Dong Kyung Chang

Epidemiology of inflammatory bowel disease in the Songpa-Kangdong district, Seoul, Korea, 1986-2005: a KASID study.

Background: Crohns disease (CD) and ulcerative colitis (UC) are considered rare diseases in developing countries. We have evaluated the incidence and prevalence of CD and UC over time in a district of Seoul, Korea. Methods: A population‐based study was performed from 1986 to 2005 in the Songpa‐Kangdong district of Seoul. To recruit patients as completely as possible, multiple information sources, including all medical facilities in the study area and 3 referral centers nearby but outside the study area, were used. Results: During the 20‐year study period, 138 incident cases of CD (102 men, 36 women) and 341 incident cases of UC (170 men, 171 women) were identified. For the 20‐year period, the adjusted mean annual incidence rates of CD and UC per 100,000 inhabitants were 0.53 (95% CI 0.44–0.62) and 1.51 (95% CI 1.34–1.67), respectively. When analyzed by 5‐year intervals, the mean annual incidence rates of CD and UC increased significantly, from 0.05 and 0.34 per 100,000 inhabitants, respectively, in 1986–1990 to 1.34 and 3.08 per 100,000 inhabitants, respectively, in 2001–2005. The adjusted prevalence rates of CD and UC per 100,000 inhabitants on December 31, 2005, were 11.24 (95% CI 9.29–13.18) and 30.87 (95% CI 27.47–34.27), respectively. Conclusions: The incidence and prevalence of CD and UC in Seoul, Korea, are still low compared with those in Western countries, but are rapidly increasing.

Efficacy and tolerability of split-dose magnesium citrate: low-volume (2 liters) polyethylene glycol vs. single- or split-dose polyethylene glycol bowel preparation for morning colonoscopy.

OBJECTIVES:Preparation regimens for morning colonoscopy are suboptimal. The aim of this study was to test the efficacy and tolerance of a split-dose magnesium citrate–low-volume (2 liters) polyethylene glycol (PEG) regimen for morning colonoscopy.METHODS:A total of 232 patients were randomly assigned to receive 4 liters PEG (day before procedure; group 1, n=79), 2 liters PEG (day before procedure) followed by another 2 liters PEG (day of procedure; group 2, n=80), or magnesium citrate (250 ml, day before procedure) followed by 2 liters PEG (day of procedure; group 3, n=73). The quality of bowel cleansing, tolerability, and adverse effects in group 3 were compared with those in groups 1 and 2.RESULTS:Satisfactory bowel preparation was more frequently reported for group 3 than for group 1 (75% vs. 51%, P=0.001) and was similar to that for group 2 (75% vs. 76%, P=0.896). A significantly greater proportion of patients in group 3 graded their overall satisfaction as satisfactory compared with group 1 (43% vs. 23%, P=0.010), and the proportion was similar to that in group 2 (43% vs. 35%, P=0.133). Patients in group 3 were more willing to repeat the same preparation regimen, if necessary, than those in group 1 (93% vs. 48%, P<0.001) or group 2 (93% vs. 62%, P<0.001).CONCLUSIONS:The split-dose magnesium citrate–low-volume (2 liters) PEG regimen was more efficient than and preferred to the conventional regimen of 4 liters of PEG, and it was equally efficient as, but, again, preferred to the split-dose (2+2 liters) regimen for morning colonoscopy.

Molecular features of colorectal hyperplastic polyps and sessile serrated adenoma/polyps from Korea.

