History Of Ulcerative Colitis Research Articles

Primary Colorectal Non-Hodgkinʼs Lymphoma in the Setting of Ulcerative Colitis: A Rare Occurrence with an Unusual Presentation

Introduction: The GI tract is a common site for primary lymphoma (10-15%), and also as an extranodal site (30-40%). Colorectal involvement, however, is rare, accounting for 3% of GI lymphoma and only 0.3 % of colonic malignancies. The concomitant presence of ulcerative colitis and DLBCL is exceedingly rare, and diagnosis is often delayed, owing to overlap of symptoms. Case: A 71-year-old man with a history of ulcerative colitis (UC) and coronary artery disease was admitted with abdominal pain, persistent diarrhea and weight loss. He had an antecedent history of colitis for at least 8 years, with biopsies consistent with infectious colitis vs. early inflammatory bowel disease, treated with mesalamine and, intermittently, with antibiotics during exacerbations; he was never treated with immune modulators. Prior imaging, including CT scans, had revealed mild colonic mural thickening with a “featureless” transverse colon, suggestive of ulcerative colitis, but no radiographic evidence of malignancy. While undergoing bowel prep for colonoscopy, he complained of sudden worsening of abdominal pain. A CT scan revealed a large volume of intraperitoneal free air, consistent with a bowel perforation and an inflammatory state of the sigmoid and descending colon, compatible with ulcerative colitis. An emergent resection and colostomy was performed. The histopathology was consistent with a diffuse large B cell lymphoma (DLBCL) with adjacent segments of colon showing chronic colitis and focal ulceration, negative for transmural inflammation, consistent with the diagnosis of ulcerative colitis. He was subsequently treated with six cycles of rituxan and EPOCH, and is currently in remission and followed by oncology. Repeat PET/CT imaging to date has not shown any recurrence of disease. Discussion: We present this case of DLBCL in a patient with UC who presented with vague abdominal symptoms and was not on immunosuppressive medications. The link between UC and colonic lymphoma remains unresolved. Hypotheses include ongoing treatment with immunosuppressive agents vs. chronic inflammation in the setting of UC as the inciting factor for development of lymphoma. Further study is needed to define the relationship between UC and primary colonic lymphoma. Colonic lymphoma tends to present with vague abdominal and systemic symptoms often overlapping with those characteristic of inflammatory bowel disease. This, along with the potential for colonic lymphomas to present as ulcerative lesions, makes it difficult to distinguish from UC. Perforations are exceedingly rare. Given the unusual occurrence of primary colonic lymphoma in the setting of UC and the overlap of symptoms, a high index of suspicion is needed.

Five-Year Mortality in Colorectal Cancer Patients with Ulcerative Colitis or Crohnʼs Disease

The impact of inflammatory bowel disease (IBD) on colorectal cancer (CRC) prognosis, taking into account other comorbidities, is not clear. We studied the overall mortality in CRC patients with a history of ulcerative colitis (UC) or Crohn's disease (CD) compared with non-IBD-CRC patients. Data on all CRC and IBD patients diagnosed with CRC between 1977 and 2009 were retrieved from Danish medical registries. One-year and 5-year overall mortality were evaluated with the Kaplan-Meier method and with Cox regression, adjusting for year of CRC diagnosis, sex, Duke's stage, age at CRC diagnosis, and Charlson Comorbidity Index score. We identified 653 CRC patients diagnosed with UC, 238 patients with CD, and 107,024 CRC patients without IBD. The patients with IBD were younger at diagnosis than patients without IBD. The Duke's stage distribution was similar for UC-CRC patients and non-IBD-CRC patients. The CD-CRC patients had a lower frequency of Duke's A and B stage tumors (36% versus 42%), a higher frequency of Duke's C stage tumors (31% versus 27%) and Duke's D-stage tumors (23% versus 21%), and a similar frequency of unknown stage tumors (10%) compared with non-IBD-CRC patients. After 5-years of follow-up, 59% of the UC and the non-UC-CRC patients had died compared with 62% of the patients with CD and 56% of the non-CD-CRC patients. The 5-year adjusted mortality rate ratios for patients with UC or CD were 1.14 (95% confidence interval, 1.03-1.27) and 1.26 (95% confidence interval, 1.07-1.49), respectively, compared with patients without IBD. A history of IBD in patients with CRC may be associated with increased mortality.

