Woo Chul Chung

Eradication of Helicobacter pylori According to 23S Ribosomal RNA Point Mutations Associated With Clarithromycin Resistance

BACKGROUND Clarithromycin-resistant Helicobacter pylori is associated with point mutations in the 23S ribosomal RNA (rRNA) gene. METHODS A total of 1232 patients participated and were divided into 2 control groups and 1 case group. Patients in the APC control group, which consisted of 308 randomly assigned participants, were treated with standard triple therapy, consisting of amoxicillin, rabeprazole, and clarithromycin; 308 participants in the APM control group were treated with amoxicillin, rabeprazole, and metronidazole. For the 616 participants in the case group, a test for point mutations in the 23S rRNA gene of H. pylori was conducted. A total of 218 individuals in the case group received a new tailored therapy regimen, in which amoxicillin, rabeprazole, and clarithromycin were given in the absence of a mutation, whereas clarithromycin was replaced by metronidazole if the mutation was detected. RESULTS The rate of eradication of H. pylori in the tailored group was 91.2% (176/193), which was significantly higher than that in the APC (75.9% [214/282]; P < .001) and APM (79.1% [219/277]; P < .001) control groups. CONCLUSION The rate of H. pylori eradication among patients who received tailored therapy on the basis of detection of a clarithromycin resistance mutation by polymerase chain reaction was much higher than the rate among patients who received a standard triple therapy regimen. CLINICAL TRIALS REGISTRATION NCT0145303.

Efficacy and long-term outcome of endoscopic treatment of sporadic nonampullary duodenal adenoma.

BACKGROUND/AIMS Endoscopic resection has proven to be a safe and effective alternative to surgery for duodenal adenomas. However, few data are available on the adequacy of resection and long-term outcomes. This study evaluated the efficacy and longterm endoscopic findings in a cohort of Korean patients who underwent endoscopic mucosal resection (EMR) of sporadic duodenal adenomas. METHODS Seventeen patients with nonampullary duodenal adenomas without familial polyposis syndrome and who were treated by EMR between January 2001 and December 2007 were evaluated retrospectively. Their management, follow-up, and outcomes were reviewed. RESULTS In total, seventeen lesions were removed from EMR in 17 patients (mean age, 59.3 years; 6 women, 11 men). The mean size of the tumors was 15.1 mm (median, 13 mm, range, 8-27 mm). Of these 17 adenomas, 16 adenomas were tubulous and 1 was tubulovillous. The EMR was performed successfully in all 17 patients in a single session. After a median follow-up period of 29 months (range, 13-72 months), all patients remained in remission. One patient had bleeding at the site of the EMR. There were no perforations after the EMR. CONCLUSIONS EMR for sporadic duodenal adenomas seemed to be a safe and effective treatment modality.

Concomitant therapy achieved the best eradication rate for Helicobacter pylori among various treatment strategies.

AIM To compare the Helicobacter pylori (H. pylori) eradication rate of clarithromycin-based triple therapy, metronidazole-based triple therapy, sequential therapy and concomitant therapy. METHODS A total of 680 patients infected with H. pylori were divided into 4 groups and each group was treated with a different eradication therapy. Clarithromycin-based triple therapy was applied to the first group [rabeprazole, amoxicillin and clarithromycin (PAC) group: proton pump inhibitor (PPI), amoxicillin, clarithromycin], whereas the second group was treated with metronidazole-based triple therapy [rabeprazole, amoxicillin and metronidazole (PAM) group: PPI, amoxicillin, metronidazole]. The third group was treated with rabeprazole and amoxicillin, followed by rabeprazole, clarithromycin and metronidazole (sequential group). The final group was simultaneously treated with rabeprazole, amoxicillin clarithromycin and metronidazole (concomitant therapy group). In the case of a failure to eradicate H. pylori, second-line quadruple and third-line eradication therapies were administered. RESULTS The per protocol (PP) analysis was performed on 143, 139, 141 and 143 patients in the PAC, PAM, sequential and concomitant groups, respectively. We excluded patients who did not receive a C(13)-urea breath test (22, 20, 23 and 22 patients, respectively) and patients with less than an 80% compliance level (5, 11, 6 and 5 patients, respectively). The eradication rates were 76.2% (109/143) in the PAC group, 84.2% (117/139) in the PAM group, 84.4% (119/141) in the sequential group and 94.4% (135/143) in the concomitant group (P = 0.0002). All 14 patients who failed second-line therapy were treated with third-line eradication therapy. Among these 14 patients, 6 infections were successfully eradicated with the third-line therapy. Both PP and intention-to-treat analysis showed an eradication rate of 42.9% (6/14). In the PAC group, 3 of 4 patients were successfully cured (3/4, 75%); 2 of 2 patients in the PAM group (2/2, 100%) and 1 of 5 patients in the sequential group (1/5, 20%) were also cured. In the concomitant group, all 3 patients failed (0/3, 0%). CONCLUSION The eradication rate for the concomitant therapy was much higher than those of the standard triple therapy or sequential therapy (ClinicalTrials.gov number NCT01922765).

