Specific Colonoscopic Findings of Intestinal Graft-Versus-Host Disease, Intestinal TMA, and CMV Colitis After Allogenic Hematopoietic Stem Cell Transplantaion

Specific Colonoscopic Findings of Intestinal Graft-Versus-Host Disease, Intestinal TMA, and CMV Colitis After Allogenic Hematopoietic Stem Cell Transplantaion

Abstracts T1456 Diabetes Treatments, Gastrointestinal Symptoms and Lower Gastrointestinal Endoscopy Alex J. Kent, Bethan Graf, Priyajit B. Prasad, Mi...

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Abstracts

T1456 Diabetes Treatments, Gastrointestinal Symptoms and Lower Gastrointestinal Endoscopy Alex J. Kent, Bethan Graf, Priyajit B. Prasad, Michael D. Feher, Matthew R. Banks

T1458 Risk Factors for Lymph Node Metastasis After Endoscopic Resection for Early Colorectal Cancer Seok Won Jung, In Du Jeong, Sung-Jo Bang, Jung Woo Shin, Neung Hwa Park, Do Kim

Introduction: Many medications for diabetes mellitus (DM) are associated with GI symptoms which may prompt a referral for lower GI endoscopy. Metformin immediate-release preparation and acarbose are often associated with symptoms, including diarrhoea, nausea and abdominal pain. We hypothesized that a greater proportion of DM patients undergo lower GI endoscopy due to symptoms related to DM medication. Aims: (1) Assess the prevalence of GI symptoms and pathology in a cohort of DM subjects referred for lower GI endoscopy. (2) Assess if there was link between use of conventional oral DM medication with normal endoscopy, thereby highlighting the need to use alternative drug therapies/preparations with lower incidence of GI side-effects. (3) Compare symptoms and findings between the DM and non-diabetic (control) populations. Methods: From January-June 2008 prospective DM patients undergoing lower GI endoscopy were identified, along with age and sex-matched controls, and invited to complete a standardised questionnaire detailing GI symptoms, risk factors and DM history. Endoscopy results and questionnaires were collated to find associations. Results: 31 DM patients underwent lower GI endoscopy from a total cohort of 751. 58% were male, mean age 68 years. The majority had Type 2 DM (84%); 90% were treated with oral medication (75% on metformin), 48% had evidence of end-organ damage. Compared to the non-diabetic group the DM group had a significantly higher BMI: 30.6 vs 24.9, and both diarrhoea and abdominal pain were a more common. 19 DM patients had endoscopy for weight loss, anaemia or routine surveillance. From the 12 subjects with symptoms, 9 were referred with symptoms potentially related to DM medications; 7 were on metformin. Diarrhoea occurred in all 9 patients, with associated abdominal pain in 7 and bloating in 5 subjects. In these 9 patients only one endoscopic diagnosis would account for their symptoms: microscopic colitis. 3 had a single small polyp, while 5 had entirely normal endoscopies. Compared to the non-diabetic group the incidence of colorectal cancer was higher in the DM group (6 vs 1, p!0.05), but colonic adenomas and all other pathology occurred equally between the groups. Conclusion: There was a low referral rate of DM patients for lower GI endoscopy. Considerable numbers of DM patients had pathology at endoscopy. However over half of those with symptoms had normal findings, suggesting the symptoms were due to DM medication. Newer formulations of the drugs, e.g. modified-release metformin, may reduce GI symptoms compared to the immediate-release, and may be a therapeutic option in many patients before referral for endoscopy.

