Intestinal Research

Genomic Instability and Epigenetic Alteration in Colorectal Carcinogenesis: Young-Ho Kim; Intest Res 2007;5(2):111-121. Published online December 30, 2007

Abstract PDF: Colorectal cancer results from the progressive accumulation of genetic and epigenetic alterations that lead to cellular transformation and tumor progression, which is known as the adenoma-carcinoma sequence. Genomic instability, including chromosomal instability and microsatellite instability, creates a permissive state in which a cell acquires enough mutations to be transformed to a cancer cell. Epigenetic alteration is a more recently appreciated heritable alteration that has been found to occur commonly in colorectal cancer. Epigenetic alterations are clonal changes in gene expression without accompanying changes in primary DNA coding sequences. A subset of colorectal cancer shows cancer-specific promoter hypermethylation of several genes simultaneously, so-called CpG island methylator phenotype (CIMP) positive. The understanding of genetic and epigenetic alterations in colorectal carcinogenesis will yield more effective diagnostic and therapeutic strategies for colorectal cancer. (Intest Res 2007;5:111-121)

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Multimodality Treatment of Colorectal Cancer: Seun Ja Park; Intest Res 2007;5(2):122-130. Published online December 30, 2007

Abstract PDF: Polyps that contain carcinomatous changes that are confined to the mucosa (carcinoma-in-situ or severe dysplasia) do not have metastatic potential and are adequately treated with complete polypectomy or endoscopic mucosal resection. If deep invasion into the stalk has occurred or if adverse features (such as lymphatic invasion, or positive margins) are present, then en bloc colectomy is indicated. For lesions in the mid to upper rectum, a low anterior resection is the treatment of choice. To decrease the risk of local recurrence, patients should undergo optimal pelvic dissection with sharp mesorectal excision. Patients with pathologic lymph node-negative T3 or T4 lesions or any lymph node-positive cancer should receive preoperative or postoperative combined modality therapy. A major goal of preoperative therapy is to decrease the volume of the primary tumor and thus enhance sphincter preservation. For resectable colon cancer, the surgical procedure of choice is colectomy with en bloc removal of the regional lymph nodes. Laparoscopic colectomy has been advanced as an approach to the surgical management of colon cancer. Recently, the outcomes of cancer from a randomized trial comparing laparoscopically assisted and open surgery for curable colon cancer was reported. After a median of 4.4 years follow-up, similar cancer recurrence rates were observed in the two groups. The current management of disseminated metastatic colon cancer uses various active drugs, both in combination and as single agents: 5-FU/leucovorin, irinotecan, oxaliplatin, capecitabine, bevacizumab, and cetuximab. The choice of therapy is based on consideration of the type and timing of the prior therapy that has been administered and the differing toxicity profiles of the constituent drugs. As primary therapy for metastatic disease in a patient with good tolerance to intensive therapy, combination therapy consisting of fluoropyrimidines: FOLFOX (oxaliplatin, infusional fluorouracil, and leucovorin) or FOLFIRI (irinotecan, infusional fluorouracil, and leucovorin), with or without bevacizumab; bolus 5-FU/leucovorin/irinotecan with bevacizumab; 5-FU/leucovorin with bevacizumab were recommened. (Intest Res 2007;5:122-130)

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Molecular Characterization of hSRBC, a Candidate Tumor Suppressor Gene anda Upstream Regulator of p53 in Human Colon Cancer: Wan Jung Kim, Hyo Jong Kim, Sung-Gil Chi, Jin Oh Kim, Joo Young Cho, Chan Sup Shim; Intest Res 2007;5(2):131-143. Published online December 30, 2007

