[Show abstract][Hide abstract] ABSTRACT: Objectives
. Recent studies suggest that histological healing is a treatment goal in ulcerative colitis (UC). We aimed to evaluate the correlation between histological activity and clinical, endoscopic, and serologic activities in patients with UC.
. We retrospectively reviewed medical records from patients with UC who underwent colonoscopy or sigmoidoscopy with biopsies. The Mayo endoscopic subscore was used to assess endoscopic activity. Biopsy specimens were reviewed by two blinded pathologists and scored using the Geboes scoring system.
. We analyzed 154 biopsy specimens from 82 patients with UC. Histological scores exhibited strong correlation with endoscopic subscores (Spearman’s rank correlation coefficient
) and moderate correlation with C-reactive protein levels (
) and partial Mayo scores (
). Active histological inflammation (Geboes score ≥ 3.1) was observed in 6% (2 of 33) of the endoscopically normal mucosa samples, 66% (19 of 29) of mild disease samples, and 98% (90 of 92) of moderate-to-severe disease samples.
. Histological activity was closely correlated with the endoscopic, clinical, and serologic UC activities. However, several patients with mild or normal endoscopic findings exhibited histological evidence of inflammation. Therefore, histological assessment may be helpful in evaluating treatment outcomes and determining follow-up strategies.
Full-text · Article · Feb 2016 · Gastroenterology Research and Practice
[Show abstract][Hide abstract] ABSTRACT: Background/aims:
Patients undergoing cholecystectomy may have small intestinal bacterial overgrowth (SIBO). We investigated the prevalence and characteristics of SIBO in patients with intestinal symptoms following cholecystectomy.
Sixty-two patients following cholecystectomy, 145 with functional gastrointestinal disease (FGID), and 30 healthy controls undergoing hydrogen (H2)-methane (CH4) glucose breath test (GBT) were included in the study. Before performing GBT, all patients were interrogated using bowel symptom questionnaire. The positivity to GBT indicating the presence of SIBO, gas types and bowel symptoms were surveyed.
Post-cholecystectomy patients more often had SIBO as evidenced by a positive (+) GBT than those with FGID and controls (29/62, 46.8% vs 38/145, 26.2% vs 4/30, 13.3%, respectively; P = 0.010). In the gas types, the GBT (H2)+ post-cholecystectomy patients was significantly higher than those in FGID patients (P= 0.020). Especially, positivity to fasting GBT (H2) among the GBT+ post-cholecystectomy patients was high, as diagnosed by elevated fasting H2 level. The GBT+ group had higher symptom scores of significance or tendency in abdominal discomfort, bloating, chest discomfort, early satiety, nausea, and tenesmus than those of the GBT negative group. The status of cholecystectomy was the only significant independent factor for predicting SIBO.
The SIBO with high levels of baseline H2 might be the important etiologic factor of upper intestinal symptoms for post-cholecystectomy patients.
Preview · Article · Sep 2015 · Journal of neurogastroenterology and motility
[Show abstract][Hide abstract] ABSTRACT: Background/aims:
Two comparable anti-tumor necrosis factor (TNF) agents with different routes of administration (intravenous [iv] infliximab [IFX] vs subcutaneous [sc] adalimumab [ADA]) are available for patients with Crohn's disease (CD) in Korea. This study aimed to identify the preferences of Korean CD patients for a specific anti-TNF agent and the factors contributing to the decision.
A prospective survey was performed among anti-TNF-naive CD patients in 10 tertiary referral hospitals. A 16-item questionnaire addressed patient preferences and the factors contributing to the decision in favor of a particular anti-TNF agent. A logistic regression was conducted to assess predictive factors for ADA preference.
Overall, 189 patients (139 males; mean age, 32.47±11.71 years) completed the questionnaire. IFX and ADA were preferred by 63.5% (120/189) and 36.5% (69/189) of patients, respectively. The most influential reason for choosing IFX was 'doctor's presence' (68.3%, 82/120), and ADA was "easy to use" (34.8%, 24/69). Amid various clinicodemographic data, having a >60-minute travel time to the hospital was a significant independent predictive factor for ADA preference.
