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Ming-Shiang Wu

Publications and source records attributed to Ming-Shiang Wu.

At least 55 records · Page 3Linked to original sources

Patients with functional heartburn are more likely to report retrosternal discomfort during wireless pH monitoring.

BACKGROUND: Although the wireless Bravo pH system is effective, some patients experience retrosternal sensations possibly caused by esophageal sensitivity that may complicate clinical application. METHODS: Ambulatory pH of 40 consecutive patients with GERD who had erosive esophagitis or nonerosive reflux disease, were monitored for 2 days with the Bravo system. Results were stratified and compared on the basis of self-awareness of the intraesophageal capsule. RESULTS: Pathologic acid reflux was diagnosed in 20 patients and normal reflux was diagnosed in 20 patients. Seventeen patients (42.5%) reported retrosternal discomfort, and 12 of them (70.6%) had normal reflux. Patients with retrosternal discomfort were less likely to have moderate endoscopic esophagitis, i.e., Los Angeles classification grades B, C, and D endoscopic esophagitis (p = 0.006), and were less likely to have significantly elevated esophageal acid exposure (p = 0.0036) than those who did not perceive the discomfort. Reported discomfort was not associated with age, gender, or the presence of endoscopic esophagitis. CONCLUSIONS: The negative correlation between Bravo-capsule-induced retrosternal discomfort and esophageal-acid exposure indicates modified mechanical afferent nerve function after long-term acid stimulation. Capsule-induced retrosternal discomfort in the presence of normal acid exposure suggests functional heartburn.

Adult↗

The optimal age threshold for screening upper endoscopy for uninvestigated dyspepsia in Taiwan, an area with a higher prevalence of gastric cancer in young adults.

BACKGROUND: It is estimated that 1% to 2% of patients with dyspepsia are associated with gastric cancer. To avoid missing gastric cancer, most guidelines recommend that patients over 45 years old should undergo EGD for uninvestigated dyspepsia. In Taiwan, however, the prevalence of gastric cancer in younger patients is higher than that of Western countries. The optimal age threshold for endoscopy in patients with uninvestigated dyspepsia in Taiwan remains controversial. Therefore, we aimed to determine an optimal age threshold for screening endoscopy in patients with uninvestigated dyspepsia to avoid missing gastric cancer in Taiwan. METHODS: We reviewed the findings in all adult patients who underwent upper endoscopy because of uninvestigated dyspepsia at the National Taiwan University Hospital. In those patients with confirmed gastric cancer histology, further analysis was performed. Cumulative age frequency distributions for gastric cancer were calculated according to gender and to the presence or the absence of alarm features. The stages of gastric cancer also were analyzed according to the presence or the absence of alarm symptoms. RESULTS: During the 5-year period, a total of 17,894 patients received upper endoscopy caused by uninvestigated dyspepsia. Gastric cancer was found in 225 (12.6 cases per 1000 EGDs) patients who presented with uninvestigated dyspepsia, 135 men and 90 women. Thirty-one (13.7%) and 17 (7.6%) patients were aged less than 45 and 40 years old, respectively. Among these 225 patients with gastric cancer, 114 (50.7%) patients did not have alarm symptoms (simple dyspepsia), whereas 111 (49.3%) had alarm symptoms. About 5.3% (12/225) of gastric cancer cases would have been missed if endoscopy had been omitted in patients without alarm symptoms and aged less than 45 years. The cumulative age relative frequencies of patients with gastric cancer who presented with simple dyspepsia were 1.8 (12/6720), 1.02 (5/4920), and 0.59 (2/3411) cases per 1000 EGDs for uninvestigated dyspepsia in patients aged less than 45, 40, and 35 years, respectively. When the frequencies of gastric cancer were stratified by age and gender, we found a trend of male predominance in older patients but not in younger patients. The cutoff age was 60 years old ( p < 0.05). Early gastric cancer was detected in 9.9% (11/111) and 26.3% (30/114) of patients with and without alarm symptoms, respectively (p = 0.002). CONCLUSIONS: Gastric cancer is not uncommon in patients with dyspepsia aged less than 45 years in Taiwan. The age threshold of screening endoscopy for uninvestigated dyspepsia should be the same for both genders in view of comparable frequencies of gastric cancer in a young age population. Because more than 5% of gastric cancer cases would be missed in Taiwan if endoscopy was omitted in simple dyspeptic patients who were aged less than 45 years, we recommend that 40 years old might be an optimal age threshold for screening endoscopy for uninvestigated dyspepsia in Taiwan, in both men and women patients.

