Chang Soo Eun

Comparison of Guaiac-Based and Quantitative Immunochemical Fecal Occult Blood Testing in a Population at Average Risk Undergoing Colorectal Cancer Screening

OBJECTIVES:Although some studies have shown that the quantitative, immunochemical fecal occult blood test (FOBT) (qFIT) has better performance characteristics than the standard guaiac-based FOBT (GT) for identifying advanced colorectal neoplasia (ACRN), there is limited information on test performance of these tests in average-risk populations.METHODS:Seven hundred seventy consecutive average-risk patients from four centers who were undergoing screening colonoscopy also provided stool samples. Stool specimens from three consecutive bowel movements were applied to a hemoccult II test card (Beckman Coulter, Fullerton, CA) and OC-SENSA MICRO (Eiken Chemical, Tokyo, Japan) sampling probes at the same time. We measured the diagnostic value of the qFIT for detecting an ACRN by using three criteria: sensitivity, specificity, and likelihood ratios. A receiver operating characteristic curve for determining the qFIT cutoff values and the number of tests that best discriminated between ACRNs and other findings were determined.RESULTS:Seventy-eight ACRNs were identified during colonoscopy. At all hemoglobin thresholds, the sensitivity of the qFIT was higher than that of the GT for cancer or ACRN. The sensitivity and specificity of the GT for detecting advanced adenomas, cancer, and ACRNs were 13.6%/92.4%, 30.8%/92.4%, and 16.7%/92.9%, respectively. Using the 100 ng/ml cut point and three-sample qFIT results, the sensitivity and specificity of the qFIT for detecting advanced adenomas, cancer, and ACRNs were 33.9%/90.6%, 84.6%/89.8%, and 43.7%/91.9%, respectively. The area under the curve for cancer indicated that using either 2 or 3 tests provided the best discrimination for cancer.CONCLUSIONS:The qFIT provides a higher sensitivity for detecting ACRN and cancer than the GT, and has an acceptable specificity that significantly reduces the need for colonoscopic evaluation in the screened population.

An adequate level of training for technical competence in screening and diagnostic colonoscopy: a prospective multicenter evaluation of the learning curve

BACKGROUND Various training programs in colonoscopy recommend that trainees should perform at least 100 to 200 procedures to be considered technically competent at diagnostic colonoscopy. OBJECTIVE Our purpose was to determine the adequate level of training for technical competence in screening and diagnostic colonoscopy. DESIGN A prospective multicenter trial. SETTING Fifteen tertiary care academic medical centers. PATIENTS Over 8 months we prospectively evaluated the procedures of 24 first-year GI fellows in 15 tertiary care academic medical centers. A total of 4351 colonoscopies were assessed prospectively with variable clinical factors. INTERVENTION Cecal intubation was documented by photographing the identified cecal landmarks, including the appendiceal orifice and the ileocecal valve. MAIN OUTCOME MEASUREMENTS Acquisition of competence (success rate) was evaluated for colonoscopic training on the basis of 2 objective criteria: (1) adjusted completion rate (>90%) and (2) cecal intubation time (<20 minutes). RESULTS The overall success rate was 83.5% (3635/4351). The mean cecal intubation time was 9.23 +/- 4.63 minutes. The success rate significantly improved and reached the requisite standard of competence after 150 procedures (71.5%, 82.6%, 91.3%, 94.4%, 98.4%, and 98.7%, respectively, for every 50 consecutive blocks). The polyp detection rate did not improve significantly during the 8 months and was not correlated with the learning curve. In addition, mean time to cecal intubation decreased significantly, from 11.16 to 8.39 minutes, after 150 procedures. Logistic regression analysis found that prolonged cecal intubation was caused by the following factors: elderly patients, female sex, low body mass index, poor bowel preparation, poor American Society of Anesthesiologists status, abdominal pain as an indication, instructors supervision, and low case volume. LIMITATIONS We did not record final pathologic reports of detected polyps and withdrawal time. CONCLUSIONS Competence in technically efficient screening and diagnostic colonoscopy generally requires experience with more than 150 cases. Also, factors associated with prolonged cecal intubation for typical trainees did not differ from those for experienced colonoscopists.

