Yu-Chung Su

Gastroparesis: Prevalence, clinical significance and treatment

The application of novel techniques to quantify gastric motor function and gastric emptying has yielded important insights into the prevalence, pathogenesis and clinical sequelae of gastroparesis. Both acute and chronic gastroparesis occur frequently; gastric emptying of solids is delayed in 30% to 50% of patients with diabetes mellitus, functional dyspepsia and gastroesophageal reflux disease. While many patients with gastroparesis experience upper gastrointestinal symptoms that adversely affect quality of life, the concept that symptoms are inevitably the direct outcome of delay in gastric emptying is now recognized to be overly simplistic. In contrast, the potential impact of gastroparesis on oral drug absorption and blood glucose control in patients with diabetes mellitus has probably been underestimated. While the use of prokinetic drugs (cisapride, domperidone, metoclopramide and erythromycin) forms the mainstay of therapy in symptomatic patients with gastroparesis, a number of novel pharmacological therapies are being evaluated, and preliminary studies using gastric pacing show promise.

Prognostic significance of multiple molecular markers for patients with stage II colorectal cancer undergoing curative resection.

Objective:The aim of this study was to determine whether our constructed high-sensitivity colorimetric membrane-array method could detect circulating tumor cells (CTCs) in the peripheral blood of stage II colorectal cancer (CRC) patients and so identify a subgroup of patients who are at high risk for relapse. Summary Background Data:Adjuvant chemotherapy is not routinely recommended in patients diagnosed with UICC stage II CRC. However, up to 30% of patients with stage II disease relapse within 5 years of surgery from recurrent or metastatic disease. The identification of reliable prognostic factors for high-risk stage II CRC patients is imperative. Methods:Membrane-arrays consisting of a panel of mRNA markers that included human telomerase reverse transcription (hTERT), cytokeratin-19 (CK-19), cytokeratin-20 (CK-20), and carcinoembryonic antigen (CEA) mRNA were used to detect CTCs in the peripheral blood of 194 stage II CRC patients who underwent potentially curative (R0) resection between January 2002 and December 2005. Digoxigenin (DIG)-labeled cDNA were amplified by RT-PCR from the peripheral blood samples, which were then hybridized to the membrane-array. All patients were followed up regularly, and their outcomes were investigated completely. Results:Overall, 53 of 194 (27.3%) stage II patients were detected with the expression of all 4 mRNA markers using the membrane-array method. After a median follow up of 40 months, 56 of 194 (28.9%) developed recurrence/metastases postoperatively. Univariately, postoperative relapse was significantly correlated with the depth of invasion (P < 0.001), the presence of vascular invasion (P < 0.001), the presence of perineural invasion (P = 0.048), the expression of all 4 mRNA markers (P < 0.001), and the number of examined lymph nodes (P = 0.031). Meanwhile, using a multivariate logistic regression analysis, T4 depth of tumor invasion (P = 0.013), the presence of vascular invasion (P = 0.032), and the expression of all 4 mRNA markers (P < 0.001) were demonstrated to be independent predictors for postoperative relapse. Combination of the depth of tumor invasion, vascular invasion, and all 4 mRNA markers as predictors of postoperative relapse showed that patients with any 1 positive predictor had a hazard ratio of about 27-fold to develop postoperative relapse (P < 0.001; 95% CI = 11.42–64.40). The interval between the detection of all 4 positive molecular markers and subsequently developed postoperative relapse ranged from 4 to 10 months (median: 7 months). Furthermore, the expression of all 4 mRNA markers in all stage II CRC patients, or either stage II colon or rectal cancer patients were strongly correlated with poorer relapse-free survival rates by survival analyses (all P < 0.001). Conclusions:The pilot study suggests that the constructed membrane-array method for the detection of CTCs is a potential auxiliary tool to conventional clinicopathological variables for the prediction of postoperative relapse in stage II CRC patients who have undergone curative resection.

Predictive factors of early relapse in UICC stage I–III colorectal cancer patients after curative resection

To predict the clinicopathologic factors for early relapse of UICC stage I–III colorectal cancer (CRC) patients undergoing curative resection and thus to identify a subgroup of patients who are at high risk for postoperative early relapse.

Guar gum reduces postprandial hypotension in older people.

OBJECTIVE: To determine whether slowing of gastric emptying and glucose absorption with guar gum would reduce the fall in blood pressure after an oral glucose load in older subjects.

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.