Early Life Factors and Risk of Inflammatory Bowel Disease in Adulthood

Early life factors have been postulated to play a role in development of immune tolerance and intestinal microbiome, which in turn may influence the risk of inflammatory bowel disease. We conducted a prospective cohort study of 60,186 U.S. women enrolled since 1976 in the Nurses Health Study (NHS) I and 86,495 women enrolled since 1989 in the NHS II with no history of ulcerative colitis (UC) or Crohn's disease (CD). Information about breastfeeding, birth weight, and preterm birth were collected in 1992 in NHS I and 1991 in NHS II. Diagnoses of CD and UC were confirmed through review of medical records. We used Cox proportional hazards models to calculate hazard ratios and 95% confidence intervals. Among 146,681 women over 3,373,726 person-years of follow-up, we documented 248 cases of CD and 304 cases of UC through 2007 in NHS II and 2008 in NHS I. The median age of diagnosis was 51 for CD and 49 for UC. Compared with women who were not breastfed, women who were breastfed had multivariate-adjusted hazard ratios of 0.99 (95% confidence interval, 0.76-1.30) for CD and 1.03 (95% confidence interval, 0.81-1.32) for UC. Similarly, low or high birth weight and preterm birth were not significantly associated with risk of UC or CD. In 2 large prospective cohorts of U.S. women, we did not observe a significant association between early life factors including having been breastfed, birth weight, preterm birth, and risk of adult-onset UC and CD.

P429 Natural history of ulcerative colitis by the age group at diagnosis: a 10-year nationwide retrospective cohort from the Veterans Affairs healthcare system

P429 Natural history of ulcerative colitis by the age group at diagnosis: a 10-year nationwide retrospective cohort from the Veterans Affairs healthcare system

P356 The natural history of systemic corticosteroid therapy in ulcerative colitis: a nationwide, retrospective cohort from the Veterans Affairs healthcare system

Background: Data on the natural history of Ulcerative Colitis (UC) after corticosteroid (CS) therapy is limited. Our aim was to assess the pharmacological and clinical outcomes over a threeyear observational period after the index steroid exposure in patients with UC. Methods: Nationwide data was obtained from the Veterans Affairs (VA) healthcare system. UC patients followed in the VA between 2001 and 2011 were identified using ICD9 codes. To increase the specificity UC diagnosis, all the included patients needed to have 5Aminosalicylate exposure during the observation period. Patients needed to have prednisone dispensed prior to 2008 in order to have a follow-up of 3 year. We captured the index oral prednisone dispense date and during the three year observational period we tracked their prednisone, thiopurines, infliximab dispense activity and the need for colectomy. Our primary aim was to assess the disease activity patterns after the first CS use based upon steroid use. Patients were classified as “sustained response” if they had no CS filling activity for at least a year towards the end of the observation period. This could achieved either “early” if the cessation happens within 6 months of CS initiation or “late” if it took longer than six months. Those who dispensed CS episodically were classified as “relapsers”. These could be either “high frequency” if there was less than six months or “low frequency” if there was at least a year of CS free interval. Those who continued dispensing CS were classified as steroid dependent. Results: We identified 22,762 UC patients in the VA system. Of these 6,210 met our inclusion criteria. We identified five patterns of steroid use after index CS course among those who didn’t require colectomy (Figure).

Always a Suspect: CMV in Ulcerative Colitis

In June 2011, a 60-year-old white woman with history of ulcerative colitis presented with severe bloody diarrhea, reporting up to 12 bowel movements per day, vomiting and fatigue. She had initially presented with painless diarrhea and urgency 14 years ago. After the initial colonoscopic and histologic diagnosis of ulcerative colitis, she was placed on tapering doses of steroids and eventually on 100 mg of 6-mercaptopurine (6-MP). Over the next 5 years, she was treated for intermittent flares of ulcerative colitis with oral steroids in addition to 6-MP. Colonoscopy performed for a flare 6 years ago revealed viral inclusions in the cecal and rectal biopsies, consistent with cytomegalovirus (CMV). Serum IgG and IgM levels were elevated at 50.1 and 3.1, respectively. She was treated with ganciclovir 900 mg for 6 weeks in addition to 6-MP and prednisone, with subsequent clearance of histologic CMV inclusions. Over the next 5 years, she had a total of six colitis flares which were treated with short courses of steroids. However, because of an episode of pancreatitis in October 2006, 6-MP was discontinued in favor of methotrexate 12.5 mg weekly. Infliximab infusions were included in her regimen in March 2011 and were continued every 8 weeks thereafter. Her past medical history was otherwise significant for hepatitis A, hypothyroidism, hyperlipidemia, sclerosing cholangitis (for which she was treated with ursodeoxycholic acid 900 mg orally daily) and Sjogren’s syndrome. She was a non-smoker and non-drinker and worked as a librarian. Upon presentation in June 2011, her physical examination revealed a pale woman with a soft, non-distended, non-tender abdomen with positive bowel sounds. She was re-started on 40 mg of prednisone with continuation of methotrexate and infliximab; severe diarrhea persisted. Colonoscopy revealed severe ulcerative colitis with several large nodules suggestive of ‘‘dysplasia-associated lesion or mass’’ (DALM) (Fig. 1). Biopsies revealed high-grade dysplastic epithelium in the sigmoid and rectal nodules (Fig. 2). Viral inclusion bodies specific to CMV were observed with conventional histology and with immunohistochemal stains (Fig. 3). Infliximab infusions were stopped in favor of ganciclovir 900 mg given orally twice daily for 6 weeks. After one week of therapy, bowel movements decreased to 5–6 per day, her fatigue improved, but her hematocrit decreased by 4 points to 28.8 %. Intravenous iron was initiated to treat iron deficiency. Ten days after stopping ganciclovir, her hematocrit normalized. Upon follow-up colonoscopy 4 months later, severe ulcerative colitis with more dysplastic nodular lesions in several locations were identified. Because of this, she underwent a laparascopically-assisted total proctocolectomy with an end-ileostomy. The specimen revealed welldifferentiated adenocarcinoma in the cecum and sigmoid colon. Sixty-two lymph nodes identified were negative. When seen at follow up 2 months post colectomy, she felt more energetic and had discontinued prednisone, infliximab and methotrexate. Ursodeoxycholic acid was continued as the treatment for her primary sclerosing cholangitis. S. Kommareddy C. L. Chun W. Rogers G. Triadafilopoulos El Camino Hospital, Mountain View, CA, USA