A large number of anti-TNF-naive Korean patients with CD preferred anti-TNFs with an iv route of administration. The reassuring effect of a doctor's presence might be the main contributing factor for this decision.
[Show abstract][Hide abstract] ABSTRACT: For decades, thiopurines have been the mainstay of inflammatory bowel disease (IBD) treatment and will play an important role in the future. However, complex metabolism and various side effects limit the use of these potent drugs in clinical practice. The Korean Association for the Study of Intestinal Diseases developed a set of consensus statements with the aim of guiding clinicians on the appropriate use of thiopurines in the management of IBD.
Sixteen statements were initially drafted by five committee members. The quality of evidence and classification of recommendation were assessed according to the Grading of Recommendations Assessment, Development and Evaluation system. The statements were then circulated to IBD experts in Korea for review, feedback, and then finalized and accepted by voting at the consensus meeting.
The consensus statements comprised four parts: (1) pre-treatment evaluation and management strategy, including value of thiopurine S-methyltransferase screening, dosing schedule, and novel biomarkers for predicting thiopurine-induced leukopenia; (2) treatment with thiopurines with regards to optimal duration of thiopurine treatment and long-term outcomes of combination therapy with anti-tumor necrosis factors; (3) safety of thiopurines, especially during pregnancy and lactation; and (4) monitoring side effects or efficacy of therapy using biomarkers.
Thiopurines are an effective treatment option for patients with IBD. Management decisions should be individualized according to the risk of relapse and adverse events.
[Show abstract][Hide abstract] ABSTRACT: We investigated the relationships between biomarkers related to endoplasmic reticulum stress proteins (glucose-regulated protein of molecular mass 78 [GRP78] and Cripto-1), pathologic response, and prognosis in locally advanced rectal cancer.
All clinical stage II and III rectal cancer patients received 50.4 Gy over 5.5 weeks, plus 5-fluorouracil (400 mg/m2/day) and leucovorin (20 mg/m2/day) bolus on days 1 to 5 and 29 to 33, and surgery was performed at 7 to 10 weeks after completion of all therapies. Expression of GRP78 and Cripto-1 proteins was determined by immunohistochemistry and was assessed in 101 patients with rectal cancer treated with neoadjuvant chemoradiotherapy (CRT).
High expression of GRP78 and Cripto-1 proteins was observed in 86 patients (85.1%) and 49 patients (48.5%), respectively. Low expression of GRP78 protein was associated with a significantly high rate of down staging (80.0% vs. 52.3%, respectively; p=0.046) and a significantly low rate of recurrence (0% vs. 33.7%, respectively; p=0.008) compared with high expression of GRP78 protein. Mean recurrence-free survival according to GRP78 expression could not be estimated because the low expression group did not develop recurrence events but showed a significant correlation with time to recurrence, based on the log rank method (p=0.007). GRP78 also showed correlation with overall survival, based on the log rank method (p=0.045).
GRP78 expression is a predictive and prognostic factor for down staging, recurrence, and survival in rectal cancer patients treated with 5-flurouracil and leucovorin neoadjuvant CRT.
Preview · Article · Jan 2015 · Cancer Research and Treatment
[Show abstract][Hide abstract] ABSTRACT: Objective:
Real-world epidemiological data on tuberculosis (TB) infection in patients with inflammatory bowel disease (IBD) receiving TNF-α inhibitors are scarce. We investigated the risks for and case characteristics of TB in a large cohort of IBD patients treated with TNF-α inhibitors in Korea, where TB is endemic.
Materials and methods:
We performed an observational study on all TB cases identified in a cohort of 873 IBD subjects treated with TNF-α inhibitors from January 2001 to December 2013. The standardized incidence ratio (SIR) of TB was calculated using data from the matched general population.
A total of 25 newly developed TB cases were identified in the cohort (pulmonary TB, 84% [21/25]; extrapulmonary TB, 16% [4/25]). The adjusted SIR of TB was 41.7 (95% confidence interval, 25.3-58.0), compared with that of the matched general population. Nineteen of the 25 patients (76%) developed TB within 2-62 months of initiation of TNF-α inhibitor treatment despite screening negative for latent TB infection (LTBI), whereas three patients with LTBI (12%, 3/25) developed TB 3 months after completion of chemoprophylaxis. The outcomes of TB treatment were mostly favorable, although one death from peritoneal TB was noted. The type of TNF-α inhibitor prescribed (infliximab) was a significant predictor of TB (p = 0.033).
