Long-standing Colitis Research Articles

High Definition Colonoscopy (HDC) vs. Dye Spraying Chromo-colonoscopy (DSC) in Screening Patients With Long-standing Inflammatory Bowel Disease (IBD)

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805 Improving Chromoendoscopy Utilization in Dysplasia Surveillance of Patients With Inflammatory Bowel Disease

INTRODUCTION: Given the increased risk of colon cancer, patients with longstanding inflammatory bowel disease (IBD) of at least 8 years are recommended to undergo screening every 1-2 years. Chromoendoscopy has been shown to provide up to 9-fold detection of dysplastic lesions versus standard-definition endoscopy. However, it has not yet been widely adopted. A background needs assessment at our institution suggested that lack of familiarity and comfort with chromoendoscopy in our endoscopy ancillary staff had contributed to its low implementation rate. Our baseline data also showed that a majority of endoscopy ancillary staff preferred in-person, small group educational sessions to learn more about chromoendoscopy, as opposed to mandatory online training. We aim to improve the implementation of chromoendoscopy at our institution via in-person, small group education of endoscopy ancillary staff. METHODS: Two in-service small group sessions with endoscopy nurses at Rhode Island Hospital (RIH) focusing on chromoendoscopy were held in December 2016 and January 2017. A pre-intervention survey was sent to the staff. Staff were asked whether they had ever heard of/personally participated in chromoendoscopy and how comfortable they were with it. Possible concerns, including safety, time constraint, and cost of procedure, were also evaluated in the pre-intervention assessment. A post-intervention survey, consisting of the same questions, was sent after the two education sessions. The number of chromoendoscopy performed over a 22-month period prior to the sessions and following the sessions were evaluated. RESULTS: Prior to the intervention, 31% staff had never heard of chromoendoscopy and 22% reported feeling very uncomfortable with it. Post-intervention, less than 10% reported never having heard of chromoendoscopy or feeling very uncomfortable with it. While less than half of the staff reported they would want a physician to use chromoendoscopy for dysplasia surveillance if they themselves had IBD prior to the educational sessions, more than two-thirds after the sessions reported they would. Three cases of chromoendoscopy were done in the 22 months prior to the sessions, compared to 16 cases in the 22 months following. CONCLUSION: In-person, small group education of endoscopy ancillary staff on chromoendoscopy decreased their unfamiliarity and discomfort with assisting physicians in chromoendoscopy procedures. The number of chromoendoscopies done at our institution was also higher post-intervention.

Colorectal cancer surveillance in inflammatory bowel disease: Practice guidelines and recent developments

Patients with long-standing inflammatory bowel disease (IBD) involving at least 1/3 of the colon are at increased risk for colorectal cancer (CRC). Advancements in CRC screening and surveillance and improved treatment of IBD has reduced CRC incidence in patients with ulcerative colitis and Crohn’s colitis. Most cases of CRC are thought to arise from dysplasia, and recent evidence suggests that the majority of dysplastic lesions in patients with IBD are visible, in part thanks to advancements in high definition colonoscopy and chromoendoscopy. Recent practice guidelines have supported the use of chromoendoscopy with targeted biopsies of visible lesions rather than traditional random biopsies. Endoscopists are encouraged to endoscopically resect visible dysplasia and only recommend surgery when a complete resection is not possible. New technologies such as virtual chromoendoscopy are emerging as potential tools in CRC screening. Patients with IBD at increased risk for developing CRC should undergo surveillance colonoscopy using new approaches and techniques.

Mo1703 CORRELATION BETWEEN ENDOSCOPIC AND HISTOLOGIC FINDINGS DETECTED DURING HIGH DEFINITION AND VIRTUAL ELECTRONIC CHROMOENDOSCOPY ON INFLAMMATORY BOWEL DISEASE: RESULTS FROM A LATIN-AMERICAN REFERRAL CENTER

Patients with longstanding inflammatory bowel disease (IBD) (ulcerative colitis [UC] or colonic Crohn’s disease [CD]) have an increased risk of colorectal cancer (CRC). International consensuses recommend description of visible lesions according to the Paris classification, although little is known about the correlation between each type of lesion and the risk of dysplasia.