Acute Hemorrhagic Rectal Ulcer Syndrome: A New Clinical Entity? Report of 19 Cases and Review of the Literature

PURPOSE:Acute hemorrhagic rectal ulcer syndrome is characterized by sudden onset, painless, and massive hemorrhage from rectal ulcer(s) in patients with serious underlying illnesses. It is a matter of controversy whether acute hemorrhagic rectal ulcer syndrome is a distinct clinical entity. This is the first Asian report on acute hemorrhagic rectal ulcer syndrome to be made outside Japan.METHODS:From January 1989 to December 1999, 8,085 patients underwent total colonoscopy at our institution. We retrospectively analyzed the medical records and colonoscopic files. The diagnosis of acute hemorrhagic rectal ulcer syndrome was made by means of the clinical, histologic, and colonoscopic findings.RESULTS:Among the 8,085 patients, 19 patients (11 males; mean age, 71.2 ± 10.1 years) were diagnosed with acute hemorrhagic rectal ulcer syndrome, which accounted for 2.8 percent of the patients with massive lower gastrointestinal bleeding. The duration from hospitalization to the onset of massive bleeding ranged from 3 to 14 (mean, 9 ± 3.3) days. Characteristics of colonoscopic appearance were solitary or multiple rectal ulcer(s), with round, circumferential, geographical, or Dieulafoy-like lesions located within a mean of 4.7 cm ± 1.5 cm from the dentate line. Histopathologically, the lesions appeared as necrosis with denudation of covering epithelium, hemorrhage, and multiple thrombi in the vessels of the mucosa and underlying stroma, which is considered to be similar to stress-related mucosa injury. Successful hemostasis was obtained in 74 percent (14/19) of patients with direct therapeutic maneuvers. Prognosis was largely dependent on accurate diagnosis and management of the underlying disorders.CONCLUSIONS:We assert that acute hemorrhagic rectal ulcer syndrome is a rare but important entity and stress that awareness of this clinical entity should lead to a high index of suspicion resulting in early detection, diagnosis, and appropriate therapy.

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.

Amoxicillin resistance with β‐lactamase production in Helicobacter pylori

Background  Amoxicillin‐resistant Helicobacter pylori with minimal inhibitory concentration (MIC) ≥ 256 mg L−1 was isolated from a gastritis patient. The aims were to investigate the mechanism of high‐level amoxicillin resistance in H. pylori.

Impaired dendritic cell maturation and IL-10 production following H. pylori stimulation in gastric cancer patients

The current study was to investigate the interaction between Helicobacter pylori and human dendritic cells (DCs). Whether impaired DC function can influence the outcome of H. pylori infections. Human monocyte-derived DCs (MDDCs) from five gastric cancer patients and nine healthy controls were stimulated with H. pylori. Maturation markers of MDDC were examined by flow cytometry. IL-10 and TNF-α released by MDDCs and IL-17 produced by T cells were measured by ELISA. Regulatory signaling pathways of IL-10 were examined by ELISA, western blotting, and chromatin immunoprecipitation assay. The results showed that as compared with healthy individuals, the maturation marker CD40 in MDDCs, IL-17A expression from T cells, and IL-10 expression from MDDCs were significantly lower in gastric cancer patients. Blocking DC-SIGN, TLR2, and TLR4 could reverse H. pylori-associated IL-10 production. Activation of the p38 MAPK and NF-kB signaling pathways concomitant with decreased tri-methylated H3K9 and increased acetylated H3 accounted for the effect of H. pylori on IL-10 expression. Furthermore, upregulated IL-10 expression was significantly suppressed in H. pylori-pulsed MDDCs by histone acetyltransferase and methyltransferase inhibitors. Taken together, impaired DC function contributes to the less effective innate and adaptive immune responses against H. pylori seen in gastric cancer patients. H. pylori can regulate IL-10 production through Toll-like and DC-SIGN receptors, activates p-p38 MAPK signaling and the transcription factors NF-kB, and modulates histone modification.

Current pharmacological management of gastroesophageal reflux disease

Gastroesophageal reflux disease (GERD), a common disorder with troublesome symptoms caused by reflux of gastric contents into the esophagus, has adverse impact on quality of life. A variety of medications have been used in GERD treatment, and acid suppression therapy is the mainstay of treatment for GERD. Although proton pump inhibitor is the most potent acid suppressant and provides good efficacy in esophagitis healing and symptom relief, about one-third of patients with GERD still have persistent symptoms with poor response to standard dose PPI. Antacids, alginate, histamine type-2 receptor antagonists, and prokinetic agents are usually used as add-on therapy to PPI in clinical practice. Development of novel therapeutic agents has focused on the underlying mechanisms of GERD, such as transient lower esophageal sphincter relaxation, motility disorder, mucosal protection, and esophageal hypersensitivity. Newer formulations of PPI with faster and longer duration of action and potassium-competitive acid blocker, a newer acid suppressant, have also been investigated in clinical trials. In this review, we summarize the current and developing therapeutic agents for GERD treatment.