TNF-α inhibitor treatment strikingly increases the risk of TB infection in an IBD population from a TB endemic area. Continuous evaluation of the development of de novo TB infection in IBD patients subjected to long-term TNF inhibitor therapy is mandatory.
No preview · Article · Jan 2015 · Scandinavian Journal of Gastroenterology
[Show abstract][Hide abstract] ABSTRACT: Background/Aims
Several recent studies have reported that the early use of infliximab (IFX) improves the prognosis of Crohn's disease (CD). However, no data are available from Asian populations, as the forementioned studies have all been conducted in Western countries. The aim of the current study was to evaluate the impact of early use of IFX on the prognosis of Korean patients with CD.
Patients with a diagnosis of CD established between July 1987 and January 2012 were investigated in 12 university hospitals in Korea. Because insurance coverage for IFX treatment began in August 2005, patients were assigned to either of 2 groups based on diagnosis date. The first group included patients diagnosed from July 1987 to December 2005, and the second from January 2006 to January 2012. We compared the cumulative probabilities of operation and reoperation between the two groups using the Kaplan-Meier method and a log-rank test.
Of the 721 patients investigated, 443 (61.4%) comprized the second group. Although the cumulative probabilities of immunosuppressant (P<0.001) and IFX use (P<0.001) after diagnosis were significantly higher in the second group, there were no significant differences in cumulative probabilities of operation (P=0.905) or reoperation (P=0.418) between two groups.
The early use of IFX did not reduce CD-related surgery requirements in Korean patients with CD. These study results suggest that the early use of IFX may have little impact on the clinical outcome of CD in Korean patients in the setting of a conventional step-up algorithm.
[Show abstract][Hide abstract] ABSTRACT: The epidemiology, genetics, and clinical manifestations of Crohn's disease (CD) vary considerably among geographic areas and ethnic groups. Thus, identifying the characteristics of Korean CD is important for establishing management strategies appropriate for Korean patients. Since the mid-2000s, many studies have investigated the characteristic features of Korean CD. The incidence and prevalence rates of CD have been increasing rapidly in Korea, especially among the younger population. Unlike Western data, Korean CD shows a male predominance and a lower proportion of isolated colonic disease. Perianal lesions are more prevalent than in Western countries. Genome-wide association studies have confirmed that genetic variants in TNFSF15, IL-23R, and IRGM, but not ATG16L1, are associated with CD susceptibility in the Korean population. Studies of the associations between genetic mutations and the clinical course of CD are underway. Although it has been generally accepted that the clinical course of Korean CD is milder than that in Western countries, recent studies have shown a comparable rate of intestinal resection in Korean and Western CD patients. An ongoing nationwide, hospital-based cohort study is anticipated to provide valuable information on the natural history and prognosis of Korean CD in the near future.
Preview · Article · Sep 2014 · The Korean Journal of Internal Medicine
[Show abstract][Hide abstract] ABSTRACT: Misoprostol is reported to prevent non-steroidal anti-inflammatory drug (NSAID)-associated gastroduodenal complications. There is, however, limited information regarding the efficacy of DA-9601 in this context. We performed a comparative study on the relative efficacy of DA-9601 and misoprostol for prevention of NSAID-associated complications. In this multicenter, double-blinded, active-controlled, stratified randomized, parallel group, non-inferiority trial, 520 patients who were to be treated with an NSAID (aceclofenac, 100 mg, twice daily) over a 4-week period were randomly assigned to groups for coincidental treatment with DA-9601 (60 mg, thrice daily) (236 patients for full analysis) or misoprostol (200 μg, thrice daily) (242 patients for full analysis). A total of 236 patients received DA-9601 and 242 received misoprostol. The primary endpoint was the gastric protection rate, and secondary endpoints were the duodenal protection rate and ulcer incidence rate. Endpoints were assessed by endoscopy after the 4-week treatment period. Drug-related adverse effects, including gastrointestinal (GI) symptoms, were also compared. At week 4, the gastric protection rates with DA-9601 and misoprostol were 81.4 % (192/236) and 89.3 % (216/242), respectively. The difference between the groups was -14.2 %, indicating non-inferiority of DA-9601 to misoprostol. Adverse event rates were not different between the two groups; however, the total scores for GI symptoms before and after administration were significantly lower in the DA-9601 group than in the misoprostol group (-0.2 ± 2.8 vs 1.2 ± 3.2; p < 0.0001). DA-9601 is as effective as misoprostol in preventing NSAID-associated gastroduodenal complications, and has a superior adverse GI effect profile.
