Incidence and clinical features of Clostridium difficile infection in Korea: a nationwide study.

The incidence and severity of Clostridium difficile infections (CDI) have increased in Western countries. However, there are limited data regarding the epidemiology of CDI in Eastern countries. This nationwide study was conducted in 17 hospitals to determine temporal trends in CDI incidence (from 2004 to 2008) in South Korea. The total incidence of CDI in Korea was 1·7 cases/1000 adult admissions in 2004, and 2·7/1000 cases in 2008 (P = 0·028). When analysing the clinical features of 1367 CDI patients diagnosed in 2008, oral metronidazole was effective as a first-line treatment for CDI (61·9%). Relapse rate was 8·9% and complicated CDI was only observed in 3·6%. The incidence of CDI increased significantly in Korea from 2004 to 2008. Although the clinical features were milder than in Western countries, the increasing burden of CDI needs ongoing surveillance systems.

Mouse hepatoma cell lines differing in aryl hydrocarbon receptor-mediated signaling have different activities for glucuronidation.

For studies on the aryl hydrocarbon receptor (AhR)-dependent toxicity of the mycotoxins alternariol (AOH) and alternariol methyl ether (AME), three mouse hepatoma (Hepa-1) cell lines with intact and with compromised AhR signaling were compared with respect to their activities for hydroxylation, methylation, and glucuronidation. Whereas the activities of cytochrome P450-mediated monooxygenase and catechol-O-methyl transferase were very low and did not differ between the three cell lines, a pronounced difference was observed for UDP-glucuronosyl transferase activity, which was much higher in Hepa-1c1c4 than in c1c7 and c1c12 cells. In all three cell types, the rate of glucuronidation of AOH was about four times higher than that of AME. Whereas AME caused a concentration-dependent G2/M arrest in each cell line, AOH arrested Hepa-1c1c7 and c1c12 cells but not c1c4 cells. However, Hepa-1c1c4 cells were arrested by AOH when ß-glucuronidase was added to the incubation medium in order to reverse the formation of AOH glucuronides. We conclude that the failure of AOH to cause cell cycle inhibition in Hepa-1c1c4 cells is due to its efficient glucuronidation. The considerable UDP-glucuronosyl transferase activity of Hepa-1c1c4 cells should be taken into account when other compounds are studied in this cell line. Moreover, we demonstrate that differences in glucuronide formation between cell types can be overcome by the addition of ß-glucuronidase to the cell culture medium.

Criteria for decision making after endoscopic resection of well-differentiated rectal carcinoids with regard to potential lymphatic spread.

BACKGROUND AND STUDY AIM: Rectal carcinoids are low-grade malignancies that are usually treated by endoscopic resection. However, on pathologic examination, resection margins that are positive for carcinoid cells are frequently found. Patient outcomes were reviewed after endoscopic resection of rectal carcinoids and the clinical significance of possible residual disease, as defined by pathologic and endoscopic examination, was evaluated. PATIENTS AND METHODS: The medical records and endoscopic findings of 347 patients presenting with rectal carcinoids to 14 university hospitals in Korea between January 1999 and June 2007 were retrospectively analyzed. RESULTS: A total of 304 patients were treated with endoscopic resection, and 43 patents were treated with surgery. In the endoscopic resection group, the complete resection rate was 88.2% based on endoscopic appearance (CR-E) and 60.2% based on pathologic evaluation (CR-P). The agreement between CR-E and CR-P was low (κ=0.192). No residual tumors were found in 77 of 85 patients (90.6%) who were CR-E but not CR-P and who had endoscopic biopsy taken at 24-month follow-up. The receiver-operating characteristic curve identified an optimal cut-off value of 10.5 mm, at which the sensitivity and the specificity for metastasis were 100% and 89%, respectively. The risk factors for metastasis by multivariate analysis were tumor size, increased mitotic rate, and lymphovascular invasion. CONCLUSIONS: Endoscopic resection is a safe and effective modality for treating well-differentiated rectal carcinoids smaller than 10 mm in diameter. Discrepancies were observed between CR-E and CR-P. The risk factors for metastasis were tumor size, increased mitotic rate, and lymphovascular invasion.

Diagnostic yield of advanced colorectal neoplasia at colonoscopy, according to indications: an investigation from the Korean Association for the Study of Intestinal Diseases (KASID).

