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Ulcerative colitis (UC), a relapsing-remitting chronic inflammatory bowel disease (IBD), has a variable natural course but potentially severe disease course. Since the development of anti-tumor necrosis factor (TNF) agents has changed the natural disease course of moderate-to-severe UC, therapeutic options for patients who failed conventional treatments are expanding rapidly. IBD clinical trials have demonstrated the potential efficacy and safety of novel biologics such as anti-integrin α4β7 and anti-interleukin-12/23 monoclonal antibodies and small molecules such as a Janus kinase inhibitor. Anti-TNF biosimilars also have been approved and are widely used in IBD patients. Wise drug choices should be made considering evidence-based efficacy and safety. However, the best position of these drugs remains several questions, with limited data from direct comparative trials. In addition, there are still concerns to be elucidated on the effect of therapeutic drug monitoring and combination therapy with immunomodulators. The appropriate treatment regimens in acute severe UC and the risk of perioperative use of biologics are unclear. As novel biologics and small molecules have been approved in Korea, we present the Korean guidelines for medical management of adult outpatients with moderate-to-severe UC and adult hospitalized patients with acute severe UC, focusing on biologics and small molecules.
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Background/Aims@#The short- and long-term effects of adalimumab (ADA) on Korean patients with intestinal Behcet’s disease (BD) for remain unclear. Therefore, a multicenter study was performed to evaluate the efficacy and safety of ADA in Korean patients with intestinal BD in a real-world setting. @*Methods@#The medical records of 67 patients with BD prescribed ADA between January 2012 and December 2020 at five referral centers in Korea were retrospectively analyzed and the safety and efficacy of ADA within 52 weeks were assessed. To evaluate the clinical efficacy of ADA, the Disease Activity Index for Intestinal BD (DAIBD) and representative blood biochemical markers were compared at 0, 12, 24, and 52 weeks of ADA treatment. @*Results@#During the follow-up period of 52 weeks, 46 patients continued ADA treatment. The cumulative drug survival rate was 83.5%. The DAIBD score decreased over the study period (p < 0.001). Moreover, the erythrocyte sedimentation rate, serum C-reactive protein levels, and serum albumin levels significantly improved at 12, 24, and 52 weeks of ADA treatment (all, p <0.05). @*Conclusions@#As ADA is effective for refractory intestinal BD with few safety concerns in real-world situations, it is a potential treatment option for Korean patients with intestinal BD.
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Objectives@#Adenosine triphosphate-binding cassette subfamily G member 2 (ABCG2) and CD133 are recognized stem cell markers of gastric cancer. Extensive research has examined the significance of these markers in different types of cancers and their impact on prognoses, linking them to unfavorable clinical outcomes in various tumors. However, the prognostic value of these markers for gastric cancer remains unclear. We investigated the expression of ABCG2 and CD133 and their relationship with clinical outcomes in gastric cancer. @*Methods@#ABCG2 and CD133 expression levels were analyzed, using immunohistochemistry and tissue microarrays, in tumor samples from 459 patients who underwent surgical resections due to gastric cancer. ABCG2 and CD133 expression levels were defined by intensity and dichotomized as medians. The associations among the expression levels of these markers, disease severity, and patient survival were also determined. @*Results@#In the 411 patients for whom we analyzed the expression levels of these markers, 74.9% and 80.5% were found to have high levels of ABCG2 and CD133, respectively. High expression levels of ABCG2 and CD133 were more commonly observed in well-differentiated (p<0.001 and p=0.004, respectively) and intestinal lesions (p<0.001 and p=0.002, respectively). High ABCG2 expression correlated with improved survival outcomes, whereas high CD133 expression was associated with poorer outcomes. Cox regression analysis confirmed that stage, high ABCG2 (overall survival [OS]: hazard ratio [HR], 0.61; 95% confidence interval [CI], 0.41–0.91; p=0.015; recurrencefree survival [RFS]: HR, 0.55; 95% CI, 0.34–0.88; p=0.012), and CD133 expression (OS: HR, 1.59; 95% CI, 1.00–2.51; p=0.049; RFS: HR, 2.29; 95% CI, 1.21–4.34; p=0.011) were predictors of survival. A subgroup analysis indicated that ABCG2 expression was also associated with an improved RFS rate in patients who received systemic chemotherapy. @*Conclusions@#High ABCG2 expression and low CD133 expression in tumors correlated with improved survival outcomes in post-resection patients with gastric cancer, suggesting their potential utility as prognostic biomarkers.