Coronary Artery Aneurysms and Inflammatory Bowel Disease: A Rare Association Case Report

Inflammatory bowel disease is a complex entity that involves not only intestinal but also systemic manifestations. Several studies describing cardiovascular complications, such as coronary atherosclerosis, aortic aneurysms, vasculitis and pericarditis, have been published. However, the presence of coronary artery aneurysms has not been previously associated with this disease. In this report, we describe a 76-year-old patient with history of ulcerative colitis and coronary artery disease with a coronary angiography revealing the presence of several coronary aneurysms. Since endothelial dysfunction and destruction of elastic fibers due to inflammation could conceivably lead to coronary artery dilatation and aneurysms, we suggest that the inflammatory response in ulcerative colitis may play an important role in the development of some of the aforementioned cardiac complications.

Diffuse gastroduodenitis associated with ulcerative colitis: Treatment by infliximab

Diffuse gastroduodenitis resembling ulcerative colitis in respect to macro- and microscopic findings occurs in ulcerative colitis, although it is rare. Reports of gastroduodenitis associated with ulcerative colitis treated with infliximab are rare. A 58-year-old man had tarry stool in March 2011. He had a history of ulcerative colitis that was diagnosed in 1984. He underwent subtotal colectomy in 1991. Endoscopy and radiography revealed diffuse friable mucosa throughout the duodenum and an ulcer in the middle of the descending portion, resulting in a narrow portion.In the stomach, numerous small aphthae were observed in the antrum. Biopsy specimens of the duodenum and antrum showed marked inflammatory cell infiltration in both areas and cryptitis in the duodenum. Standard induction therapy of infliximab was started in April. The ulcer in the descending portion became a scar without diffuse mucosal friability in September 2011.

Abstract 37: Genetic variation in prostaglandin synthesis and related pathways, NSAID use, and risk of colorectal cancer in the Colon Cancer Family Registry.