Adult↗

Host-environment interactions: their impact on progression from gastric inflammation to carcinogenesis and on development of new approaches to prevent and treat gastric cancer.

Revelation of the connection between Helicobacter pylori infection and gastric adenocarcinoma has prompted new investigations pertaining to its basic and clinical aspects. H. pylori-induced persistent and uncontrolled gastric inflammation nearly always precedes the development of cancer and is instrumental in initiating a multistep process leading to carcinogenesis. Despite initial optimism about the potential of combination anti-H. pylori therapy to ultimately eradicate gastric adenocarcinoma, recent investigations suggest its use should be targeted and tailored to a selected patient group considering the multifaceted role of H. pylori in disease and the disease heterogeneity of gastric adenocarcinoma. The clinical spectrum of H. pylori infection ranges from asymptomatic gastritis and peptic ulcer to gastric malignancies. The occurrence of one versus another is the result of differences in the magnitude of gastritis, and the current disease paradigm suggests gastric inflammation is common to all H. pylori-associated gastroduodenal diseases. Therefore, the host inflammatory responses to environmental triggers, rather than to bacteria or environmental factors per se, would dictate the variable outcomes of H. pylori infection. Putative factors that are expected to play an important role in stimulating inflammatory pathways and modulating the cross-talk between host and environment are age at the time of infection, environmental cofactors, H. pylori virulence, and host genetics. Elucidation of the intimate relationship between host-environment interaction and gastric inflammation, although currently a formidable task, is essential in the development of new prevention and treatment strategies. Such knowledge might provide clues that allow more accurate prediction of variable outcomes of gastric inflammation and appropriate adjustment of treatment strategies, and might open up novel areas for studying gastric carcinogenesis. The evolving new technologies, such as microarray, proteomic, and functional genomic analyses, promise to shed new light on the immense complexity of the presumed host-environment interactions and will reveal more useful markers for the diagnosis and prognosis of gastric adenocarcinoma.

Adenocarcinoma↗

Distinct chromosomal aberrations of ampulla of Vater and pancreatic head cancers detected by laser capture microdissection and comparative genomic hybridization.

Despite the continuous progress in molecular methodology, the genetic events involved in the carcinogenesis of pancreatic head ductal carcinomas (PHDCs) and ampulla of Vater cancer (AVC) remain largely unknown. Their proximity within the confined region lends them to very similar clinical presentations and operative approaches. However, it is unclear why AVC has a significantly better outcome than PHDCs. The drastic difference may arise from the distinct tumor origins. Therefore, the study of genetic alterations within these two neighboring tumors may elucidate their mechanisms. However, previous genetic analysis of PHDCs may have been influenced by contamination of excessive stromal and inflammatory cells in the background. To date, most comparative genomic hybridization (CGH) studies of pancreatic cancer are based in cell lines or specimens that were not microdissected. Even AVC has a paucity of data. To determine the differences of the genetic alterations of PHDCs and AVC, we used laser capture microdissection combined with degenerated oligonucleotide polymerase chain reaction and CGH to identify the chromosomal aberrations. Frequent gains were found on 5p, 13q, 3q, 8q, 1p, 2p, 2q, 3q, 7p, 8p, 9p, 13q, and 21q, while frequent losses were located on 7p, 18q, 1p, 11q, 16q, 19q, 1q, 2q, 3p, 19p, and 17p in PHDCs. In AVC, chromosomal gains occurred frequently in 7p, 8q, 1q, 2q, 3p, 4p, 7p, 3q, 5p, 20p, 20q, 4q, 5q, 7q, 11p, 12p, 13q, 14q, 18p, 18q, 21q, 9p, 10p, and 15q, and losses frequently in 17q, 1p, 18q, 19p, 5q, 10p, and 10q. This is the first report on the CGH profiles of AVC. These data provide evidence that chromosomal gains/amplifications of AVC differ from those of PHDCs. Among them, chromosomal gains on 1q25, 7p15, 8q23, and 3p21, and losses on 17q24, were statistically higher in AVC than PHDCs (P<0.05). The gains and losses suggest possible putative tumor suppressors and oncogenes that may be involved in the different carcinogenic pathways of AVC.

