prognosis of gastric cancer in 112 patients., Results: Positive p53 staining was found in 61 (54.5%) of 112 tumors examined. There was no association of p53 expression with sex, age, lymph node metastasis, H. pylori infection or prognosis. A significantly higher frequency of p53-positive staining was observed in advanced (60.7%), intestinal (69.8%) and cardia (76.5%) than in early (30.4%, p < 0.01), diffuse (34.7%, p < 0.01) and noncardia (50.5%, p < 0.05) carcinoma, respectively. Expression of c-erbB-2 was found in 34 cases (30.3%), and was not related to sex, age, H. pylori infection and tumor location. Tumors with positive c-erbB-2 staining appeared to behave more aggressively in view of higher rates of nodal metastasis (38.0% vs 17.1%, p < 0.05), advanced stage (37.1% vs 4.3%, p < 0.01) and poor mean survival (p < 0.01). Patients with intestinal type tumors also had a significantly higher rate of c-erbB-2 expression than those with diffuse tumors (39.7% vs 18.4%, p < 0.01)., Conclusions: Our results indicate that immunohistochemical expressions of p53 and c-erbB-2 are significantly associated with some histopathological phenotypes. Genetic alterations of c-erbB-2 or p53 may not be affected by H. pylori infection. C-erbB-2 expression may be used as a marker for identifying more aggressive gastric cancer for designing further therapy.

The coexistence of incomplete pancreas divisum and anomalous union of pancreaticobiliary duct is uncommon and, to the best of our knowledge, has been reported only in three patients who also presented with choledochal cysts. We have encountered a 54-year-old patient with symptom of intermittent right upper quadrant pain. Endoscopic retrograde cholangiopancreatography revealed coexistence of incomplete pancreas divisum and anomalous union of pancreaticobiliary duct, but no dilatation of bile duct.

Background/aims: To investigate the frequency of endoscopic transmission of Helicobacter pylori and the efficiency of disinfection in different washing methods of endoscopes., Materials and Methods: IgG antibodies to H. pylori in patients prospectively followed who underwent first endoscopic examination at the National Taiwan University Hospital from 1982 to 1993 were measured. A total of 132 subjects who were negative for H. pylori IgG antibody test before examination and who were with negative endoscopic findings were enrolled. Among the 132 seronegative patients, 60 were examined before June 1989 when manual washing was adopted for endoscope cleaning and 72 received examination after mechanical washing were routinely used in our endoscopy unit., Results: During a follow-up period of 6 months or more, 5 patients in the manual washing group sero-converted while none in the mechanical washing group seroconverted (5/60 vs 0/72. p = 0.02)., Conclusion: The results suggested that the risk of endoscopic transmission of H. pylori is substantial and mechanical washing is efficient in preventing this iatrogenic spread.

The influence of Helicobacter pylori infection on serum levels of pepsinogen I and gastrin in gastric carcinoma was investigated by simultaneous determination of serum pepsinogen I, gastrin, and IgG antibodies against Helicobacter pylori in 100 patients with gastric carcinoma, and in another 100 age- and sex-matched healthy controls. Serum pepsinogen I level was significantly lower in gastric carcinoma than in controls (55.5 +/- 28.1 vs. 76.9 +/- 25.1 ng/ml, p < 0.005), but there was no difference in serum gastrin between them (63.2 +/- 30.2 vs. 57.4 +/- 28.5 pg/ml, p = 0.16). Helicobacter pylori infection caused a significant increase in serum PGI level in advanced, intestinal type, and non-cardia gastric carcinoma. The serum gastrin level was affected by neither Helicobacter pylori infection nor any of the tumor characteristics. It is concluded that pepsinogen I, rather than gastrin, in the serum is greatly influenced by Helicobacter pylori infection and tumor characteristics in gastric carcinoma.

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.