Chang-Yi Chen

The association between Helicobacter pylori infection and functional dyspepsia in patients with irritable bowel syndrome.

OBJECTIVE:Irritable bowel syndrome (IBS) is associated with an exaggerated response to a variety of physiological and nonphysiological gastrointestinal stimuli. Many patients with IBS also have functional dyspepsia. Our aim was to examine the hypothesis that Helicobacter pylori (H. pylori) infection may predispose IBS patients to functional dyspepsia.METHODS:In 69 IBS patients, dyspeptic symptoms, H. pylori status, and sociodemographic and psychological variables (perceived stress, trait anxiety, and depression) were assessed. Sociodemographic and psychological variables were also evaluated in 52 control subjects.RESULTS:Mean scores for perceived stress (17.1 ± 6.0 vs 14.9 ± 6.0, p = 0.05), trait anxiety (45.6 ± 9.1 vs 41.1 ± 7.8, p = 0.004) and depression (9.9 ± 8.4 vs 5.0 ± 5.5, p = 0.0002) were higher in IBS patients than in controls. In all, 33 of the 69 patients (47.8%) had H. pylori infection, and this was associated with relevant symptoms of epigastric pain (odds ratio [OR] = 6.77, 95% confidence interval [CI] 1.89–24.3) and postprandial upper abdominal fullness (OR = 4.23, 95% CI 1.38–13.2). H. pylori infection and female gender were independent predictors of the presence of relevant dyspepsia (OR = 8.31, 95% CI 2.35–29.5 and 6.06, 95% CI 1.71–21.5, respectively). Symptom intensity was associated with the level of perceived stress (total relevant symptom number ≥3 vs <3, OR = 1.16 per point on a 40-point perceived stress scale, 95% CI 1.01–1.34).CONCLUSIONS:In IBS patients, the presence of dyspepsia is associated with H. pylori infection, female gender, and perceived stress.

Combined modalities of resistance in an oxaliplatin-resistant human gastric cancer cell line with enhanced sensitivity to 5-fluorouracil

To identify mechanisms underlying oxaliplatin resistance, a subline of the human gastric adenocarcinoma TSGH cell line, S3, was made resistant to oxaliplatin by continuous selection against increasing drug concentrations. Compared with the parental TSGH cells, the S3 subline showed 58-fold resistance to oxaliplatin; it also displayed 11-, 2-, and 4.7-fold resistance to cis-diammine-dichloroplatinum (II) (CDDP), copper sulphate, and arsenic trioxide, respectively. Interestingly, S3 cells were fourfold more susceptible to 5-fluorouracil-induced cytotoxicity due to downregulation of thymidylate synthase. Despite elevated glutathione levels in S3 cells, there was no alteration of resistant phenotype to oxaliplatin or CDDP when cells were co-treated with glutathione-depleting agent, l-buthionine-(S,R)-sulphoximine. Cellular CDDP and oxaliplatin accumulation was decreased in S3 cells. In addition, amounts of oxaliplatin- and CDDP–DNA adducts in S3 cells were about 15 and 40% of those seen with TSGH cells, respectively. Western blot analysis showed increased the expression level of copper transporter ATP7A in S3 cells compared with TSGH cells. Partial reversal of the resistance of S3 cells to oxaliplatin and CDDP was observed by treating cell with ATP7A-targeted siRNA oligonucleotides or P-type ATPase-inhibitor sodium orthovanadate. Besides, host reactivation assay revealed enhanced repair of oxaliplatin- or CDDP-damaged DNA in S3 cells compared with TSGH cells. Together, our results show that the mechanism responsible for oxaliplatin and CDDP resistance in S3 cells is the combination of increased DNA repair and overexpression of ATP7A. Downregulation of thymidylate synthase in S3 cells renders them more susceptible to 5-fluorouracil-induced cytotoxicity. These findings could pave ways for future efforts to overcome oxaliplatin resistance.

High seroprevalence of IgG against Helicobacter pylori among endoscopists in Taiwan.

A prospective survey to investigate the seroprevalence of IgG againstHelicobacter pylori among endoscopists in Taiwan was conducted by analyzing blood samples of 70 study subjects and 64 nonendoscopist physicians with quantitative ELISA. Personal information and the practices of infection control related to gastroscopy examination were obtained by a self-administered questionnaire. Significant differences were detected in the IgG prevalence between study and control subjects (80.0% vs 51.6%;P<0.05). The serum level of antibody in endoscopists (385.2±36.1 unit/ml) was significantly higher than that of nonendoscopists (211.8±33.0 unit/ml;P=0.018). Endoscopists performing 30 or more sessions of gastroscopy per week had higher seroprevalence than those performing less than 30 sessions (90.9% vs 70.3%;P=0.0126). In conclusion, endoscopists in Taiwan had a high prevalence ofH. pylori infection. The cause might be related to the frequency of gastroscopies performed.

