Presence Of Low-grade Dysplasia Research Articles

A238 BEST APPROACH TO SURVEILLANCE COLONOSCOPY FOR COLORECTAL CANCER IN PATIENTS WITH PRIMARY SCLEROSING CHOLANGITIS AND INFLAMMATORY BOWEL DISEASE

Abstract Background Primary sclerosing cholangitis (PSC) is a chronic, cholestatic liver disease and it has been recognized as a risk factor for hepatobiliary and colorectal carcinoma (CRC). Inflammatory bowel disease (IBD) is associated with a 6-fold increased risk of CRC as compared to the general population but with co-existing PSC, this risk rises to 30-fold and hence CRC surveillance is critical in these patients. Aims We performed a systematic review of the literature on surveillance colonoscopy for CRC in patients with PSC-IBD, with the aim of identifying the most effective approach. Methods The protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO) under ID 472215. The search was executed in the databases Medline, EMBASE, Cochrane, Web of science, Scopus and Google Scholar databases from 1947 to May 2023. Observational or randomized controlled studies were included if patients had PSC-IBD (paediatric or adult) undergoing surveillance colonoscopy. There was no restriction for language. We used a modified version of the Newcastle–Ottawa Quality Assessment Scale to assess the risk of bias. Neoplasia was defined as the presence of low-grade dysplasia, high grade dysplasia or colorectal carcinoma. Results Amongst 2900 studies identified, 7 studies met the inclusion criteria with a total number of 379 PSC-IBD patients and 1884 IBD patients (all adult). The median frequency of surveillance colonoscopy was every 0-2 years. The most common endoscopic presentation of dysplasia in PSC-IBD was a normal appearing mucosa or subtle abnormalities such as mild inflammation. Three studies performed random and targeted biopsies and only one study did quadruple random biopsy (every 10 cm of the colon). Two studies used chromoendoscopy and high-definition endoscopy whereas another two studies used white light colonoscopy. Studies varied in terms of the number of biopsies taken and timing for the frequency and initiation of surveillance. Outcomes included intensive surveillance, resection, and colectomy. Our meta-analysis of 2 studies that reported the prevalence of colorectal dysplasia in PSC-IBD patients revealed a pooled prevalence of 21% (95% CI 1.4%-28%, I2 = 0%, Pampersand:003C0.597, shown in Figure 1) Conclusions Colorectal dysplasia is prevalent in patients with PSC-IBD and is associated with worse disease outcomes. As a result, PSC-IBD patients should be screened annually from the diagnosis of PSC. However, there is variation in practice, and no clear consensus on the best approach to perform screening colonoscopy in this population. Literature comparing various approaches is very sparse. Additional high-quality studies on this subject are needed to guide practice, particularly in paediatrics where data are non-existent. Figure 1: Forest plot for meta-analysis of CRC dysplasia prevalence in PSC-IBD Funding Agencies None

Study of Helicobacter pylori infection in patients with chronic atrophic gastritis and its relationship with lifestyle habits and dietary nutrient intake: A retrospective analysis.

To explore Helicobacter pylori (Hp) infection status and its relationship with lifestyle habits and dietary factors in patients with chronic atrophic gastritis. Six hundred thirty-eight patients with chronic atrophic gastritis, who were admitted to our hospital from March 2021 to April 2023, were selected for the study. All patients underwent the 13C urea breath test. The relationship between the detection rate of Hp infection and the clinical characteristics, lifestyle habits, and dietary factors of the patients was analyzed. Among the 638 patients with chronic atrophic gastritis, 531 patients were tested positive for Hp infection, the positive rate for Hp infection was approximately 83.23%. Analyzing the clinical characteristics of the patients, it was found that age, family history of gastric cancer, degree of chronic inflammation, degree of glandular atrophy, presence of low-grade dysplasia, and intestinal metaplasia all have an impact on the positive detection rate of patients (P < .05). Analyzing the patients' lifestyle habits, it was found that BMI, smoking history, alcohol consumption, preference for spicy food, dining location, consumption of pickled foods, frequent consumption of grilled/barbecued foods, preference for strong tea, consumption of sweets, and work-related stress had an impact on the positive rate of Hp infection in patients (P < .05). The discovery showed that the levels of total protein, albumin, hemoglobin, cholesterol, and the intake of livestock and poultry meat, seafood, dairy products, vegetables, fruits, and fats have an impact on the positivity rate of Hp infection in patients (P < .05). A multiple logistic regression analysis was performed, and it was found that patients' age, family history of gastric cancer, degree of chronic inflammation, degree of glandular atrophy, presence of low-grade dysplasia, presence of wasting or obesity, history of alcohol consumption, preference for spicy food, dining location, frequent consumption of strong tea, high work pressure, high intake of fish and seafood, low intake of dairy products, low intake of vegetables, low intake of fruits, and low intake of fats all had an impact on the occurrence of Hp infection in patients (P < .05). There is a certain correlation between patients' lifestyle habits, dietary factors, and clinical characteristics with the occurrence of Hp infection. These factors can assist in the prevention of Hp infection.