P53 genetic polymorphism of gastric cancer in Korea.

Background/Aims Deletion or functional loss of the p53 tumor suppression gene plays a role in oncogenic transformation. The codon 72 polymorphism on exon 4 in the p53 gene produces variant proteins with either arginine (Arg) or proline (Pro), and is associated with an increased susceptibility of cancers of the lung, esophagus, breast, cervix and nasopharynx on a genetic basis. We designed this study to evaluate the influence of the p53 codon 72 polymorphism on gastric cancer in Korea. Methods We extracted the peripheral blood samples in 84 patients with gastric cancer, 66 patients with H. pylori-associated chronic gastritis and 43 controls without H. pylori infection. PCR-RFLP analysis was performed to detect p53 codon 72 polymorphism in these patients. Results There was no specific genotype of p53 polymorphism in the gastric cancer group compared to the other groups and no difference in genotypes by histologic subtypes. Classified by tumor location, Pro/Pro genotype was associated with an increase in proximal cancer and Arg/Arg genotype with distal cancer. As the frequency of p53 Arg allele increased, the cancer was of a more poorly differentiated type. Conclusions The specific genotype of p53 polymorphism seems to correlate with tumor location. Increased frequency of p53 Arg allele is associated with more poorly differentiated cancers.

Association between toll-like receptors/CD14 gene polymorphisms and inflammatory bowel disease in Korean population.

The innate immune response in patients who develop inflammatory bowel disease (IBD) may be abnormal. However, the exact role of Toll-like receptors (TLRs) / CD14 gene in the pathogenesis of IBD has not been fully elucidated. We aimed to investigate the association between polymorphisms of TLR1, 2, 4, 6, and CD14 gene and susceptibility to IBD in Korean population. A total 144 patients of IBD (99 patients with ulcerative colitis, 45 patients with Crohns disease) and 178 healthy controls were enrolled. Using a PCR-RFLP, we evaluated mutations of TLR1 (Arg80Thr), TLR2 (Arg753Gln and Arg677Trp), TLR4 (Asp299Gly and Thr399Ile), TLR6 (Ser249Pro) genes and the -159 C/T promoter polymorphism of CD14 gene. No TLR polymorphisms were detected in Korean subjects. T allele and TT genotype frequencies of CD14 gene were significantly higher in IBD patients than in healthy controls. In subgroup analysis, T allelic frequency was higher in pancolitis phenotype of ulcerative colitis. In Korean population, the promoter polymorphism at -159 C/T of the CD14 gene is positively associated with IBD, both ulcerative colitis and Crohns disease.

Breath methane positivity is more common and higher in patients with objectively proven delayed transit constipation.

Objectives Methane (CH4)-producing intestinal bacteria might be related to constipation. This study was carried out to evaluate the association between breath CH4, colonic transit, and anorectal pressure in constipated patients. Methods A database of consecutive 62 constipated patients fulfilling the Rome III with the lactulose CH4 breath test (LMBT), a colon marker study, and anorectal manometry was studied. The profile of LMBT in patients was compared with 49 healthy controls. The positivity to LMBT (LMBT+) was defined as CH4 of at least 10 ppm in baseline or above baseline within 90 min. There were two types of constipation: normal and delayed transit. Results There were significant differences in the breath CH4 between patients with delayed transit and (a) normal transit from 0 to 135 min or (b) healthy controls from 0 to 180 min. The LMBT+ was higher in delayed transit patients than in healthy controls (58.8 vs.12.2%) or in normal transit patients (vs. 13.3%), respectively (P<0.01). The delayed transit was the only independent factor for LMBT+ [odds ratio (95% confidence interval), 27.8 (3.32–250.00), P<0.01]. The left and total colonic transit time were significantly increased in LMBT-positive than in LMBT-negative patients. Significant correlations were found between total CH4 and the time of left or total colonic transit. However, no difference was found in the parameters of manometry by LMBT status. Conclusion A positive breath CH4 was associated with delayed colonic transit and left colon, and it could be a new therapeutic target for the management of constipated patients with delayed colonic transit.

Efficacy of levofloxacin and rifaximin based quadruple therapy in Helicobacter pylori associated gastroduodenal disease: a double-blind, randomized controlled trial.