Preview · Article · May 2014 · Archives of Pharmacal Research
[Show abstract][Hide abstract] ABSTRACT: Background and study aims: The effectiveness of the prophylactic clip for the prevention of postpolypectomy bleeding in pedunculated colonic polyps has not been confirmed. The aim of this prospective, randomized study was to compare the efficacy of prophylactic clip and endoloop application in the prevention of postpolypectomy bleeding in large pedunculated polyps. Patients and methods: A total of 195 patients who had pedunculated colorectal polyps, with heads ≥ 10 mm and stalks ≥ 5 mm in diameter, were included in the study between July 2010 and January 2013. Polyps were randomized to receive either clips or endoloops. Both devices were applied to the base of the stalk before conventional snare polypectomy. Bleeding complications were analyzed with a noninferiority margin of 5 %. Results: A total of 203 polyps were included in the study (98 in the clip group and 105 in the endoloop group). Bleeding occurred after five polypectomies in the clip group (5.1 %) and after six in the endoloop group (5.7 %) (P = 0.847). Noninferiority of the prophylactic clip to the endoloop could not be confirmed (absolute bleeding rate difference - 0.6 %, 95 % confidence interval - 5.6 % to 6.8 %) due to small sample size. Immediate bleeding episodes occurred in 4/5 polyps in the clip group and 5/6 polyps in the endoloop group. Delayed bleeding occurred in one polyp in each group. Conclusions: These results suggest that the application of a prophylactic clip is as effective and safe as an endoloop in the prevention of postpolypectomy bleeding in large pedunculated colonic polyps. Clinical trial registration: ClinicalTrials.gov (NCT01406379).
[Show abstract][Hide abstract] ABSTRACT: Background/Aims
The natural history of Crohn's disease (CD) is characterized by a remitting and relapsing course and a considerable number of patients ultimately require bowel resection. Moreover, postoperative recurrence is very common. Relatively few studies have investigated the postoperative recurrence of CD in Korea. The aim of the current study was to assess postoperative recurrence rates - both clinical and endoscopic - in CD as well as factors influencing postoperative recurrence.
Electronic medical records of patients who underwent surgery due to CD were reviewed and analyzed. Patients with incomplete surgical resection, a follow-up period of less than a year, and a history of strictureplasty or perianal surgery were excluded.
Of 112 CD patients, 39 patients had history of bowel resection, and 34 patients met the inclusion criteria. Among them, 26 were male (76%) and the mean age of onset was 32.8 years. The mean follow-up period after operation was 65.4 months. Cumulative clinical recurrence rates were 8.8%, 12.5%, and 33.5% at 12, 24, and 48 months, respectively. Use of immunomodulators for prophylaxis was the only predictor of clinical recurrence in univariate analysis (P=0.042). Of 21 patients who had undergone follow-up colonoscopy after surgery, cumulative endoscopic recurrence rates were 33.3%, 42.9%, and 66.1% at 6, 12, and 24 months, respectively. No significant predicting factor for endoscopic recurrence was detected.
Postoperative recurrence rates in Korean patients with CD are high, and endoscopic recurrence rates are comparable to those reported from Western studies. Appropriate medical prophylaxis seems to be important for preventing postoperative recurrence in CD.