Even non-experts identify non-dysplastic lesions in inflammatory bowel disease via chromoendoscopy: results of a screening program in real-life.

Background and study aims Chromoendoscopy with targeted biopsy is the technique of choice for colorectal cancer screening in longstanding inflammatory bowel disease. We aimed to analyze results of a chromoendoscopy screening program and to assess the possibility of identifying low-risk dysplastic lesions by their endoscopic appearance in order to avoid histological analysis. Materials and methods We retrospectively reviewed chromoendoscopies performed between February 2011 and June 2017 in seven Spanish hospitals in a standardized fashion. We analyzed the findings and the diagnostic yield of the Kudo pit pattern for predicting dysplasia. Results A total of 709 chromoendoscopies (569 patients) were reviewed. Median duration of disease was 16.7 years (SD 8.1); 80.4 % had ulcerative colitis. A total of 2025 lesions (3.56 lesions per patient) were found; two hundred and thirty-two lesions were neoplastic (11.5 %) (223 were LGD (96.1 %), eight were HGD (3.4 %), and one was colorectal cancer (0.5 %). The correlation between dysplasia and Kudo pit patterns predictors of dysplasia (≥ III) was low, with an area under the curve of 0.649. Kudo I and II lesions were correctly identified with a high negative predictive value (92 %), even by non-experts. Endoscopic activity, Paris 0-Is classification, and right colon localization were risk factors for dysplasia detection, while rectum or sigmoid localization were protective against dysplasia. Conclusions Chromoendoscopy in the real-life setting detected 11 % of dysplastic lesions with a low correlation with Kudo pit pattern. A high negative predictive value would prevent Kudo I and, probably, Kudo II biopsies in the left colon, reducing procedure time and avoiding complications.

New developments in ulcerative colitis: latest evidence on management, treatment, and maintenance.

Ulcerative colitis (UC) is a chronic idiopathic inflammatory disorder that involves any part of the colon starting in the rectum in a continuous fashion presenting typically with symptoms such as bloody diarrhea, abdominal pain, and rectal urgency. UC is diagnosed based on clinical presentation and endoscopic evidence of inflammation in the colon starting in the rectum and extending proximally in the colon. The clinical presentation of the disease usually dictates the choice of pharmacologic therapy, where the goal is to first induce remission and then maintain a corticosteroid-free remission. There are multiple classes of drugs that are available and are used based on the clinical severity of the disease. For mild-to-moderate disease, oral or rectal formulations of 5-aminosalicylic acid are used. In moderate-to-severe UC, corticosteroids are usually used in induction of remission with or without another class of medications such as thiopurines or biologics including anti-tumor necrosis factor, anti-integrins, or Janus kinase inhibitors for maintenance of remission. Up to 15% of the patients may require surgery as they fail to respond to medications and have risk of developing dysplasia secondary to longstanding colitis.

Endoscopic Submucosal Dissection for Colitis-Associated Dysplasia.

Dysplasia is a precancerous lesion of colorectal cancer in patients with long-standing inflammatory bowel diseases (IBDs), such as ulcerative colitis and Crohn’s disease. Recent guidelines suggest endoscopic resection as a key modality for the treatment of endoscopically resectable dysplasia in patients with colitis. Endoscopic submucosal dissection (ESD) has been suggested as one of the therapeutic options for dysplasia that is potentially resectable but not suitable for the conventional endoscopic mucosal resection technique. Several recent studies supported the feasibility of ESD for the treatment of colitis-associated dysplasia in terms of the en bloc and complete resection rates and the risk of procedure-related complications. However, these studies were performed exclusively in expert centers. Moreover, the local and metachronous recurrence rates were relatively high, and long-term outcome data are still lacking. Endoscopists should be highly skilled in colorectal ESD and have an intensive understanding of not only the lesions but also the conditions of patients with IBDs. Therefore, the decision to perform ESD for colitis-associated dysplasia should be made scrupulously after careful discussion with patients, in collaboration with a multidisciplinary IBD team including physicians, surgeons, and pathologists specialized in IBDs.