Background/Aims: Although endoscopic resection is widely adopted for the treatment of early colorectal cancer, the risk factors for lymph node metastasis are not clear. This study was designed to clarify risk factors for lymph node metastasis in patients with colorectal cancer who were treated with endoscopic resection. Methods: The medical records of patients with histologically proven early colorectal who underwent endoscopic resection between January 2002 and September 2008 were retrospectively reviewed. Information regarding the demographic data of patients, clinicopathological characteristics were recorded and analyzed. Results: A total of 29 patients with early colorectal cancer who underwent subsequent surgical treatment were enrolled in this study. The ages of studied population ranged from 37 to 77 years with a mean age of 57  10 years. The male to female ratio was 21: 8 and the mean size of the tumor was 20.6  7.3 mm. The rectum was the most commonly involved location of colorectal cancer (13 cases, 44.8%), followed by sigmoid colon (11 cases, 37.9%). Concerning the shape of the tumor, polypoid lesions were 17 cases (58.6%), while non-polypoid flat lesions were 12 cases (41.4%). The depth of submucosal invasion was ranged from 530 to 5,000 mm with mean invasion depth of 1,807  1,040 mm. In nine patients (31%), the carcinomatous changes extended into the vascular or lymphatic channel. Concerning the resection margin, 11 patients (37.9%) had tumor cells at the vertical resection margin and 4 patients (13.8%) had tumor cells at the lateral resection margin. When we observed the background histology around the cancer cell, 18 patients (62.1%) had adenomatous component around the cancer cells, while 11 patients (37.9%) did not have any adenomatous component suggesting de novo carcinoma. After additional surgical treatment and lymph node dissection, 6 patients (20.7%) had lymph node metastases on surgical pathologic examination. When we evaluated the risk factors for lymph node metastasis after endoscopic resection, the predicting factors for lymph node metastasis are non-polypoid flat tumors (pZ0.019), absence of background adenoma (pZ0.033), and deep submucosal invasion of 2,000 um (pZ0.012). Unexpectedly, the presence of vascular invasion and positive resection margin were not associated with lymph node metastasis. Conclusions: The presence of vascular invasion alone might not be absolute indication of additional surgical treatment for the early colorectal cancer. However, deep submucosal invasion, accompanying gross tumor non-polypoid flat morphology, and absence of background adenoma are potential risk factors for lymph node metastasis.

T1457 Metal Stents Treatment of Acute Malignant Colonic Obstruction Allows Laparoscopic Elective Surgery Diego Fregonese, Attilio Pirillo, Pieralberta Ravagnan, Giovanna Andrian, Manuela Dinca, Emilio Morpurgo, Barbara Termini, Sara Maria Tosato, Annibale D’Annibale Treatment of acute intestinal occlusion in patients (pts) with colonic cancer using a stent is wide experienced. Also the use of metal stent to bridge to surgery (BTS) is already established. Still remain unclear if this emergency treatment allows a subsequent colonic laparoscopic surgery (LS). Due to the great distension of the colon usually these pts undergo to a traditional Open Surgery (OS) that requires a two or a three stage operation with a colostomy. To understand if BTS, followed by colon deflation, made LS feasible we have prospectively enrolled in our Study all the pts with severe intestinal occlusion consecutively admitted in our Department between 2001 and 2008. Our Study consider for BTS only pts suffering by an acute occlusion due to a primitive cancer; once admitted, they have undergone to a colonoscopy within 12 hours, and immediately treated with a stent if necessary. When the stool passage has been effective, the pts have prepared for LS. Of the all admitted occluded cases in 46 pts a colonic obstructive cancer has been detected. In all these cases we attempt a stent insertion, using an endoscopic approach with fluoroscopic guidance if necessary. 44 cases (95.6%) have received a stent with an OTW procedure (16 Ultraflex PrecisionÒ) or a TTS procedure (21 Colonic WallstentÒ and 7 Colonic WallflexÒ). We suffer only two failures (4.3%), and these pts have immediately undergone to OS. In one of these cases, going to death within one month from admission, a perforation has been rolled out with fecal peritonitis. In 40 cases the stent insertion has been clinically successful and 35 among these pts have all successfully prepared for LS within a mean of 11.5 days from procedure. 5 underwent to a Hartmann Operation for advanced disease. In two cases (4.5%) colon deflation was ineffective even with a good patency of the stent and they have undergone to OS. In one of these two pts, a small perforation at the cancer site complicated by a minimal localized peritonitis was surgically detected. In other two cases we suffer a clear perforation at the end of the endoscopic procedure and OS has been necessary. No other major complications were recorded. In conclusion our prospectively Study confirm the highly efficacy of BTS procedure, that allows a subsequent LS treatment in almost 76.0% of the cases. An acceptable complication rate of 8.6% and a mortality rate of 2.1% let us conclude that BTS is a safe and reliable step on the way of laparoscopic colon resection in occlusive cancers.