Novel Biomarkers for Inflammatory Bowel Disease and Colorectal Cancer: An Interplay between Metabolic Dysregulation and Excessive Inflammation.

Persistent inflammation can trigger altered epigenetic, inflammatory, and bioenergetic states. Inflammatory bowel disease (IBD) is an idiopathic disease characterized by chronic inflammation of the gastrointestinal tract, with evidence of subsequent metabolic syndrome disorder. Studies have demonstrated that as many as 42% of patients with ulcerative colitis (UC) who are found to have high-grade dysplasia, either already had colorectal cancer (CRC) or develop it within a short time. The presence of low-grade dysplasia is also predictive of CRC. Many signaling pathways are shared among IBD and CRC, including cell survival, cell proliferation, angiogenesis, and inflammatory signaling pathways. Current IBD therapeutics target a small subset of molecular drivers of IBD, with many focused on the inflammatory aspect of the pathways. Thus, there is a great need to identify biomarkers of both IBD and CRC, that can be predictive of therapeutic efficacy, disease severity, and predisposition to CRC. In this study, we explored the changes in biomarkers specific for inflammatory, metabolic, and proliferative pathways, to help determine the relevance to both IBD and CRC. Our analysis demonstrated, for the first time in IBD, the loss of the tumor suppressor protein Ras associated family protein 1A (RASSF1A), via epigenetic changes, the hyperactivation of the obligate kinase of the NOD2 pathogen recognition receptor (receptor interacting protein kinase 2 [RIPK2]), the loss of activation of the metabolic kinase, AMP activated protein kinase (AMPKα1), and, lastly, the activation of the transcription factor and kinase Yes associated protein (YAP) kinase, that is involved in proliferation of cells. The expression and activation status of these four elements are mirrored in IBD, CRC, and IBD-CRC patients and, importantly, in matched blood and biopsy samples. The latter would suggest that biomarker analysis can be performed non-invasively, to understand IBD and CRC, without the need for invasive and costly endoscopic analysis. This study, for the first time, illustrates the need to understand IBD or CRC beyond an inflammatory perspective and the value of therapeutics directed to reset altered proliferative and metabolic states within the colon. The use of such therapeutics may truly drive patients into remission.

A personalized and dynamic risk estimation model: The new paradigm in Barrett's esophagus surveillance.

ObjectivesThe current surveillance strategy in Barrett’s esophagus (BE) uses only histological findings of the last endoscopy to assess neoplastic progression risk. As predictor values vary across endoscopies, single measurements may not be an accurate reflection. Our aim was to explore the value of using longitudinal evolutions (i.e. successive measurements) of histological findings (low-grade dysplasia (LGD)) and immunohistochemical biomarkers (p53 and SOX2) by investigating the association with Barrett’s progression.MethodsIn this proof-of-principle study of a longitudinal dynamic risk estimation model with a multicenter cohort design, 631 BE patients from 15 Dutch hospitals who were under surveillance were included. Longitudinal dynamic values of LGD, p53, and SOX2 were included in a multivariate joint model to estimate the risk of high-grade dysplasia (HGD)/esophageal adenocarcinoma (EAC).ResultsLongitudinal evolutions of aberrant expression of p53 (HR 1.26, p<0.01) and SOX2 (HR 1.43, p<0.01) were associated with an increased HGD/EAC risk. We also found weak evidence of an association with the longitudinal evolution of the presence of LGD (HR 1.02, p = 0.12). The performance of the model was good (AUC 0.80–0.88). Using this model, for each future BE patient the probability of aberrant expression of biomarkers based on multiple longitudinal observations can be estimated. This probability is translated in progression risk, expressed as HR.ConclusionsThis study provides solid ground to further explore a paradigm shift from currently recommended fixed intervals towards personalized surveillance, in which tailored risk estimations and corresponding surveillance intervals can be updated at every FU endoscopy for individual BE patients.