P278 Comparison of long-standing paediatric-onset and adult-onset inflammatory bowel disease

P278 Comparison of long-standing paediatric-onset and adult-onset inflammatory bowel disease

Characterization of γδ T Cells in Intestinal Mucosa From Patients With Early-Onset or Long-Standing Inflammatory Bowel Disease and Their Correlation With Clinical Status.

Inflammatory bowel disease [IBD] is a complex chronic inflammatory disease of the human gut with no clear aetiology. Traditionally, dysregulated adaptive immune responses play an important role even though accumulating evidence suggests a role also for innate immunity. Because of the well-known plasticity of γδ T cells, we investigated their percentage occurrence, phenotypic features and effector functions in the intestinal mucosa of early-onset and long-standing IBD patients, as compared to healthy subjects. Fresh biopsies from 30 Crohn's disease and ulcerative colitis patients were obtained and digested, and cells were analysed by flow cytometry. We found a reduced frequency of Vδ1 T cells in tissue from early and late IBD patients (2.24% and 1.95%, respectively, vs 5.44% in healthy tissue) but an increased frequency of Vδ2 T cells in the gut of late IBD patients (3.19% in late patients vs 1.5% in early patients and 1.65% in healthy tissue). The infiltrating Vδ2 T cells had predominant effector memory and terminally differentiated phenotypes and produced elevated levels of tumour necrosis factor-α [TNF-α] and interleukin-17 [IL-17]. The frequency of tissue Vδ2 T cells correlated with the extent of the inflammatory response and the severity of IBD. Our study shows that tissue Vδ1 T cells are decreased in IBD patients while Vδ2 T cells are increased in the gut of IBD patients and contribute to TNF-α production. Moreover, we identify an as yet unappreciated role of Vδ2 T cells in IL-17 production in the gut of long-standing IBD patients, suggesting that they also participate in the chronic inflammatory process.

Endoscopy in inflammatory bowel disease: from guidelines to real life.

Endoscopy has a central role in the management of inflammatory bowel disease (IBD), providing crucial data for diagnostic and therapeutic decisions, treating disease-related complications, and assisting in the early detection of dysplasia and prevention of colorectal cancer in the setting of IBD. Treatment targets have significantly shifted in IBD, focusing on achieving mucosal healing, a more meaningful endpoint than clinical remission. With the emergence of novel therapies, we aim to alter the course of the disease and prevent irreversible damage to the bowel. To that end, obtaining reliable and reproducible assessments of endoscopic disease activity has become an issue of great importance. Although several guidelines include recommendations regarding endoscopic surveillance in patients with long-standing IBD, there is an open debate regarding the best examination method and the appropriate follow-up intervals. Another important issue is whether surveillance guidelines are actually implemented in real-life practice and what is the preferred surveillance method among endoscopists. Significant changes have occurred in the endoscopic world with the development of new diagnostic and therapeutic modalities and their incorporation in everyday practice. We aimed to assess the real-life application of guideline recommendations regarding endoscopy in IBD patients and to review newly emerged data which might impact these recommendations in the near future.

High frequency of secondary, but not primary ocular manifestations of inflammatory bowel disease in patients treated at a tertiary care center.