BACKGROUND AND STUDY AIMS: The factors that more accurately predict the detection of colorectal cancers and adenomas at colonoscopy are different. We conducted a prospective multicenter study to evaluate which indications were most closely associated with advanced colorectal neoplasm (CRN), including colorectal cancer, in a group of patients undergoing colonoscopy. PATIENTS AND METHODS: The 17 468 patients were enrolled in this study between July 2003 and March 2004, from 11 tertiary medical centers in Korea. They were recruited according to 11 itemized colonoscopic indications. The term "advanced adenoma" refers here to tubular adenomas of diameter of 11 mm or more, or to tubulovillous, villous, or severely dysplastic adenomas, irrespective of their size. Cancer was defined as the invasion of malignant cells beyond the muscularis mucosa. Advanced CRN was defined as advanced adenoma or invasive cancer. RESULTS: Advanced CRN was found in 1227/17 307 patients (1176 advanced adenomas plus 51 carcinomas, 7.1 %). According to univariate and multivariate analysis, the factors associated with advanced CRN included age >60 years (odds ratio (OR) 2.1, 95 % confidence interval (CI) 1.8 - 2.4, P < 0.0001), male gender (OR 2.1, 95 %CI 1.7 - 2.7, P < 0.0001), referral for colonoscopy from primary care physician (OR 3.1, 95 %CI 2.5 - 3.7, P < 0.0001), and several other indications (OR 1.8, 95 %CI 1.5 - 2.3, P < 0.001). The yield of colonoscopy for advanced CRN was lower (2.2 %) than expected in patients with iron-deficiency anemia (OR 0.5, 95 %CI 0.2 - 0.9, P = 0.03). CONCLUSIONS: Age, gender, and referral for colonoscopy from primary care physician constituted important independent predictors of advanced CRN in patients undergoing colonoscopy.

Primary colon lymphoma in Korea: a KASID (Korean Association for the Study of Intestinal Diseases) Study.

Although almost all primary colorectal lymphomas are of B-cell lineage in Western countries, primary colorectal T-cell lymphomas are not uncommon in the East. The aim of this study was to review the clinical characteristics and treatment outcomes of primary colorectal lymphomas, with special emphasis on the differences between T-cell and B-cell lymphomas. Ninety-five cases of primary colorectal lymphomas that satisfied Dawson's criteria were identified from the clinical databases of 13 university hospitals in Korea. The mean age at the time of presentation was 51.1 years and the male:female ratio was 64:31. The clinical information, including endoscopic and histological characteristics, was retrospectively analyzed. Of the primary colorectal lymphomas, 78 cases (82.1%) were of B-lineage and 17 cases (17.9%) were of T-cell lineage. Patients with T-cell lymphomas presented at a younger age than patients with B-cell lymphomas (42.8 vs 52.9 years, respectively; P = 0.016). The most common presenting symptom was abdominal pain (87.1%) for B-cell lymphomas, whereas hematochezia or night fever was more common for T-cell lymphomas (52.9% and 35.3%, respectively). The most common endoscopic type was fungating mass (54.0%) for B-cell lymphomas and ulcerative/ulcero-infiltrative lesions (80.0%) for T-cell lymphomas. Intussusception was more common in B-cell lymphomas than in T-cell lymphomas (30.8% vs 5.9%, respectively; P = 0.035), but perforation was more common in T-cell lymphomas than in B-cell lymphomas (23.5% vs 3.8%, respectively; P = 0.005). The prognosis was significantly worse for T-cell lymphomas than for B-cell lymphomas (P = 0.002). Primary colorectal T-cell lymphomas are characterized by multifocal ulcerative lesions in relatively young patients, a high rate of hematochezia, fever, or perforation, and a poor prognosis even for cases of localized disease.

Atypical endoscopic features of rectal carcinoids.

BACKGROUND AND STUDY AIMS: It is not normally difficult to diagnose carcinoid tumors (well-differentiated endocrine neoplasms) of the rectum endoscopically, as they usually have a characteristic appearance. However, little is known about the atypical endoscopic findings in some rectal carcinoids and the present study was performed to analyze these. PATIENTS AND METHODS: The endoscopic findings in 67 consecutive patients with rectal carcinoids (37 men, 30 women; age range 23 - 76) were analyzed retrospectively. RESULTS: Tumor size ranged from 2 mm to 30 mm (average 7.4 mm). Of the 67 patients, 52 (78 %) displayed the characteristic endoscopic findings of smooth, round, sessile elevations covered with normal-appearing or yellow-discolored mucosa; in 15 (22 %) there were one or more atypical endoscopic findings. These included a semipedunculated appearance (n = 6), hyperemia (n = 5), a central depression (n = 6), erosion (n = 5), and ulceration (n = 4). Atypical findings were noted in none of 20 carcinoids &lambda< 5 mm in diameter; in six (20 %) of the 30 carcinoids between 5 mm and 9 mm; in six (43 %) of the 14 carcinoids between 10 mm and 19 mm; and in three (100 %) of the three carcinoids >/= 20 mm in diameter ( P < 0.001). Invasion into the muscularis propria or metastasis to the liver or lymph nodes occurred in three of the four patients with ulceration, but it was confirmed in only one of the 63 patients without ulceration ( P < 0.001). CONCLUSIONS: Atypical endoscopic appearances of rectal carcinoids are observed more frequently as the size of the tumor increases and a finding of ulceration may have a prognostic value.