Long-term results of an endoscopic screening program for superficial esophageal cancer in patients with head and neck squamous cell carcinoma.

Background and study aims Patients with head and neck squamous cell carcinoma (HNSCC) are at risk of a second primary tumor in the gastrointestinal tract, most commonly in the esophagus. Screening these patients for esophageal carcinoma may help detect asymptomatic dysplasia and early cancer, thus allowing curative treatment and more prolonged survival, but the impact of endoscopic screening remains uncertain. Here we aimed to describe the long-term results of an esophageal SCC screening program in patients with head and neck cancer in terms of prevalence, associated risk factors, and survival. Patients and methods We performed an observational study of a prospectively collected database including patients with HNSCC who had undergone high-definition endoscopy with chromoscopy between 2010 and 2018 at a Brazilian tertiary academic center. Results The study included 1,888 patients. The esophageal SCC prevalence was 7.9 %, with the majority (77.8 %) being superficial lesions. Significant risk factors for esophageal high-grade dysplasia (HGD) and invasive cancer included tumors of the oral cavity and oropharynx and the presence of low-grade dysplasia (LGD). Overall survival (OS) was significantly shorter among patients in whom esophageal cancer was diagnosed at an advanced stage ( P < .001). OS did not significantly differ between patients with HGD and early esophageal cancer versus those without esophageal cancer ( P = .210) Conclusions Endoscopic screening for superficial esophageal neoplasia in patients with HNSCC improves esophageal cancer detection. Screening could potentially benefit patients with primary cancer located at the oropharynx or oral cavity. In addition, the detection of esophageal LGD indicates a need for endoscopic surveillance.

Length of Barrett\u2019s esophagus in the presence of low-grade dysplasia, high-grade dysplasia, and adenocarcinoma

IntroductionThe identification and follow-up of ultra-short Barrett’s esophagus (BE) is controversial. BE surveillance guidelines emphasize mainly on long-segment BE. However, in practice a substantial proportion of esophageal adenocarcinoma (EAC) are found close to the gastro-esophageal junction (GEJ). Our study aims to chart the length of BE when low-grade dysplasia (LGD), high-grade dysplasia (HGD) and EAC arise in BE.MethodsEndoscopic findings from all cases with a diagnosis of LGD and HGD in BE between June 2014 and June 2019, and 100 consecutive cases of EAC diagnosed between June 2018 and August 2019, were reviewed. Additionally, 438 consecutive gastroscopies were reviewed to identify 100 cases of non-dysplastic BE.Results99 cases of LGD and 61 cases of HGD were reviewed. LGD and HGD when diagnosed, was located in BE ≤ 1 cm in 20% and 18% cases, respectively. LGD and HGD when diagnosed, was located in BE ≤ 3 cm in 48.5% and 40.9% cases, respectively. LGD and HGD when diagnosed in BE ≤ 3 cm was found at index endoscopy in 67% and 42% cases, respectively. Of the 100 cases of EAC, only 23 had concurrent visible BE, with BE higher than the level of EAC in seven. EAC when found, had its proximal extent ≤ 1 cm from GEJ in 22% and ≤ 3 cm from GEJ in 40% cases. Of the 100 non-dysplastic BE, 53% were ≤ 1 cm and 78% were ≤ 3 cm long.ConclusionAlmost 20% of all dysplasia in BE occurs in BE < 1 cm. Over 40% occurs in BE < 3 cm. Similarly, 20% of EAC occurs within 1 cm of GEJ and 40% occur within 3 cm. A majority of dysplasia diagnosed within 3 cm of the GEJ is found on index endoscopy. We propose that all lengths of columnar lined epithelium above the GEJ are recognized as BE and subjected to a thorough biopsy protocol.

Barrett Esophagus Length, Nodularity, and Low-grade Dysplasia are Predictive of Progression to Esophageal Adenocarcinoma.