Ocular manifestations of inflammatory bowel disease (IBD) are relevant complications of IBD. Only a few prospective studies are available on the characteristics of these manifestations. The aim of this study was to characterize the frequency of eye disease in patients with IBD, including primary and secondary ocular manifestations of IBD, and to identify patients who may need specialized ophthalmologic care. In a prospective observational study, patients with IBD were examined for ocular symptoms in comparison with control participants without IBD. All patients with IBD underwent a thorough ophthalmologic examination (including slit-lamp, tonometry, tear breakup time, Schirmer's test, and coherence tomography). The results were analyzed with respect to sociodemographic and disease-related characteristics. A total of 61 patients (33 women, 39 Crohn's disease, 22 ulcerative colitis, age 43.3±12.9 years, disease duration 12.4±9.3 years) were included. Ophthalmologic symptoms were reported by 53 patients (86.9%, most frequently deterioration of vision 42.6%, foreign body sensation 36.1%) compared with 60.6% in healthy controls (P=0.001). A clinically relevant, previously undetected ophthalmologic diagnosis was identified in 56 patients (91.8% - dry eye syndrome 75.4%, cataract 67.2%, blepharitis 45.9%, fundus hypertonicus 14.8%, other 16.4%). Although primary ocular manifestations of IBD are rare in intensively treated patients, the high frequency of unrecognized secondary manifestations should give reason to refer especially patients with longstanding or complicated IBD to an eye specialist - irrespective of ocular symptoms.

Consecutive negative findings on colonoscopy during surveillance predict a low risk of advanced neoplasia in patients with inflammatory bowel disease with long-standing colitis: results of a 15-year multicentre, multinational cohort study

ObjectivesSurveillance colonoscopy is thought to prevent colorectal cancer (CRC) in patients with long-standing colonic IBD, but data regarding the frequency of surveillance and the findings thereof are lacking. Our aim...

604 - Consecutive Negative Findings on Colonoscopy During Surveillance Predict a Low Risk of Advanced Neoplasia in Patients with Longstanding Colitis: Results of a 15-Year Multicenter, Multinational Cohort Study

604 - Consecutive Negative Findings on Colonoscopy During Surveillance Predict a Low Risk of Advanced Neoplasia in Patients with Longstanding Colitis: Results of a 15-Year Multicenter, Multinational Cohort Study

Multi-target stool DNA test in the surveillance of inflammatory bowel disease: a cross-sectional cohort study

Background and aim: Colonoscopic surveillance is recommended in patients with longstanding inflammatory bowel disease (IBD) as they are at increased risk of colorectal cancer (CRC). Non-invasive surveillance may improve compliance and access. Multi-target stool DNA (MT-sDNA) has been validated for screening of sporadic CRC but has not been assessed in IBD. Our aim was to assess the performance of a MT-sDNA test in a real-life surveillance setting of patients with longstanding IBD.Material and methods: A total of 192 IBD patients enrolled from two prospective cohorts submitted an EDTA buffered stool sample and underwent chromo- or white light colonoscopy. Stools were assayed for methylated BMP3 & NDRG4, mutant KRAS and β-actin by a laboratory blinded to clinical data.Results: The multitarget-sDNA panel was positive in 2/2 CRC and 5/15 low-grade dysplasia (LGD) < 1 cm in diameter. Sensitivities were 100% (95% CI 16–100%) for CRC and 33% (95% CI 13–61%) for LGD lesions <1 cm, with specificities of 87% (95% CI 81–91%) and 93% (95% CI 88–96%), respectively. The estimated number of patients needed to screen to detect a single CRC was 96 (95% CI 93–99%) and was 28 (95% CI 22–34%) to detect any colorectal neoplasia (CRN).Conclusion: The MT-sDNA panel detected CRC in IBD. Sensitivity for sub-centimeter colorectal neoplasms in IBD patients appears similar to that observed in the general population. The test may be a valuable tool for detection of malignancy during structured surveillance of long-term IBD in a first line hospital setting.

A Randomized Trial Comparing High Definition Colonoscopy Alone With High Definition Dye Spraying and Electronic Virtual Chromoendoscopy for Detection of Colonic Neoplastic Lesions During IBD Surveillance Colonoscopy.