Abstract Introduction: Inflammation is known to affect the risk of colorectal cancer (CRC). Although use of non-steroidal anti-inflammatory drugs (NSAIDs) is effective in decreasing CRC risk, inherited variation in genes that affect NSAID metabolism may alter their potential as a preventive agent. As NSAIDs function by inhibiting cyclooxygenase (COX) enzymes, which control the conversion of arachidonic acid to prostaglandins and thromboxane, we investigated whether variation in prostaglandin synthesis and related pathways affects the risk of CRC in the Colon Cancer Family Registry. Methods: We examined associations between 221 tagging and candidate single nucleotide polymorphisms (SNPs) within 18 candidate genes (ALOX12, ALOX5, ALOX5AP, CRP, EGFR, GIPC1, HPGD, PARP12, PKN1, PLA2G1B, PTGER1, PTGER2, PTGER3, PTGER4, PTGES, PTGIS, PTGS2, and TBXAS1) and the risk of CRC. We further assessed whether the association between SNPs and CRC risk varied by use of NSAIDs. Using a case-unaffected-sibling-control design, this study included 4,213 Caucasian men and women age 20-74 with no known familial adenomatous polyposis and no personal history of ulcerative colitis or Crohn's disease. Cases (N=1,621) were recruited from six registry centers and were diagnosed with primary invasive CRC from 1998-2002. Controls (N=2,592) were siblings not diagnosed with CRC at the time of ascertainment. We computed odds ratios and 95% confidence intervals using conditional logistic regression and corrected for multiple comparisons using the Conneely and Boehnke method. All models were adjusted for age and sex; NSAID interactions were further adjusted for BMI, smoking, and physical activity. Results: After adjustment for multiple comparisons, two intronic SNPs were associated with a decreased risk of rectal cancer: rs45525634 in PTGER2 (ORhet/hzv 0.49, 95% CI 0.29-0.82) and rs6091005 in PTGIS (ORhet 0.73, 95% CI 0.52-1.03; ORhzv 0.39, 95% CI 0.22-0.68). Additionally, an intronic SNP, rs11571364, in ALOX12 was associated with an increased risk of rectal cancer (ORhet/hzv 1.87, 95% CI 1.19-2.95). The risk of CRC associated with NSAID use differed by genotype at three intronic SNPs: rs10142849 (p = 0.02) in PTGER2 as well as rs11239516 (p = 0.04) and rs2115819 (p = 0.05) in ALOX5. These SNPs in ALOX5 shared low LD among Caucasian controls (r2 = 0.28). There was also evidence for interactions between SNP genotypes and NSAID use for colon cancer for two intronic SNPs, rs11239516 (p = 0.04) in ALOX5 and rs7806848 (p = 0.02) in TBXAS1, and for rectal cancer for rs16870224 (p = 0.05) located in the 3' UTR of PTGER4, the coding SNP rs35416389 (R641Q, p = 0.02) in PKN1, and two intronic SNPs rs17222919 (p = 0.03) in ALOX5 and rs6664305 (p = 0.01) in PTGER3. Conclusion: The results of this study suggest that genetic variation in ALOX12, PTGER2, and PTGIS may affect the risk of rectal cancer. In addition, this study suggests that current use of NSAIDs may modify associations between CRC risk and SNPs in ALOX5, PKN1, PTGER2, PTGER3, PTGER4, and TBXAS1. These findings may aid in the development of genetically targeted cancer prevention strategies with NSAIDs. Citation Format: Alexa J. Resler, Laura Heath, Karen W. Makar, John Whitton, Nina Habermann, Hansong Wang, Polly A. Newcomb, Loic LeMarchand, John D. Potter, Cornelia M. Ulrich. Genetic variation in prostaglandin synthesis and related pathways, NSAID use, and risk of colorectal cancer in the Colon Cancer Family Registry. [abstract]. In: Proceedings of the AACR Special Conference on Post-GWAS Horizons in Molecular Epidemiology: Digging Deeper into the Environment; 2012 Nov 11-14; Hollywood, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2012;21(11 Suppl):Abstract nr 37.

Primary Gallbladder Carcinoma in a Patient with Ulcerative Colitis and Primary Sclerosing Cholangitis (PSC)

Case: 46-year-old male with history of ulcerative colitis (UC) diagnosed 28 years ago presented to clinic with three days of abdominal pain, diffuse pruritis and found to have mild jaundice on exam. Initial blood work demonstrated abnormal liver function tests in a mixed cholestatic/hepatotoxic pattern prompting hospital admission. Magnetic resonance cholangiopancreatography showed abrupt narrowing of proximal common bile duct (CBD) with severe dilatation of intra-hepatic bile ducts, suggestive of primary sclerosing cholangitis (PSC). Endoscopic retrograde cholangiopancreatography showed a dominant biliary stricture in the CBD as well as dilatation of proximal CBD and left and right main hepatic ducts. The stricture was treated with dilation and stent placement. CBD brush biopsy results were positive for adenocarcinoma. The patient then underwent a resection of CBD, gallbladder as well as liver biopsy and reconstruction of hepatic ducts. Final pathology revealed poorly differentiated primary gallbladder adenocarcinoma with local tumor extension as well as portal inflammation and fibrosis, consistent with PSC. The patient completed four cycles of chemotherapy and radiation with subsequent re-staging imaging showing no recurrence of disease with normal tumor markers one year after diagnosis. Discussion: PSC is a chronic cholestatic disorder of unclear etiology involving both the intra- and extra-hepatic bile ducts with histology most prominently showing fibrotic and inflammatory changes. Up to 90% of PSC cases are associated with inflammatory bowel disease (IBD), of these 87% have UC. The majority of PSC patients have extensive intestinal and hepatobiliary inflammation that may promote carcinogenesis and are at a high risk for developing hepatobiliary and intestinal neoplasms, mainly cholangiocarcinoma, whereas gallbladder carcinoma (GBC) is rarely reported. The present case demonstrates that prompt recognition of alarming symptoms and aggressive workup led to cancer-free survival despite the diagnosis of GBC, which typically has a very poor prognosis. Therefore, high level of suspicion and attention should be applied to IBD and PSC patients who present with acute signs of possible hepatobiliary pathology as it could represent early signs of hepatobiliary carcinoma.Figure: MRCP showing narrowing of proximal CBD with dilatation of intra-hepatic bile ducts.