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T1459 Specific Colonoscopic Findings of Intestinal Graft-Versus-Host Disease, Intestinal TMA, and CMV Colitis After Allogenic Hematopoietic Stem Cell Transplantaion Katsuya Endo, Yoshitaka Kinouchi, Takashi Arai, Tomoya Kimura, Nobuo Ueki, Hiroki Aizawa, Hisashi Shiga, Masaki Matsuura, Yoichi Kakuta, Ken Umemura, Kenichi Negoro, Seiichi Takahashi, Tooru Shimosegawa Background: After allogenic hematopoietic stem cell transplantation (HSCT), significant complications involving the gastrointestinal tract occur, such as graftversus -host disease (GVHD), thrombotic microangiopathy (TMA), and cytomegalovirus (CMV) colitis. Although the therapeutic strategies for these disorders are completely different, it is difficult to establish the differential diagnosis based on the clinical grounds alone. Little is known about the specific colonoscopic findings of these three disorders. Aim: To clarify the specific colonoscopic findings of intestinal GVHD, intestinal TMA, and CMV colitis. Patients and Methods: Between April 2001 and March 2008, 31 patients suffering from GI symptoms within the first 100 days after allogenic HSCT underwent 38 colonoscopies. The final diagnoses of these patients were made by a retrospective review of the medical records, and all 38 colonoscopic findings were analyzed. We picked up the relatively specific findings such as ‘‘spotty redness’’, ‘‘sloughing of the mucosa’’, ‘‘tortoiseshell pattern’’, ‘‘diffuse redness’’, and ‘‘punched-out ulcer’’ which are not usually observed in infectious colitis or inflammatory bowel diseases. To examine the diagnostic values of these colonoscopic findings, the sensitivity and, if possible, specificity of these findings for diagnosis were examined, retrospectively. Results: All 38 cases were finally diagnosed as intestinal GVHD. Eight cases were diagnosed as intestinal GVHD overlapping intestinal TMA. One case was diagnosed as intestinal GVHD overlapping CMV colitis. Spotty redness, sloughing of the mucosa, tortoiseshell pattern, diffuse redness, and punched-out ulcer were observed in 19/38 (50.0%), 29/38 (76.3%), 38/38 (100%), 7/38 (18.4%), and 1/38 (2.6%) respectively. Spotty redness, sloughing of the mucosa, and tortoiseshell pattern tended to be frequently observed in intestinal GVHD. Diffuse redness tended to be frequently observed in the cases which were diagnosed as GVHD overlapping intestinal TMA. The calculated sensitivity and specificity of this finding for the diagnosis of intestinal TMA were 75.0% and 96.8%, respectively. In only one case diagnosed as CMV colitis overlapping intestinal GVHD, multiple punched-out

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Abstracts

ulcers were detected in the descending and sigmoid colon. Conclusions: Specific colonoscopic findings may be valuable for making a differential diagnosis of intestinal GVHD, intestinal TMA, and CMV colitis after HSCT. The proposed specific findings are as follows. 1) Spotty redness, sloughing of the mucosa, and tortoiseshell pattern for intestinal GVHD. 2) Diffuse redness for intestinal TMA. 3) Punched-out ulcer for CMV colitis.

transfusion, none was died of lower gastrointestinal bleeding. Conclusion: Because most of patients showed left-sided colonic bleeding, colonoscopy is a useful diagnostic modality in acute lower gastrointestinal bleeding. In addition, emergent endoscopic hemostasis is technically possible when the bleeding sites can be identified. Anticoagulation drugs, antiplatelets, and NSAIDs toxicity is one of the major causes in the elderly. Large controlled studies are warranted to strengthen our investigation.

T1460 Therapeutic Effects of Immunosuppressive Therapy After AntiViral Treatment in Patient Refractory Ulcerative Colitis with Cytomegalovirus Infection Mitsuyuki Murano, Kazuki Kakimoto, Kumi Ishida, Ken Kawakami, Yosuke Abe, Takuya Inoue, Naoko Murano, Eijiro Morita, Eiji Umegaki, Kazuhide Higuchi

T1462 Comparison of the Ascending Colon Fluids in Ulcerative Colitis Patients in Relapse Versus Remission Constantinos Goumas, Maria Vertzoni, Erik So ¨ derlind, Bertil Abrahamsson, Jennifer B. Dressman, Androniki Poulou, Christos Reppas