Dye spraying chromoendoscopy (DCE) is recommended for the detection of colonic neoplastic lesions in inflammatory bowel disease (IBD). The majority of neoplastic lesions are visible endoscopically and therefore targeted biopsies are appropriate for surveillance colonoscopy. To compare three different techniques for surveillance colonoscopy to detect colonic neoplastic lesions in IBD patients: high definition (HD), (DCE), or virtual chromoendoscopy (VCE) using iSCAN image enhanced colonoscopy. A randomized non-inferiority trial was conducted to determine the detection rates of neoplastic lesions in IBD patients with longstanding colitis. Patients with inactive disease were enrolled into three arms of the study. Endoscopic neoplastic lesions were classified by the Paris classification and Kudo pit pattern, then histologically classified by the Vienna classification. A total of 270 patients (55% men; age range 20-77 years, median age 49 years) were assessed by HD (n=90), VCE (n=90), or DCE (n=90). Neoplastic lesion detection rates in the VCE arm was non-inferior to the DCE arm. HD was non-inferior to either DCE or VCE for detection of all neoplastic lesions. In the lesions detected, location at right colon and the Kudo pit pattern were predictive of neoplastic lesions (OR 6.52 (1.98-22.5 and OR 21.50 (8.65-60.10), respectively). In this randomized trial, VCE or HD-WLE is not inferior to dye spraying colonoscopy for detection of colonic neoplastic lesions during surveillance colonoscopy. In fact, in this study HD-WLE alone was sufficient for detection of dysplasia, adenocarcinoma or all neoplastic lesions.

Current health status and medical therapy of patients with pediatric-onset inflammatory bowel disease: a survey-based analysis on 1280 patients aged 10-25 years focusing on differences by age of onset.

There are inconsistent reports on age-related differences in inflammatory bowel disease (IBD). On the basis of patient information, we describe the clinical presentation and therapy in relation to age at diagnosis in longstanding pediatric IBD. Two surveys were conducted in children and young adults (age: 10-25 years) by pretested postal questionnaires. The main analyses are descriptive, showing proportions and distributions per grouped age of diagnosis. Exploratory logistic regression was used to identify sociodemographic and disease-related factors associated with prognosis. Recent disease course, use of biological therapy, and resecting surgery were chosen as indicators of disease severity. Patients with a diagnosis in infancy (<2 years of age) are presented as a case series. Information of 1280 cases was available [804 Crohn's disease (CD), 382 ulcerative colitis (UC), 94 IBD not specified] (response: 44.6 and 49.6%). Stable remission during the preceding year was reported by 675 (56.7%) patients; 825 (60.9%) patients reported feeling currenty well. Anti-tumor necrosis factor therapy was reported by 33% of CD patients and 9.3% of UC patients, immunomodulation in 82.1 and 63.2%, and corticosteroids by 78.4 and 76.1%, respectively (ever use). Age at diagnosis was not associated with indicators of severe disease. Diagnosis in infancy was reported by 37 patients. Our data do not support age at diagnosis-related differences in prognosis in pediatric-onset IBD.

Colitis-associated colorectal cancer in patients with inflammatory bowel disease

Colitis-associated colorectal cancer (CACRC) is a major concern in patients with long-standing inflammatory bowel disease (IBD). CACRC can develop under the influence of several risk factors including longer duration and disease extent and shows clinical and molecular features different from those of sporadic CRC. Several academic societies have recommended surveillance guidelines for CACRC that develops in IBD patients. Patients are stratified according to risk for CRC and differentiated by surveillance colonoscopy and management. In the current article, we review CACRC in IBD patients generally and introduce future directions.

CD169 Expressing Macrophage, a Key Subset in Mesenteric Lymph Nodes Promotes Mucosal Inflammation in Dextran Sulfate Sodium-Induced Colitis.