Multi-System Organ Infarction Due to Ulcerative Colitis Induced Disseminated Intravascular Coagulation

Introduction: Disseminated intravascular coagulation (DIC) has been reported in patients with ulcerative colitis (UC). However, these cases are rare. We report a case of DIC in the setting of UC with toxic megacolon leading to ischemia of the bowel, bladder and ureters. Case Presentation: A 24-year-old male with a history of ulcerative colitis, diagnosed 9 months prior to admission after an episode of pancolitis, presented with a two-week history of abdominal pain and bloody diarrhea. He had self-discontinued sulfasalazine 6 months prior to presentation. On admission, he was nontoxic, afebrile and normotensive with a heart rate of 120 beats per minute. Abdominal exam revealed diffuse tenderness without peritoneal signs and normoactive bowel sounds. Labs demonstrated a WBC of 16.4 K/uL with 9% bands; Hb 12.4 g/dL; platelets 189 K/uL; CRP 248 mg/L. Creatinine, urinalysis and lactate were normal. Blood, urine, and stool cultures had no growth. C. difficile toxin PCR was negative. CT scan was consistent with pancolitis with filling defects in the SMV and IMV. Solumedrol, sulfasalazine, ciprofloxacin and metronidazole were started. Within 12 hours of presentation, the patient became toxic in appearance with gross hematuria, tachycardia, and hypotension. Abdominal exam was unchanged from admission. Repeat labs demonstrated WBC 34.5 K/uL; Hb 8.0 g/dL; platelets 64 K/uL; lactate 7.3 meq/L; creatinine 2.9 mg/dL; PTT 43 sec; INR 2.5; fibrinogen 175 mg/dL. Urgent laparotomy revealed frank ischemia of the bowel extending from the ascending colon to the rectum, as well as the prostate, bladder and ureters. A proctocolectomy with end ileostomy and cysto-prostatectomy was performed with placement of bilateral percutaneous nephrostomy tubes. Pathology showed chronic severely active colitis with ulceration and pseudomembranous formation as well as diffuse thrombosis with mucosal and transmural necrosis of the colon, rectum, bladder, prostate, and ureters consistent with DIC. Following surgical intervention, patient's condition improved. He is currently undergoing rehabilitation with plans for neobladder construction and ileostomy reversal in the future. Discussion: This case highlights the rare but serious complications of coagulopathic disorders in UC. There are several possibilities for the driving force behind the patient's progression to DIC including toxic megacolon. Although workup was negative, an unrecognized infection could have precipitated DIC in our patient. Also, filling defects suggestive of thrombus in the SMV and IMV on admission could have caused endothelial injury thus leading to DIC. Further investigation into UC-associated coagulopathies must ensue.

A Rare Complication of Ulcerative Colitis: ST Elevation Myocardial Infarction

Purpose: A 44-year-old female presented to the emergency room (ER) with sudden onset substernal chest pain. The patient had no known cardiac risk factors. She had a history of Ulcerative Colitis (UC), which had been in remission until two days prior to the presentation, when she started having abdominal pain and bloody diarrhea. This episode was similar to her prior exacerbations but she was currently not on any treatment. The physical exam was only remarkable for mild diffuse tenderness in the abdomen. The EKG done in the ER showed ST segment elevations in leads II, III and aVF and the lab work was significant for elevated cardiac enzymes (Troponin I-25 ng/ml). The patient underwent an urgent cardiac catheterization which revealed total occlusion of the right coronary artery. The artery could not be stented due to the presence of extensive thrombus and even though, thrombectomy was attempted, it was not successful. The decision was made to manage the patient medically and she was started on a beta blocker, ACE inhibitor and statin for acute MI and mesalamine for Ulcerative colitis exacerbation. Aspirin and Clopidogrel were held in the light of bloody diarrhea but it was decided to start intravenous heparin. The patient responded well to the treatment. The hematocrit remained stable and there were no further episodes of bleeding. She was eventually discharged in a stable condition. Ulcerative colitis is frequently associated with many extra-intestinal manifestations, mostly in the form of dermatological, hepatobiliary or ocular involvement but cardiac involvement is rare. It usually manifests as either pericarditis with or without myocardial involvement or conduction abnormalities. Myocardial infarction, as seen in our patient, is an extremely rare complication of Ulcerative colitis. The hypercoagulable state in UC is postulated to be due to increased levels of platelets, prothrombin fragment, fibrinogen, homocysteine and reduced levels of anticoagulants. These alterations in the coagulation cascade can result in deep venous thrombosis, pulmonary embolism, atrial thrombi and rarely coronary artery thrombosis. Interestingly, intravenous heparin has been suggested as a treatment for UC exacerbation along with standard therapy, with no increase in the incidence of bleeding. The exact mechanism by which heparin ameliorates the exacerbation is still unclear but it makes it particularly beneficial in the setting of a MI. We would like to conclude that physicians should be aware of this rare complication of Ulcerative colitis and it is important to recognize chest pain during UC exacerbation as it can indicate an impending Myocardial Infarction.