To investigate factors predictive of progression from nondysplastic Barrett esophagus (NDBE) or low-grade dysplasia (LGD) to high-grade dysplasia (HGD) or esophageal adenocarcinoma (EAC) using a large, prospective cohort of patients, wherein all esophageal biopsies undergo expert gastrointestinal pathologist review. Efficacy and cost-effectiveness of endoscopic surveillance to detect incident EAC in the setting of Barrett esophagus (BE), particularly in NDBE patients, is questioned. Previous studies have reported factors predictive of progression to EAC to guide surveillance intervals, but their strength is limited by small sample size and absence of expert gastrointestinal pathologist involvement in esophageal biopsy review. NDBE and LGD subjects were identified from a prospective registry in a tertiary care center. "Progressors" were BE subjects who developed HGD/EAC>12 months after the initial NDBE or LGD diagnosis. Cox proportional hazards model were used to identify predictors of progression. In total, 318 with NDBE and 301 with BE-LGD (mean age, 62.6 y, 85% male) were included. The mean follow-up was 5.3 years. The 7 NDBE and 21 LGD subjects progressed to HGD/EAC. BE length [hazards ratio (HR), 1.16; 95% confidence interval (CI), 1.03-1.29], presence of nodularity (HR, 4.98; 95% CI, 1.80-11.7), and baseline LGD (HR, 2.57; 95% CI, 1.13-6.57) were significant predictors of progression on multivariate analysis. In this well-defined cohort of NDBE and BE-LGD subjects, BE length, presence of LGD, and nodularity were independent predictors of progression to HGD/EAC. These factors may aid in identifying high-risk patients who may benefit from closer endoscopic surveillance/therapy.

External validation of a model to determine risk of progression of Barrett's oesophagus to neoplasia.

A risk prediction model containing sex, smoking history, Barrett's oesophagus length and presence of low-grade dysplasia was found to identify individuals at a higher risk of progression to oesophageal adenocarcinoma or high-grade dysplasia. To externally validate the model predicting risk of progression from Barrett's oesophagus to neoplasia and assess the predictive utility of additional factors. We conducted a retrospective cohort study among individuals from the population-based Northern Ireland Barrett's register with a histologically confirmed diagnosis of Barrett's oesophagus (with intestinal metaplasia) between 1993 and 2005. The association between a points based model and risk of progression to high-grade dysplasia or oesophageal adenocarcinoma until 2010 was assessed using Cox Proportional Hazards model. Model performance was assessed using area under the receiver operating characteristics curves (AUROC), sensitivity and specificity. We identified 1198 individuals with Barrett's oesophagus of whom 54 progressed. The model discriminated reasonably well between progressors and nonprogressors, with an AUROC of 0.70 (95% CI 0.63-0.78). When categorised into low, intermediate and high risk groups, the AUROC was 0.68 (95% CI 0.61-0.74). Compared to using data on dysplasia and segment length for risk stratification, the model resulted in a net reclassification improvement of 20.9%. This external validation provides further evidence that a model based on sex, smoking, Barrett's segment length and baseline low-grade dysplasia may help to risk stratify patients after an initial diagnosis of Barrett's oesophagus. The model also performed better than the use of low-grade dysplasia status alone for risk-stratification.

Increasing prevalence of high-grade dysplasia and adenocarcinoma on index endoscopy in Barrett’s esophagus over the past 2 decades：data from a multicenter U.S. Consortium