Background and Aim: Cytomegalovirus (CMV) infection has been reported as a cause of refractory ulcerative colitis (UC). In some cases, CMV infection is associated with a poor outcome but it is not clear which patients are more likely to be affected and in which stage of the disease. Our previous study (2008DDW) suggested that it is very important to decide on a patient’s medication by relying on exact diagnosis concerning the condition of UC by endoscopy. Further, Ganciclovir (GCV) is useful for treatment of CMV-associated UC after immunosuppressive therapy. However, regarding to maintain the remission in UC with CMV infection after antiviral therapy, it remains unknown. The aim of this study was to evaluate the prevalence, outcome and therapeutic effect of anti-viral treatment and additional other medical treatment (FK5o6, apherasis) of UC with CMV infection. Methods: The subjects were a total of 85 patients with refractory UC at our Hospital between the years 1990 and 2008 in the study. Fifty four patients were identified with, defined as poor response to high-dose systemic steroids (refractory UC). Patients were evaluated for CMV by using serology, and histopathological assessment of hematoxylin-eosin and immunohistchemical-stained colonic biopsies. Positive result in any test was considered as CMV infection. We studied refractory UC with CMV infection for the outcome and therapeutic effect of GCV and other treatment. Results: The prevalence of CMV infection in the steroidrefractory UC patients was 46.3% (25/54), CMV was diagnosed. There was no difference in the CMV infection rate between males and females (males 44.0%, females 51.9%). Of 25 refractory UC patients with CMV detected, 15 (60.0%) were refractory to steroids and other immunosuppressive drugs, and had undergone. Of 17 refractory UC patients with CMV treated with GCV, 11 (64.7%) temporally obtained remission by first anti-virus medication, otherwise 4 (55.6%) of 11 patients responded by GCV were fared up and was operated on. Only 7 (41.2%) patients went into remission after anti-viral treatment (Term of observation: 14.5  8.9 month). Regarding to additional treatment, Twelve of 17 those patients treated with GCV (70.6%) were treated with immunosuppressants such as FK506, cyclosporine A, and Azathiopurin. Fifteen of these 17 patients (88.2%) were treated with apherasis. Conclusions: GCV is useful for treatment of UC with CMV infection. UC patients with CMV infection more often required surgical treatment (60%) and is associated with poor outcome. Further, immunosuppressants such as FK506 and AZA are useful for maintaining the remission in UC with CMV infection after antiviral therapy.

T1461 A Role of Colonoscopy in Patients with Acute Lower Gastrointestinal Bleeding Hideharu Okanobu, Tomotaka Tanaka, Toshihide Ohya Background: Acute lower gastrointestinal bleeding is increasing disease with aging today. Occasionally, its condition may be complicated by hemorrhage and blood clots. Aim: To investigate the usefulness of colonoscopy in acute lower gastrointestinal bleeding and discuss its clinical features. Methods: A total of 125 patients (65 men, 60 women, mean age: 67.4 years) who received colonoscopy with suspected acute lower gastrointestinal bleeding were examined retrospectively during last two years. We analyze colonoscopic findings and their clinical backgrounds. Patients with melena after endoscopic mucosal resection were excluded in this study. Results: All of patients were diagnosed by colonoscopy except 2 patients (1.6%) with small intestinal bleeding. There were 110 patients (88%) with left-sided colonic bleeding and 13 patients (10.4%) with right-sided colonic bleeding. Forty patients were diagnosed as ischemic colitis, 26 patients were colon diverticula and 13 patients were rectal ulcer. Forty-two patients (33.6%) had a history of ischemic heart disease or ischemic stroke. Out of all patients, anticoagulation drugs, antiplatelets, and NSAIDs were administrated in 49 patients (39.2%). Seventy-one percent of the patients who administered theses drugs were over 70 years old, compared with 37% of patients not administered (p!0.05). Emergent endoscopic hemostasis was successfully performed in 16 patients (12.8%) who diagnosed colon diverticula, rectal ulcer, radiation colitis, and angioectasia. Mechanical clipping, epinephrine injection, and argon plasma coagulation therapy was performed in 9 patients, 5 patients, and 2 patients, respectively. On the other hand, remaining 109 patients (87.2%) were recovered without endoscopic hemostasis. While seven patients were required blood