Adult↗

Heart rate variability in patients with different manifestations of gastroesophageal reflux disease.

BACKGROUND: Autonomic nervous dysfunction has frequently been observed in patients with gastroesophageal reflux diseases (GERD) and impacts the pathogenesis of GERD. However, the characteristics that distinguish between GERD patients with different manifestations remain unknown. AIM: To investigate the autonomic nervous function in subgroups of GERD patients. PATIENTS: Of the 164 participants in this study, 57 were healthy controls, 34 had non-erosive reflux disease (NERD), 40 had symptomatic esophagitis (SE), and 33 asymptomatic esophagitis (AE). METHODS: Resting autonomic activity was assessed by measuring the 5-min heart rate variability (HRV) and HRV indices including time-domain parameters (standard deviation of normal-to-normal intervals [SDNN] and root mean square of successive differences [RMSSD]) and frequency-domain parameters (low-frequency power [LF; 0.04-0.15 Hz], high-frequency power [HF; 0.15-0.4 Hz], and LF/HF power ratio). Mental stress was assessed by use of a self-reported questionnaire (Brief Symptom Rating Scale [BSRS]). RESULTS: HF power was (ANOVA, p=0.041) but time-domain parameters, LF power, LF/HF power ratio, and BSRS parameters were not significantly different between the four groups. A higher HF power was found in examinees with NERD than in those with SE and AE (LSD methods: both p=0.02). When split into two groups (erosive vs. non-erosive), nearly all measures of autonomic tonus were significantly lower in the erosive than non-erosive group. Age and the presence of endoscopic esophagitis influenced the RMSSD and HF power results in the regression analysis. Mental stress or gender did not correlate with any HRV index. CONCLUSION: In comparison with NERD subjects, autonomic tonus in patients with endoscopically confirmed esophagitis (even without symptom) is lower. This finding may suggest that the structural state of esophagus but not symptomatology dictates autonomic function status.

Adult↗

Nuclear expression of BCL10 or nuclear factor kappa B predicts Helicobacter pylori-independent status of early-stage, high-grade gastric mucosa-associated lymphoid tissue lymphomas.