Introduction Data on time trends of dysplasia and esophageal adenocarcinoma (EAC) in Barrett’s esophagus (BE) during the index endoscopy (ie, prevalent cases) are limited. Our aim was to determine the prevalence patterns of BE-associated dysplasia on index endoscopy over the past 25 years. Methods The Barrett’s Esophagus Study is a multicenter outcome project of a large cohort of patients with BE. Proportions of patients with index endoscopy findings of no dysplasia (NDBE), low-grade dysplasia (LGD), high-grade dysplasia (HGD), and EAC were extracted per year of index endoscopy, and 5-yearly patient cohorts were tabulated over years 1990 to 2010+ (2010-current). Prevalent dysplasia and endoscopic findings were trended over the past 25 years using percentage dysplasia (LGD, HGD, EAC, and HGD/EAC) to assess changes in detection of BE-associated dysplasia over the last 25 years. Statistical analysis was done using SAS version 9.4 software (SAS, Cary, NC). Results A total of 3643 patients were included in the analysis with index endoscopy showing NDBE in 2513 (70.1%), LGD in 412 (11.5%), HGD in 193 (5.4%), and EAC in 181 (5.1%). Over time, there was an increase in the mean age of patients with BE (51.7 ± 29 years vs 62.6 ± 11.3 years) and the proportion of males (84% vs 92.6%) diagnosed with BE but a decrease in the mean BE length (4.4±4.3 cm vs 2.9±3.0 cm) as time progressed (1990-1994 to 2010-2016 time periods). The presence of LGD on index endoscopy remained stable over 1990 to 2016. However, a significant increase (148% in HGD and 112% in EAC) in the diagnosis of HGD, EAC, and HGD/EAC was noted on index endoscopy over the last 25 years (P Conclusion Our results suggest that the prevalence of HGD and EAC has significantly increased over the past 25 years despite a decrease in BE length during the same period. This increase parallels an increase in the detection of visible lesions, suggesting that a careful examination at the index examination is crucial.

Increasing prevalence of high-grade dysplasia and adenocarcinoma on index endoscopy in Barrett’s esophagus over the past 2 decades: data from a multicenter U.S. consortium

Data on time trends of dysplasia and esophageal adenocarcinoma (EAC) in Barrett's esophagus (BE) during the index endoscopy (ie, prevalent cases) are limited. Our aim was to determine the prevalence patterns of BE-associated dysplasia on index endoscopy over the past 25 years. The Barrett's Esophagus Study is a multicenter outcome project of a large cohort of patients with BE. Proportions of patients with index endoscopy findings of no dysplasia (NDBE), low-grade dysplasia (LGD), high-grade dysplasia (HGD), and EAC were extracted per year of index endoscopy, and 5-yearly patient cohorts were tabulated over years 1990 to 2010+ (2010-current). Prevalent dysplasia and endoscopic findings were trended over the past 25 years using percentage dysplasia (LGD, HGD, EAC, and HGD/EAC) to assess changes in detection of BE-associated dysplasia over the last 25 years. Statistical analysis was done using SAS version 9.4 software (SAS, Cary, NC). A total of 3643 patients were included in the analysis with index endoscopy showing NDBE in 2513 (70.1%), LGD in 412 (11.5%), HGD in 193 (5.4%), and EAC in 181 (5.1%). Over time, there was an increase in the mean age of patients with BE (51.7 ± 29 years vs 62.6 ± 11.3 years) and the proportion of males (84% vs 92.6%) diagnosed with BE but a decrease in the mean BE length (4.4±4.3 cm vs 2.9±3.0 cm) as time progressed (1990-1994 to 2010-2016 time periods). The presence of LGD on index endoscopy remained stable over 1990 to2016. However, a significant increase (148% in HGD and 112% in EAC) in the diagnosis of HGD, EAC, and HGD/EAC was noted on index endoscopy over the last 25 years (P< .001). There was also a significant increase in the detection of visible lesions on index endoscopy (1990-1994, 5.1%; to 2005-2009, 6.3%; and 2010+, 16.3%) during the same period. Our results suggest that the prevalence of HGD and EAC has significantly increased over the past 25 years despite a decrease in BE length during the same period. This increase parallels an increase in the detection of visible lesions, suggesting that a careful examination at the index examination is crucial.

Early Dysplasia After Initial Diagnosis of Barrett’s Esophagus: When Should We Initiate Surveillance?

