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Purpose Predicting lymph node metastasis (LNM) risk is crucial in determining further treatment strategies following endoscopic resection of T1 colorectal cancer (CRC). This study aimed to establish a new prediction model for the risk of LNM in T1 CRC patients. Materials and methods The development set included 833 patients with T1 CRC who had undergone endoscopic (n=154) or surgical (n=679) resection at the National Cancer Center. The validation set included 722 T1 CRC patients who had undergone endoscopic (n=249) or surgical (n=473) resection at Daehang Hospital. A logistic regression model was used to construct the prediction model. To assess the performance of prediction model, discrimination was evaluated using the receiver operating characteristic (ROC) curves with area under the ROC curve (AUC), and calibration was assessed using the Hosmer-Lemeshow (HL) goodness-of-fit test. Results Five independent risk factors were determined in the multivariable model, including vascular invasion, high-grade histology, submucosal invasion, budding, and background adenoma. In final prediction model, the performance of the model was good that the AUC was 0.812 (95% confidence interval [CI], 0.770 to 0.855) and the HL chi-squared test statistic was 1.266 (p=0.737). In external validation, the performance was still good that the AUC was 0.771 (95% CI, 0.708 to 0.834) and the p-value of the HL chi-squared test was 0.040. We constructed the nomogram with the final prediction model. Conclusion We presented an externally validated new prediction model for LNM risk in T1 CRC patients, guiding decision making in determining whether additional surgery is required after endoscopic resection of T1 CRC.

Purpose While perianal disease (PAD) is a characteristic of patients with Crohn disease, it has been overlooked in patients with ulcerative colitis (UC). Thus, our study aimed to analyze the incidence and the clinical features of PAD in patients with UC. Methods We reviewed the data on 944 patients with an initial diagnosis of UC from October 2003 to October 2015. PAD was categorized as hemorrhoids, anal fissures, abscesses, and fistulae after anoscopic examination by experienced proctologists. Data on patients' demographics, incidence and types of PAD, medications, surgical therapies, and clinical course were analyzed. Results The median follow-up period was 58 months (range, 12-142 months). Of the 944 UC patients, the cumulative incidence rates of PAD were 8.1% and 16.0% at 5 and 10 years, respectively. The incidence rates of bleeding hemorrhoids, anal fissures, abscesses, and fistulae at 10 years were 6.7%, 5.3%, 2.6%, and 3.4%, respectively. The cumulative incidence rates of perianal sepsis (abscess or fistula) were 2.2% and 4.5% at 5 and 10 years, respectively. In the multivariate analyses, male sex (risk ratio [RR], 4.6; 95% confidence interval [CI], 1.7-12.5) and extensive disease (RR, 4.2; 95% CI, 1.6-10.9) were significantly associated with the development of perianal sepsis. Conclusion Although the clinical course of PAD in patients with UC is not serious, in clinical practice, PAD is not rare in such patients. Therefore, careful examination and appropriate management for PAD is needed if the quality of life for patients with UC is to be improved.

Background and aim In some patients with ulcerative proctitis (UP), skip inflammation is noted in the right side of the colon, but little is known about its clinical course. The aim of this study was to evaluate the clinical course of UP with skip inflammation and the efficacy of topical 5-aminosalicylate (5-ASA) monotherapy. Methods This study reviewed the data of 388 patients with an initial diagnosis of UP from January 2005 to October 2015. This study matched each UP patient with skip inflammation 1:2 with controls who had UP without skip inflammation; to reduce bias, this study matched the controls with the cases by age, gender, and initial disease activity. Results During the follow-up period (median: 69.5 months), the overall progression rates for the control group (n = 192) and the skip inflammation group (n = 96) were 24.0% and 32.9% at 10 years, respectively (log-rank P = 0.71). In the skip inflammation group, the progression rates were not significantly different between the 5-ASA combination group and the topical group, 33.4% and 26.6% at 10 years, respectively (log-rank P = 0.96). The overall acute exacerbation rates for the control and skip inflammation groups were 17.2% and 26.8% at 10 years, respectively (log-rank P = 0.68). In the skip inflammation group, the exacerbation rates were also not significantly different between the combination and topical treatment groups, 26.6% and 23.6% at 10 years, respectively (log-rank P = 0.88). Conclusion The clinical course of UP with skip inflammation was not different from that of typical UP, and topical 5-ASA monotherapy for maintaining remission was as effective as 5-ASA combination therapy irrespective of the presence of skip lesions.

Background An adequate level of bowel preparation before colonoscopy is important. The ideal agent for bowel preparation should be effective and tolerable. Objective The purpose of this study was to compare the clinical efficacy and tolerability of polyethylene glycol with ascorbic acid and oral sulfate solution in a split method for bowel preparation. Design This was a prospective, multicenter, randomized controlled clinical trial. Settings Outpatients at the specialized clinics were included. Patients A total of 186 subjects were randomly assigned. After exclusions, 84 subjects in the polyethylene glycol with ascorbic acid group and 83 subjects in the oral sulfate solution group completed the study and were analyzed. Interventions Polyethylene glycol with ascorbic acid or oral sulfate solution in a split method was the included intervention. Main outcome measures The primary end point was the rate of successful bowel preparation, which was defined as being excellent or good on the Aronchick scale. Tolerability and adverse events were also measured. Results Success of bowel preparation was not different between 2 groups (91.7% vs 96.4%; p = 0.20), and the rate of adverse GI events (abdominal distension, pain, nausea, vomiting, or abdominal discomfort) was not significantly different between the 2 groups. In contrast, the mean intensity of vomiting was higher in the oral sulfate solution group than in the polyethylene glycol with ascorbic acid group (1.6 ± 0.9 vs 1.9 ± 1.1; p = 0.02). Limitations All of the colonoscopies were performed in the morning, and the subjects were offered enhanced instructions for bowel preparation. In addition, the results of tolerability and adverse effect may have a type II error, because the number of cases was calculated for confirming the efficacy of bowel preparation. Conclusions Oral sulfate solution is effective at colonoscopy cleansing and has acceptable tolerability when it is compared with polyethylene glycol with ascorbic acid. The taste and flavor of oral sulfate solution still need to be improved to enhance tolerability.