Role of IL-17A in the development of colitis-associated cancer

A close relationship between inflammation and colon cancer has been widely accepted, and interleukin (IL)-17A plays an important role in controlling colonic inflammation. However, the role of IL-17A has not yet been validated in colitis-associated cancer (CAC). This study aims to identify the effects of IL-17A in tumorigenesis utilizing IL-17A-deficient mice in an experimental CAC model. CAC was induced in both the IL-17A-deficient and the C57BL/6 (wild-type, WT) mice by injection of 12.5 mg/kg azoxymethane followed by three rounds of 1.7% dextran sodium sulfate exposure to elicit colitis. On day 63 after the start of the study, mice were sacrificed. Colonic inflammation, proliferation and tumorigenesis were evaluated. Tumor numbers per mouse (1.43 versus 5.80; P = 0.02) and mean tumor size (1.17 versus 3.58 mm; P = 0.01) were significantly decreased in IL-17A-deficient mice compared with WT mice. Furthermore, the inflammation and the proliferation scores of IL-17A-deficient mice were significantly lower than WT mice. In the analysis of inflammatory mediators, IL-6, interferon-γ, tumor necrosis factor-α and IL-17A were markedly decreased in IL-17A-deficient mice compared with WT mice. In the western blot analysis, p-STAT3, cyclin D1, cyclin-dependent kinase 2, cyclin E, Glycogen synthase kinase 3-β and p-Akt were downregulated in IL-17A-deficient mice. Immunohistochemical staining with p-STAT3, Ki-67 and β-catenin revealed lower number of stained cells in IL-17A-deficient mice compared with WT mice. IL-17A ablation significantly decreases CAC tumorigenesis and thus may play an important role associated with chronic colitis.

Efficacy of prepackaged, low residual test meals with 4L polyethylene glycol versus a clear liquid diet with 4L polyethylene glycol bowel preparation: a randomized trial.

Background and study aims:  A prepackaged low residue one‐day diet (breakfast, lunch and dinner) has been recently developed to improve patient tolerance for bowel preparation prior to colonoscopy. The aims of this study were to evaluate the efficacy and tolerability of bowel preparation protocols based on a low residue diet and 4L polyethylene glycol (PEG) solution, and to compare these new options with the traditional liquid diet and the PEG 4L lavage.

Influences of thiopurine methyltransferase genotype and activity on thiopurine-induced leukopenia in Korean patients with inflammatory bowel disease: a retrospective cohort study.

Background and Aim Myelotoxicity has been shown to be very common in Korean patients with inflammatory bowel disease (IBD) during azathioprine (AZA) or 6-mercaptopurine (6–MP) treatment. The purpose of this study was to investigate the relative risk of the thiopurine methyltransferase (TPMT) and inosine triphosphate pyrophosphatase (ITPA) genotypes and TPMT activity for the development of leukopenia in Korean IBD patients during AZA/6-MP treatment. Methods We retrospectively analyzed 286 Korean patients with IBD who had been treated with AZA/6-MP for at least 6 months between June 1996 and September 2006. Common TPMT mutations, including TPMT*1, *2, *3A, *3B, and *3C, and ITPA mutations, including 94C>A and IVS2+21A>C, were determined using a high-performance liquid chromatography method. TPMT activity was measured using liquid chromatography with coupled mass spectrometry/mass spectrometry. Results Leukopenia occurred in 118 cases (41.3%). TPMT *1/*3C was detected in 7 cases (2.4%), and ITPA 94 C>A was detected in 66 cases (23.1%), including 63 heterozygotes (22.1%) and 3 homozygotes (1.0%). The median TPMT activity was 9.3 U/mL (interquartile range 10.4, range 2.1 to 76.2). Cox regression analysis revealed that patients with heterozygous *3C type TPMT had a higher probability of leukopenia than those with wild type TPMT (P=0.02). Patients with intermediate TPMT activity had a lower probability of leukopenia than those with low activity (P=0.01). However, the ITPA genotype did not affect the risk of leukopenia. Conclusions Our data showed that it could be helpful to examine TPMT genotypes and to measure TPMT activity in Korean patients taking AZA/6-MP to predict the development of leukopenia.

The Miss Rate for Colorectal Adenoma Determined by Quality-Adjusted, Back-to-Back Colonoscopies.

Background/Aims Colonoscopy is considered to be the gold standard for detecting adenomatous polyps. Polyps are missed during colonoscopic examination at a rate that varies from 6% to 27%. The adenoma miss rate affects colonoscopic surveillance intervals and procedural quality. We aimed to assess the adenoma miss rate and the variables affecting the rate using same-day, quality-adjusted, back-to-back colonoscopies. Methods This prospective study was performed at a single institution and included 149 patients. Two consecutive same-day colonoscopies were performed by two experienced endoscopists. The adenoma miss rates and variables affecting the missed adenomas, including polyp characteristics and procedure times, were evaluated. Results The miss rates of polyps, adenomas, and advanced adenomas were 16.8%, 17%, and 5.4%, respectively. The smaller polyps and increased number of polyps detected during the first colonoscopy were more likely to be missed. A longer insertion time during the colonoscopy was correlated with an increased adenoma detection rate. Conclusions There was a significant miss rate in the detection of colonic adenomas even in quality-adjusted, back-to-back colonoscopies. The adenoma miss rate can be reduced with a sufficient observation time during colonoscopic insertion. The development of specific technological methods to reduce the adenoma miss rate is necessary.