Introduction: Barrett’s Esophagus (BE) is a risk factor for developing esophageal adenocarcinoma (EAC). The rate of progression of BE to EAC increases in the presence of low grade dysplasia (LGD) and high grade dysplasia (HGD). However, the optimal time to initiate surveillance for dysplasia is not known. The American College of Gastroenterology guidelines recommend against starting dysplasia surveillance 1 year after initial diagnosis, a conditional recommendation that is supported by very low quality evidence. Our aim is to evaluate rates of early dysplasia after the initial diagnosis of Non-Dysplastic Barrett’s Esophagus (NDBE). Methods: We retrospectively analyzed a cohort of patients diagnosed with BE at a large tertiary care referral VA medical center. Endoscopic and histologic data were reviewed to determine the date of initial diagnosis of BE and the time to development of dysplasia. Patients who had LGD, HGD, or indeterminate for dysplasia (IFD) as the initial histological finding and those who had a history of BE prior to initial endoscopy were excluded. Early dysplasia was defined as LGD or HGD developing within 18 months of the initial diagnosis of NDBE. Results: Of 847 unique patients with BE, 97 with LGD or HGD were selected, of which 30 had an initial diagnosis of NDBE. The average age was 60.6 years, all were men, and 77% were Caucasian. 9 patients developed HGD. In this group 5 progressed early and 1 developed early IFD that would become HGD (6/9, 66.7%). 21 patients developed LGD. In this group 4 progressed early and 5 developed early IFD that would become LGD (9/21, 42.8%). The total number of patients who developed early dysplasia was 15 out of 30 (50%). The average time to early LGD, HGD, or IFD (that would become LGD or HGD) was 12.3 months. 6 patients (20%) had no endoscopic surveillance between the initial diagnosis of NDBE and that of LGD or HGD with an average time to dysplasia of 72.3 months. Conclusion: In a high risk cohort of NDBE patients, a significant proportion of those who developed dysplasia did so in the first 18 months. It is possible this represents an underestimate given that 20% of our cohort did not have appropriate endoscopic follow up between initial diagnosis and dysplasia. Thus, we find that a 1-year surveillance interval after initial diagnosis of NDBE in high-risk cohorts is warranted. Limitations of this study include its small sample size and retrospective design. Future large prospective studies are needed to confirm our findings.

Abstract 4536: Rapid evaporative ionization mass spectrometry (REIMS) analysis of the mucosal lipidome has a high diagnostic accuracy for adenomas and early colorectal cancer

Abstract Introduction The aim of this study was to determine the diagnostic accuracy of REIMS for dysplasia in human adenomas and early colorectal cancer and to determine changes in mucosal lipid chemistry during cancer initiation. Moreover, we attempted to develop a proof of concept first in man study of a novel REIMS-based endoscope for in-vivo chemical phenotyping of adenomas based on the real time analysis of phosphatidic acid (PA) and phosphatidylethanolamine (PE) metabolism. Experimental procedure A prospective, observational cross-sectional cohort study was performed in patients undergoing elective resection for colorectal cancer or colonoscopy at Imperial College London NHS Trust. Two tissue types were obtained - early colorectal cancer (defined as T1 or T2 according to TNMv6 criteria) and adenomatous polyps. Patients with familial adenomatous polyposis, inflammatory bowel disease or hereditary non-polyposis colon cancer were excluded. Specimens were analyzed ex-vivo using a modified electro-surgical hand piece with the aerosol aspirated into a Xevo G2-S QTof mass spectrometer (Waters Corporation). Multivariate analyses were used to create models which underwent cross-validation using SIMCA (V14, Umetrics, Sweden). Characteristic lipid species were identified using univariate statistics in R Studio (V1.0.44) and Metlin. An endoscopic set up was created using a standard endoscope for proof of concept. Summary of data 19 patients (12:7 F:M) were included with a median age of 74 (range 50-92). Six patients had T1/2 adenocarcinoma and 13 had adenomatous polyps. REIMS was able to accurately distinguish the presence of low grade dysplasia (LGD) vs high grade dysplasia (HGD) in adenomatous polyps (sensitivity 95.0%, specificity 100%). Phosphatidic acids (PA) 38:2 and 38:1 were more abundant in high vs low grade dysplasia (p=0.003). REIMS was also able to identify adenomatous polyps from early cancer (sensitivity 100%, specificity 96.3%). Phosphatidylethanolamine (PE) 36:1, phosphatidic acid (PA) 38:1, glucosylceramide (Glc-Cer) 30:1 and ceramide phosphoethanolamines (PE-Cer) d16:1(4E)/20:0 and d14:1(4E)/22:0 were associated with early cancer formation rather than adenomas (p&amp;lt;0.001, p&amp;lt;0.001, p=0.03, p=0.04 respectively). Endoscopic REIMS was successfully deployed in-vivo in six patients undergoing polypectomy. Spectra with good signal to noise ratio were acquired and the technology was able to correctly stratify adenomas. Conclusion Dysplastic adenomas exhibit mucosal lipid chemistry that is discrete from early colorectal cancer. PA, PE and Glc-Cer have potential use as diagnostic biomarkers. First in man studies of the endoscopic application of REIMS suggest it could serve as a real-time tool for early cancer detection based on in vivo analysis of the mucosal lipidome. Citation Format: Petra Paizs, Eftychios Manoli, Sam E. Mason, James L. Alexander, Zsolt Bodai, Emma White, Afeez Adebesin, Jonathan Hoare, Robert Goldin, Ara W. Darzi, James M. Kinross, Zoltan Takats. Rapid evaporative ionization mass spectrometry (REIMS) analysis of the mucosal lipidome has a high diagnostic accuracy for adenomas and early colorectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4536.