AIMS The aim of this study was to determine whether human mutL homologue 1 (hMLH1) inactivation precedes the progression of sessile serrated lesion (SSL) into SSL with cytological dysplasia (SSL/D) and to define the histological stage at which promoter methylation and inactivation of hMLH1 occur. METHODS AND RESULTS Using the MassARRAY EpiTYPER assay and immunohistochemistry, we examined methylation levels and the protein expression status of hMLH1 in 33 SSL/Ds with conventional epithelial dysplasia and compared the results with those of control hyperplastic polyps (HPs) and SSLs. The methylation level of hMLH1 was higher in the dysplastic component than in the non-dysplastic component of SSL/Ds (P = 0.005), and differed significantly with regard to the degree of dysplasia (P = 0.002). The methylation levels of hMLH1 in the dysplastic component of SSL/Ds tended to be higher than those of control SSLs and HPs (P = 0.063 and P = 0.017, respectively). The loss of hMLH1 protein expression was identified in only 13 of 33 (39.39%) dysplastic components of SSL/Ds. CONCLUSION Promoter methylation and loss of protein expression of hMLH1 are not parallel processes that occur concurrently. hMLH1 methylation is an early molecular event which occurs even in HP. However, the loss of hMLH1 expression is a much later step, found in approximately 40% of SSL/Ds at various histological stages. Notably, the loss of hMLH1 protein expression does not necessarily precede the development of cytological dysplasia in SSL.

Background Composite intestinal adenoma-microcarcinoid (CIAM) is a rare colorectal lesion that mostly comprises a conventional adenomatous component with a minute proportion of neuroendocrine (NE) component. Although microcarcinoids are well-recognized in the setting of chronic inflammatory disorders of the gastrointestinal tract, large intestinal microcarcinoids associated with intestinal adenoma are exceedingly rare and their clinicopathologic characteristics are yet to be elucidated. This study was performed to clarify their clinicopathologic characteristics and to review the relevant literature. Methods In total, 24 cases of CIAM in which tumors were excised endoscopically (n = 22) or surgically (n = 2) were retrieved from the Department of Pathology, Daehang Hospital. We analyzed their clinicopathologic characteristics and performed immunohistochemical staining for NE markers to determine their endocrine nature. Results CIAM usually developed in middle-aged and elderly patients, with a mean age of 62.0 years (range, 44–81 years). Thirteen patients were men and 11 were women, indicating a nearly equal sex ratio. Unlike classic carcinoid tumors, CIAMs occurred mostly in the colon (83.3% of cases), particularly in the proximal colon. Histologically, the microcarcinoid component consisted of low-grade NE cells arranged in small nests, glands or cords interspersed with glandular elements or less frequently resembled squamous morules. There was no expansile nodular or organoid growth pattern, which is typical of carcinoid tumors. The microcarcinoids were 1–20 mm in size (mean size, 4.7 mm) and were mostly situated in the basal lamina propria with no submucosal layer involvement; none showed desmoplastic reaction or increased proliferative activity. Follow-up data (mean, 23.1 months) were available for 18 patients; all patients are alive and well. Conclusions To the best of our knowledge, ours is the largest series of patients with CIAM in the English-language literature. Microcarcinoids found in CIAMs appear to show favorable clinical outcomes regardless of their size, likely due to the absence of submucosal extension and/or increased proliferative activity. We recommend avoiding additional radical surgeries in patients who have endoscopically undergone complete CIAM excision unless they exhibit ominous histologic features such as submucosal extension or increased proliferative activity.

In some patients with ulcerative proctitis (UP), skip inflammation is noted in the right side of the colon, but little is known about its clinical course. The aim of this study was to evaluate the clinical course of UP with skip inflammation and the efficacy of topical 5-aminosalicylate (5-ASA) monotherapy.This study reviewed the data of 388 patients with an initial diagnosis of UP from January 2005 to October 2015. This study matched each UP patient with skip inflammation 1:2 with controls who had UP without skip inflammation; to reduce bias, this study matched the controls with the cases by age, gender, and initial disease activity.During the follow-up period (median: 69.5 months), the overall progression rates for the control group (n = 192) and the skip inflammation group (n = 96) were 24.0% and 32.9% at 10 years, respectively (log-rank P = 0.71). In the skip inflammation group, the progression rates were not significantly different between the 5-ASA combination group and the topical group, 33.4% and 26.6% at 10 years, respectively (log-rank P = 0.96). The overall acute exacerbation rates for the control and skip inflammation groups were 17.2% and 26.8% at 10 years, respectively (log-rank P = 0.68). In the skip inflammation group, the exacerbation rates were also not significantly different between the combination and topical treatment groups, 26.6% and 23.6% at 10 years, respectively (log-rank P = 0.88).The clinical course of UP with skip inflammation was not different from that of typical UP, and topical 5-ASA monotherapy for maintaining remission was as effective as 5-ASA combination therapy irrespective of the presence of skip lesions.