Plasma isocitrate dehydrogenase as a marker of centrilobular hepatic necrosis in patients with hyperthyroidism.

Isocitrate dehydrogenase (ICDH) may be useful for differentiating centrilobular from periportal necrosis in rats with liver injury. In this study, we assessed the usefulness of ICDH as a marker of centrilobular necrosis in patients with hyperthyroidism. Isocitrate dehydrogenase and alanine aminotransferase (ALT) activities were measured in the plasma of 56 patients with hyperthyroidism, 16 patients with chronic viral hepatitis (CVH), and 17 controls. Isocitrate dehydrogenase levels were higher in patients with hyperthyroidism than in those with CVH or in the controls (p < 0.01 and p < 0.001, respectively), even though ALT levels were higher in patients with CVH than in patients with hyperthyroidism (p < 0.01). Isocitrate dehydrogenase/ALT ratios were also higher in patients with hyperthyroidism than in those with CVH (p < 0.0001). Isocitrate dehydrogenase correlated to ALT levels in patients with hyperthyroidism or CVH (p < 0.05). In a patient with hyperthyroidism, ICDH levels decreased progressively to normal, and the ALT level and thyroid function were normalized. Thus, the plasma ICDH or ICDH/ALT ratio might be useful for differentiating centrilobular from periportal necrosis and for monitoring the degree of hepatic necrosis in patients with hyperthyroidism.

Incidence and prevalence of ulcerative colitis in the Songpa-Kangdong District, Seoul, Korea, 1986-1997.

BACKGROUND AND AIMS: Ulcerative colitis (UC) is regarded as a rare disease in developing countries, but accurate data are generally lacking. We performed the present study to evaluate the incidence and prevalence of UC in Korea. METHODS: A retrospective study was performed from 1986 to 1997 in the Songpa-Kangdong district of Seoul, Korea. To recruit UC patients as completely as possible, multiple information sources including all medical facilities in the study area and three referral centres located nearby, but outside the study area were used. The incidence and prevalence rates were adjusted using the 1997 Korean population statistics. RESULTS: During the study period, a total of 94 incident cases were identified, for an adjusted mean annual incidence rate of 0.68 per 100,000 inhabitants. On 31 December 1997, 91 patients with UC lived in the study area, giving an adjusted prevalence rate of 7.57 per 100,000 inhabitants. By using the Poisson regression analysis, the annual incidence rate increased significantly from 0.20 per 100,000 inhabitants in 1986-1988 to 1.23 per 100,000 inhabitants in 1995-1997 (P < 0.005). Patient age at diagnosis, the interval from onset of symptoms to diagnosis, and the disease extent at diagnosis were fairly constant throughout the study period. CONCLUSIONS: The incidence and prevalence of UC in our study area are still low compared with those of Western countries, but the incidence rate is steadily increasing.

Experimental model of hepatic fibrosis following repeated periportal necrosis induced by allylalcohol.

BACKGROUND/AIMS: In most patients with chronic viral hepatitis the predominant lobular location of hepatic necrosis and fibrosis is the periportal zone. We established a new simple model of hepatic fibrosis in rats by repetitive periportal necrosis with allylalcohol. METHODS: Of 40 male adult rats, 30 were injected with 0.62 mmol/kg of allylalcohol intraperitoneally twice a week, the remaining 10 with normal saline as controls. Ten rats were killed at each of 4, 8, and 16 weeks later. The extent of fibrosis was evaluated according to the portal-portal extent. Transforming growth factor (TGF) beta1 mRNA in liver tissues was detected by reverse transcriptase polymerase chain reaction, and its levels were determined by the endpoint titers of serial two-fold dilutions of cDNA. RESULTS: After 4 weeks, periportal fibrosis was produced in only 6 out of 10 rats, and was mild in extent. However, after 8 weeks, 8 out of 9 survivors showed moderate to severe fibrosis, which corresponded to a score of 7 or more. The extent of fibrosis correlated significantly with the amount of collagen and TGFbeta1 mRNA expression in liver tissues. The collagen content and expression of TGFbeta1 mRNA were also upregulated significantly in liver tissues with a fibrosis score of 7 or more. CONCLUSIONS: Hepatic fibrosis can be sufficiently induced by repetitive intraperitoneal injection of 0.62 mmol/kg of allylalcohol twice a week for 8 weeks. This simple model of hepatic fibrosis, in which TGFbeta1 is overexpressed at the transcriptional level, may be useful in the study of patients who have predominantly periportal necrosis and fibrosis.