Colonization with enterotoxigenic Bacteroides fragilis is associated with early-stage colorectal neoplasia

BackgroundEnterotoxigenic Bacteroides fragilis (ETBF) is a toxin-producing bacteria thought to possibly promote colorectal carcinogenesis by modulating the mucosal immune response and inducing epithelial cell changes. Here, we aim to examine the association of colonic mucosal colonization with ETBF and the presence of a range of lesions on the colonic neoplastic spectrum.MethodsMucosal tissue from up to four different colonic sites was obtained from a consecutive series of 150 patients referred for colonoscopy. The presence and relative abundance of the B. fragilis toxin gene (bft) in each tissue sample was determined using quantitative PCR, and associations with clinicopathological characteristics were analysed.FindingsWe found a high concordance of ETBF between different colonic sites (86%). Univariate analysis showed statistically significant associations between ETBF positivity and the presence of low-grade dysplasia (LGD), tubular adenomas (TA), and serrated polyps (P-values of 0.007, 0.027, and 0.007, respectively). A higher relative abundance of ETBF was significantly associated with LGD and TA (P-values of < 0.0001 and 0.025, respectively). Increased ETBF positivity and abundance was also associated with left-sided biopsies, compared to those from the right side of the colon.ConclusionOur results showing association of ETBF positivity and increased abundance with early-stage carcinogenic lesions underlines its importance in the development of colorectal cancer, and we suggest that detection of ETBF may be a potential marker of early colorectal carcinogenesis.

Endoscopic Ultrasound for Risk Stratification of Pancreatic Cystic Neoplasms

Introduction: Endoscopic Ultrasound (EUS) plays a large role in the workup and evaluation of both incidental and symptomatic pancreatic cysts. EUS can aid in risk stratification of pancreatic cystic neoplasms (PCNs). A subset of PCN, intraductal papillary mucinous neoplasms (IPMNs) have the potential for malignant transformation and risk is stratified from high to low. EUS can aid in differentiation between benign and malignant IPMNs and is used in current guidelines used to direct patients to observation or resection. Methods: A total of 80 patients were identified who underwent both endoscopic ultrasound and surgical resection of a cystic pancreatic lesion between the dates of January 2008 to January 2014. A total of 36 were found to have IPMNs. A retrospective chart analysis was conducted on patients with diagnosis of IPMN to identify features seen at the time of EUS and to collect data such as age, gender and CEA value. Descriptive statistics, including counts and percentages and means and standard deviations, were calculated and reported for patient specific demographics and cyst characteristics including cyst pathology, mural nodules, wall and duct characteristics, CEA level and cyst size. Low risk IPMNs were identified on surgical pathology by the presence of low grade dysplasia or no dysplasia. High risk IPMNs were identified on surgical pathology as high grade dysplasia or invasive adenocarcinoma. The two groups were compared. For data measured on an interval scale, student's t-test was used. If the data were ordinal or not normally distributed, the Wilcoxon rank-sum test was employed. For nominal data, the chi-square test or Fisher's exact test was performed. SAS Enterprise Guide®, version 5.1, was used for all analyses. A two-tailed p-value of less than 0.05 was considered statistically significant. Results: A comparison of high and low risk IPMNs showed a statistically significant difference in main ductal dilatation and in cytology obtained during EUS. gender, presence of mural nodule, tortuosity of the pancreatic duct, wall thickness, age, CEA level and cyst size were not found to be significantly different between the two groups. Conclusion: For IPMNs, measurement of main ductal dilatation and results of cytology observed and obtained during EUS were statistically significant differences between low and high risk IPMNsTable 1: Results