Abundant recent data suggest that sessile serrated adenoma/polyp (SSA/P) is an early precursor lesion in the serrated pathway of carcinogenesis. It is believed that SSA/Ps develop cancer by an SSA/P-dysplasia-carcinoma sequence. Hyperplastic polyps (HPs) share some histologic and molecular characteristics with SSA/P, but it is unclear whether SSA/Ps are derived from HPs or whether they develop by a different pathogenetic pathway. Previous studies have shown that serrated polyps from Korean patients show different prevalence rates of certain molecular abnormalities compared with similar lesions from American patients, and this suggests that lifestyle and dietary factors may influence the serrated neoplasia pathway. The purpose of this study was to evaluate the molecular features of HPs and SSA/Ps, the latter both with and without dysplasia, from Korean patients and to compare the findings with similar lesions from American patients. One hundred and eleven serrated polyps, consisting of 45 HPs (30 microvesicular, 11 goblet cell, 4 mucin depleted) and 56 SSA/Ps (36 with dysplasia, 20 without dysplasia), were retrieved from the pathology files of a large medical center in Korea and 38 SSA/P from American patients were evaluated for BRAF and KRAS mutations, microsatellite instability, and hypermethylation of O6-methylguanine-DNA methyltransferase (MGMT), hMLH1, adenomatous polyposis coli (APC), p16, methylated in tumor-1 (MINT-1), MINT2, and MINT31. Methylation of hMLH1 was performed using 2 different sets of primers. Twenty-three conventional adenomas from Korean patients were included as controls. The data were compared between polyp subtypes and between polyps in the right versus the left colon. With regard to HP, KRAS mutations were present in 31.1% of polyps and BRAF mutations in 46.7% of polyps. KRAS mutations were significantly more common in goblet cell HP and BRAF in microvesicular HP (MVHP). Methylation of MGMT, hMLH1, APC, p16, MINT1, MINT2, and MINT31 were present in 42.2%, 64.4% (and 24.4%), 37.8%, 60%, 68.9%, 51.1%, and 60% of HPs. CpG island methylator phenotype high was noted in 60% of HPs. Methylation of hMLH1, p16, MINT2, and MINT31 were more frequent in MVHPs compared with other types of HPs. In contrast, SSA/Ps showed KRAS and BRAF mutations in 12.5% and 60.7% of cases, respectively. Methylation of all tumor-related genes, except hMLH1 (23.2% using 1 type of primers) and APC (37.5%), occurred in >50% of lesions, and CpG island methylator phenotype (CIMP) high was noted in 76.8% of cases. None of the molecular findings were significantly more common in SSA/P with, versus those without, dysplasia, but only 2 of the 36 polyps with dysplasia were of the conventional adenomatous type; the remainder (34 of 36) was of the serrated type. Nevertheless, both SSA/P with conventional adenomatous dysplasia showed methylation of MGMT, APC, MINT1, and MINT31 and were CIMP high. BRAF mutations, methylation of most tumor related genes, and CIMP high occurred more frequently in HPs and SSA/Ps in the right colon, compared with the left colon. In fact, no significant differences were observed between HPs and SSPs of the right colon and HPs and SSA/Ps from the left colon. Furthermore, compared with American patients, Korean male individuals were affected more frequently than female individuals, and both BRAF mutations and hMLH1 methylation were less frequent in the latter compared with the former. We conclude that HPs and SSA/Ps in Korean patients share some, but not all, clinical and molecular characteristics to those that occur in Americans. The data support the theory that the right and left colon are biologically different with regard to susceptibility to serrated cancer, and that anatomic location (right vs. left) may be a more significant risk factor of progression than the histologic type of polyp. Our data also support the theory that right-sided MVHPs may be a precursor to SSA/P.

Colorectal cancer in inflammatory bowel disease: The risk, pathogenesis, prevention and diagnosis