The aim of this study was to evaluate the efficacy of levofloxacin and rifaximin based quadruple regimen as first-line treatment for Helicobacter pylori infection. A prospectively randomized, double-blinded, parallel group, comparative study was performed. Three hundred consecutive H. pylori positive patients were randomized to receive: omeprazole, amoxicillin, clarithromycin (OAC); omeprazole, amoxicillin, levofloxacin (OAL); and omeprazole, amoxicillin, levofloxacin, rifaximin (OAL-R). The eradication rates in the intention to treat (ITT) and per protocol (PP) analyses were: OAC, 77.8% and 85.6%; OAL, 65.3% and 73.6%; and OAL-R, 74.5% and 80.2%. The eradication rate achieved with OAC was higher than with OAL on the ITT (P = 0.05) and PP analysis (P = 0.04). OAL-R regimen was not inferior to OAC. The frequency of moderate to severe adverse effects was significantly higher in OAC treatment group. Especially, diarrhea was most common complaint, and there was a significantly low rate of moderate to severe diarrhea with the rifaximin containing regimen. In conclusion, the levofloxacin and rifaximin based regimen comes up to the standard triple therapy, but has a limited efficacy in a Korean cohort. The rifaximin containing regimen has a very high safety profile for H. pylori eradication therapy.

Prognostic Factors Associated with Survival in Patients with Primary Duodenal Adenocarcinoma

Background/Aims The prognostic factors in primary duodenal adenocarcinoma remain controversial. This study evaluated the prognostic factors associated with survival in patients with primary duodenal adenocarcinoma. Methods From March 1996 to June 2008, the medical records of 30 patients with a final diagnosis of primary duodenal epithelial malignancy seen at two referral centers were reviewed retrospectively. The prognostic factors for survival were evaluated 6 months and 1, 2, and 5 years after the diagnosis. Results The median survival was 5.7 months. The survival rate was 46.7% (14/30), 16.7% (5/30), 10% (3/30), and 6.7% (2/30) at 6 months and 1, 2, and 5 years, respectively. Multivariate analysis showed that cancer-directed treatment, including curative surgery or chemotherapy, was a common independent risk factor at all follow-up times. Total bilirubin, cytology, and TNM stage were independent risk factors for survival at 1, 2, and 5 years. The white blood cell count was an independent risk factor at 1 year only. The actuarial probability of survival in patients undergoing cancer-directed treatment was significantly higher than in those without treatment at 6 months (71.4 vs. 25.0%, p < 0.01), 1 year (28.6 vs. 6.3%, p < 0.01), 2 years (21.4 vs. 0%, p < 0.01), and 5 years (14.3 vs. 0%, p < 0.01). Conclusions The prognostic factors in patients with primary duodenal adenocarcinoma were total bilirubin, TNM stage, cytology, and cancer-directed treatments until the 5-year follow-up. Especially, cancer-directed treatments improved patient survival.

Association between acute pancreatitis and peptic ulcer disease.

AIM To evaluate the relationship between peptic ulcer disease (PUD) and acute pancreatitis. METHODS A cohort of 78 patients with acute pancreatitis were included in this study. The presence of PUD and the Helicobacter pylori (H. pylori) status were assessed by an endoscopic method. The severity of acute pancreatitis was assessed using Ransons score, the Acute Physiology and Chronic Health Evaluation (APACHE) II score, computed tomography severity index and the clinical data during hospitalization, all of which were compared between the patients with and without PUD. The risk factors for PUD were also evaluated. RESULTS Among 78 patients, 41 patients (52.6%) with acute pancreatitis suffered from PUD, but only 13 (31.7%) patients with PUD were infected by H. pylori. On univariate analysis, male gender, an etiology of alcohol-induced pancreatitis, a history of smoking or alcohol consumption, elevated triglyceride and C-reactive protein levels, and high APACHE II score were significantly associated with PUD. However, on multivariate logistic regression analysis, the APACHE II score (odds ratio: 7.69; 95% confidence interval: 1.78-33.33; P < 0.01) was found to be the only independent risk factor for PUD. CONCLUSION Patients with acute pancreatitis are liable to suffer from PUD. PUD is associated with severe acute pancreatitis according to the APACHE II score, and treatment for PUD should be considered for patients with severe acute pancreatitis.

Clinical Significance of Colonic Diverticulosis Associated with Bowel Symptoms and Colon Polyp

This study was done to evaluate prospectively the clinical significance of colonic diverticulosis. In the 1,030 consecutive outpatients undergoing colonoscopy, the information on the demographics, the patterns of bowel symptoms, and the prevalence of colon polyp were analyzed according to the presence of colonic diverticulosis. The mean age of 1,030 patients were 52.2 yr and 59.3% were male. The prevalence of diverticulosis was 19.7% (203/1,030). Of 203 diverticulosis patients 85.2% were in proximal group, 5.4% in distal group and 9.4% in both group. Six (3.0%) patients were found to have diverticulitis. Multivariate logistic regression analysis showed that an old age, diabetes and the presence of polyp were significant factors associated with proximal or both diverticulosis. A significant difference was demonstrated between the patients of distal diverticular group and the controls for the symptom frequency scores within the previous 4 weeks. The items, which showed difference, were hard stool, urgency, flatus, chest discomfort and frequent urination. In conclusion, old age, diabetes and the presence of colon polyp were associated with proximal diverticulosis. The temporal symptoms were more frequent in distal diverticulosis than in proximal diverticulosis in the study subjects.