Inflammatory bowel disease (IBD) including Crohn’s disease (CD) and ulcerative colitis is a relapsing-remitting illness. Patients with long-standing extensive colitis are easy to develop colorectal cancer (CRC). The increasing incidence of IBD and a substantial increase in the risk of CRC make the necessity to pay more attention on the regulation of inflammation especially by specific macrophages subset. The present study reported that a key subset of sinus macrophage expressing CD169 in mesenteric lymph nodes (mLNs) played an essential role in promoting mucosal inflammation. The results revealed that the subset expressing CD169 in mLNs increased significantly during the dextran sulfate sodium (DSS)-induced colitis. The colitic symptoms were alleviated in CD169-diphtheria toxin receptor (DTR) mice at least partially due to the deletion of CD169+ macrophages in mLNs. In addition, the levels of inflammatory cytokines as well as the percentage of Th17 cells in mLNs from CD169-DTR mice were much lower than those from WT mice with DSS-induced colitis. Further experiment in vitro demonstrated that the supernatant from whole cells of mLNs or colon tissues could promote the production of inflammatory factors by mLN cells or colon tissues from CD169-DTR mice. These results could be explained by the cell sorting result that CD11b+CD169+ macrophages expressed higher level of inflammatory factors directly. All these data indicated that CD169+ sinus macrophage in mLNs played an essential role on regulating mucosal inflammation.

Radiation-associated colon cancer: A case report.

Radiation-associated colon cancer is a rare clinical entity. We herein describe the case of a patient with radiation-associated colon cancer who had undergone low anterior resection for rectal cancer following preoperative radiotherapy. Certain characteristics of radiation-associated colon cancer are highlighted. The patient was a 48-year-old man who had undergone low anterior resection for rectal cancer following preoperative radiotherapy at a total dose of 50 Gy, at the age of 29 years. When the patient presented at the University of Tokyo Hospital, 19 years after the surgery, he complained of severe anal pain and frequent defecation. Colonoscopy revealed two flat tumors in the sigmoid colon, located 10 cm to the oral side of the anastomosis site, which were diagnosed as well-differentiated adenocarcinomas. In addition, colonoscopy identified five flat polyps near the tumors, which were resected endoscopically. Computed tomography and magnetic resonance imaging revealed a mass in the sigmoid colon and no evidence of distant metastasis. Laparoscopic-assisted intersphincteric resection of the rectum and sigmoid colon with diverting ileostomy was performed. There were no specific postoperative complications and the patient was discharged from the hospital on the 20th postoperative day. On pathological examination, the resected rectum and sigmoid colon contained two separate tumors and six flat polyps. The two tumors were diagnosed as well-differentiated adenocarcinomas with invasion of the subserosa and submucosa, respectively. A total of 17 regional lymph nodes without metastasis were resected. The six flat polyps were diagnosed as tubular adenomas. We herein present a case of a radiation-associated colon cancer in a patient who had undergone low anterior resection for rectal cancer following preoperative radiotherapy 19 years prior. Colonoscopic surveillance of radiation-associated colon cancer may be indicated for rectal cancer patients treated with preoperative radiotherapy, particularly for those with long-standing radiation-induced colitis.

Chronic inflammation confers to the metabolic reprogramming associated with tumorigenesis of colorectal cancer

ABSTRACTIt's well known that microenvironment inflammatory signals could promote cancer development and progression. In colorectal cancer (CRC), chronic inflammation is a major driving mechanism for the development of CRC in patients having long-standing inflammatory bowel disease (IBD). Though it has been addressed that cancer cells ferment much of their glucose supply into lactate regardless of the presence of oxygen, it is unclear whether cell metabolism has been reprogramed during the process from IBD to CRC. Herein, with dextran sulfate sodium (DSS)-induced mouse colitis model, we found that inflammation upregulated key glycolytic enzymes expression via activation of STAT3/c-Myc signaling pathway. Interestingly, during the whole phase of chronic inflammation, the key metabolic enzymes demonstrated increased expression constantly, indicating the metabolic reprogramming was induced by long-term inflammatory signal. Moreover, either the inhibition of STAT3 signaling or c-Myc activity could block the glycolytic enzymes expression induced by interleukin 6 (IL-6). Thus, we presented the view that inflammation could induce the metabolic reprogramming and promote the progression from chronic colitis to colorectal cancer.