Patients with inflammatory bowel disease (IBD) are at increased risk for developing colorectal cancer (CRC), although the overall incidence of IBD-associated CRC has been diminishing in recent decades in western countries. As demonstrated in previous studies, the risk of CRC in IBD increases with longer duration, extent of colitis, a familial history of CRC, coexistent primary sclerosing cholangitis, and the degree of inflammation. The pathogenesis of CRC in IBD is poorly understood. Similar to sporadic CRC, IBD-associated CRC is a consequence of sequential episodes of genomic alteration. Multiple inter-related pathways, including immune response by mucosal inflammatory mediators, oxidative stress, and intestinal microbiota, are also involved the pathogenesis of IBD-associated CRC. Continuing colonic inflammation appears to be a factor in the development of CRC; therefore, anti-inflammatory agents such as 5-aminosalicylate compounds and immune modulators have been considered as potential chemopreventive agents. Colonoscopic surveillance is widely accepted as being effective in reducing the risk of IBD-associated CRC, although no clear evidence has confirmed that surveillance colonoscopy prolongs survival in patients with extensive colitis. The traditional recommendation has been quadrantic random biopsies throughout the entire colon; however, several guidelines now have endorsed chromoendoscopy with a target biopsy because of increasing diagnostic yields and reduced workloads for endoscopists and pathologists. New technologies such as narrow band imaging, confocal endomicroscopy, and autofluorescence imaging have not yet been confirmed as surveillance strategies in IBD.

KRAS mutations in traditional serrated adenomas from Korea herald an aggressive phenotype.

The pathogenesis and risk of malignancy of traditional serrated adenomas (TSAs) are unclear. In North America, TSAs are relatively uncommon, occur mainly in the left colon, and in some studies, have not been shown to have a strong association with hyperplastic polyp (HPP) or sessile polyp adenoma (SSA) precursor lesions. In the Far East, and particularly in Korea, TSAs are more common and occur both in the left and right colon. However, the pathogenesis of TSAs in Korean patients, and the similarity to those that occur in North America, have never been evaluated. The purpose of this study was to determine the frequency and type of precursor lesion in TSAs, and to determine the molecular profile according to the grade of histologic dysplasia and/or cancer and anatomic location of the colon in a cohort of Korean patients. One hundred and twelve TSAs were evaluated pathologically and categorized according to the grade of dysplasia (either low or high grade) and the presence or absence of adenocarcinoma. TSAs were also separated into those with serrated versus conventional adenomatous dysplasia. As controls 35 conventional adenomas were evaluated, 14 of which had adenocarcinoma. All lesions were evaluated for the presence and type of precursor lesions and for KRAS and BRAF mutations and methylation of MGMT, hMLH1, and APC. A nondysplastic precursor lesion (HPP or SSA) was identified in 35 TSAs (31.3%). TSAs with a precursor lesion were more commonly found in the right colon compared with the left colon (P=0.03). Mutations of KRAS and BRAF and methylation of MGMT, hMLH1, and APC were present in 29%, 55%, 63%, 56%, and 37% of TSAs, respectively. TSAs with high-grade dysplasia and intramucosal adenocarcinoma showed a significantly higher frequency of KRAS mutation and MGMT methylation, and a significantly lower frequency of BRAF mutations, compared with TSAs with low-grade dysplasia (P<0.05). KRAS mutations were more prevalent in TSAs from the left colon and correlated significantly with higher grades of dysplasia. In a subgroup of TSAs in which both the precursor and neoplastic components were evaluated, a similar molecular profile was shown in both types of epithelium. Our results suggest that up to one-third of TSAs show a histologically identifiable nondysplastic HPP or SSA precursor lesion, particularly in lesions from the right colon. The development of KRAS mutations and methylation of MGMT may herald the onset of an aggressive phenotype in the neoplastic progression of TSAs and also suggests that a fusion between the serrated pathway of carcinogenesis and the chromosomal instability pathway may occur in some TSAs. Further studies are needed to determine the natural history and risk of malignancy of TSAs, specifically related to the anatomic site of development.

