Anti-MAdCAM-1 antibody (PF-00547659) for active refractory Crohn's disease in Japanese and Korean patients: the OPERA study.

BACKGROUND/AIMS: PF-00547659 is a monoclonal antibody against human mucosal addressin cell adhesion molecule-1 (MAdCAM-1) that prevents the binding of α4ß7+ lymphocytes to MAdCAM-expressing sites in the gastrointestinal tract with high affinity and selectivity, and is being developed for the treatment of Crohn's disease (CD). METHODS: OPERA is a randomized, multicenter, double-blind, placebo-controlled study to investigate the efficacy, safety, and pharmacokinetics of PF-00547659 following subcutaneous administration in subjects with active CD, a history of failure or intolerance to anti-tumor necrosis factor and/or immunosuppressants, high-sensitivity C-reactive protein > 3.0 mg/L, and ulcers on colonoscopy. The primary endpoint was Crohn's Disease Activity Index-70 response at week 8 or 12. Subpopulation analyses for Asian subjects were performed as some differences are observed in genetics and clinical phenotypes in Asian CD patients compared with Western patients. RESULTS: In this study, 265 CD subjects were randomized, with a subpopulation of 21 subjects (8 Japanese and 13 Korean) defined as the Asian population. In the overall and Asian populations; PF-00547659 was pharmacologically active as evidenced by soluble MAdCAM and circulating ß7+ central memory CD4+ T-lymphocytes, although no clear evidence of efficacy was observed in any clinical endpoints; pharmacokinetics of PF-00547659 in the Asian subpopulation was generally comparable to the overall population; and the safety profile of PF-00547659 appeared acceptable up to 12 weeks of treatment. CONCLUSIONS: In the overall and Asian populations, efficacy of PF-00547659 could not be demonstrated using any clinical endpoints compared with placebo. Pharmacokinetics and safety of PF-00547659 were generally comparable. Further studies with larger numbers of patients are required to confirm our results. (Trial Registration Number: NCT01276509).

The Novel Scoring System for 30-Day Mortality in Patients with Non-variceal Upper Gastrointestinal Bleeding.

BACKGROUND: Although the mortality rates for non-variceal upper gastrointestinal bleeding (NVUGIB) have recently decreased, it remains a significant medical problem. AIM: The main aim of this prospective multicenter database study was to construct a clinically useful predictive scoring system by using our predictors and compare its prognostic accuracy with that of the Rockall scoring system. METHODS: Data were collected from consecutive patients with NVUGIB. Logistic regression analysis was performed to identify the independent predictors of 30-day mortality. Each independent predictor was assigned an integral point proportional to the odds ratio (OR) and we used the area under the curve to compare the discrimination ability between the new predictive model and the Rockall score. RESULTS: The independent predictors of mortality included age >65 years [OR 2.627; 95 % confidence interval (CI) 1.298-5.318], hemodynamic instability (OR 2.217; 95 % CI 1.069-4.597), serum blood urea nitrogen level >40 mg/dL (OR 1.895; 95 % CI 1.029-3.490), active bleeding at endoscopy (OR 2.434; 95 % CI 1.283-4.616), transfusions (OR 3.811; 95 % CI 1.640-8.857), comorbidities (OR 3.481; 95 % CI 1.405-8.624), and rebleeding (OR 10.581; 95 % CI 5.590-20.030). The new predictive model showed a high discrimination capability and was significantly superior to the Rockall score in predicting the risk of death (OR 0.837;95 % CI 0.818-0.855 vs. 0.761; 0.739-0.782; P = 0.0123). CONCLUSIONS: The new predictive score was significantly more accurate than the Rockall score in predicting death in NVUGIB patients. We need to prospectively validate the accuracy of this score for predicting mortality in NVUGIB patients.

Clinical differences in Clostridium difficile infection based on age: a multicenter study.

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.

Factors associated with development of complications after endoscopic foreign body removal.