PURPOSE: A high percentage of early-stage, high-grade gastric mucosa-associated lymphoid tissue (MALT) lymphomas remain Helicobacter pylori dependent. t(11;18)(q21;q21), a genetic aberration highly predictive of H. pylori-independent status in low-grade gastric MALT lymphoma, is rarely detected in its high-grade counterpart. This study examined whether nuclear expression of BCL10 or nuclear factor kappa B (NF-kappaB) is useful in predicting H. pylori-independent status in patients with stage IE high-grade gastric MALT lymphomas. PATIENTS AND METHODS: Twenty-two patients who had participated in a prospective study of H. pylori eradication for stage IE high-grade gastric MALT lymphomas were studied. The expression of BCL10 and NF-kappaB in pretreatment paraffin-embedded lymphoma tissues was evaluated by immunohistochemistry and confocal immunofluorescence microscopy. The presence of t(11;18)(q21;q21) was identified by a multiplex reverse transcriptase polymerase chain reaction of the API2-MALT1 chimeric transcript. RESULTS: Aberrant nuclear expression of BCL10 was detected in seven (87.5%) of eight H. pylori-independent and in none of 14 H. pylori-dependent high-grade gastric MALT lymphomas (P <.001). All seven patients with nuclear BCL10 expression had nuclear expression of NF-kappaB, compared with only two of 15 patients without nuclear BCL10 expression (P =.002). As a single variable, the frequency of nuclear expression of NF-kappaB was also significantly higher in H. pylori-independent tumors than in H. pylori-dependent tumors (seven of eight [87.5%] v two of 15 [12.3%]; P =.002). The API2-MALT1 fusion transcript was detected in only one (12.5%) of eight H. pylori-independent lymphomas. CONCLUSION: Nuclear expression of BCL10 or NF-kappaB is highly predictive of H. pylori-independent status in high-grade gastric MALT lymphoma, and coexpression of these two markers in the nuclei is frequent.

Adaptor Proteins, Signal Transducing↗

Promoter polymorphisms of tumor necrosis factor-alpha are associated with risk of gastric mucosa-associated lymphoid tissue lymphoma.

Genes involved in regulating antimicrobial immunity and inflammation may modulate the risk of Helicobacter pylori-associated diseases. IL-1 and TNF-alpha are major cytokines detected in H. pylori-infected tissues. We aimed to determine the role of gene polymorphisms for these cytokines and their receptors in 2 distinct H. pylori-related gastric malignancies, adenocarcinoma (GAC) and maltoma. Genotyping for IL-1beta (-31 C/T, -511 C/T), TNF-alpha (-238 G/A, -308 G/A, -857 C/T, -863 C/A, -1031 T/C), TNFR1 (-383 A/C) and TNFR2 (196 G/T) was undertaken for 70 patients with maltoma and 204 patients with noncardia GAC and compared to 210 unrelated healthy controls. Genotype frequencies showed no differences among patients with GAC or maltoma and controls for IL-1beta, TNFR1 or TNFR2. The TNF-alpha -857 T variant was significantly underrepresented in maltoma compared to controls (6.4% vs. 14.3%, p = 0.018), conferring a 3-fold decrease in risk (OR = 0.33, 95% CI 0.15-0.75). Comparison of allele frequencies between GAC and controls failed to show any statistical significance for TNF-alpha polymorphisms. We concluded that TNF-alpha -857 T itself or a neighboring gene may modify the risk of maltoma. The differences in genetic background as well as divergent clinicopathologic features between GAC and maltoma support the notion that fundamental mechanistic differences exist in these 2 well-defined H. pylori-related malignancies.

Adenocarcinoma↗

Modification effects of GSTM1, GSTT1 and CYP2E1 polymorphisms on associations between raw salted food and incomplete intestinal metaplasia in a high-risk area of stomach cancer.

Incomplete intestinal metaplasia (IM) is a precursor of stomach cancer. To identify risk factors of incomplete IM, a 2-stage survey was carried out in 1995 among 1,485 residents in Matzu, an area with highest mortality from stomach cancer in Taiwan. There were 312 study subjects including 174 men and 138 women sampled for the gastroendoscopic examination of IM. Information on personal and familial history of stomach cancer, cigarette smoking, alcohol consumption and intake frequency of various salted food items were obtained by personal interview based on a structured questionnaire. Blood samples were collected from each participant. Four biopsies per subject were taken from all subjects at gastroendoscopic examination to diagnose the status of IM pathologically. The Helicobacter pylori in biopsies was detected by the histomorphological or immunochemistry method, and antibodies against H. pylori in serum by the enzyme-linked immunosorbent assay. Plasma level of selenium was determined by atomic absorption spectrometry, plasma level of retinol, alpha-tocopherol, alpha-carotene, and beta-carotene by high performance liquid chromatography, genotypes of glutathione S-transferase (GST) M1 and T1 and cytochrome P450 (CYP) 2E1 by polymerase chain reaction. The significant association between history of stomach cancer among first-degree relatives and incomplete IM was found (odds ratio [OR] = 2.50; 95% confidence interval [CI] = 1.15-5.43). There was no association between H. pylori infection and incomplete IM. Alcohol drinkers for >20 years had an elevated risk compared to non-drinkers (OR = 3.34; 95% CI = 1.19-9.39). No associations between incomplete IM and plasma levels of selenium, retinol, alpha-tocopherol, alpha-carotene and beta-carotene were found. Salted food including salted meat, dehydrated salted vegetables and raw salted seafood consumed at ages of </=15 and 16-30 years old was associated with an increased IM risk with OR ranging from 2-3. More striking associations between incomplete IM and salted food intake were observed among subjects with genotypes of GSTM1 null, GSTT1 non-null and CYP2E1 c1/c1. Our study suggests the importance of gene-environment interaction on the development of incomplete IM.