Quantification of Helicobacter pylori infection: Simple and rapid 13C-urea breath test in Taiwan.

Abstract: The 13C-urea breath test (13C-UBT) is a non-invasive method for detecting Helicobacter pylori. This study was performed to determine the cutoff value and evaluate the sensitivity and specificity of 13C-UBT in Taiwan. 13C-Urea (100 mg of 99% 13C-labeled urea) was dissolved in 50 ml sterile water for the test. The test meal for delaying gastric emptying was 100 ml fresh milk. Patients fasted for at least 6 h. A baseline breath sample was collected 5 min after they had the test meal. Two other samples were collected at 15 and 30 min after the patients ingested the 13C-urea. The test was evaluated in 352 patients after routine upper gastrointestinal endoscopy, and the urease test, culture, and histopathology were taken as the gold standards for detecting H. pylori. According to the receiver operating characteristic (ROC) curves, we chose values of 2.8 and 4.2 excess δ13CO2 per mil as the cut-off values for 15 and 30 min, respectively, post 13C-urea. The sensitivity and specificity of 13C-UBT were 99% and 93% at 15 min, and 98% and 93% at 30 min post 13C-urea, respectively. The 13C-UBT breath test is an efficient non-invasive method of high sensitivity and high specificity for detecting H. pylori infection. We suggest that the use of fresh milk as the test meal and the detection of excess δ13CO2 15 min after the ingestion of 13C-urea are suitable for the clinical use of 13C-UBT. This test is simple and rapid.

Simplified 13C-urea breath test for the diagnosis of Helicobacter pylori infection--the availability of without fasting and without test meal.

The conventional 13C-urea breath test (13C-UBT) for detecting Helicobacter pylori infection was performed during fasting state and with a test meal to delay gastric emptying during the test. For the convenience of propagating this test, we assessed the availability of non-fast and without test meal in 13C-UBT for the diagnosis of H. pylori infection. One hundred and five consecutive patients who received endoscopic examination were studied. All of them received endoscopic biopsy for urease test, culture and histopathology to determine whether there was a presence of H. pylori infection. Each patient received four separate 13C-UBT under the following four testing conditions. Test I) fasting state with test meal (100 ml fresh milk), Test II) non-fast (taking usual food) but with test meal, Test III) fasting state without test meal, and Test IV) non-fast and without test meal. The excess delta 13CO2 values were calculated via the breathed samples that were collected at 15 minutes after ingestion of 13C-urea. There were 61 H. pylori positive and 44 negative patients in this study, with an excess delta 13CO2 values 3.0, 4.0, 3.5 and 4.0 as a cut-off value in the four tests respectively, according to the ROC curve. The results of test I, a conventional procedure, had a good correlation with the gold standard. The sensitivity and specificity were 100% and 95% respectively. The alternative procedures in other tests also have high sensitivity and specificity at 15-minute detecting time. The sensitivity of the tests II, III and IV at 15-minute detecting times were 98%, 98% and 100%, and the specificities of those were 95%, 98% and 95% respectively. We therefore suggest that fasting and test meal possibly be omitted when the cut-off value is 4.0 per mil in the simplified 13C-UBT (non-fast and without test meal, and detection at 15 minutes after ingestion of 13C-urea) which is a simple and available procedure for clinical diagnosis of H. pylori infection.

Clinicopathologis Study of Gastric Carcinoma with Duodena Invasion

Clinicopathologic features of 319 patients who underwent gastrectomy for adenocarcinoma of stomach were studied whether disease involved duodenum or not. Thirty-eight patients (11.9%) had duodenum invasion. Gastric carcinoma with duodenal invasion was most often Borrmann III or Borrmann IV (65.8%) type, with pylorous invasion by endoscopy (39.5%), large tumor size (73.7% > or = 5cm), lymph node metastasis (78.9%), serosal invasion (97.4%) and the incidence of the resection line not being free was high (13.2%). Duodenal invasion was most often (55.3%) direct through the deep layer or through lymphatics or venules. We need to pay more attention to finding duodenum invasion. More than 3 cm width of duodenal resection is recommended if duodenum invasion is suspected.