Objectives: To investigate the clinicopathologic and endoscopic features of precursor lesions associated with traditional serrated adenomas (TSAs). Methods: Mutation studies for BRAF, KRAS, PIK3CA, and EGFR and immunohistochemical staining for Ki-67 were performed on 107 TSAs from 104 patients. Results: Nondysplastic hyperplastic polyp (HP) or sessile serrated adenoma/polyp (SSA/P) precursor lesions were found in 56 (52.3%) TSAs, among which 32 (57.1%) cases showed a flat-elevated lesion with a type II pit pattern during endoscopy. TSAs with an SSA/P precursor lesion were usually found in the proximal colon, while TSAs with an HP or with no precursor lesion were mainly located in the distal colon and rectum ( P < .001). TSAs with a precursor lesion showed a lower frequency of conventional epithelial dysplasia and KRAS mutation as well as a higher frequency of BRAF mutation compared with those with no precursor lesion ( P = .002, P < .001, and P < .001, respectively). Conclusions: A significant proportion of HP or SSA/P precursor lesions accompanied by TSAs can be detected by endoscopy based on both their flat-elevated growth and type II pit patterns. The heterogeneity of TSAs in terms of clinicopathologic and molecular features correlated with the status or type of precursor lesions.

In this study, we describe a previously undescribed pedunculated serrated polyp of the colon showing typical features of sessile serrated adenoma/polyp (SSA/P). All polyps were pedunculated, located in the proximal colon, small in size, and occurred in elderly patients. Histologically, the polyps showed typical features of SSA/P in the basal crypts with irregular, asymmetric expression of Ki-67. All polyps showed the BRAF-V600E mutation. The cells in the polyps did not show obvious cytologic dysplasia, prominent serration, or diffuse cytoplasmic eosinophilia with any occurrence of the so-called "ectopic crypt formation." We consider pedunculated serrated polyp showing features of SSA/P as a previously undescribed form of serrated adenoma/polyp in the spectrum of serrated neoplasia, which might represent a pedunculated variant of SSA/P or a precursor lesion of proximally located traditional serrated adenomas in the earliest stage.

See Article on Page 73-78 Fecal incontinence (FI) is defined as the uncontrolled passage of feces or gas over at least 1-month duration in an individual of at least 4 years of age who had previously achieved control [1,2,3,4]. Incontinence has a negative impact on self-esteem and quality of life (QoL) and may result in significant secondary morbidity, disability, and cost [1]. Prevalence rates vary widely depending on the method used for fecal incontinence examination and the target population examined, but, in general, they range between 1.4% and 18%. In institutionalized patients, however, incontinence may affect up to 50%, which is a frequent reason for transfer to nursing homes [2,3,4,5,6]. The Mature Woman's Health Study, which used Neilson data to survey women aged ≥45 years, indicated that nearly 20% of women have FI at least once per year and that 9.5% have at least 1 episode per month [7]. According to the recommended standard for the treatment of patients with FI specified by the American Society of Colon and Rectal Surgeons Clinical Practice Guideline, medical management is 1C, sphincter repair for external anal sphincter defects is 1B, biofeedback is 1B, and sacral neuromodulation is 1B as well. The recommended standard for injection of bulking agents is 2B, which is lower than other treatment methods [1]. Injection of bulking agents was first used on patients suffering from urinary incontinence, and the first report of such a method being used for anal incontinence was presented in 1993 when Shafik [8] injected polytetrafluoroethylene paste (Teflon, Dupont, Wilmington, DE, USA) into the anus to treat a patient with FI. An ideal bulking agent should be nonirritable, biocompatible, nonimmunogenic and durable. Other elements that must be considered when selecting a bulking agent are ease of implant, migration, inflammation reaction, and more [9]. Of the numerous bulking agents used, the main ones include bovine glutaraldehyde cross-linked collagen (Contigen, Bard Urological, Convington, GA, USA), autologous fat, and carbon-coated zirconium-oxide beads in water-based gel (Durasphere, Boston Scientific Corp., Boston, MA, USA) while dextranomer microspheres in nonanimal stabilized hyaluronic acid gel (Solesta, Oceana Therapeutics Inc., Edison. NJ, USA), porcine dermal collagen (Permacol, Covidien, Gosport, UK), polytetrafluoroethylene paste (Teflon, Dupont, Wilmington, DE, USA), polydimethylsiloxane elastomer in hydrogel carrier (PTQ, Uroplasty BU, Geleen, The Netherlands), synthetic calciumhydroxylapatite ceramic microspheres in an aqueous-based gel carrier (Coaptite, Bioform Medical Inc., San Mateo, CA, USA), and ethylene vinyl alcohol dissolved in dimethyl sulphoxide are also widely used. Newly created or enhanced bulking agents continue to be released into the market [9]. Permacol is cross-linked porcine dermal collagen. It has been designed to resist breakdown by collagenase in the body and maintain a long-standing increase in bulk. The product is biocompatible and once injected is incorporated into host tissue, with associated cellular and microvascular in growth. No evidence has been found for its being associated with irritancy or allergenicity [10,11]. Although the characteristics of Permacol are known, previous research about Permacol injection has shown that the number of patients with recurring symptoms of anal incontinence increases in as little as 6 weeks, which leads one to question the durability of Permacol [12]. In other words, the conditions just after an injection are not maintained, but rather the bulking agent is absorbed by surrounding tissues, often leading to the need for another injection. This research lacks objective data on, for example, anal pressure as it merely assessed patients' conditions centered on an evaluation of QoL. Also, the number of target patients is small while that of tracked and observed patients is even smaller. Six of the 9 research papers on anal manometry presented in this systematic journal review failed to show meaningful changes in the mean resting pressure [13]. Similarly, this research does not show a significant difference from previous research results [14]. Despite the relatively short period of tracking and observation, the QoL showed a meaningful change, which is a result similar to those of other studies done in the past. With the injection of bulking agents, the treatment method normally used in urology clinics has been applied to patients with anal incontinence. The action mechanisms are similar; however, a greater amount of inflating agent is used, and the procedure is less likely to be effective.