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Background/Aims@#Inflammatory bowel disease (IBD) is no longer a rare disease in Asia, thus it needs to prepare recommendations relevant to Asian patients. This study aimed to identify disparities in the process of the diagnosis of IBD in Asian countries/regions. @*Methods@#In line with the 2020 Asian Organization for Crohn’s and Colitis annual meeting, a multinational web-based survey about Asian physicians’ perspectives on IBD was conducted. @*Results@#A total of 384 Asian physicians (99 in China, 93 in Japan, 110 in Korea, and 82 in other Asian countries/regions) treating IBD patients from 24 countries/regions responded to the survey. Most respondents were gastroenterologists working in an academic teaching hospital. About half of them had more than 10 years of clinical experience in caring for patients with IBD. The European Crohn’s Colitis Organisation guideline was used most commonly for the diagnosis of IBD except for Japanese physicians who preferred their own national guideline. The Mayo score and Crohn’s Disease Activity Index were the most commonly used activity scoring systems for ulcerative colitis and Crohn’s disease, respectively. Endoscopy, not surprisingly, was the main investigation in assessing the extent and activity of IBD. On the other hand, there were disparities across countries/regions with regard to the favored modalities of small bowel and perianal evaluation of Crohn’s disease, as well as the use of serologic markers. @*Conclusions@#Results of the present survey revealed practical behaviors of Asian physicians in the diagnosis of IBD. Investigating the reasons for different diagnostic approaches among countries/regions might help us develop Asian guidelines further.
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Background/Aims@#Polyethylene glycol (PEG)-based bowel preparations are effective cleansing agents for colonoscopy. However, they require relatively large volumes to be used even with agents such as 2 L PEG with ascorbate (2LPEG). This phase 3, randomized, single-blinded, multicenter, parallel-group study compared the efficacy of 1 L PEG with high-dose ascorbate, TJP-008, to 2LPEG. @*Methods@#Patients undergoing colonoscopy were randomized (1:1:1) to receive TJP-008 as 1-day split dose (TJP-008-1) or 2-day split dose (TJP-008-2) regimen or to receive 2LPEG as a 2-day split dose regimen. Cleansing efficacy was evaluated using the Harefield Cleansing Scale. The primary endpoint was overall bowel cleansing success. Full analysis set (FAS) and per protocol set (PPS) analyses were performed. @*Results@#Of the 314 screened patients, efficacy was assessed in the following patient numbers (FAS/PPS): total (293/285), TJP-008-1 (98/94), TJP-008-2 (97/95), and 2LPEG (98/96). FAS revealed noninferiority between TJP-008 and 2LPEG with regard to overall success (TJP-008-2, 99.0%; TJP-008-1, 95.9%; 2LPEG, 94.9%; p=0.100 and p=0.733, respectively). PPS also showed noninferiority (p=0.721 and p=0.211, respectively). However, the PPS analyses showed a higher bowel cleansing score for TJP-008-2 for high-quality cleansing in the right colon (TJP-008-2 83.2% vs 2LPEG 62.5%; p=0.005). @*Conclusions@#TJP-008 is a new low-volume cleansing agent with a colon cleansing efficacy comparable to that of standard 2LPEG that exhibits significant safety and tolerability
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Background/Aims@#The aim of this in vivo animal study was to evaluate the effectiveness and safety of dedicated cold snare (DCS) compared with those of traditional snare (TS) for cold snare polypectomy (CSP). @*Methods@#A total of 36 diminutive (5 mm) and 36 small (9 mm) pseudolesions were made by electrocoagulation in the colons of mini-pigs. @*Results@#For the diminutive lesions, there were no significant differences in technical success rate, procedure time, or complete resection rate between the DCS and TS groups; the rate of uneven resection margin in the DCS group was significantly lower than that of the TS group. For small lesions, technical success rate and complete resection rate were significantly higher in the DCS group than in the TS group (100% [18/18] vs. 55.6% [10/18], p=0.003; 94.4% [17/18] vs. 40% [4/10], p=0.006). In addition, the procedure duration was significantly shorter, and the rate of uneven resection margin was significantly lower in the DCS group (28.5 sec vs. 66.0 sec, p=0.006; 11.1% [2/18] vs. 100% [10/10], p<0.001). Two cases of perforation occurred in the DCS group. Multivariate analysis revealed that DCS use was independently associated with complete resection. @*Conclusions@#DCS is superior to TS in terms of technical success, complete resection, and reducing the duration of the procedure for CSP of small polyps.