BACKGROUND/AIMS: We analyzed the clinical characteristics of patients who underwent endoscopic foreign body removal and the risk factors of complications. PATIENTS AND METHODS: The medical records of 415 patients treated from January 2000 to August 2011 for suspected foreign bodies were retrospectively reviewed. Patient characteristics, endoscopic findings, clinical outcomes, and risk factors of complications were analyzed. RESULTS: Foreign bodies were detected endoscopically in 315 patients. Fish bone fragment (36.9%) and coins (15.3%) were the most common type of foreign bodies in adults and children, respectively. Complications associated with endoscopic procedure occurred in 26 patients (8.3%); 20 of the patients were treated conservatively and the other six patients underwent surgical treatment. Perforation (14%) was the most common complication. By univariate and multivariate analysis, the risk factors associated with complication after endoscopic foreign body removal were long duration from ingestion to endoscopy ( P = 0.009) and existence of initial mucosal injury ( P = 0.018). CONCLUSIONS: Most foreign bodies were successfully removed by endoscopy without complication, but long duration from ingestion to endoscopy and mucosal injury were risk factors of complications of endoscopic foreign body removal. Patients with these risk factors could require more careful treatment.

Endoscopic submucosal dissection for early gastric cancer with undifferentiated histology: could we extend the criteria beyond?

BACKGROUND: Endoscopic submucosal desection (ESD) is an effective treatment for selected patients with early gastric cancer (EGC). The purpose of this study was to examine the short-term and long-term outcomes of ESD of undifferentiated early gastric cancer. METHODS: Data for 1,241 patients who underwent ESD for treatment of EGC between February 2003 and May 2010 were collected. We performed a retrospective analysis of the medical records of 74 patients diagnosed with undifferentiated EGC. We divided the enrolled cases into two groups: the expanded-criteria group (EC group) versus the non-EC group, according to lesion size, presence of ulceration, and pathologic review. RESULTS: Of a total of 74 lesions with undifferentiated EGC, as a result of pathologic examination the EC group included 29 cases and the non-EC group included 45 cases. The mean diameter of lesions was 19.86 ± 12.5 mm. The overall rates of en bloc resection and complete resection were 90.5% (67/74) and 73% (54/74), respectively. The curative resection rate was low at 31.1%. If limited to the pathologically diagnosed EC group, the curative resection rate was 79.3% (23/29). During median follow-up periods of 34 months (range 7-81), local recurrences were observed in 5.5% (4/74) of patients. All of these were in the non-EC group and all underwent noncurative resection. There was no mortality related to ESD for treatment of EGC during follow-up. CONCLUSIONS: ESD may be a feasible treatment for selected patients with undifferentiated EGC; this should be validated by development of new criteria for ESD for treatment of EGC.

Efficacy of rifaximin compared with ciprofloxacin for the treatment of acute infectious diarrhea: a randomized controlled multicenter study.

BACKGROUND/AIMS: Ciprofloxacin has been widely prescribed for acute infectious diarrhea. However, the resistance to this drug is increasing. Rifaximin is a novel but poorly absorbed rifamycin derivative. This study evaluated and compared the efficacies of rifaximin and ciprofloxacin for the treatment of acute infectious diarrhea. METHODS: We performed a randomized controlled multicenter study in Korea. Patients with acute diarrhea were enrolled and randomized to receive rifaximin or ciprofloxacin for 3 days. The primary efficacy endpoint was the time to last unformed stool (TLUS). Secondary endpoints were enteric wellness (reduction of at least 50% in the number of unformed stools during 24-hour postenrollment intervals), general wellness (subjective feeling of improvement), and proportion of patients with treatment failure. RESULTS: Intent-to-treat analysis (n=143) showed no significant difference between the rifaximin and ciprofloxacin groups in the mean TLUS (36.1 hours vs 43.6 hours, p=0.163), enteric wellness (49% vs 57%, p=0.428), general wellness (67% vs 78%, p=0.189), or treatment failure rate (9% vs 12%, p=0.841). The adverse events did not differ significantly between the two groups. CONCLUSIONS: These results suggest that rifaximin is as safe and effective as ciprofloxacin in the treatment of acute infectious diarrhea.