Endoscopic submucosal dissection (ESD) is a very useful endoscopic technique, making it possible to perform en bloc resection regardless of lesion size. Since the introduction of ESD at our hospital, we have performed 1,000 colorectal ESDs during 56 months. The purpose of this study was to evaluate the clinical outcomes of our colorectal ESD experience and to access the efficacy and safety of colorectal ESD. Between October 2006 and August 2011, we performed ESD on 1,000 consecutive colorectal tumors in 966 patients. We evaluated the clinical outcomes of all said cases. The mean resected tumor size was 24.1 ± 13.3 (3–145) mm. Our overall endoscopic en bloc resection rate was 97.5 % (975/1,000), and our R0 resection rate was 91.2 % (912/1,000) respectively. Our perforation rate was 5.3 % (53/1,000). Of these 53 perforations, 50 cases were treated through conservative management with/without endoscopic clipping, whereas the remaining 3 patients received laparoscopic operation. Pathological examination showed adenocarcinoma in 37.2 % of cases (372/1,000) and neuroendocrine tumors in 11.2 % (112/1,000). We recommended additional radical surgery to 82 patients who had a risk of lymph node metastasis. Follow-up colonoscopies were performed on 722 patients. During the median follow-up period of 13 (1–62) months, there were three recurrences (0.4 %). ESD is technically difficult, with a substantial risk of perforation. However, ESD enabled en bloc resection and pathologically complete resection of large colorectal epithelial tumors and submucosal tumors. As experience with the technique increases, ESD may gradually replace piecemeal endoscopic mucosal resection and radical colon resection in the treatment of colorectal tumors.

The possible risk of colonic perforation during endoscopic submucosal dissection (ESD) for colorectal tumors is a barrier to wide application. This retrospective study was performed to evaluate the risk and the predictive factors for perforation during ESD procedure.Between October 2006 and November 2010, a total of 499 consecutive patients (mean age 60.0 ± 11.3 years) who underwent ESD for large-sized (≥ 20 mm), nonpedunculated colorectal tumor were analyzed. First, incidence rate and clinical course of perforation were evaluated. Second, patient-related variables (age, sex, history of aspirin or antiplatelet agents, and comorbidity), endoscopic variables (tumor size, location, and type), procedure-related variables (experience of procedures, procedure time, and materials of submucosal injection), and pathologic diagnosis were analyzed.The mean size of the lesions was 28.9 mm. The overall en bloc resection rate was 95.0%. Perforation occurred in 37 out of 499 patients (7.4%). Thirty-four patients could be successfully treated conservatively. The type (laterally spreading tumor) and the location (right-sided colon) of the tumors, less experience of the procedure (100 cases) in each endoscopist, and submucosal injection without hyaluronic acid were associated with higher frequency of perforation (all P0.05). On multivariate analysis, laterally spreading type of tumor [odds ratio (OR) 4.10, 95% confidence interval (CI) 1.17-14.34] and submucosal injection with hyaluronic acid (OR 0.31, 95% CI 0.13-0.72) were independent predictive factors.Perforation rate was 7.4%, and most cases could be successfully managed nonsurgically. In case of laterally spreading type of tumor, more caution is needed during submucosal dissection and long-lasting submucosal cushion is important for preventing perforation.

For asymptomatic individuals aged 40–49 years, screening for colorectal cancer is recommended only if individuals are at an increased risk. A family history of colon cancer (FHCRC) is considered to increase risk, however, whether family history of stomach cancer (FHSC) increases the risk of adenoma is not well known. We aimed to see whether FHSC increases the risk in asymptomatic individuals aged 40–49 years in Korea. Among asymptomatic individual aged 40–49 years who underwent colonoscopy screening, risk of adenoma was assessed according to FHCRC or FHSC. Of 3,160 individuals, male comprised 1,602 individuals (50.7%). FHCRC and FHSC was noticed in 163 (5.2%) and 227 (7.0%) individuals, respectively. Prevalence of adenoma was 31.9 %, 28.8%, and 22.3% for individuals with FHCRC, individuals with FHSC, and individuals without family history of cancer, respectively. FHSC was an independent risk factor for adenoma (odds ratio, 1.38; 95% confidence interval, 1.02–1.87, P = 0.039) in asymptomatic individuals aged 40–49 years. Compared with individuals with FHCRC, individuals with FHSC showed no difference in risk for adenoma (P = 0.347). As with individuals with FHCRC, individuals with FHSC might need to be considered as an individual with increased risk for adenoma. Therefore, earlier screening might be needed for asymptomatic individuals aged 40–49 years with FHSC in Korea.

