Chinese journal of digestive diseases最新文献

Objective: Hereditary non-polyposis colorectal cancer (HNPCC) syndrome is the most common cause of hereditary colorectal cancer with an early age of onset. Microsatellite instability (MSI) and germline mutation in one of the DNA mismatch repair (MMR) genes are found in the majority of HNPCC families and provide an opportunity for genetic diagnosis and prophylactic screening. The MMR gene mutation spectrum may vary across different populations and be influenced by founder mutations that prevail in specific ethnic groups. China is a big and ancient nation with enormous genetic diversity, which is especially notable between the northern and southern Chinese populations. A MMR gene mutation database for the southern Chinese population based in Hong Kong has been previously established. This study compares the MMR gene mutation spectrum and the MSI of HNPCC between the northern and southern Chinese populations.

Methods: Twenty-five HNPCC families from northern China were systematically analyzed. The MSI analysis was performed using five loci in the USA National Cancer Institute (NCI) panel (D2S123, D5S346, BAT-25, BAT-26 and BAT-40) by PCR from the tumor and normal tissue. MSH2, MSH6 and MLH1 were performed using immunohistochemical staining. Two founder mutations of MSH2 and MLH1 were examined by PCR base analyses using primers flanking the two deletion sites (c.1452_1455delAATG in MSH2 and 1.8 kb deletion involving exon 11 of MLH1).

Results: Of the 25 families collected, 19 met Bethesda guideline (BG) 1 and six met BG3. Twenty-two (15.7%) were extra-colonic cancers with gastric cancer (in seven patients) being the most common cancer type. Of the 25 tumors analyzed, 21 (84%) were high level microsatellite instability (MSI-H) and four (16%) were microsatellite stable (MSS). Eighteen (86%) of the 21 MSI-H tumors showed loss of either the MLH1 or the MSH2 protein. Three MSI-H tumors and all four MSS tumors showed no loss of expression of the three MMR proteins. Out of the 21 patients with MSI-H tumors, 12 (57%) showed pathogenic germline mutations in either MLH1 (n = 8) or MSH2 (n = 4). Overall, three novel mutations (in patients H22, H17 and H29) have been identified. One of them, c.503_4insA, caused a frameshift mutation in the MLH1 gene. The other two were found in the MSH2 gene, including a frameshift (c.899_890insAT) and a splice junction (IVS7-1G-->A, SA of Exon 8) mutation.

Conclusions: The results suggest a distinctly different mutation spectrum of MMR genes between northern and southern Chinese populations and call for a systematic, nationwide study to facilitate the design of a MMR gene mutation detection strategy tailored for individual populations in China.

Non-erosive reflux disease (NERD) has emerged as a real entity in the spectrum of gastroesophageal reflux disease (GERD) and may, indeed, represent the most common manifestation of reflux disease. Recent information indicates NERD can be further subclassified based on the results of pH studies and suggests that functional heartburn needs to be differentiated as that subgroup of patients in which there appears to be no relationship between symptoms, however 'typical' of GERD, and acid exposure. Other aspects of NERD need to be appreciated, including overlap with functional dyspepsia and the potential variations in response to such therapeutic interventions as acid-suppressive therapy and fundoplication. It seems quite possible that our failure to separate functional heartburn from NERD, in general, has contributed, in large measure, to diagnostic difficulties and therapeutic disappointment in GERD. An appreciation of the range of entities, of different etiology and pathology, within NERD will foster the development of effective approaches to the assessment and therapy of this challenging disorder.

Objectives: Evaluate the effect of an implanted percutaneous left subclavian artery port-catheter drug delivery system for regional chemotherapy of inoperable pancreatic carcinoma.

Methods: One hundred and forty patients with inoperable pancreatic carcinoma were enrolled and randomized into two groups to receive the FAM regimen on a 6-day cycle at 1-month intervals: 70 patients in the regional interventional chemotherapy group in which treatment was infused directly into the common hepatic artery, and 70 patients who received the same chemotherapy regimen via the peripheral vein.