Utility of Brushing Cytology in the Diagnosis of Helicobacter pylori Infection

OBJECTIVE We performed brushing cytology during routine gastroendoscopic examinations to evaluate the utility of gastric brushing cytology in the diagnosis of Helicobacter pylori infection. STUDY DESIGN The brushing cytology materials were obtained from the antrum of the stomach in 107 patients. The urea breath test, biopsy urease test and histology with hematoxylineosin staining were also performed on each patient. We then compared the results of brushing cytology with those of the three other tests (13C urea breath test, biopsy urease test, histology). RESULTS Fifty-nine of 103 patients (57%) were diagnosed as positive for H pylori organisms using brushing cytology. Using positive or negative results from any two of the other three tests as the gold standard, a true positive result was found in 57 cases, a true negative in 43 cases, a false positive in 2 cases and a false negative in 1 case. The sensitivity and specificity of brushing cytology were 98% and 96%, respectively. CONCLUSION Gastric brushing cytology provides an accurate, inexpensive and easy technique in the rapid detection of H pylori infection. Brushing cytology also has the advantage of being applicable to diagnostic endoscopy without waiting days for results.

Evaluation of the Severity of Helicobacter Pylori Infection with Urease Test: Its Correlation with Histopathology and Bacterial Density.

In 69 patients, the severity of Helicobactor pylori (H. pylori) infection was evaluated by bacterial density of tissue implants and inflammatory responses by histology. The specimens were taken from gastric angle and antrum (greater and lesser curvature sides) by gastroduodenal endoscopy. In urease test, the severity was measured in 3 grades according to color change of the agar: those change are within 30 minutes (grade 3), 30 minutes to 3 hours (grade 2), and 3 to 6 hours (grade 1), respectively; while the grade 0 indicated no color change occurring 6 hours after tissue inoculation. The severity of infection was assessed according to the bacterial density under high power microscopic fields (Grams stain). Grade 0 indicated no bacterium seen; grade 1, only 1 to 10 bacteria at all fields; grade 2, 1 to 3 bacteria in each high power field; and grade 3 was 4 bacteria or more on average in each high power field. The degree of inflammatory response was evaluated by inflammatory cell infiltration (H & E stain) and classified into grade 0, 1 and 2, which indicated the inflammatory cell infiltration below 50%, between 50% and 75%, and above 75%, respectively. There are no positive relationships among urease test reaction time, bacterial density grading and degrees of inflammatory cell infiltration. Clinically, the reaction time of urease test cannot reflect the severity of H. pylori infection semi-quantitatively, either in terms of bacterial density or cellular inflammatory response.

Incidence of Massive Rebleeding from Nonbleeding Visible Vessels in Benign Gastroduodenal Lesions and Prospective Study in Assessing the Efficacy of Endoscopic Hemostasis with Local Ethanol Injection

Twenty-seven patients presenting with massive upper gastrointestinal bleeding in whom endoscopy revealed nonbleeding visible vessels in benign gastroduodenal lesions were prospectively and nonrandomly allocated to receive endoscopic injection therapy with pure ethanol or conservative treatment. Those who received conservative therapy were used as a control group. The purpose of this study is to evaluate the incidence of massive rebleeding from the nonbleeding visible vessel which was defined by a more rigid criteria and to evaluate the efficacy of endoscopic pure ethanol local injection to prevent rebleeding. Nine out of the 10 (90%) controls had recurrent major bleeding, in contrast to the 2/17 (12%) of those who received hemostatic endoscopy (p less than 0.0002). Pure ethanol local injections also minimized further transfusion requirements (p less than 0.03). The complications of hemostatic endoscopy in this study are negligible. It is concluded that 1) by restrictive definition nonbleeding visible vessels in benign gastroduodenal lesions carry a high potential of recurrent massive bleeding; 2) rebleeding can be safely and effectively prevented by pure ethanol local injection.

Metastatic Testicular Choriocarcinoma of the Stomach: An Unusual Cause of Massive Upper Gastrointestinal Hemorrhage

A 43-year-old patient with past history of recurrent bleeding from chronic duodenal ulcer presented with dyspnea, massive gastrointestinal bleeding and a testicular mass. Endoscopy revealed deformed duodenal bulb and a bleeding, ulcerated submucosal tumor at the anterior wall of the lower body of the stomach. Trans-scrotal testicular and endoscopic biopsies both demonstrated choriocarcinoma. The upper gastrointestinal bleeding was controlled after conservative treatment and systemic combination chemotherapy containing methotrexate, actinomycin-D, cyclophosphamide and leucovorin was given. After three courses of chemotherapy, follow-up endoscopy showed subsidence of the metastatic lesion. The patient died of wide-spread metastatic disease 11 months later without further bleeding.