Sessile serrated adenoma/polyps (SSA/Ps) usually appear flat to sessile with a smooth-appearing surface. However, macroscopic appearances of SSA/P can vary from flat-elevated to nodular and can even show a pedunculated configuration as we previously reported. The aim of the current study was to evaluate the clinicopathologic features of another under-recognized form of SSA/P which shows a depressed surface. Among 634 cases of sessile serrated adenoma/polyp, a total of seven sessile serrated adenoma/polyps showing a depressed surface were identified in 6 patients during the review of endoscopic images between January 2013 and November 2013. One of these was found during the review of previous endoscopic images of the same patient. Patients were more often middle-aged to elderly men (83.3 %) and had synchronous conventional adenomas and/or SSA/Ps except for one man. The polyps usually occurred in the proximal colon (71.4 %) and the mean size of polyps was 9.3 mm (range; 6-13 mm). Most cases (71.4 %) were of a flat-elevated type, and the remaining polyps (28.6 %) were sessile. The majority of polyps (85.7 %) showed a mucus cap. All but one of the cases (85.7 %) showed BRAF-V600E mutations. Our findings are that SSA/Ps can show a central depression although such cases are rare. The endoscopic and clinicopathologic features of SSA/Ps showing a depressed surface appear to be similar to usual SSA/Ps except for the presence of a depressed surface and marked male preponderance. Virtual slides: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1562070886167874 .

Background Ectopic crypts, defined as abnormally positioned crypts that have lost their orientation toward the muscularis mucosae, have been suggested to be the best defining histologic feature of traditional serrated adenoma (TSA). However, the significance of ectopic crypt formation (ECF) in the distinction between TSA and conventional adenoma (CA) has rarely been studied. Methods We designed this study to determine if ECF can be found in CA and its presence is exclusive to TSA. We studied 107 TSAs and 191 CAs including 106 tubular adenomas (TAs), 66 tubulovillous adenomas (TVAs), and 19 villous adenomas (VAs). Results ECF was identified in most (79.4%) but not all TSAs. Additionally, ECF was not infrequent in CA (62 of 191, 32.5%), and its presence correlated with the presence of a villous component and larger tumor size (each p

PURPOSE: Several treatments are used for the treatment of levator syndrome, such as rectal massage, biofeedback, and galvanic stimulation. But their effects are inconsistent, and multiple treatment sessions are usually required. Triamcinolone acetonide and lidocaine mixture was injected locally into the tenderest point in levator syndrome under the hypothesis that levator syndrome is caused by tendinitis of pelvic floor musculature. METHODS: A mixture of 40 mg of triamcinolone acetonide and 1 ml of 2 percent lidocaine was injected into the tenderest point transanally in 104 patients (33 males; mean age, 51 years) with levator syndrome from December 1996 to May 1998 at Daehang Clinic. Additional injections were repeated at two-week intervals to a maximum of three injections in cases of poor response. Follow-up was performed prospectively concerning patient's perception of pain level using a visual analog scale. Depending on the response, the patients were classified into four groups: pain-free, good, fair, and no response. More than 50 percent pain reduction was classified as “good,” and less than 49 percent reduction as “fair.” RESULTS: The injection regions, where the tenderest points were identified on digital rectal compression, were left anterior anal canal in 71.2 percent of patients, right anterior in 3.8 percent of patients, and posterior in 25 percent of patients. The results of treatment were as follows: at three months after injection, response was classified as pain-free in 36.8 percent of patients, good in 35 percent of patients, fair in 19.5 percent of patients, and no response in 8.7 percent of patients; at six months the response was pain-free in 30.1 percent of patients, good in 46.5 percent of patients, fair in 18.2 percent of patients, and no response in 5.2 percent of patients. Most patients, except 8.7 percent at three months and 5.2 percent at six months, experienced treatment benefits. There were no complications during the follow-up periods. CONCLUSION: Transanal injection of triamcinolone acetonide and lidocaine mixture into the tenderest point is such a simple, safe, and very effective modality that it can be recommended as a primary therapy for levator syndrome.

The pathways leading to activation in lamina propria (LP) T cells are different from peripheral T cells. LP T cells exhibit enhanced IL-2 secretion when activated through the CD2 pathway. Coligation of CD28 leads to synergistic enhancement of IL-2 secretion. Previous studies have characterized the CD28 augmentation of TCR-mediated signaling in peripheral blood T cells through transcriptional activation of an IL-2 promoter CD28 response element (CD28RE), along with enhanced mRNA stability. This study characterized molecular events involved in CD28 costimulation of IL-2 production in LP mononuclear cells (LPMC). LPMC exhibited increased IL-2 production in response to CD28 costimulation, compared with cells activated through CD2 alone. IL-2 secretion was paralleled by increased expression of IL-2 mRNA, resulting from enhanced IL-2 mRNA stability. In contrast to transcriptional activation in PBMC, EMSA revealed that CD28 coligation of CD2-activated LPMC does not result in increased binding of trans-factors to the CD28RE, nor did Western blots detect changes in I-κBα or I-κBβ levels following CD28 coligation. Furthermore, CD28 coligation fails to enhance IL-2 promoter-reporter or RE/AP construct expression in CD2-activated LPMC. The results reported herein indicate that the molecular mechanisms involved in CD28 cosignaling and regulation of IL-2 secretion in LP T cells are unique to that compartment and differ from those seen in peripheral blood T cells. These observations suggest a biological significance for different mechanisms of IL-2 activation in initiation and maintenance of the cytokine repertoire found in the mucosa.

To investigate the clinicopathologic and endoscopic features of precursor lesions associated with traditional serrated adenomas (TSAs).Mutation studies for BRAF, KRAS, PIK3CA, and EGFR and immunohistochemical staining for Ki-67 were performed on 107 TSAs from 104 patients.Nondysplastic hyperplastic polyp (HP) or sessile serrated adenoma/polyp (SSA/P) precursor lesions were found in 56 (52.3%) TSAs, among which 32 (57.1%) cases showed a flat-elevated lesion with a type II pit pattern during endoscopy. TSAs with an SSA/P precursor lesion were usually found in the proximal colon, while TSAs with an HP or with no precursor lesion were mainly located in the distal colon and rectum (P.001). TSAs with a precursor lesion showed a lower frequency of conventional epithelial dysplasia and KRAS mutation as well as a higher frequency of BRAF mutation compared with those with no precursor lesion (P = .002, P.001, and P.001, respectively).A significant proportion of HP or SSA/P precursor lesions accompanied by TSAs can be detected by endoscopy based on both their flat-elevated growth and type II pit patterns. The heterogeneity of TSAs in terms of clinicopathologic and molecular features correlated with the status or type of precursor lesions.