Recognition of the p53 Null Staining Pattern Increases the Detection of p53 Alterations in Inflammatory Bowel Disease-Associated Carcinomas

Purpose: Colorectal cancer (CRC) occurring in the setting of Inflammatory Bowel Disease (IBD) is relatively uncommon. Mutations in p53 have been found in these cancers, and have been proposed as a possible genetic marker with utility in detection of these cancers and their precursor dysplasias. We undertook this study to determine the frequency of p53 null alterations, a recently observed pattern that has not previously been described in colitis-associated neoplasia. Methods: Patients with CRC were selected from the pathology database of Miraca Life Sciences. The database includes demographic and clinical information, summary of the endoscopic report, biopsy location, and the histopathologic report for each biopsy specimen. Cases of CRC with a report date from 11/1/2007 to 11/30/2011 were extracted from the database. From these cases, a database search was performed to extract patients with a history of Ulcerative Colitis (UC) and Crohn Disease (CD). p53 immunohistochemical staining was performed on the carcinomas and interpreted as wild-type (<20% 2-3+ nuclear positivity), point mutant (>50% 2-3+ nuclear positivity) or null (no nuclear positivity). Results: Biopsies from 917,599 colonoscopies were interpreted on 878,835 patients (51% female, 49% male) during the study period. Of these, 16,631 unique patients (48% female, 52% male) had histological and clinical features of UC while 5,736 patients had histological and clinical features of CD. During this period, 6,211 CRCs were diagnosed (52% male, 48% female). Of these cancers, 22 occurred in patients with UC (prevalence of 22/16,631 = 0.13%), and 5 occurred in patients with CD (prevalence of 5/5,736 = 0.09%). 19 IBD patients were male (70.4%) and 8 were female (29.6%). The mean age was 58 years (median 56 years, standard deviation 13.5 years, range 33 to 84 years). Of these tumors, 14 (51.9%) were moderately differentiated (MD) and 13 (48.1%) were poorly differentiated (PD). Immunohistochemical staining for p53 showed abnormalities in 24/27 (89%), including 14 carcinomas with null pattern (51.9%), 10 with mutant pattern (37.0%) and 3 with wild-type pattern (11.1%). One MD carcinoma and 2 PD carcinomas showed wild-type p53 staining. Conclusion: The p53 null staining pattern is very common in colitis-associated carcinoma, and more than doubles the detectable frequency of p53 immunohistochemical alterations in these tumors. This finding indicates that p53 alterations are one of the most common genetic abnormalities in colitis-associated neoplasia, and has important implications for the potential use of p53 in screening and early detection programs. We also found that CRC occurring in the setting of IBD is rare, occurs predominantly in males and tends to be PD.Table: [1549]

Isolated Oral Pyoderma Gangrenosum Following Proctocolectomy

Purpose: A 20-year-old man with a 6 month history of ulcerative colitis (UC) presented with a severe flare requiring corticosteroids and infliximab. He presented 3 months later with worsening symptoms of bloody diarrhea and fever despite escalating doses of infliximab. After two weeks of intensive treatment, he ultimately underwent a proctocolectomy. In the postoperative period, steroids were tapered and he gradually developed severe odynophagia and mouth pain. Examination revealed what appeared to be angular cheilitis and aphthous ulcers on the tongue, uvula and posterior oropharynx (Figure 1). No skin lesions were noted on examination. The oral lesions were biopsied, given their suboptimal response to conservative management, demonstrating squamous mucosa with acute inflammation and ulceration. The underlying soft tissue showed diffuse granulomatous inflammation characterized by epithelioid histiocytes with focal giant cells surrounding central neutrophilic infiltrates with leukocytoclasia (Figure 2). No vasculitis or viral inclusions were present. Special stains for fungi (GMS) and acid-fast bacilli (AFB) were negative. A diagnosis of PG was established and confirmed by an expert pathologist. The patient was given high-dose intravenous corticosteroids and he began to show improvement in symptoms as well as ulcer healing by three days. Pyoderma Gangrenosum (PG) is a primarily dermatologic manifestation of inflammatory bowel disease seen in 1-12% of patients with UC and less commonly in Crohn's colitis. Fewer than 10 cases of stomal PG have been reported and we describe a unique case of isolated PG of the oral cavity in a post-colectomy patient with UC.Figure: No Caption available.Figure: [1305]