A matched case-control study of a novel Acid-pump antagonist and proton-pump inhibitor for the treatment of iatrogenic ulcers caused by endoscopic submucosal dissection.

BACKGROUND/AIMS: Revaprazan, a novel acid-pump antagonist, and proton-pump inhibitors (PPIs) have pH-independent effects on ulcer healing. The addition of a PPI promotes the cell restitution rate as well as vessel regeneration and maturation for ulcer repair. Revaprazan is known to protect the mucosa by increasing the prostaglandin concentration. METHODS: We reviewed the medical records of patients who underwent endoscopic submucosal dissection (ESD) for gastric neoplasia at Yeungnam University Hospital between January 2008 and May 2009. We conducted a matched case-control study to compare the healing rates effected by revaprazan and rabeprazole. RESULTS: Each group consisted of 30 patients. The baseline characteristics did not differ significantly between the two groups. Stage S1 disease was observed in 97% and 100% of patients after 8 weeks of treatment in the revaprazan and rabeprazole groups, respectively. In the revaprazan group, only one patient had stage H2 disease: a 54-year-old man with a 5.5-cm lesion after ESD of the ulcer, type IIa early gastric cancer, and adenocarcinoma. No serious adverse effects occurred during the treatment period in either group. CONCLUSIONS: The safety and efficacy profiles of revaprazan and rabeprazole are similar for the treatment of ESD-induced ulcers.

A Matched Case-Control Study Using the Propensity Score on Differences in the Characteristics of Colorectal Polyps between Younger and Older Koreans: Proximal Shift in the Distribution of Colorectal Polyps among Older Koreans.

BACKGROUND/AIMS: Several studies have found that the frequency of colorectal polyps increases significantly from the age of 50 years. The goal of this study was to determine the differences in the clinical characteristics of colorectal polyps between patients aged 50 years and older, and younger patients. METHODS: The colonoscopy database of 3,304 patients at the Yeungnam University Medical Center between January 2009 and December 2009 was reviewed retrospectively. In total, 679 patients were divided into the younger group (n=170) and the older group (aged ≥50 years) (n=509). A matched case-control study was performed using propensity scores and 117 patients selected from each group. RESULTS: Compared to the younger group, the older group had a significantly higher proportion of female patients, and patients with hypertension, a smoking history, and a history of taking medications. After performing the matched case-control study, 234 patients and 679 colon polyps were included in the analysis. Compared to the younger patients, the older patients had a significantly higher proportion of multiple lesions (57.3% vs 25.6%, p<0.001), left- and right-side distribution (35.9% vs 12.0%, p<0.001), and larger polyps (mean 9.1 mm vs 6.3 mm, p<0.001). A left-sided distribution was less common in the older group than in the younger group (35.0% vs 51.3%, p=0.025). CONCLUSIONS: The methods used to screen for colorectal cancer in older patients should include colonoscopy due to the shift to the right side as a common location for colorectal polyps in that age group.

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, instructor's 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.

A common bile duct stone formed by suture material after open cholecystectomy.

The use of non-absorbable suture materials for cystic duct ligation after cholecystectomy can expose patients to the risk of recurrent stone formation in the common bile duct (CBD). However, in Korea suture materials have rarely been found to act as a nidus for common bile duct calculus formation. Recently, we experienced a case in which suture material, that had migrated from a previous cholecystectomy site into the CBD, probably served as a nidus for common bile duct stone formation. The stone was confirmed by endoscopic retrograde cholangiopancreatography (ERCP) and removed successfully using a basket. The authors report a case of surgical suture migration and discuss its subsequent role as a stone forming nucleus within the CBD in a patient who underwent open cholecystectomy; and include a review of the literature.