BACKGROUND Snare polypectomy of a giant pedunculated colorectal polyp is sometimes technically demanding, and, therefore, piecemeal resection is inevitable, despite the relative risk of invasive cancer and postpolypectomy bleeding. OBJECTIVE The aim of this study was to evaluate the efficacy and safety of endoscopic submucosal dissection in comparison with conventional snare polypectomy for giant pedunculated polyps DESIGN AND SETTINGS We retrospectively reviewed the clinical outcomes and complications of endoscopic polypectomy for giant pedunculated polyps from October 2006 to November 2011. PATIENTS All the patients who underwent endoscopic submucosal dissection (n = 23) or snare polypectomy (n = 20) for pedunculated polyps ≥ 3 cm were enrolled consecutively. In the case of a giant pedunculated polyp with 1) poor visualization of the stalk, 2) technical difficulties in snare positioning for en bloc resection, or 3) need for trimming of the head, we did not attempt piecemeal snare polypectomy, and we performed endoscopic submucosal dissection instead. (These were arbitrarily defined as "difficult" giant pedunculated polyps.) MAIN OUTCOME MEASURES Data on the patient's demography, endoscopic and histopathologic findings, clinical outcomes, and complications were analyzed. RESULTS Among the 43 giant pedunculated polyps, 23 polyps were defined as "difficult" polyps and were removed with endoscopic submucosal dissection. Subpedunculated (stalk

Inflammatory pseudopolyps are formed in the regenerative and healing phases of ulcerated epithelium. Giant pseudopolyposis of the colon (pseudopolyp larger than 1.5 cm in size) is a very rare complication of inflammatory bowel disease and it may lead to colonic intussusception or luminal obstruction, but the more important clinical significance is that it can be endoscopically confused with a malignancy, although it is generally regarded as having no malignant potential. It has been reported that giant pseudopolyposis of the colon rarely regresses with medical management alone and this sometimes require surgical or endoscopic resection. This report illustrates 2 unusual cases of giant pseudopolyps associated with Crohn's disease and ulcerative colitis, and these giant pseudopolyps were initially confused with villous adenoma or adenocarcinoma, but they showed regression after adequate medical therapy.

AIM: To evaluate the efficacy and acceptability of magnesium citrate and a single dose of oral sodium phosphate (45 mL) solution for morning colonoscopy bowel preparation. METHODS: A total of 159 patients were randomly assigned to receive two split doses of 90 mg of sodium phosphate (Group I, n = 79) or magnesium citrate (250 mL, the day before the procedure) followed by 45 mL of sodium phosphate (the day of procedure, Group II, n = 80). The quality of bowel cleansing and the acceptability of each regimen were compared, including the satisfaction, taste, willing to repeat and adverse effects of each regimen. RESULTS: The quality of bowel cleansing of Group II was as good as that of Group I (An Aronchick scale score of good or excellent: 70.9% vs 81.0%, respectively, P = 0.34; the Ottawa system score: 4.4 ± 2.6 vs 3.8 ± 3.0, respectively, P = 0.76). There was no statistically significant difference between both groups with regard to acceptability, including the satisfaction, taste and willingness to repeat the regimen. A significantly greater number of older patients (over 65 years old) in Group II graded the overall satisfaction as satisfactory (48.1% vs 78.1%, respectively; Group I vs Group II, P = 0.01). There were no significant adverse reactions. CONCLUSION: Magnesium citrate and a single dose of sodium phosphate was as effective and tolerable as the conventional sodium phosphate regimen and is a satisfactory option.

A stapled hemorrhoidopexy (SH) is widely used for treatment of patients with grades III and IV hemorrhoids. The SH is easy to perform, is associated with less pain and allows early return to normal activities. However, complications, whether severe or not, have been reported. Here, we present the case of a female patient with persistent bleeding after a SH. The bleeding was caused by the formation of granulation tissue at the stapler line, diagnosed with sigmoidoscopy, and successfully treated via transanal excision (TAE) under spinal anesthesia. The biopsy showed inflammatory granulation tissue. After the TAE, her symptom was completely gone.