Seeing the World through Rose Colored Glasses: The Etiology of Eosinophilic Infiltration of the Upper GI Tract in a Patient with Ulcerative Colitis

Introduction: Eosinophilic disease of the upper GI tract is an uncommon disease. The differential diagnosis is often broad and includes parasitic infection, eosinophilic gastroenteritis, and Crohn's. We report a patient with a history of “ulcerative colitis” found to have eosinophils in the stomach and duodenum upon performance of an upper endoscopy. Methods (Case Report): A 36-year-old female with a history of ulcerative colitis and no prior travel history presented with persistent nausea. The patient had a bout of bloody diarrhea two months previously, at which time a colonoscopy revealed procto-sigmoiditis, with a normal right colon and terminal ileum. The patient underwent mesalamine therapy and saw remission. Laboratory evaluation, which included a CBC, CMP, ESR, CRP, TSH, and Β-HCG were all within normal limits. Treatment with a proton pump inhibitor and ondansetron yielded no significant improvement. Upper endoscopy was performed. Although only mild gastritis was found, biopsies of the stomach and duodenum showed greater than thirty eosinophils per high powered field. A capsule endoscopy was performed. More than five deep ulcerations were seen in the termindal ileum consistent with a diagnosis of Crohn's disease. ASCA antibodies and pANCA antibodies were negative. The patient was treated with oral budesonide with resolution of symptoms. Discussion: Eosinophili of the upper GI tract is a relatively uncommon disease. Although Crohn's disease of the upper GI tract typically presents with severe ulceration and granulomas, eosinophilic infiltration has been reported. Eosinophils in the upper GI tract have not been demonstrated with ulcerative colitis. There is one case report of a patient with simultaneous ulcerative colitis and eosinophilic gastroenteritis. Although it would seem reasonable, it is much more common to see Crohn's in patients with upper GI tract eosinophilia compared to ulcerative colitis. The capsule endoscopy can be a useful tool to confirm the diagnosis of and rule out an “overlap syndrome.”Figure: No Caption available.

Poster 114 Multifocal Acquired Demyelinating Sensory and Motor (MADSAM) Neuropathy Secondary to Infliximab Infusion: A Case Report

Disclosures: A. Sinha, No Disclosures. Case Description: A 69-year-old man with a history of ulcerative colitis, status post C4-C7 fusion (secondary to myelopathy over 10 years ago), presented with a 1-year history of right upper extremity pain and paresthesia. Recent MRI of the cervical spine showed evidence of a well-healed fusion from C4-C7 with findings of degenerative changes at C3-4 and C7-T1. The patient did have an MRI of the brachial plexus, which was unremarkable. The patient denied any lower extremity symptoms; however, he did have some paresthesias in the sole of his feet. The patient noted that most of his symptoms began after infliximab infusion therapy for ulcerative colitis. His last infliximab infusion was 8 weeks prior to this appointment. He denied any bowel or bladder dysfunction. On physical examination, the patient was neurologically intact, except for except for 4/5 strength in the right hand intrinsics. There were no upper motor neuron signs. Setting: Outpatient spine practice. Results or Clinical Course: Electrodiagnostic studies of the upper and lower extremities showed prolonged latencies, diminished amplitudes and conduction velocities, in multiple nerves in a non-focal distribution. Diminished recruitment and polyphasic potentials were found in the majority of muscles in the upper and lower extremities. The patient was diagnosed with multifocal acquired demyelinating sensory and motor (MADSAM) neuropathy. He was referred to neurology where he was advised to begin intravenous immunoglobulin (IVIg) therapy. Discussion: Multifocal acquired demyelinating sensory and motor (MADSAM) neuropathy is defined clinically by a multifocal pattern of motor and sensory loss, with nerve conduction studies showing conduction block and features of demyelination. Also known as Lewis-Sumner syndrome, this neuropathy is a rarely reported complication in patients undergoing treatment with the antitumor necrosis factor (TNF) monoclonal antibody infliximab. Symptoms may resolve after cessation of the antibody treatment; however IV Ig infusion therapy is the treatment of choice if symptoms persist. Conclusions: We present a rarely reported case of MADSAM, or Lewis-Sumner syndrome, following infliximab treatment. Clinicians should be aware that electrodiagnostic studies are essential in the diagnosis of this complex neuropathy.