Changing pattern of antimicrobial resistance of Helicobacter pylori in Korean patients with peptic ulcer diseases

Background. Antibiotic resistance of Helicobacter pylori is problematic because it reduces the efficacy of eradication therapy. It has been suggested that the incidence of resistance is rising. In Korea, information on the antimicrobial resistance of H. pylori is rare. The aim of this study was to assess the prevalence of H. pylori antibiotic resistance at a single center in Korea, and the changes in its antimicrobial resistance, and to detect the mutation foci of clarithromycin-resistant strains. Methods. H. pylori isolates obtained from 224 patients with peptic ulcer disease in Korea between June 1996 and March 2000 were tested for antimicrobial resistance. The minimum inhibitory concentration (MIC) for metronidazole and clarithromycin was determined by the broth microdilution method. Isolates were considered resistant when the MIC was more than 8 μg/ml for metronidazole and more than 1 μg/ml for clarithromycin. To detect H. pylori 23S rRNA mutations, polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was performed. Sequencing was performed on the two strands of the nonrestricted amplicons. Results. Overall, resistance to metronidazole and clarithromycin was detected in 41.9% and 5.4% of patients, respectively. There was no significant difference in metronidazole and clarithromycin resistance according to age group and sex. Six strains were resistant to both metronidazole and clarithromycin. Six of nine clarithromycin-resistant isolates possessed the A2144G mutation in the gene encoding 23S rRNA. Sequencing of the three non-restricted clarithromycin-resistant strains revealed a T-to-C mutation at position 2182. Conclusions. In Korea, there was no significant increase in the prevalence of metronidazole resistance, but clarithromycin-resistant H. pylori strains had increased relatively over the 5-year period. There was an increasing tendency for the emergence of strains with dual resistance to metronidazole and clarithromycin. Many of the clarithromycin-resistant strains possessed the A2144G mutation.

Lactobacillus casei prevents impaired barrier function in intestinal epithelial cells

Eun CS, Kim YS, Han DS, Choi, JH, Lee AR, Park YK. Lactobacillus casei prevents impaired barrier function in intestinal epithelial cells. APMIS 2010

Association between GERD-related erosive esophagitis and obesity.

Background and Objectives To date, many studies have reported on the association of obesity with gastroesophageal reflux disease (GERD), although none of these have been systematic. In light of this, we conducted this study to examine the association of obesity and GERD. Subjects and Methods A total of 3363 patients underwent gastroscopy at Hanyang University Health Promotion Center. Among these patients, we prospectively examined patients who were diagnosed with GERD-related erosive esophagitis on endoscopy. Results Multivariate analysis showed that the significant risk factors were waist-to-hip ratio (WHR), hiatal hernia, body mass index (BMI), and smoking. As compared with patients who had a WHR less than 0.8, the multivariate odds ratio for erosive esophagitis were 4.055 for a WHR more than 1.0 and 2.316 for a WHR of 0.8 to 1.0. As compared with patients who had a BMI of 20 to 22.5, the multivariate odds ratio for erosive esophagitis was 3.308 (95% confidence interval, 1.792 to 6.107) for a BMI greater than 30. Conclusions Obesity, especially abdominal obesity, was the significant risk factor for erosive esophagitis.

Association between erosive esophagitis and visceral fat accumulation quantified by abdominal CT scan.

Background and Aims There were no objective data presented about the association between erosive esophagitis and abdominal fat. We conducted this study to examine the association of abdominal fat and gastroesophageal reflux disease-related erosive esophagitis. Methods Between May 2004 and October 2005, a total of 100 erosive esophagitis patients diagnosed by upper endoscopy were evaluated in a prospective manner. All study patients and controls underwent abdominal computed tomography (CT) scan. Body fat distribution was assessed by CT with a 10-mm-thick slice at the level of the fourth lumbar vertebra. Results Erosive esophagitis patients presented with a significantly higher mean visceral fat (VF) area (104.68±39.47 vs. 75.90±49.10 cm2, P=0.014) than the control group. However, there was no association between erosive esophagitis and subcutaneous fat area (109.72±49.09 vs. 98.66±52.43 cm2, P=0.379) or total fat area (214.41±78.78 vs. 172.59±90.49 cm2, P=0.054). Multivariate logistic regression analysis demonstrated that high VF areas (P=0.0035), VF/subcutaneous fat area (P=0.005), hiatal hernia (P=0.001), high body mass index (P=0.047), high waist-to-hip ratio (P=0.042), and smoking (P=0.005) are independent risk factors of erosive esophagitis. Conclusions These results suggest a role for visceral obesity, quantified by CT, as a risk factor for erosive esophagitis.