See Article on Page 176-181 Perianal involvement of Crohn disease (CD) is known to be a common complication of CD. Due to the wide variety of anal manifestations of CD, the exact prevalence of perianal Crohn disease (PCD) is not known. However, it is estimated that a majority of patients with CD may undergo surgical treatment for PCD. The most common causes of operative treatment are perianal abscesses and anal fistulas because surgical treatment is mandatory to control acute sepsis. Contrary to fistulas of a cryptoglandular origin, those of CD are different in terms of pathogenesis and clinical course. Due to the unpredictable clinical course and increased risk of recurrence, conservative treatment is generally accepted to be more appropriate for treating patients with PCD. Repeated surgical treatment may deteriorate continence, which results in decreased quality of life for the patient. Therefore, an estimate of the clinical course and a prediction of recurrence after surgical treatment have clinical significance in the treatment of patients with PCD. Despite the clinical importance of PCD, literature concerning the risk factors of repeat surgical treatment for PCD is scarce. A recent retrospective study reported the cumulative risks of reoperation for patients operated on for PCD, as well as the related risk factors [1]. According to the study, the risk of reoperation increases during the disease's course, reaching up to 50% after the first surgical treatment, and risk factors associated with reoperation are a young age at the onset of CD, a history of abdominal surgery for CD, and the type of surgery. Although some controversies may exist, the risk of reoperation most likely increases in proportion to the time. Therefore, early onset of CD may be related with an increased risk of reoperation for PCD. Also, considering that the clinical course of CD with fistulizing PCD seems to be more aggressive, patients with abdominal surgery may have aggressive PCDs. Concerning surgical treatment, conservative treatment is recommended. However, a curative treatment such as a fistulotomy can be done in selected cases [2]. Compared with incision and drainage or seton placement, a fistulotomy or a fistulectomy would reduce the risk of reoperation because of the its radical characteristics. However, the choice of radical treatment should be prudent because of sphincter division, the risk of incontinence, and compromised wound healing. While this study is a clinically significant attempt to investigate factors related with repeat surgery, it lacks data regarding whether and how the usage of a biologic agent influences the clinical course of PCD. Some reports showed the effectiveness of using the anti-tumor necrosis factor (TNF) antibody in fistula healing for Crohn anal fistulas [3,4]. Although anti-TNF therapy seems to be promising, a multidisciplinary approach is mandatory because surgical treatment is essential to control acute sepsis and may be a preliminary procedure to enhance the effect of medical treatment.

Activation of lamina propria (LP) T cells via the CD2 pathway enhances IFN-γ (IFN-γ) secretion with further enhancement after CD28 coligation. The molecular mechanisms regulating IFN-γ expression in LP T cells remain unknown. Previous studies in PBL and T cell lines identified cis- and trans-regulatory elements in TCR-mediated expression of IFN-γ. This study examines CD2 and PMA/ionophore-responsive IFN-γ promoter elements. Activation of LPMC via CD2-induced IFN-γ secretion and a parallel up-regulation of mRNA expression. CD28 coligation enhanced mRNA stability without up-regulating transcription as measured by nuclear run-on. Transfection of a −2.7-kb IFN-γ promoter-reporter construct into PBL and LP mononuclear cells (LPMC) revealed significant promoter activity after CD2 activation, with additional transactivation after CD2/CD28 costimulation in PBL, but not in LPMC. Functional analysis using truncated promoter fragments identified distinct cis-regulatory regions selectively transactivating IFN-γ expression in PBL compared with LPMC. In PBL, CD2 activation elements reside within the −108- to +64-bp region. However, in LPMC the upstream region between −204 and −108 bp was essential. Transfection of the proximal and distal AP-1-binding elements, as well as TRE/AP-1 constructs, revealed functional activation of AP-1 subsequent to CD2 signaling, with activation critical in PBL but diminished in LPMC. Electromobility shift analysis using oligonucleotides encompassing the proximal, distal, and BED/AP-1-binding regions failed to demonstrate selective transactivation after CD2 signaling of LPMC. This report provides evidence that activation of LPMC results in transactivation of multiple promoter elements regulating IFN-γ expression distinct from those in PBL.

Purpose: Anal problems due to ingested foreign bodies are rare and usually present as acute anal pain. However, various clinical presentations are possible. This study was performed to identify the diverse manifestations of and the outcomes of treatments for anal diseases caused by ingested foreign bodies. Methods: Between September 1995 and June 2003, seven patients were treated for anal diseases due to the impaction of ingested foreign bodies in Seoul National University Hospital and Daehang Hospital. We retrospectively reviewed the medical records of those unusual patients. Results: All patients were males, and their mean age was 49.4 yr (range, 37 to 74 yr). The detected foreign bodies were fish bones (n=3), fish fins (n=2), a chicken bone (n=1), and a toothpick (n=1). Four patients had acute anal pain as the primary symptom while two patients presented anal pus discharge, and one patient presented anal bleeding. In the four patients with acute anal pain, the foreign bodies were easily found on digital rectal examination and inspection with anoscopy. Those patients underwent simple removal of the foreign body at the outpatient clinic. In three patients, the foreign bodies were found during surgery for hemorrhoids or fistulas. The two fistulas detected were complex types and needed seton placement. Conclusion: Anal problems caused by ingested foreign bodies usually involve acute anal pain, but our results indicate that, in some cases, the anal foreign bodies are also the cause or an aggravating factor in chronic anal disease.

Purpose: Endoscopic submucosal dissection (ESD), a recently introduced endoscopic technique, makes it possible to perform an en-bloc resection of a lesion regardless of its size. The aim of this study was to report early experiences with colorectal ESD performed in our hospital. Methods: Between October 2006 and December 2008, we performed an ESD for 260 consecutive cases of colorectal neoplasia in 255 patients. We evaluated the clinical outcomes, except for two failure cases of bowel perforation. Results: The mean resected tumor size was 24.2±9.8 (5-60) mm. Our overall endoscopic en-bloc resection rate was 93.0% (240/258). and the pathologically margin free rate was 91.5% (236/258). Perforation occurred in 7.7% (20/260) of the cases. In 17 patients, perforation was managed by endoscopic clipping without salvage surgery; the other three patients underwent a laparoscopic operation. Pathological examination showed an adenocarcinoma in 35.4% of the cases (92/260). We recommended additional radical surgery in 13 cases (submucosal invasion less than 1 mm with unfavorable pathology: 1 case; unknown depth of submucosal invasion: 1 case; submucosal invasion ≥1 mm: 9 cases; invasion to proper muscle: 2 cases). We were able to check the recurrence rate through colonoscopy for 125 patients. During the mean follow-up period of 8.0± 4.3 (3-21) mo, there were no recurrences. Conclusion: ESD was technically difficult, had a substantial risk of perforation, and needed a long procedure time. However, ESD enabled en-bloc resection of large colorectal tumors. As experience with the technique increases, ESD might gradually replace piecemeal endoscopic mucosal resection (EMR) and radical colon resection in the treatment of colorectal tumors.