The clinical, endoscopic and histological spectrum of the solitary rectal ulcer syndrome: a single-center experience of 116 cases

BackgroundSolitary rectal ulcer syndrome (SRUS) is an uncommon although benign defecation disorder. The aim of this study was to evaluate the variable endoscopic manifestations of SRUS and its association with other diseases.MethodsAll the patients diagnosed with SRUS histologically from January 1990 to February 2011 at The Aga Khan University, Karachi were included in the study. The medical records were reviewed retrospectively to evaluate the clinical spectrum of the patients along with the endoscopic and histological findings.ResultsA total of 116 patients were evaluated. The mean age was 37.4 ± 16.6 (range: 13–80) years, 61 (53%) of the patients were male. Bleeding per rectum was present in 82%, abdominal pain in 49%, constipation in 23% and diarrhea in 22%. Endoscopically, solitary and multiple lesions were present in 79 (68%) and 33 (28%) patients respectively; ulcerative lesions in 90 (78%), polypoidal in 29 (25%), erythematous patches in 3 (2.5%) and petechial spots in one patient. Associated underlying conditions were hemorrhoids in 7 (6%), hyperplastic polyps in 4 (3.5%), adenomatous polyps in 2(2%), history of ulcerative colitis in 3 (2.5%) while adenocarcinoma of colon was observed in two patients. One patient had previous surgery for colonic carcinoma.ConclusionSRUS may manifest on endoscopy as multiple ulcers, polypoidal growth and erythematous patches and has shown to share clinicopathological features with rectal prolapse, proctitis cystica profunda (PCP) and inflammatory cloacogenic polyp; therefore collectively grouped as mucosal prolapse syndrome. This may be associated with underlying conditions such as polyps, ulcerative colitis, hemorrhoids and malignancy. High index of suspicion is required to diagnose potentially serious disease by repeated endoscopies with biopsies to look for potentially serious underlying conditions associated with SRUS.

Tu1249 Environmental Factors Impact the Natural History of Ulcerative Colitis (UC): Indian-Americans With UC Have a Higher Riks for Colectomy Than Asian Indian Counterparts

Tu1249 Environmental Factors Impact the Natural History of Ulcerative Colitis (UC): Indian-Americans With UC Have a Higher Riks for Colectomy Than Asian Indian Counterparts

105 Natural History of Ulcerative Colitis in the Elderly: A Population-Based Study

105 Natural History of Ulcerative Colitis in the Elderly: A Population-Based Study

Sa2074 Title: Successful Treatment of Refractory Clostridium difficile Infection(Cdi) With Intestinal Microbiota Transplant (IMT) in Two Patients With Inflammatory Bowel Disease (IBD) and Its Effects on IBD

C. difficile is responsible for 15-25% of antibiotic associated diarrhea and overall incidence of CDI is increasing including in patients with IBD. Among the various therapeutic modalities used for the treatment of IBD, only the use of steroids is found to be associated with increased risk of CDI; however the role of immunosuppressant use is controversial and the use of biologics has not been shown to have a clear association with development of CDI. Physicians are often reluctant to use immunosupression in the setting of CDI given fear of exacerbation of CDI, which in turn results in poor control of IBD. IMT has been demonstrated to be an effective treatment for refractory CDI. Methods: A 27-year-old woman with Crohns ileocolitis and refractory CDI for over one year had failed multiple prolonged tapering courses of vancomycin and probiotics. She had endoscopically proven active ileocolonic Crohns disease, which was not aggressively treated with immunosuppressants given her CDI. She had up to 25 stools a day and had lost 25 pounds, therefore she underwent successful IMT with approximately 250 g of donor stool from her mother, which was placed endoscopically into her ileum. Her diarrhea improved but did not completely resolve despite negative stool cultures two weeks post procedure. She was started on prednisone 40 mg a day, which was slowly tapered and started on Adalimumab concomitantly. She has been in clinical remission for over a year on 40 mg Adalimumab alone without recurrent CDI. A 39 yr old male with history of Ulcerative colitis diagnosed 15 ys ago with concomitant refractory CDI. He had been treated for CDI over 12 times in 15 years with multiple courses of flagyl, oral vancomycin and Rifaximin with no improvement. He continued to have 15 bowel movements per day. He was unable to tolerate adalimumab and azothioprine in the past and was felt to be high risk for steroids secondary to CDI. He underwent successful IMT on 2/2011 with donor stool from his mother. He has improved significantly since then and was started on high dose prednisone after negative C difficile testing with improvement of diarrhea. He has not had any relapse of CDI but still has evidence of active IBD on sigmoidoscopy five months post IMT. He has been maintained on 5 ASA drugs and a tapering course of steroids and being considered for colectomy. IMT with ileal infusion of the bacteriotherapy should be considered for treatment of refractory CDI in patients with concomitant IBD since it provides an opportunity to maximize therapy for IBD. A published case series of 6 patients demonstrated complete resolution of ulcerative colitis after IMT. Contrary to their study our experience with 2 patients showed resolution of CDI but no change in IBD with up to 1 year follow up. Further studies are needed to assess the role of IMT in the treatment of IBD.