Result: In the interventional chemotherapy group, there were 5 cases of complete remission (CR) and 49 cases of partial remission (PR), giving a response rate (CR+PR) of 77.1%; pain control was effective in 95.7% cases; survival time was 3-34 months (median 13.5). There was no case of CR in the systemic chemotherapy group, and 25 cases of PR, giving a response rate of 35.7%; pain control was effective in 35.7%, and survival time was 1-13 months (median 6.2). The differences between the two groups in response rate and survival were statistically significant (P < 0.005). Nausea and vomiting occurred in 48.6% of the interventional chemotherapy group and 41.3% of the systemic chemotherapy group (NS). There were three cases of serious myelosuppression in the systemic chemotherapy group and one case died. There was a significant difference between the two groups in white blood cell count after the chemotherapy, indicating that the myelosuppressive effect was serious in the systemic chemotherapy group.

Conclusion: Interventional arterial infusion chemotherapy could significantly improve quality of life and prolong the survival of patients with inoperable pancreatic carcinoma.

Objective: Endoscopic ultrasound has emerged as the leading modality to assess the T and N stage in gastric cancer. This study aimed to assess the accuracy of TN staging by endoscopic ultrasound in routine clinical practice in Singapore.

Methods: Over a period of 7 years, 77 patients (male: 70%; median age 62.8 years) with gastric cancer underwent preoperative staging with endoscopic ultrasound. Fifty-seven patients eventually underwent surgery with tissues available for histopathological staging and comparison.

Results: The tumor locations were: cardia: 13; corpus: 20; incisura: 19; antrum: 25. The majority was poorly differentiated (57.1%); 26% were moderately differentiated and 16.9% were well differentiated adenocarcinoma. Compared to pathological staging, the overall accuracy of T staging by endoscopic ultrasound was 77.2% (17.5% under-staged: 5.3% over-staged). The staging accuracy of T1 (92.9%) and T3 (81.8%) was higher than T2 (57.1%) and T4. For N staging, the accuracy of endoscopic ultrasound was 59.6% (26.3% under-staged; 14% over-staged); this was significantly superior to computer tomography (43.9%).

Conclusion: Endoscopic ultrasound is useful for the T staging of gastric cancer, with an overall accuracy rate of 77%, and up to 93% for T1 lesions. Under-staging may occur due to microscopic tumor infiltration, while over-staging may arise due to inflammatory reactions. The accuracy of N staging is lower at 60%, but could be further improved with the use of fine needle aspiration.

Objective: Irritable bowel syndrome (IBS) is a common disorder in clinical practice, but the pathophysiology of IBS has not been completely elucidated yet. Experiments have revealed that the concentrations of some kinds of brain-gut peptides, such as substance P, were abnormal in the plasma and/or the intestinal mucosa. In order to explore further the possible role of substance P containing nerve fibers in the enteric nervous system and central nervous system, the expression of c-fos, a well-established marker of activated neural pathway, was induced to show substance P containing a neural pathway in the rat model of constipation-predominant IBS by rectal distention.

Methods: The rat model was set up by intragastric instillation of 2.0 mL water at 0-4 degrees C in 20 male Wistar rats for two weeks. Both the model group and the controls underwent rectal distention under deep anesthesia. Sections containing the anatomical areas of interest were obtained and processed for c-fos protein and substance P immunohistochemistry using the strept avidin-biotin complex (SABC) method. The staining results were analyzed semi-quantitatively, using a computerized color image analyzer with two parameters: opacity density and immunoreactive areas. The statistical difference of the opacity density and immunoreactive areas between the two groups was analyzed by a t-test. Correlation analysis was used to investigate the relationship between the expression of substance P and c-fos protein of the same region in the model group.