Purpose: This study is to compare the rate and pattern of anastomotic leakage (AL) for rectal cancer after laparoscopic vs. conventional open surgery at high and low rectal anastomosis and to evaluate whether the number of linear staples used for distal rectal resection is related to AL in laparoscopic group. Methods: One hundred ninety-seven patients who underwent a curative resection for rectal cancer between March 2002 and February 2006 were studied retrospectively (107 laparoscopic, 90 open). The proportions of patients with anastomosis above vs. below 5 cm from AV were not different between the laparoscopic and the open groups; (above/below: 54/53 and 41/49, respectively, P=0.57). The protective stoma rate, the overall rate of AL, the rate of AL according to the height of the anastomosis, and the number of distal linear staples were evaluated for both groups. Results: Clinical AL occurred in 11 of 107 patients (10.3%) for the laparoscopic group and in 5 of 90 patients (5.6%) for the open group. The rates of AL in patients without protective stoma were not significantly different for high rectal anastomosis (6.0% for laparoscopic vs. 2.6% for open, P= 0.63) and for low rectal anastomosis (25.8% for laparoscopic vs. 12.1% for open, P=0.21). The risk of AL was 4.9 times higher when 3 linear staples were used than when 2 linear staples were used in the laparoscopic group. Conclusions: There was no statistical difference in AL between the laparoscopic group and the open group. The rate of AL could be reduced by using fewer linear staples for distal rectal resection in the laparoscopic group.

Purpose: This study was designed to assess the early outcome of a stapled transanal rectal resection (STARR) in obstructed defecation syndrome (ODS) patients with rectocele and rectal intussusception. Methods: From January to December in 2005, 41 patients with the symptoms of obstructed defecation and the findings of rectocele and rectal intussusception in defecography, who failed in conservative management, were enrolled in this study. All patients underwent the STARR procedure. Preoperatively all patients received colonoscopy, a colon transit time test, cinedefecography, etc. The constipation score was evaluated by using the Cleveland Clinic Florida (CCF) constipation score preoperatively and at 1 month and 3 months after operation. Results: The mean age of the patients was 55.3 (19～76) years. There were three males and thirty-eight females. The mean operation time was 39.3 (25～80) minutes, and the mean hospital stay was 4.2 (4～6) days. Complications were fecal urgency in 9 cases (21.9%), which improved after 3 months, bleeding in 5 cases (12.2%), and anastomotic stenosis in 1 case (2.4%). At postoperative defecography, both intussusception and rectocele had disappeared in most patients. All constipation symptoms were significantly improved (P＜0.01). The mean CCF constipation score was 17.6 (11～24) preoperatively, and improved to 9.1 after 1 month and 8.2 after 3 months (P＜0.01). The overall patient satisfaction was graded as excellent, good, fairly good and poor in 19 cases (46.3%), 13 cases (31.7%), 4 cases (9.7%), and 5 cases (12.2%), respectively. Conclusions: The STARR procedure seems to be a safe and effective procedure in ODS patients with rectocele and rectal intussusception. However, further study of the long-term results is required.

conservative management. Perianal abscess or fistula was present in three patients (0.3%), who underwent incision and drainage or a simple fistulotomy. Incontinence was present in two cases (0.2%). One patient was lost to follow up, and the other patient was improved by conservative management. Conclusions: LIS is a safe and effective treatment for patients with chronic anal fissure, and recurrence and complications of LIS are rare. J Korean Soc Coloproctol 2007;23:292-296

The pathways leading to T cell activation in lamina propria (LP) T cells are different from those of peripheral T cells. LP T cells have enhanced IL-2 secretion through activation of the CD2 pathway. Coligation of the CD28 molecule leads to a synergistic effect further enhancing IL-2 secretion and cell proliferation (J. Immunol. 1995, 154:664-675). Previous studies have characterized CD28 mediated augmentation of TCR signaling in PBL through transcriptional activation of an IL-2 promoter CD28 response element (CD28RE), as well as by enhanced mRNA stabilization. The aim of our study was to characterize the molecular basis involved in CD28 costimulation of IL-2 production in LP T cells. LP T cells were highly responsive to CD28 costimulation exhibiting a 7 to 10 fold increase in IL-2 secretion as compared to cells activated through the CD2 pathway alone. Increased IL-2 production was paralleled with upregulation of IL-2 mRNA, as detected in Northern blot analysis. This increase in mRNA was due in part to increased IL-2 mRNA stability as determined following actinomycin D treatment. In contrast to CD28 mediated transcriptional activation in PBL, electrumobility shift assays revealed that CD28 coligation of LP T cells does not result in increased binding of transacting factors to the CD28RE. Likewise, Western blots failed to detect any changes in IKBcc or IKB13 levels following CD28 coligation. Moreover, although CD2 enhanced IL-2 secretion is reflected by upregulation of activity of IL-2 promoter reporter constructs transfected into LP T cells, there was no enhanced CD28 mediated promoter activation following coligation. Our results indicate that unique molecular mechanisms are involved in CD28 cosignaling and regulation of IL-2 secretion in lamina propria T cells which differ from those seen in peripheral T cells. These observations suggest a biological significance for different mechanisms of 1L-2 gene activation in initiating and maintaining cytokine production in the mucosa. This work was supported by USPHS Grant DK43211.