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Background/Aims@#The aim of this in vivo animal study was to evaluate the effectiveness and safety of dedicated cold snare (DCS) compared with those of traditional snare (TS) for cold snare polypectomy (CSP). @*Methods@#A total of 36 diminutive (5 mm) and 36 small (9 mm) pseudolesions were made by electrocoagulation in the colons of mini-pigs. @*Results@#For the diminutive lesions, there were no significant differences in technical success rate, procedure time, or complete resection rate between the DCS and TS groups; the rate of uneven resection margin in the DCS group was significantly lower than that of the TS group. For small lesions, technical success rate and complete resection rate were significantly higher in the DCS group than in the TS group (100% [18/18] vs. 55.6% [10/18], p=0.003; 94.4% [17/18] vs. 40% [4/10], p=0.006). In addition, the procedure duration was significantly shorter, and the rate of uneven resection margin was significantly lower in the DCS group (28.5 sec vs. 66.0 sec, p=0.006; 11.1% [2/18] vs. 100% [10/10], p<0.001). Two cases of perforation occurred in the DCS group. Multivariate analysis revealed that DCS use was independently associated with complete resection. @*Conclusions@#DCS is superior to TS in terms of technical success, complete resection, and reducing the duration of the procedure for CSP of small polyps.
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Recent data showed that DNA mismatch repair deficiency can be a predictive biomarker for a favorable response of immune checkpoint inhibitors regardless of tumor type due to give rise to high tumor mutational burden (TMB) and microsatellite instability (MSI). Loss-of-function mutations of a specific tumor suppressor gene can also lead to good response to immunotherapy. Herein, we report a case exhibiting good response to pembrolizumab in a jejunal adenocarcinoma patient with low programmed death-ligand 1 (PD-L1) expression. A 67-yearold man underwent surgical resection followed by adjuvant chemotherapy. After 10 months, he was treated with palliative chemotherapy due to hepatic and pulmonary metastases. However, palliative chemotherapy did not have any effect whatsoever. Based on genetic testing results of high TMB and high MSI in the resected primary tumor, pembrolizumab treatment was performed. After the three cycles of treatment, all metastatic lesions shrank remarkably. Considering the mechanism of immune checkpoint inhibitors, this case establishes the importance of genetic markers as TMB and MSI rather than PD-L1 expression by the prediction of their anti-tumor activities.
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Receptor-interacting serine/threonine-protein kinase (RIPK) 3 is a member of the TNF receptor-I signaling complex and mediates necroptosis, an inflammatory cell death. Ulcerative colitis (UC) is an excessive inflammatory disease caused by uncontrolled T cell activation. The current study is aimed to determine whether RIPK3 inhibitor attenuates UC development inhibiting inflammation and necroptosis using experimental colitis mice model. Dextran sulfate sodium-induced colitis mice were administered RIPK3 inhibitor (3 mg/ml) 3 times and their tissues were analyzed by immunohistochemistry. RIPK3, mixed lineage kinase domain-like (MLKL), phosphorylated MLKL, IL-17, and CD4 in colitis patient colon tissues were detected using confocal microscopy. Protein levels were measured using immunohistochemistry and ELISA. The differentiation of Th17 cells was evaluated using flow cytometry. The expression of proinflammatory cytokines and necroptosis in peripheral blood mononuclear cells from UC patients was decreased markedly by RIPK3 inhibitor treatment. We also observed that the injection of RIPK3 inhibitor improves colitis severity and protects intestinal destruction. RIPK3 inhibitor reduced necroptosis factors and proinflammatory cytokines in the colon and consequently protected colon devastation. The expression of inflammatory mediators in experimental colitis mice splenocytes was decreased significantly by RIPK3 inhibitor treatment. These results suggest that RIPK3 inhibitor ameliorates severity of experimental colitis and reduces inflammation through the inhibition of inflammatory response and necroptosis and support RIPK3-targeting substances for treatment of UC.