Adolescent↗

Colonic abscess.

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Abscess↗

Low prevalence of Helicobacter pylori but high prevalence of cytomegalovirus-associated peptic ulcer disease in AIDS patients: Comparative study of symptomatic subjects evaluated by endoscopy and CD4 counts.

BACKGROUND AND AIMS: The role of Helicobacter pylori infection in gastroduodenal lesions might be different between the general population and AIDS patients. The aim of the present study was to compare the prevalence of H. pylori and cytomegalovirus (CMV) infection in AIDS patients and HIV-negative controls. The impact of CD4 lymphocyte counts on H. pylori and CMV infection in the same subjects was also assessed. METHODS: One hundred and fifty-six patients (52 HIV-positive, 104 HIV-negative) with gastrointestinal symptoms were evaluated with upper gastrointestinal endoscopy and biopsy. Comparison of the prevalence of H. pylori and CMV infection was made by dividing AIDS patients into two groups: those with CD4 counts >100/mm3 and those with CD4 counts <100/mm3, and ulcer and non-ulcer patients. RESULTS: In comparison with HIV-negative controls, AIDS patients had a lower prevalence of H. pylori infection (P < 0.0001) but a higher prevalence of CMV infection (P < 0.0001). Cytomegalovirus infection was frequently found in AIDS patients with CD4 count <100/mm3, in comparison with those with a CD4 count >100/mm3. In AIDS patients, CMV was more frequently detected in subjects with peptic ulcers (P = 0.0125). Conversely, the prevalence of H. pylori infection in AIDS patients was not different between those with and without peptic ulcers. CONCLUSIONS: The low prevalence of H. pylori infection and peptic ulcer in AIDS patients suggests a different role of H. pylori infection in peptic ulcer or even a different mechanism of peptic ulcerogenesis in HIV-positive subjects. Cytomegalovirus, rather than H. pylori, may be the main causative pathogen of peptic ulcers in AIDS patients.

AIDS-Related Opportunistic Infections↗

Relationship between Helicobacter pylori infection and erosive gastroesophageal reflux disease.

BACKGROUND AND PURPOSE: The role of Helicobacter pylori in the pathogenesis of gastroesophageal reflux disease remains controversial. The aims of the study were to assess the factors that influence the severity of erosive esophagitis in Taiwanese and to determine the prevalence of H. pylori infection in symptomatic patents. METHODS: Patients with erosive esophagitis confirmed by upper endoscopy from January 2002 to December 2002 at National Taiwan University Hospital were enrolled. The severity of erosive esophagitis was graded endoscopically according to the Los Angeles classification. H. pylori infection was determined by pathology and culture of biopsies at the gastric body and/or antrum. A sex-matched control was selected to determine the prevalence of H. pylori infection. RESULTS: A total of 104 patients were recruited for the study, 3 of whom were excluded due to previous eradication of H. pylori infection. The prevalence of H. pylori infection in the 101 eligible patients with erosive esophagitis was 34.7%, which was significantly lower than the 64.9% prevalence in the control group (p < 0.001). Age and hiatal hernia were significantly associated with the severe erosive esophagitis (odds ratio, 1.05 and 4.44, respectively). H. pylori infection status, gender, smoking, alcohol drinking, and coexistent systemic diseases such as diabetes and hypertension were not correlated with the severity of erosive esophagitis. CONCLUSIONS: The overall prevalence of H. pylori infection was significantly lower in symptomatic patients with erosive esophagitis than in controls. Age and hiatal hernia were significantly associated with the severity of erosive esophagitis. H. pylori infection was inversely correlated with the occurrence of erosive esophagitis, but was not correlated with its severity.