Results: The opacity density of substance P immunoreactive tissues in the ileocecal junction, colon, the posterior horn of the spinal cord and the hypothalamus of the model group were all significantly higher compared with those in the control group (176.6 vs 155.5, 172.3 vs 152.0, 182.1 vs 160.2, 128.3 vs 117.9; P < 0.05, respectively). Meanwhile in the ileocecal junction, colon, the posterior horn of the spinal cord and the hypothalamus of the model group, the opacity density of c-fos protein-positive tissue were all significantly higher than those of the same region in the controls (120.9 vs 109.0, 101.3 vs 92.2, 125.4 vs 88.7, 115.5 vs 88.6; P < 0.05, respectively). The distribution of c-fos protein-positive tissue is similar to that of the substance P and the analysis shows that there is close correlation between the expression of substance P and c-fos protein of the same region in the model group (r = 0.594-0.721, P < 0.05).

Conclusions: The expression of substance P and c-fos protein in both the enteric nervous system and the central nervous system of the constipation-predominant IBS rat model is abnormal, which suggests that an abnormal change in substance P may be involved in the pathogenesis of IBS and the substance P-containing neural pathway may be one of the neural pathways that play important role in the regulation of the gastrointestinal funct

Objective: Controversies exist regarding the virulence factors, such as vacA, babA2 and Lewis blood group antigens, of Western and Asian strains of Helicobacter pylori. The aim of the present study was to determine the significance of these potential virulence factors in the Chinese population.

Methods: Seventy-two strains of H. pylori isolated from patients in Zhengzhou, China, including 43 cases of peptic ulcer (PU) and 29 cases of chronic gastritis, were determined. Vacuolating cytotoxin assay was performed by HeLa cells. The expression of Le blood group antigens (Le(a), Le(b), Le(x) and Le(y)) was performed by enzyme-linked immunosorbent assay (ELISA). babA2 gene was identified by polymerase chain reaction. Frequencies were compared using two-tailed Fisher's exact test. Cytotoxin activities were compared using Spearman's rank correction test.

Results: Vacuolating cytotoxin activity was detected in 61 of the 72 strains (84.7%), but there was no significant difference in vacuolating cytotoxin activity (83.7% vs 86.2%, P = 0.821) or titer (4.4 +/- 3.8 vs 4.2 +/- 4.1, P = 0.876) between the PU and gastritis strains. Significantly more PU strains expressed two or more Lewis antigens (Le(x), Le(y), Le(a) or Le(b)) than strains from the chronic gastritis patients (90.7% vs 65.5%, P = 0.029). Of the 43 strains from PU patients, 17 (39.5%) were positive for babA2, compared with 11 (38.5%) of the 29 strains from gastritis patients (P = 0.924). There was no significant difference in the vacuolating cytotoxin activity or titer between strains expressing two or more Lewis antigens and less than two antigens (84.5% vs 85.7%, P = 1.000; 4.4 +/- 4.2 vs 4.3 +/- 3.2, P = 0.965). Of the 72 H. pylori strains, 28 were babA2 positive, of which 24 were cytotoxic, compared with 37 of 44 babA2-negative strains (P = 1.000).

Conclusion: The present study suggests that PU is associated with increased Lewis antigen expression, but not vacuolating cytotoxin production or the presence of babA2, in the H. pylori strains in the Chinese population.

Objective: The aim of the present study was to test a prebiotic-phytotherapic compound in an experimental model of oral allergenicity.

Methods: Antigen-specific immunoglobulin E (IgE) elevated mice were prepared by injecting them intraperitoneally with 10 microg of ovalbumin. Subsequently, the mice were exposed to ovalbumin solution intranasally and blood samples were obtained on weekly intervals for 4 weeks to measure serum-ovalbumin-specific IgE and total immunoglobulin G. Mice with high titers of ovalbumin-IgE were intragastrically administered with 0.3 mL of phosphate buffered solution containing either 20 mg of ovalbumin, the same solution with 5 mL of milk, or 20 mg milk added to prebiotic-phytocompound.