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The treatment of inflammatory bowel disease (IBD) has been revolutionized for the last 10 years by the increasing use of immunomodulators and biologics. With immunosuppression of this kind, opportunistic infection is an important safety concern for patients with IBD. In particular, viral hepatitis is determined by the interaction between the virus and the host’s immunity, and the risk of reactivation increases if immunity is compromised by immunosuppression therapy. Parts of Asia, including Korea, still show intermediate endemicity for the hepatitis A virus and hepatitis B virus compared with the United States and Western Europe. Thus, members of IBD research group of the Korean Association for the Study of Intestinal Diseases have produced a guideline on the prevention and management of viral hepatitis in IBD.
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Background/Aims@#The rate of nonneoplastic pathology (NNP) after endoscopic resection (ER) of gastric epithelial neoplasia (GEN) has been reported to be 3%–7%. However, to date, the associations of pretreatment characteristics with NNP have not been identified. The aim of this study was to develop a predictive model for NNP after ER. @*Methods@#Among 817 patients who underwent ER for GEN, factors associated with NNP were identified by univariate and multivariate analyses. Weighted points considering the β coef-ficient were allocated to each variable that was significant in the multivariate analysis. The predictive score was calculated by the total points. The area under the receiver operating characteristic curve (AUROC) was calculated for the predictive score. @*Results@#The rate of NNP was 8.8%. After multivariate analysis, poor demarcation from the background, no ulceration, a flat appearance, and low-grade dysplasia were significant factors predictive of NNP. One point each was allocated for no ulcer, flat appearance, and low-grade dysplasia.Two points were allocated for poor demarcation from the background. The predictive score ranged from 0 to 5 points.Patients were categorized as being at low risk (0, 1, or 2 points) or high risk (3, 4, or 5 points) for NNP. The AUROC was 0.82 (95% confidence interval, 0.77 to 0.88; p<0.01).With a cutoff value of 2.5, the sensitivity and specificity of the score for predicting NNP were 0.72 and 0.84, respectively. @*Conclusions@#We developed a model to predict NNP after ER. Endoscopic re-biopsy or re-evaluation by pathologists is strongly recommended for the high-risk group.
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Background/Aims@#We evaluated the miss rates of polyps, adenomas, and advanced neoplasia of polypectomy-referring hospitals and risk factors for missed adenomas. @*Methods@#We compared medical records and electronic images of initial colonoscopies from polypectomy-referring hospitals with those of corresponding therapeutic colonoscopies from Seoul St. Mary’s Hospital obtained from May 2014 to February 2016. @*Results@#A total of 147 patients (56.6 ± 12.1 years, 37 females) were included. The mean number of polyps and adenomas detected on initial colonoscopy was 2.4 ± 1.7 and 1.7 ± 1.4, respectively. The mean number of additionally detected polyps and adenomas per patient during therapeutic colonoscopy was 1.4 ± 1.8 and 1.0 ± 1.5, respectively. Pooled miss rate for polyps, adenomas, and advanced neoplasia was 36%, 37%, and 11%, respectively. Pooled miss rate for adenomas was significantly higher for right-sided, non-pedunculated, and small (< 1 cm) adenomas (p = 0.031, p = 0.000, and p = 0.000, respectively). The miss rate of polyps, adenomas, and advanced neoplasia per patient was 60%, 49%, and 7%, respectively. Multivariate analysis revealed age and number of adenoma on initial colonoscopy were significantly related with risk for adenoma-missing (p = 0.005 and p = 0.023, respectively). @*Conclusions@#Among patients referred for polypectomy, adenoma is missed in one of two patients and advanced neoplasm is missed in one of 13. Patients with advanced age or multiple adenoma on initial colonoscopy have a higher possibility of missed adenoma. Total colon exploration should be performed carefully during therapeutic colonoscopy.