Adult↗

Effect of interleukin-1beta and glutathione S-transferase genotypes on the development of gastric mucosa-associated lymphoid tissue lymphoma.

e tested whether polymorphic variations in glutathione S-transferase genes (GSTM1, GSTT1, GSTP1) and interleukin-1 (IL-1beta and IL-1RN) genes confer susceptibility to mucosa-associated lymphoid tissue lymphomas (MALT) in a Chinese population. The rates of GSTM1, GSTP1, IL-1beta and IL-1RN genotypes did not differ between patients and controls. However, GSTT1 null genotypes were significantly more common in patients with MALT lymphomas (43/75 vs. 138/321, p=0.029; OR=1.8, 95% CI: 1.1-3.0) than in controls. Our results suggest that a glutathione S-transferase defect plays a role in MALT lymphoma.

China↗

Urgent bedside endoscopy for clinically significant upper gastrointestinal hemorrhage after admission to the intensive care unit.

OBJECTIVE: To investigate the sources of hemorrhage and use of endoscopic hemostasis in patients with clinically significant upper gastrointestinal (UGI) hemorrhage after admission to the intensive care unit (ICU). DESIGN AND SETTING: Prospective study, 123 beds of ICU in a 1,629-bed medical center. MEASUREMENTS AND RESULTS: Of the 9,512 consecutive admissions over a 2-year period 105 UGI hemorrhage patients underwent urgent bedside UGI endoscopy. We compared two groups of these patients, one receiving and the other not receiving endoscopic hemostasis. Ulcers with profusely bleeding stigmata occurred in 31 patients (29.5%), ulcers with clean bases or firmly adherent blood clots in 27 (25.7%), stress-related mucosal diseases in 23 (21.9%), esophageal varices in 5 (4.8%), malignancy in 4 (3.8%), and no detectable bleeding site in 15 (14.3%). Endoscopic hemostasis was attempted in 34 patients (32.4%). Primary hemostasis for them was achieved in 67.6% and the rebleeding rate was 30.4%. In-hospital mortality rate was 77.1% and death related to hemorrhage 6.2%. Length of ICU stay before endoscopic diagnosis was significantly shorter in those who underwent endoscopic hemostasis than those who did not (28.2+/-26.3 vs. 41.2+/-57.5 days). CONCLUSIONS: Endoscopic hemostasis may be more beneficial when the period between ICU admission and development of hemorrhage is shorter. Bleeders can be more readily identified and controlled endoscopically in such patients. A significant proportion of bleeding sites cannot be identified by UGI endoscopy. It may indicate higher risk of small bowel hemorrhage in these critically ill patients.

Adolescent↗

Interleukin-10 genotypes associate with the risk of gastric carcinoma in Taiwanese Chinese.