Abstract PDF: Background/Aims
hSRBC [human Serum deprivation response (sdr)-Related gene product that Binds to c-kinase] was identified using PKCδ or BRCA1 as a probe and located at 11p15.5-p15.4 region. Expression of hSRBC protein was also decreased in a number of breast, lung, and ovarian cancer cell lines, suggesting that hSRBC might be a putative tumor suppressor gene. Methods: The expression status of hSRBC was analyzed in 50 primary colon tumors and their adjacent 50 normal tissues, and 20 colon cancer cell lines. Transcript and protein expression of hSRBC was studied by quantitative RT-PCR and Western blot, respectively. siRNA-mediated knockdown of hSRBC expression was utilized to investigate its association with p53. Results: The mRNA expression of hSRBC was decreased in 60% (12/20) of colon cancer cell lines and 44% (22/50) of patient's colon cancer tissues. Expression of hSRBC mRNA was significantly decreased in tumors compared to non-cancerous cells, while genomic level of hSRBC was not decreased in tumors. hSRBC expression was increased by 5-aza-2’-deoxycytidine treatment and hypermethylation of CpG sites was strongly associated with decreased expression. Ectopic transfection of hSRBC suppressed RKO cell count and hSRBC knockdown by siRNA augmented HCT116 cell numbers. Flow cytometry showed G1 arrest and apoptosis of colon cancer cells by restoration of hSRBC expression in RKO cells. Both basal and etoposide-mediated p53 expression was decreased when hSRBC expression was knockdowned with siRNA. Conclusions: hSRBC expression is frequently decreased by promoter CpG site hypermethylation. hSRBC down-regulates p53 expression in G1 phase and might be a novel upstream regulator of p53. (Intest Res 2007;5:131-143)

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Expression of Matrix Metalloproteinase in Colon Adenoma and Colon Cancer: MT1-MMP and TIMP-2: Jeong Eun Shin, Sung-Ae Jung, Seong-Eun Kim, Yang-Hee Joo*, Ki-Nam Shim, Tae Hun Kim, Kwon Yoo, Il-Hwan Moon; Intest Res 2007;5(2):144-150. Published online December 30, 2007

Abstract PDF: Background/Aims
This study investigated the expression of membrane type 1-matrix metalloproteinase (MT1-MMP) and the tissue inhibitor of metalloproteinase-2 (TIMP-2) in cases of adenoma-carcinoma sequence. Methods: Thirty-two samples of colon adenoma, 11 samples of early colon cancer (ECC) and 36 samples of advanced colon cancer (ACC) were collected from colonoscopic biopsies. Normal tissues were also collected from the same subjects. The mRNA expression levels of MT1-MMP and TIMP-2 were quantified using semiquantitative RT-PCR. Results: The mRNA expression levels of MT1-MMP were greater in the ACC samples as compared to the adenoma and ECC samples (p＜0.05, respectively). However, there was no difference in the mRNA expression levels of MT1-MMP between the adenoma and ECC samples. The mRNA expression levels of TIMP-2 were greater in the ACC samples as compared to the adenoma samples (p＜0.001) but did not differ between the adenoma and ECC, and between the ECC and ACC. The expression level of MT1-MMP mRNA was positively related to lymph node metastasis (p＜0.05). However, the mRNA expression levels of MT1-MMP and TIMP-2 did not differ for colon cancer according to differentiation and modified Dukes’ stage. Conclusions: The mRNA expression levels of MT1-MMP and TIMP-2 have limitations as useful markers for malignant degeneration of colonic neoplasm and the progression of colon cancer. (Intest Res 2007;5:144-150)

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Clinical Value of Endoscopic Resection of Large Colonic PolypsUsing a Detachable Snare: Jin Gook Huh, You Sun Kim, Sun Ok Kwon, Won Cheol Jang, Kyung Sun Ok, Tae Yeob Jeong, Soo Hyung Rye, Jung Hwan Lee, Jeong Seop Moon; Intest Res 2007;5(2):151-157. Published online December 30, 2007

Abstract PDF: Background/Aims
A large colonic polyp is a challenge for endoscopists due to the risk of serious hemorrhage, perforation or incomplete resection. We examined whether endoscopic resection of large polyps using a detachable snare is a feasible and safe procedure. We also examined the sizes of a polyp that could be removed. Methods: We retrospectively reviewed 65 cases of endoscopic resection of large colonic polyps using a detachable snare. Results: The sizes of the polyps included 3.5 cm (n=3), 3.0 to 3.4 cm (n=8), 2.0 to 2.9 cm (n=16) and 1.0 to 1.9 cm (n=38). The mean polyp size was 1.8 cm. The pathologic diagnoses of the resected polyps included 20 adenocarcinomas (30.8%), 38 adenomas (58.5%), three hyperplastic polyps, two inflammatory polyps, one hamartomatous polyp and one lymphangioma. The complete resection rate was 98.5% (64/65). There were no complications such as perforation, delayed bleeding or the need for additional surgery. Six complications of immediate bleeding (9.2%) developed after resection, but the bleeding was easily controlled by endoscopic treatment. Conclusions: According to our study, endoscopic resection of large polyps using a detachable snare can reduce not only complications of bleeding but also incomplete resection. Therefore, polyp size alone is rarely a contraindication to the endoscopic resection of a colonic polyp. (Intest Res 2007;5:151-157)