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Colorectal tumors with superficial submucosal invasion, which cannot be removed by snaring, are one of the most optimal indications for colorectal endoscopic submucosal dissection (ESD). Therefore, estimation of the invasion depth is the first key to successful colorectal ESD. Although estimation of the invasion depth based on the gross morphology may be useful in selected cases, its diagnostic accuracy could not reach the clinical requirement. The Japan Narrow-band Imaging (NBI) Expert Team (JNET) classification of NBI magnifying endoscopy findings is a useful method for histologic prediction and invasion depth estimation. However, magnifying chromoendoscopy is still necessary for JNET type 2B lesions to reach a satisfactory diagnostic accuracy. Endocytoscopy with artificial intelligence is a promising technology in invasion depth estimation; however, more data are needed for its clinical application.
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Artificial Intelligence , Classification , Colonoscopy , Colorectal Neoplasms , Endoscopy , Japan , Methods , Neoplasm Staging , SNARE ProteinsABSTRACT
From dye-assisted conventional chromoendoscopy to novel virtual chromoendoscopy, image-enhanced endoscopy (IEE) is continuously evolving to meet clinical needs and improve the quality of colonoscopy. Dye-assisted chromoendoscopy using indigo carmine or crystal violet, although slightly old-fashioned, is still useful to emphasize the pit patterns of the colonic mucosa and predict the histological structures of relevant lesions. Equipment-based virtual chromoendoscopy has the advantage of being relatively easy to use. There are several types of virtual chromoendoscopy that vary depending on the manufacturer and operating principle. IEE plays distinctive roles with respect to histologic characterization of colorectal polyps and prediction of the invasion depth of colorectal cancers. In addition, the newest models of IEE have the potential to increase adenoma and polyp detection rates in screening colonoscopy.
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Adenoma , Colon , Colonoscopy , Colorectal Neoplasms , Endoscopy , Gastrointestinal Diseases , Gentian Violet , Image Enhancement , Indigo Carmine , Mass Screening , Mucous Membrane , PolypsABSTRACT
Celiac disease (CD) is an immune-mediated enteropathy and is a rare disease in Asia, including in Korea. However, the ingestion of wheat products, which can act as a precipitating factor of CD, has increased rapidly. CD is a common cause of malabsorption, but many patients can present with various atypical manifestations as first presented symptoms, including anemia, osteopenia, infertility, and neurological symptoms. Thus, making a diagnosis is challenging. We report a case of CD that mimicked amyotrophic lateral sclerosis (ALS). The patient was a sexagenary man with a history of progressive motor weakness for 2 years. He was highly suspected as having ALS. During evaluation of his neurological symptoms, esophagogastroduodenoscopy (EGD) was performed because he had experienced loose stools and weight loss for the previous 7 months. On EGD, the duodenal mucosa appeared smooth. A biopsy revealed severe lymphoplasma cell infiltration with flattened villi. His serum endomysial antibody (immunoglobulin A) titer was 1:160 (reference, <1:40). Finally, he was diagnosed as having CD, and a gluten-free diet was immediately begun. At a 4-month follow-up, his weight and the quality of his stool had improved gradually, and the neurological manifestations had not progressed.
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Humans , Amyotrophic Lateral Sclerosis , Anemia , Asia , Biopsy , Bone Diseases, Metabolic , Celiac Disease , Diagnosis , Diet, Gluten-Free , Eating , Endoscopy, Digestive System , Follow-Up Studies , Infertility , Korea , Malabsorption Syndromes , Mucous Membrane , Neurologic Manifestations , Precipitating Factors , Rare Diseases , Triticum , Weight LossABSTRACT
Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized by a relapsing and remitting course. The direct and indirect costs of the treatment of UC are high, and the quality of life of patients is reduced, especially during exacerbation of the disease. The incidence and prevalence of UC in Korea are still lower than those of Western countries, but have been rapidly increasing during the past decades. Various medical and surgical therapies, including biologics, are currently used for the management of UC. However, many challenging issues exist, which sometimes lead to differences in practice between clinicians. Therefore, the IBD study group of the Korean Association for the Study of Intestinal Diseases established the first Korean guidelines for the management of UC in 2012. This is an update of the first guidelines. It was generally made by the adaptation of several foreign guidelines as was the first edition, and encompasses treatment of active colitis, maintenance of remission, and indication of surgery for UC. The specific recommendations are presented with the quality of evidence and classification of recommendations.