Results: Ovalbumin administration caused a significant increase of plasma ovalbumin concentration in sensitized mice while prebiotic-phytocompound-supplemented mice showed a significantly reduced peak value (P < 0.05). Prebiotic-phytocompound added to milk exerted a significant effect in lowering the ovalbumin-IgE level and the total immunoglobulin G level as compared to control plain milk (P < 0.01).

Conclusion: This study provides a rationale basis for a feasible non-pharmacological therapeutic strategy in food allergen hypersensitivity syndromes.

Background: Non-steroidal anti-inflammatory drugs such as indomethacin can inhibit the growth of tumors through both the cyclooxygenase-2 (COX-2) dependant and COX-2 independent pathways, but the exact mechanism has not yet been shown. In our previous study, COX-2 independent proteins (Bfl-1, WISP-1 and proliferating cell nuclear antigens [PCNA]) in indomethacin-treated colorectal cancer cells with the use of proteomics technology had been identified.

Objectives: To study and confirm the effect of indomethacin on the expression of Bfl-1, WISP-1 and PCNA in human colon cancer line HCT116 cells and the COX-2 independent tumor inhibiting pathway.

Methods: Human colon cancer cell line HCT116 cells were divided into a treatment with indomethacin (IC 50) group, and a treatment with dimethyl sulfoxide (DMSO) as a control group for 48 h. The expression of Bfl-1, WISP-1 and PCNA, mRNA and protein were determined by a real-time quantitative PCR and Western blot, respectively.

Results: Indomethacin down-regulated the expression of Bfl-1, WISP-1 and PCNA mRNA in vitro (9.53 +/- 0.15 vs 27.87 +/- 0.12, 7.37 +/- 0.58 vs 20.17 +/- 0.58, 5.17 +/- 0.06 vs 0.87 +/- 0.06). Indomethacin also down-regulated the expression of Bfl-1, WISP-1 and PCNA protein (40.01 +/- 1.61 vs 43.76 +/- 1.63, 22.50 +/- 1.17 vs 30.30 +/- 1.55, 17.69 +/- 1.18 vs 20.80 +/- 1.08).

Conclusions: Inducing apoptosis and inhibiting proliferation contribute to the anticancer activity of indomethacin via COX-2 independent pathway of Bfl-1, WISP-1 and PCNA. This further confirms the results of our previous study.

Objective: Data regarding the prevalence of Helicobacter pylori infection and its potential risk factors among schoolchildren from the Middle East is scarce.

Methods: An enzyme-linked immunosorbent assay was used to investigate H. pylori status in four groups of children: The first and second groups, 50 children each (25 boys, 25 girls) included children from high socioeconomic class (group 1 = 6 years old; group 2 = 9 years old). The third and fourth groups were sex- and age-matched, but from low socioeconomic class. To evaluate the association between the seroprevalence of H. pylori and selected risk factors, odds ratios (crude and adjusted) were calculated using multiple regression analysis.

Results: Overall seroprevalence rate was 55.5%. Seropositivity was 42%, 52%, 60%, and 68% for groups 1, 2, 3, and 4, respectively. Age and sex were not significantly associated with H. pylori seropositivity. In the final logistic regression model, which was adjusted for age and sex, the following risk factors were found to be significantly associated with seropositivity: living in rural areas (P = 0.015), poor sanitation (P < 0.001), overcrowding (P = 0.014), low maternal educational level (P = 0.010) and low socioeconomic status (P = 0.011).

Conclusions: The prevalence of H. pylori infection in Jordanian schoolchildren is high, suggesting that most acquisition occurs before the age of 6 years. The seroprevalence for H. pylori increases with social deprivation.

The new Rome III criteria reflects upon a more than 15 year process to legitimize, classify and bring scientific credibility to the functional GI disorders. This has occurred through a series of activities and documents including the recently published Rome III book and a journal issue in Gastroenterology published in April, 2006. The work involved has involved committees of 87 international investigators from 17 countries, 2 of whom are from China. This article will review the Rome committee process that led to the production of these documents, the Rome III classification system, a description of the changes from Rome II (published in 2000) to Rome III and information on the future of Rome Foundation activities.