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The Characteristics of Colonoscopic Findings in Differentiating Crohn's Disease from Intestinal Tuberculosis: In Soo Je, Sang Hyuk Lee, Eun Uk Jung, Myoung Joo Kang, Sang Won Park, Paul Choi, Ji Hyun Kim, Sung Jae Park, Sam Ryong Jee, Eun Taek Park, Youn Jae Lee, Sang Yong Seol; Intest Res 2007;5(2):158-164. Published online December 30, 2007

Abstract PDF: Background/Aims
The incidence of Crohn's disease (CD) is on the increase in Korea. The differentiation of Crohn's disease from intestinal tuberculosis (IT) is difficult. The aim of this study is to determine the characteristics of colonoscopic findings and factors that differentiate CD from IT. Methods: A total of 136 patients who were diagnosed with CD or IT at the Busan Paik Hospital from January 1995 to May 2005 were included in this study. We analyzed endoscopic findings, clinical characteristics and histological findings of 75 patients with CD and 61 patients with IT retrospectively. Results: For patients with IT, 18 (58.1%) of the patients had circular ulcers. For patients with CD, 27 (42.1%) of the patients had transverse ulcers, 18 (28.1%) of the patients had longitudinal ulcer, and 19 (29.6%) of the patients had both types of ulcers. The involvement of the ileocecal valve was noted in 18 (58.0%) of the patients with CD and in 37 (57.8%) of the patients with IT. The involvement of the rectum or anus was noted in 24 (51.5%) of the patients with CD and one (3.2%) patient with IT. Conclusions: According to previous studies, the presence of an ulcer was important to differentiate CD from IT. However, the presence of an ulcer was not a significant differentiating factor in our study. On colonoscopic findings, involved segments, an aphthous ulcer, cobblestone appearance, involvement of the rectum or anus and mucosal bridge should be observed carefully. (Intest Res 2007;5:158-164)

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Role of Echocardiography for the Evaluation of Ischemic Colitis: Kyu Hyung Lee, Byung Ik Jang, Kyeong Ok Kim, Si Hyung Lee, Jae Won Choi, Youn Sun Park, Sang Hoon Lee, Jun Young Lee, Jong Ryul Eun, Tae Nyeun Kim; Intest Res 2007;5(2):165-169. Published online December 30, 2007

Abstract PDF: Background/Aims
Ischemic colitis is recognized as the most common intestinal vascular disorder, especially in the elderly. Several predisposing factors, especially a cardiac embolism, have been reported for ischemic colitis. The aims of this study were to evaluate the prevalence of cardiovascular disease and the role of echocardiography in ischemic colitis. Methods: Thirty-six patients with ischemic colitis from January 2000 to February 2007 were analyzed retrospectively. Results: The mean age of subjects was 68.8±8.4 years. The prevalence of cardiovascular disease in ischemic colitis patients was 33% (12/36 cases). There were eight ischemic heart disease cases, four valvular heart disease cases, three arrhythmia cases and one hypertrophic cardiomyopathy case. Echocardiography was performed in 21 cases; cardiovascular disease could be detected in 11/12 cases (92%) and four cases were previously unknown. Anticoagulant therapy was required in 25% of the patients. Factors influencing hospital stay were the presence of cardiovascular disease. The presence of an associated medical illness did not influence hospital stay. Conclusions: Echocardiography may be useful to evaluate predisposing factors and to determine the use of anticoagulation therapy in ischemic colitis. (Intest Res 2007;5:165-169)

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Factors Affecting the Efficacy of Tegaserod in Patients with Chronic Constipation: Hwang Choi, Sang Heon Yoon, Won Chul Lee, Joo Sung Kim, Dong Kyung Chang, Yoon Tae Jeen, Jin Oh Kim, Dong Soo Han, Hyo Jong Kim, Sang Yong Seol, Won Ho Kim, Suk Kyun Yang, Jin Ho Kim; Intest Res 2007;5(2):170-176. Published online December 30, 2007