[Show abstract][Hide abstract] ABSTRACT: Background and AimAlthough differences in genetic susceptibility and the clinical features of Crohn's disease (CD) have been reported between Asian and Caucasian patients, the disease course and predictors of CD in Asians remains poorly defined. The study therefore aimed to investigate factors predictive of the clinical outcomes of patients with CD in a Korean population. Methods
This retrospective multicenter cohort study included 728 Korean CD patients from 13 university hospitals. The first CD-related surgery or need for immunosuppressive or biological agents were regarded as the clinical outcomes of interest. ResultsA total of 126 (17.3%) CD patients underwent CD-related surgery, while 473 (65.0%) and 196 (26.9%) were prescribed thiopurine drugs and infliximab, respectively. Multivariate Cox regression analysis identified current (hazard ratio [HR] = 1.86; P = 0.018) and former smoking habits (HR = 1.78; P = 0.049), stricturing (HR = 2.24; P < 0.001), and penetrating disease behavior at diagnosis (HR = 3.07; P < 0.001) as independent predictors associated with the first CD-related surgery. With respect to immunosuppressive and biological agents, younger age (< 40 years) (HR = 2.17; P < 0.001 and HR = 2.10; P = 0.006, respectively), ileal involvement (HR = 1.36; P = 0.035 and HR = 2.17; P = 0.006, respectively), and perianal disease (HR = 1.42; P = 0.001 and HR = 1.38; P = 0.038, respectively) at diagnosis were significant predictors for the need of these medications. Conclusions
In Korean patients with CD, stricturing, penetrating disease behavior, and smoking habits at the time of diagnosis are independent predictors for CD-related surgery. It was also identified that younger age (< 40 years), ileal involvement, and perianal disease at diagnosis are predictive of a need for immunosuppressive or biological agents.
Full-text · Article · Jan 2014 · Journal of Gastroenterology and Hepatology
[Show abstract][Hide abstract] ABSTRACT: Background and Aim. We aim to elucidate the association of risk factors for atherosclerosis and H. pylori infection according to the promotor polymorphism of the CD14 gene in healthy Korean population. Methods. The patients who visited our hospital for routine health examinations and 266 healthy adults (170 males and 96 females) were enrolled in this study. The promotor polymorphism at -159C/T of the CD14 gene was determined by PCR-restriction fragment length polymorphism analysis. According to genetic polymorphism and H. pylori infection, we analyzed the risk of atherosclerosis. Results. The genotype frequencies were CC 7.9%, CT 45.1%, and TT 47.0%, respectively. There were no differences between specific genotypes of CD14 gene and H. pylori infection rate. As for HDL cholesterol level, there were significant differences among the three genotypes (P < 0.01). In subjects with H. pylori infection, no significant differences were observed between specific genotypes of CD14 gene and the risk factors of atherosclerosis. Conclusion. The promotor polymorphism at -159C/T of the CD14 gene was associated with the risk factor of atherosclerosis in healthy Korean population. However, it was not associated with the rate of H. pylori infection and H. pylori induced atherosclerotic risk.
Preview · Article · Oct 2013 · Gastroenterology Research and Practice
[Show abstract][Hide abstract] ABSTRACT: Advancing age is a well-known risk factor for Clostridium difficile infection (CDI). However, age-specific clinical differences in CDI are uncertain. A retrospective comparative analysis was performed based on age in 1367 patients with CDI in Korea. Most clinical features were similar in the two age groups studied, however malignancy was more common in the older group (age ≥ 65 y) (p < 0.001), while chemotherapy and transplantation were more common in the younger group (age < 65 y) (p < 0.001). Endoscopic examinations were more commonly performed in the older group (p = 0.010), which had a high positive predictive value (88.3%). More patients recovered from CDI without specific antibiotic treatment in the younger group than in the older group (p < 0.001). Although advancing age is an important risk factor for CDI, the clinical features of younger patients are similar to those of the older patient population.
Full-text · Article · Oct 2013 · Scandinavian Journal of Infectious Diseases
[Show abstract][Hide abstract] ABSTRACT: Background:
Several recent studies have revealed that diagnostic imaging can result in exposure to potentially harmful levels of ionizing radiation in patients with inflammatory bowel disease (IBD). However, these studies have been conducted exclusively in Western countries, and no data are available in Asian populations. The aim of this study was to estimate the diagnostic radiation exposure in Korean patients with IBD and to determine the factors associated with high radiation exposure.