Protective effect of chlormethiazole, a sedative, against acetaminophen-induced liver injury in mice.

OBJECTIVES: The hepatotoxicity of acetaminophen is not a result of the parent compound but is mediated by its reactive metabolite N-acetyl-p-benzoquinone imine. Cytochrome P4502E1 (CYP2E1) is the principal enzyme of this biotransformation, which accounts for approximately 52% of the bioactivation in human microsomes. Recently, chlormethiazole a sedative drug, is reported to be an efficient inhibitor of CYP2E1 activity in human beings. In this study we wished to evaluate whether chlormethiazole, an inhibitor of CYP2E1, could prevent acetaminophen-induced liver injury in mice. METHODS: Acetaminophen, at doses ranging from 200 to 600 mg/kg, was injected into the peritoneum of female C57BL/6 inbred mice fasted for four hours. Chlormethiazole (60 mg/kg) or 5% dextrose water was given 30 min before or 2 h after acetaminophen. Serum aminotransferase activities, histologic index score, survival rate and hepatic malondialdehyde levels were compared. RESULTS: Pretreatment with chlormethiazole 30 min before 400 mg/kg of acetaminophen completely inhibited acetaminophen-induced liver injury (median 118.5 U/L, range 75 to 142 vs. 14,070 U/L, range 5980 to 27,680 for AST; 49 U/L, range 41 to 64 vs. 15,330 U/L, range 13,920 to 15,940 for ALT). In mice receiving chlormethiazole 2 h after acetaminophen, the mean AST and ALT levels were also less elevated, reaching only 20% of the value of acetaminophen-only group. These protective effects were confirmed histologically. Whereas more than 50% of mice died at 500 mg/kg of acetaminophen, all the mice pretreated with chlormethiazole survived at the same dose. CONCLUSION: Chlormethiazole effectively reduces acetaminophen-induced liver injury in mice. Further studies are needed to assess its role in humans.

Zinc deficiency manifested by dermatitis and visual dysfunction in a patient with Crohn's disease.

We report a case of Crohn's disease with low serum zinc concentration in a 26-year-old woman. She demonstrated acrodermatitis enteropathica and decreased visual acuity during total parenteral nutrition. Subsequent intravenous zinc supplementation resulted in alleviation of the skin lesions and improvement of visual acuity. This case supports the notion that depressed serum zinc in Crohn's disease may cause clinical manifestations, such as acrodermatitis enteropathica and retinal dysfunction, which may be correctable with zinc supplementation.

Ballooning of the papilla during contrast injection: the semaphore of a choledochocele.

BACKGROUND: Choledochocele is a rare abnormality involving the intramural segment of the common bile duct. ERCP is essential to demonstrate a choledochocele. The aim of this study was to investigate the duodenoscopic and cholangiographic findings during ERCP. METHODS: Over a 4-year period, 17 symptomatic patients (8 men, 9 women; age range 45 to 83 years) were identified as having choledochoceles. The diagnosis of choledochocele was made by both duodenoscopic and cholangiographic findings. RESULTS: As a characteristic duodenoscopic finding, the enlarged bulging papilla was noted in 8 patients (47%), whereas a normal-appearing papilla was noted in 9 patients (53%) before the injection of contrast media. However, in all 17 patients progressive enlargement or ballooning of the papilla was noted during contrast injection. The maximum diameter of the choledochocele, determined by cholangiography, was significantly larger (19 +/-4 mm) in patients with initially bulging papilla than in those with normal-appearing papilla (9+/-3 mm) (p < 0.05). CONCLUSIONS: Ballooning of the papilla during contrast injection may be a specific duodenoscopic finding for choledochocele. To avoid missing the diagnosis of a choledochocele, especially when it is small, it is important to watch the papilla carefully during contrast injection.

The value of pancreatoscopy in patients with mucinous ductal ectasia.

We report here on three cases of mucinous ductal ectasia in which the diagnosis was suggested by abdominal computed tomography and finally established by duodenoscopy with pancreatoscopy. Duodenoscopic examination of the ampulla of Vater demonstrated a patulous papillary orifice and extrusion of viscid mucus. Pancreatoscopic examination was carried out in all three patients, and characteristic findings such as papillary or villous mucosal projections coated with whitish gelatinous mucus were noted. In patients with mucinous ductal ectasia in whom the radiographic findings are equivocal, pancreatoscopic examination may provide valuable information for the differential diagnosis of amorphous filling defects in the main pancreatic duct, and may provide information that helps to determine the extent of the pathology and the resection margin.