Abstract PDF: Background/Aims
The effect of tegaserod has been found to differ for Caucasian and black patients. The aims of this study were to demonstrate the efficacy of tegaserod on bowel habits and to investigate the factors affecting the efficacy of tegaserod in Korean patients suffering from chronic constipation (CC). Methods: This was an open-label, multi-center, observational study. Analysis of covariance with repeated measures was used to determine the overall effect of treatment and was used to determine the changes in the number of complete spontaneous bowel movements (CSBM) from baseline during the 8-week treatment period. Demographic and baseline characteristics were compared between responders (3 or more CSBM at 8-weeks) and non-responders by the use of multivariate analysis. Results: A total of 1,798 patients were included in the study. Tegaserod treatment resulted in a significant increase in the mean number of CSBM per week over weeks 2-8 from baseline levels (from 1.0 to 3.1 CSBM per week, p＜0.0001). Tegaserod treatment was more effective for female patients, younger patients (age less than 65 years), patients with a high Bristol score at baseline, and patients with a short duration of constipation symptoms. Conclusions: Treatment with tegaserod improved bowel movements and more effective in female patients, patients under the age of 65 years, patients with a high Bristol score at baseline, and patients with a short duration of constipation symptoms. (Intest Res 2007;5:170-176)

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Clinical Features and Therapeutic Responses of Abdominal Actinomycosis: Ji Won Kim, Ji Bong Jeong, Yong Jin Jung, Byung Kwan Kim, Kook Lae Lee, Su Jong Yu, Mi Na Kim, Joo Sung Kim, Hyun Chae Jung, In Sung Song; Intest Res 2007;5(2):177-183. Published online December 30, 2007

Abstract PDF: Background/Aims
Abdominal actinomycosis is a rare entity and difficult to differentiate from a malignant neoplasm. A study of clinical features and therapeutic responses will contribute to the understanding of this disease. Methods: We analyzed the clinical features and therapeutic responses of 12 cases of abdominal actinomycosis from 1989 to 2007. Results: The male to female ratio of patients was 1：1, and the patients had a median age of 50 years (range 38-60 years). Abdominal pain was the most common symptom, and seven of twelve patients had a history of abdominal surgery, trauma, DM or IUD (intrauterine device) use. An abdominal CT examination revealed infiltrative lesions with disruption of the tissue plane in eight cases, and colonoscopic findings showed luminal stenosis, nodular lesions and ulceration in four cases. Surgical resection was performed in eleven cases with a right hemicolectomy with or without a salpingo-ooporectomy, a left hemicolectomy or mass excision. Of the eleven patients who underwent surgical resection, seven patients received intravenous penicillin G (10-15×106 U) followed by administration of oral antibiotics for a median 8 months (range 4-12 months) according to the presence of symptoms and signs. Conclusions: With combined adequate surgical resection and high-dose antibiotic therapy, the therapeutic responses are favorable in most of the abdominal actinomycosis patients. (Intest Res 2007;5:177-183)

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A Case of Acute Lower Gastrointestinal Bleeding from Appendix: Sun Mi Lee, Tae Oh Kim, Gwang Ha Kim, Jung Heo, Dae Hwan Kang, Geun Am Song, Mong Cho; Intest Res 2007;5(2):184-187. Published online December 30, 2007

Abstract PDF: It is known that the most common causes of lower gastrointestinal bleeding are diverticulosis and angiodysplasia. In addition to these causes, a malignant neoplasm, hemorrhoids, Meckel’s diverticulum, infection, Crohn’s disease, inflammatory disease due to radiation treatment, ischemic colitis, and vasculitis due to connective tissue disease can commonly produce lower gastrointestinal bleeding. A colon varix, endometriosis, or Dieulafoy's lesion rarely causes lower gastrointestinal bleeding. Lower gastrointestinal bleeding that is localized to the appendix is extremely rare, and may be caused by angiodysplasia, an ulcer due to aspirin, endometriosis, a lymphoma, or fissures on the mucous membrane associated with appendicitis. A colonoscopy, radioisotope scan, and angiography are modalities used to diagnose lower gastrointestinal bleeding, and recently, multi-detector row CT (MDCT) has been used for cases where it has been difficult to locate a lesion with other methods or to diagnose a patient when endoscopic access was not available. We report a case of a patient that came to the hospital complaining of hematochezia, and bleeding in the appendix was determined after an MDCT examination and colonoscopy. Subsequently, the patient was treated with surgery. (Intest Res 2007;5:184-187)

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A Case of Crohn’s Disease with Psoas Abscess and Enterocutaneous Fistula: Hae Sun Jung, Ki-Nam Shim, Min-Jung Kang, Su Jung Baik, Kum Hei Ryu, Sung-Ae Jung, Kwon Yoo, Seog Ki Min; Intest Res 2007;5(2):188-191. Published online December 30, 2007