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Purpose: To compare the luminal contents of the ascending colon of adult patients with ulcerative colitis (UC) in relapse vs. remission, as defined by the Clinical and Endoscopic Rachmilewicz Indices (CRI and ERI). Methods: 12 patients participated in a two-phase, crossover study. Patients were administered 10mg bisacodyl 50h and 44h prior to colonoscopy. This procedure had been shown not to affect the colonic fluid composition [1]. Subjects consumed only liquid food from 48h to 16h prior to colonoscopy, then fasted for the last 16h before colonoscopy. Enrolment to the relapse phase was based on scores of 7%CRI%12 and 7%ERI%10, and to the remission phase on scores of 1%CRI%3 and 1%ERI%3. Samples were analyzed for pH and buffer capacity immediately upon collection. The sample was then ultracentrifuged (30,000g, 15 min, 25oC) and the supernatant kept at -70oC until analysis. Osmolality, surface tension, total protein and carbohydrate contents, levels of ten bile acids and of seven short chain fatty acids (SCFAs) were measured in all supernatants. Results. MeanSD volume recovery from the ascending colon was 26.8  13.6mL in relapse and 21.2  8.8mL in remission, similar to volumes recovered from healthy adults [1]. Likewise, the aqueous fraction of the contents (64  15% relapse vs. 57  13% remission) and the surface tension (z41mM/m) was similar to healthy adults. Median pH values were similar in relapse to remission (6.6 vs. 6.5), both significantly lower than in healthy adults (7.8 pZ0.004). Buffer capacity was similar in relapse to remission (32.1  18.1 vs. 38.0  14.7mmol/L/ DpH). Osmolality was 200  127 in relapse vs. 288  150mOsm/kg in remission, both significantly higher than in healthy adults (81mOsm/kg pZ0.029). Total carbohydrate (z6 mg/mL) was similar in both UC groups to values in healthy adults. However, mean total protein (z19 mg/mL, both groups) was significantly higher than in healthy adults (9.7 mg/mL pZ0.004). Total bile acids were 76  43mM in relapse vs. 115  100mM in remission, similar to healthy adults (115 mM). Unlike in healthy adults, though, conjugated bile acids were recovered in UC patients. SCFAs in relapse (23.2  14.9 mM) were significantly lower than that in remission (45.3  26.8 mM pZ0.041), primarily due to lower acetate levels. Conclusion. In general, UC patients exhibit lower intracolonic pH, but higher osmolality and total protein than healthy adults, irrespective of whether they are in relapse or remission. SCFA recovery was significantly lower in relapse vs. remission. Furthermore, in UC patients, but not in healthy subjects, conjugated bile acids were recovered. (1) Diakidou et al. AAPS annual meeting Atlanta, GA, 15-19 Nov. 2008

T1463 Iatrogenic Causes of Gastrointestinal Symptoms and the Impact On Endoscopy Alex J. Kent, Bethan Graf, Matthew R. Banks Introduction: NHS hospitals perform approximately 2000 colonoscopies per year, and this number is likely to rise in the advent of colorectal cancer screening. Many gastrointestinal symptoms lead to endoscopy referrals, including change in bowel habit, abdominal pain and bloating. These symptoms are also commonly associated with side effects of medications. Aims and Methods: Our aim was to identify iatrogenic symptoms leading to unnecessary endoscopy. A questionnaire was given prospectively to all patients undergoing lower GI endoscopy for one month. The questionnaire obtained details regarding patient demographics, medication history, symptoms and endoscopic findings. Patients were excluded if they had alarm symptoms, anaemia or were undergoing endoscopy as part of a surveillance program. Medication history and symptoms were correlated to assess whether there could be an iatrogenic cause, and patients separated into study (iatrogenic) and control groups. Results: During the study period 158 patients were referred for lower GI endoscopy. 20 patients had a potential iatrogenic cause for their symptoms, and 54 were in the control group. The remaining patients were excluded for the reasons stated above. There was no statistical difference in patient demographics between the groups, with 45% female and mean age 54 years. 60% of patients in the iatrogenic group had a normal colonoscopy. Significantly more patients in the iatrogenic group suffered with a change in bowel habit (100% vs. 52%, p!0.0001). 7% patients in the control group were diagnosed with colorectal cancer and a further 7% with ulcerative colitis, compared to no patients in the iatrogenic study group. The incidence of polyps was similar between the groups. Drugs implicated with iatrogenicity included: proton pump inhibitors, opiate-based medications, statins, metformin, sulphonylureas, iron supplements, antidepressants (TCA & SSRI) and HAART. Only 2 patients had a trial off medication

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