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Humans , Biological Products , Classification , Colitis , Colitis, Ulcerative , Disease Management , Incidence , Inflammatory Bowel Diseases , Intestinal Diseases , Korea , Prevalence , Quality of Life , UlcerABSTRACT
Ulcerative colitis (UC) is a chronic inflammatory bowel disorder characterized by a relapsing and remitting course. The direct and indirect costs of the treatment of UC are high, and the quality of life of patients is reduced, especially during exacerbation of the disease. The incidence and prevalence of UC in Korea are still lower than those of Western countries, but have been rapidly increasing during the past decades. Various medical and surgical therapies, including biologics, are currently used for the management of UC. However, many challenging issues exist, which sometimes lead to differences in practice between clinicians. Therefore, the Inflammatory Bowel Disease Study Group of the Korean Association for the Study of Intestinal Diseases established the first Korean guideline for the management of UC in 2012. This is an update of the first guideline. It was generally made by the adaptation of several foreign guidelines as was the first edition, and encompasses treatment of active colitis, maintenance of remission, and indication of surgery for UC. The specific recommendations are presented with the quality of evidence and classification of recommendations.
Subject(s)
Humans , Biological Products , Classification , Colitis , Colitis, Ulcerative , Incidence , Inflammatory Bowel Diseases , Intestinal Diseases , Korea , Prevalence , Quality of Life , UlcerABSTRACT
Capsule endoscopy (CE) enables evaluation of the entire mucosal surface of the small bowel (SB), which is one of the most important steps for evaluating obscure gastrointestinal bleeding. Although the diagnostic yield of SB CE depends on many clinical factors, there are no reports on quality indicators. Thus, the Korean Gut Image Study Group (KGISG) publishes an article titled, “Quality Indicators for Small Bowel Capsule Endoscopy” under approval from the Korean Society of Gastrointestinal Endoscopy (KSGE). Herein, we initially identified process quality indicators, while the structural and outcome indicators are reserved until sufficient clinical data are accumulated. We believe that outcomes of SB CE can be improved by trying to meet our proposed quality indicators.
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Capsule Endoscopy , Endoscopy, Gastrointestinal , HemorrhageABSTRACT
BACKGROUND/AIMS: Although colonoscopy is not indicated in patients with hematochezia, many surgeons, internists, and physicians are recommending colonoscopy for these patients in Korea. The aim of this study is to evaluate the diagnostic value of colonoscopy for patients with hematochezia. METHODS: We retrospectively reviewed the data of colonoscopy between January 2010 and December 2010. A total of 321 patients among 3,038 colonoscopies (10.6%) underwent colonoscopy to evaluate the cause of hematochezia. The patients with previous colorectal surgery (2) or polypectomy (5) were excluded. We analyzed endoscopic diagnoses. Advanced neoplastic polyps were defined as adenomas with villous histology or high grade dysplasia, or adenomas more than 10 mm in diameter. RESULTS: Hemorrhoid was the most common diagnosis (217 cases, 67.6%). Polyps were detected in 93 patients (29.0%), but advanced neoplastic polyps were found in only 14 cases (4.4%). Colorectal cancers were diagnosed in 18 patients (5.6%) including 14 rectal cancers. There was no cancer located above sigmoid-descending junction. Diverticuli were detected in 41 patients (12.8%) but there was only one case of suspected diverticular bleeding. Colitis was diagnosed in 24 patients (7.5%). Other lesions included acute anal fissure, rectal tumor, stercoral ulcer, and radiation proctitis. CONCLUSIONS: The colonoscopy had little value in patients with hematochezia because the most pathologic lesions were located below sigmoid colon. The first choice of diagnosis in patients with hematochezia is sigmoidoscopy.