Abstract PDF: Crohn’s disease is a chronic, transmural and inflammatory disease of the gastrointestinal tract. Intraabdominal abscesses and fistulas are common complications in Crohn’s disease. However, the presence of a psoas abscess and enterocutaneous fistula in Crohn’s disease is very rare. The incidence of a psoas abscess is 0.4-4.3% and the incidence of an enterocutaneous fistula is 15-25%. Moreover, as a psoas abscess presents as a flexion contracture of the sacroiliac joint, it is apt to be misdiagnosed as arthritis, one of the common extraintestinal manifestations of Crohn’s disease. We describe here a case of a 26-year-old female who presented with pain and flexion contracture of the right sacroiliac joint. The patient was diagnosed with a psoas abscess and an enterocutaneous fistula as complications of Crohn’s disease. (Intest Res 2007;5:188-191)

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A Case of Drug-induced Interstitial Lung Disease in a Patient withUlcerative Colitis Receiving Mesalamine: Tae Hoon Lee, Suck-Ho Lee, Young-Sin Cho, Ji-Young Park, Jeong Hoon Park, Do Hyun Park, Il-Kwun Chung, Hong Soo Kim, Sang-Heum Park, Sun-Joo Kim, Mee-Hye Oh; Intest Res 2007;5(2):192-195. Published online December 30, 2007

Abstract PDF: Pulmonary involvement in ulcerative colitis is very rare and may present as a variety of disorders. Pulmonary disease in patients with inflammatory bowel disease may be due to lung involvement in the disease itself or to drugs used for treatment, such as sulfasalazine or mesalamine. The use of mesalamine was initially thought to be free of adverse effects. Recently, however, pulmonary diseases related to the use of mesalamine have been reported. In this report, we describe a patient with ulcerative colitis and mesalamine induced interstitial lung disease. (Intest Res 2007;5:192-195)

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A Case of Pulmonary Tuberculosis Misdiagnosed as Lung Metastases after Curative Resection of Early Colon Cancer: Chang Joon Kim, Dong Il Park, Sung Keun Park, Jung Ho Park, Chong Il Sohn, Woo Kyu Jeon, Young-Ho Kim, Sun-Young Lee; Intest Res 2007;5(2):196-199. Published online December 30, 2007

Abstract PDF: Early colon cancer can be cured by endoscopic mucosal resection (EMR). However, the possibility of complete resection depends on the depth of cancer invasion. Ten percent of cancers invading the submucosal layer are associated with local lymph node metastasis. Therefore, colon cancers confirmed to invade the submucosal layer after EMR require surgical resection. We treated a woman with adenocarcinoma at the hepatic flexure with submucosal invasion diagnosed after piecemeal EMR. Subsequent right hemicolectomy with lymph node dissection revealed no residual cancer. However, after 21 months, multiple pulmonary nodules were incorrectly diagnosed as pulmonary metastases, based on the radiological findings. The final diagnosis of pulmonary tuberculosis was made after lung metastasectomy. (Intest Res 2007;5:196-199)

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A Case of Stroke after Cessation of the Warfarin for a Colonoscopic Polypectomy: Ju Young Choi, Ki-Nam Shim, Su Jung Baik, Yoo Ri Kim, Sung-Eun Kim, Sung-Ae Jung, Kwon Yoo, Il Hwan Moon; Intest Res 2007;5(2):200-203. Published online December 30, 2007

Abstract PDF: It is not necessary to adjust anticoagulation for low-risk procedures, such as a gastroduodenoscopy or a colonoscopy with biopsy. For high-risk procedures of bleeding that include an endoscopic polypectomy and treatment of varices, warfarin should be discontinued for a few days. However, there is the risk of a thromboembolism by stopping warfarin treatment. We report a case of a 77-year-old man with atrial fibrillation, who stopped taking warfarin 4 days before a colonoscopic polypectomy, and developed an acute cerebral infarction after the procedure. (Intest Res 2007;5:200-203)

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Usefulness of C-Reactive Protein Level before and during Antimycobacterial Therapy in the Differential Diagnosis between Crohn's Disease andIntestinal Tuberculosis: Seok Won Jung, In Du Jeong, Do Ha Kim, Sang Hyun Park, Suk-Kyun Yang, Seung-Jae Myung; Intest Res 2007;5(2):204-206. Published online December 30, 2007

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