The association of cytokine genotypes with gastric carcinoma (GC) may be influenced by environmental factors and varies among different populations. Few studies have addressed the impact of different cytokine genotypes on the development and progression of GC. We analyzed 11 functional polymorphisms in tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1, IL-4 and IL-10 genes in 220 Taiwanese Chinese with GC and in 230 healthy controls. The risk of genotypes was adjusted with confounding environmental risks. Our results revealed that the frequency of Helicobacter pylori infection [odds ratio (OR) 1.7, 95% confidence interval (CI) 1.19-2.56], cigarette smoking (OR 2.02, 95% CI 1.38-2.95) and high IL-10 producer genotype (OR 2.67, 95% CI 1.29-5.50) was significantly increased in the entire GC patients. Among different subtypes of GC, a higher risk of developing diffuse type (OR 1.64, 95% CI 1.01-2.67) or cardia cancer (OR 2.44, 95% CI 1.13-2.67) was observed for the CT/CC genotype of IL-4 at the position -590, whereas the high IL-10 producer genotype was significantly linked with the risk of cardia cancer (OR 3.21, 95% CI 1.06-9.73) or advanced stage (OR 2.29, 95% CI 1.12-4.64). No association was noted between GC and controls in the distribution of IL-1 and TNF-alpha genotypes. Logistic regression analyses revealed that H. pylori infection (OR 1.7, 95% CI 1.14-2.52), cigarette smoking (OR 1.87, 95% CI 1.27--2.96) and IL-10 genotype (OR 2.54, 95% CI 1.24-5.61) are independent risks for GC. Independent effects of IL-10 genotype, H. pylori infection and cigarette smoking indicate that carcinogenesis of GC is influenced by a variety of host and environmental factors.

China↗

Simplified 13C-urea breath test with a new infrared spectrometer for diagnosis of Helicobacter pylori infection.

BACKGROUND AND AIM: Infrared spectrometry has correlated excellently with mass spectrometry in detecting the ratio of 13CO(2) to 12CO(2) in breath samples. The present study aimed to evaluate the accuracy of the 13C-urea breath test (13C-UBT) using a new model of infrared analyzer. METHODS: A total of 600 patients who were undergoing upper endoscopy without receiving eradication therapy were entered into the study. Culture, histology, and rapid urease test on biopsies from the antrum and corpus of the stomach were used for the determination of Helicobacter pylori infection. Breath samples were collected before and 20 min after drinking 100 mg 13C-urea in 100 mL water. The optimal cutoff value was determined by the receiver operating characteristic curve. RESULTS: Of the 586 patients who were eligible for analysis, 369 were positive for H. pylori infection, 185 were negative for H. pylori infection, and 32 were indeterminate. When the appropriate cutoff value was set at 3.5 per thousand, a sensitivity of 97.8%, a specificity of 96.8% and an accuracy of 97.5% were obtained using the 13C-UBT. The accuracy of the 13C-UBT decreased when CO(2) concentration in the breath sample was <2%, as compared with > or = 2% (93.6%vs 97.7%), mainly because of a decrease in specificity (81.8%vs 97.7%). There were 2.7% of patients with Delta13CO(2) values that fell between 3.0-4.5 per thousand, in whom the risk of error was 47%. CONCLUSIONS: The 13C-UBT performed with infrared spectrometry is a highly sensitive, specific, and non-invasive method for the detection of H. pylori infection. The immediate availability of the test result and technical simplicity make it particularly effective in routine clinical practice.

Adult↗

Genetic alterations and polymorphisms in gastric cancer.

The etiology of gastric cancer (GC) is multifactorial, and is likely to involve the actions of genes at multiple levels along the multistage carcinogenesis process. This article reviews the considerable progress that has been achieved in understanding the genetics of GC. The genetic effects consist of inherited genetic factors that predispose to GC, and the genetic targets of neoplastic progression that confer altered growth capacity to neoplastic cells. Inherited genotypes include germline mutations of high-penetrance genes directly associated with hereditary GC syndromes and genetic polymorphisms that indirectly affect the susceptibility to GC after exposure to carcinogens or Helicobacter pylori infection. Based on accumulation of different oncogenes or tumor suppressor genes alterations, 2 broad classes of genetic pathways called suppressor and mutator phenotypes are defined that participate in the development and progression of GC. Examples of genes involved in pathogenesis of GC include p53, adenomatous polyposis coli (APC), beta-catenin, E-cadherin, transforming growth factor (TGF)-betaRII, and hMLH1. Delineating genes involved in different subtypes of GC can reflect the heterogeneity and biologic characteristics of GC. Elucidation of the role of inherited genotypes and genetic alterations at different stages of gastrocarcinogenesis may provide a more coherent picture of the mechanism of this devastating disease and facilitate the development of novel approaches to effective prevention and intervention. Advances in high throughput technologies and functional genomics have rapidly increased our understanding of gene structure and function and its role in disease.