Patients with an established diagnosis of IBD between July 1987 and January 2012 were investigated in 13 university hospitals in Korea. The cumulative effective dose (CED) was calculated retrospectively from standard tables.
A total of 777 patients with Crohn's disease (CD) and 1422 patients with ulcerative colitis (UC) were included in the study. The mean CED for CD and UC were 53.6 and 16.4 mSv, respectively (P < 0.001). CTof CD and UC accounted for 81.6% and 71.2% of total effective dose, respectively. Importantly, 34.7% of patients with CD and 8.4% of patients with UC were exposed to high levels of radiation (CED > 50 mSv) (P < 0.001). High radiation exposure was associated with long disease duration, ileocolonic disease, upper gastrointestinal tract involvement, surgical intervention, hospitalization, and the requirement for oral steroids in CD, and with surgical intervention, hospitalization, and the requirement for infliximab in UC.
A substantial proportion of patients with IBD, especially patients with CD, were exposed to significantly harmful amounts of diagnostic radiation, mainly as a result of CT examination. Given that IBD is a life-long illness, strategies to reduce radiation exposure from diagnostic imaging need to be considered.
Full-text · Article · May 2013 · Inflammatory Bowel Diseases
[Show abstract][Hide abstract] ABSTRACT: Background:
Although infliximab is widely accepted as a therapeutic option for inflammatory bowel disease, its therapeutic efficacy for the treatment of intestinal Behçet's disease (BD) is unknown. We investigated the short-term and long-term response rates to infliximab in intestinal BD and predictive factors of sustained treatment response following infliximab treatment.
This study was conducted using a retrospective noncontrolled review of medical records from 8 tertiary hospitals in Korea. We collected clinical, demographic, and laboratory data for patients with 28 patients with intestinal BD who received at least 1 dose of infliximab. Response rates of infliximab at 2, 4, 30, and 54 weeks for each patient and factors predictive of sustained response were investigated. Adverse events were also identified.
The median duration of follow-up after initial infliximab infusion was of 29.5 months. The clinical response rates at 2, 4, 30, and 54 weeks were 75%, 64.3%, 50%, and 39.1%, respectively, with clinical remission rates of 32.1%, 28.6%, 46.2%, and 39.1%, respectively. After multivariate analysis, older age at diagnosis (≥40 yr), female sex, a longer disease duration (≥5 yr), concomitant immunomodulator use, and achievement of remission at week 4 were found to be predictive factors of sustained response. There was 1 serious infection but no malignancies or deaths in this study.
Infliximab was a well-tolerated and effective therapy for patients with moderate-to-severe intestinal BD. Moreover, we found 5 predictive factors associated with sustained response, which might assist in optimal patient selection for infliximab treatment.
No preview · Article · May 2013 · Inflammatory Bowel Diseases
[Show abstract][Hide abstract] ABSTRACT: We aim to evaluate the association between promoter polymorphism of the clusters of differentiation 14 (CD14) gene and Helicobacter pylori-induced gastric mucosal inflammation in a healthy Korean population.
The study population consisted of 267 healthy subjects who visited our hospital for free nationwide gastric cancer screening. Promoter polymorphism at -260 C/T of the CD14 gene was determined by polymerase chain reaction and restriction fragment length polymorphism analysis. The severity of gastric mucosal inflammation was estimated by a gastritis score based on the sum of the values of the grade and activity of the gastritis. Expression of soluble CD14 (sCD14) was assessed by quantitative sandwich ELISA.
CD14 polymorphism was not associated with H. pylori infection. There were no significant differences in gastritis scores among the genotype subgroups, but subjects carrying the CD14 -260 CT/TT genotype had significantly higher sCD14 levels than those carrying the CC genotype. Subjects with the 260-T allele of the CD14 gene and H. pylori infection had significantly higher sCD14 levels than those with the same genotype but without infection.
In individuals with the T allele at the -260 site of the promoter region of the CD14 gene, H. pylori infection accentuates gastric mucosal inflammation.