The CpG island methylator phenotype may confer a survival benefit in patients with stage II or III colorectal carcinomas receiving fluoropyrimidine-based adjuvant chemotherapy

BackgroundColorectal carcinoma (CRC) with CpG island methylator phenotype (CIMP) is recognized as a distinct subgroup of CRC, and CIMP status affects prognosis and response to chemotherapy. Identification of CIMP status in CRC is important for proper patient management. In Eastern countries, however, the clinicopathologic and molecular characteristics and prognosis of CRCs with CIMP are still unclear.MethodsA total of 245 patients who underwent their first surgical resection for sporadic CRC were enrolled and CIMP status of the CRCs was determined using the quantitative MethyLight assay. The clinicopathologic and molecular characteristics were reviewed and compared according to CIMP status. In addition, the three-year recurrence-free survival (RFS) of 124 patients with stage II or stage III CRC was analyzed in order to assess the effectiveness of fluoropyrimidine-based adjuvant chemotherapy with respect to CIMP status.ResultsCIMP-high CRCs were identified in 34 cases (13.9%), and were significantly associated with proximal tumor location, poorly differentiated carcinoma, mucinous histology, and high frequencies of BRAF mutation, MGMT methylation, and MSI-high compared to CIMP-low/negative carcinomas. For patients with stage II or III CIMP-low/negative CRCs, no significant difference was found in RFS between those undergoing surgery alone and those receiving surgery with fluoropyrimidine-based adjuvant chemotherapy. However, for patients with CIMP-high CRCs, patients undergoing surgery with fluoropyrimidine-based adjuvant chemotherapy (n = 17; three-year RFS: 100%) showed significantly better RFS than patients treated with surgery alone (n = 7; three-year RFS: 71.4%) (P = 0.022).ConclusionsOur results suggest that selected patients with CIMP-high CRC may benefit from fluoropyrimidine-based adjuvant chemotherapy with longer RFS. Further large scale-studies are required to confirm our results.

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.

Endoscopic submucosal dissection or transanal endoscopic microsurgery for nonpolypoid rectal high grade dysplasia and submucosa-invading rectal cancer.

BACKGROUND AND STUDY AIMS Transanal endoscopic microsurgery (TEM) has been shown to be highly effective for early rectal cancer, and endoscopic submucosal dissection (ESD) has been introduced to treat noninvasive colorectal neoplasia. The aim of this study was to compare the outcomes of ESD and TEM for superficial early rectal cancer. PATIENTS AND METHODS We retrospectively analyzed 63 patients with nonpolypoid rectal high grade dysplasia or submucosa-invading cancer who were treated with ESD or TEM, and compared clinical outcomes and safety between the treatment groups. RESULTS 30 patients underwent ESD and 33 underwent TEM. For ESD compared with TEM, en bloc resection rates were 96.7% vs. 100% (P = 0.476) and R0 resection rates were 96.7 % vs. 97.0 % (P = 1.000). There were no cases of local recurrence or distant metastasis in either group. Antibiotics were required in 11 patients (36.7%) in the ESD group and 33 (100%) in the TEM group (P < 0.001). There was no difference in net procedure time although ESD was associated with shorter total procedure time and hospital stay than TEM, with mean (standard deviation [SD]) 84.0 (51.2) vs. 116.4 (58.5) min (P = 0.0023), and 3.6 (1.2) vs. 6.6 (3.5) days (P < 0.001), respectively. There were no significant differences in complications between the two groups. CONCLUSIONS Both ESD and TEM are effective and oncologically safe for treating nonpolypoid rectal high grade dysplasia and submucosa-invading cancers. ESD has the additional advantages of minimal invasiveness and avoidance of anesthesia. Therefore, ESD could be recommended as a treatment option for superficial early rectal cancers.

Capsule endoscopy in small bowel tumors: A multicenter Korean study

Background and Aim:  Capsule endoscopy (CE) has proven to be highly effective at detecting small bowel lesions in a variety of clinical conditions, but studies concerning the practical impact of CE on small bowel tumors are still scarce, especially in the Asian population. The aim of this study was to evaluate the diagnostic and therapeutic impact of CE in the field of small bowel tumors.

Trends of ulcerative colitis‐associated colorectal cancer in Korea: A KASID study

Background and Aim:  The number of patients with ulcerative colitis (UC) in Korea has increased. In addition, the number of patients with colorectal cancer (CRC) associated with UC has also increased. Therefore, this population‐based nationwide study was conducted to investigate the incidence of CRC in patients with UC in Korea and compare these results to those of studies conducted in other countries.