Disease Progression↗

Association of the -160 C --> a promoter polymorphism of E-cadherin gene with gastric carcinoma risk.

BACKGROUND: A -160 C --> A polymorphism in the promoter region of E-cadherin has been shown to decrease gene transcription. This allelic variation might be a potential genetic marker for identifying individuals at risk for cancer. There remains no report regarding the polymorphism of E-cadherin in gastric carcinoma (GC). METHODS: A hospital-based case-control study, including 201 GC cases and 196 unaffected controls, was performed. DNA from peripheral blood samples was examined by polymerase chain reaction-restriction fragment length polymorphism. Logistic regression analyses were used to compute odds ratio (OR) and 95% confidence interval (CI) after adjusted for Helicobacter pylori infection, smoking, and other relevant factors. RESULTS: In 196 healthy Taiwanese, the distribution of genotype C/C was 42.3%, C/A was 48.0%, and A/A was 9.7%. The frequency of variant A/A genotype in GC case (4 of 201, 2%) was significantly lower than that of controls (19 of 196, 9.7%) (P < 0.005), conferring a 5-fold decrease in the risk of GC (OR, 0.20; 95% CI, 0.06-0.56) compared with the C/C genotype. Stratification of the GC cases according to their location (cardia and noncardia), histology (intestinal and diffuse), tumor stage (early and advanced), and lymph node metastasis (positive and negative) failed to reveal any heterogeneity with respect to E-cadherin genotype. CONCLUSIONS: The authors' data suggest that individuals with E-cadherin -160 A/A genotype have a decreased risk of GC. Further work is mandatory to clarify the functional relevance of the A allele in vivo and to confirm the inverse association of the A/A genotype with GC in large epidemiologic studies.

Adenocarcinoma↗

Genetic polymorphisms of cytochrome p450 2E1, glutathione S-transferase M1 and T1, and susceptibility to gastric carcinoma in Taiwan.

BACKGROUND AND AIMS: Cytochrome p450 (CYP) and glutathione S-transferase (GST) enzymes are involved in activation and detoxification of many potential carcinogens. Genetic polymorphisms in these enzymes have been found to influence interindividual and interethnic susceptibility to cancer. Although CYP and GST enzymes are involved in the activation and detoxification of N-nitrosamines and related compound, studies on the relationship between genetic polymorphisms of CYP2E1, GSTT1, and GSTM1 and the risk of gastric carcinoma (GC) are few, and the results have been conflicting. PATIENTS AND METHODS: We conducted a hospital-based case-control study to investigate whether such variations affect the risk of developing GC. Subjects included 356 GC patients and 278 unaffected controls. Peripheral white blood cell DNA was obtained from all subjects. Genotyping of CYP2E1 was performed using a PCR-based restriction fragment length polymorphism assay. Deletion of GSTT1 and GSTM1 genes was assessed by multiplex PCR. RESULTS: The distribution of c2/c2 genotype of CYP2E1, detected by PstI or RsaI digestion, differed significantly between GC patients and controls; the odds ratio was 2.9. It remained significant after adjustment with gender, histological subtypes (diffuse, intestinal, mixed), location (cardia, body, antrum/angle), and stage (early, advanced). In contrast, the prevalence of CYP2E1 DraI polymorphism and GSTT1 and GSTM1 null genotype was similar in controls and GC patients. CONCLUSION: Our findings suggest that the CYP2E1 genotype is a determinant of GC risk in Taiwan.

Adenocarcinoma↗