PTU-149 Barrett’s Oesophagus Patients Attending Hospital: Baseline Clinical, Patient History and Quality of Life Data from Boss and Aspect

Introduction From 2005 to 2011 two large UK studies recruited 6,327 evaluable patients with Barrett’s Oesophagus attending hospital clinics. Baseline clinical, patient history and quality of life data was collected prior to randomisation and this rich dataset is the basis for this abstract. Methods Patients were recruited to AspECT and BOSS at local centres through normal endoscopy clinics and surveillance lists including those newly diagnosed or with an existing diagnosis of Barrett’s oesophagus. Baseline information was collected on age, gender, ethnicity, length of Barrett’s, presence of hiatus hernia, intestinal metaplasia and low grade dysplasia, concomitant medications, comorbidities, duration and severity of symptoms and patients’ self-reported Quality of Life data. Results The sample was mainly male (75%, n = 6,327) with median age of 64 years (range 18–92 years, n = 6,327). Median Barrett’s length was 4 cm (range 1–24 cm, n = 6,029) and median time since diagnosis of Barrett’s was 2 years (range 0–41 years, n = 5,805). At least one symptom of reflux was experienced by 60% of patients and 46% of patients experienced at least one symptom at least once per week (n = 1,072). Length of Barrett’s was associated with age (n = 6,029), gender (n = 6,029), presence of low grade dysplasia (n = 5,955), presence of intestinal metaplasia (n = 6,026) and time since diagnosis (n = 5,913). Conclusion This is our first release of data from AspECT and BOSS with more to follow. It is a large set of data on Barrett’s patients which we expect to be typical of Barrett’s patients attending hospital clinics in the UK. The average person was a male age 62 with 4 cm Barrett’s having had a Barrett’s diagnosis for 2 years. Acknowledgements Our thanks to the patients and the sites. AspECT is sponsored by the University of Oxford with grant funding from CR-UK (A4584) and support from the Investigator-Sponsored Study Program of AstraZeneca with trial management provided by OCTO. BOSS is funded by the HTA grant number HTA 05/12/01 with trial management provided by BOSS trial office Gloucestershire Hospitals NHS Trust. The Centre for Statistics in Medicine provides statistical input to both AspECT and BOSS. Disclosure of Interest None Declared

The importance of a second opinion in the diagnosis of Barrett's esophagus: a "real life" study.

Barrett's esophagus is a precancerous lesion, and its identification with the early detection of dysplasia is of paramount importance to prevent adenocarcinoma onset. However, there is still debate on the correct pathological identification of Barrett's esophagus (and of associated dysplasia), and most studies have been conducted in an experimental setting. To assess previous uncertain diagnoses of Barrett's (with and without dysplasia) via a second opinion of an expert pathologist in a real life setting. Histological sections of 32 suspected Barrett's patients from ten general Pathology units were centralized into one single unit in which an expert pathologist reviewed the slides blindly. Overall, in 78% of cases there was diagnostic discordance; in particular, in 64% of cases the presence of low grade dysplasia was not confirmed. Of interest, 28% of cases with the original diagnosis were reclassified as non-Barrett's. The pathological diagnosis of Barrett's esophagus, especially with regard to the presence of dysplasia, is still misinterpreted, particularly in the setting of general Pathology units. Thus, a second opinion from an experienced pathologist may help in the interpretation of the results and in starting appropriate follow-up programs.

Sa1870 Fundic Gland Polyps With Dysplasia

Fundic gland polyps (FGPs) are the most common type of gastric polyp and are seen in up to 5% of patients on endoscopy. Although considered benign, FGPs are more common in patients with familial adenomatous polyposis (FAP). FGPs occur sporadically in up to 1.9% of the general population and in 84% of patients with syndromic FAP. Dysplasia in FGP is reported in 53% of syndromic FGPs and in only 2.3% of sporadic FGPs. The aim of this study is to compare patients with FGPs with dysplasia and those with FGPs without dysplasia. The pathology files from two institutions were searched from 1/1/2009 to 10/1/2013 for FGPs with dysplasia (FGPD). A similar number of control cases of FGP with no dysplasia (FGPND) were also randomly retrieved. All biopsies were reviewed, and diagnoses were agreed upon by three pathologists. Patient demographic data was recorded and included age, gender, race, diagnosis of FAP, and PPI use. Twenty-five patients with FGPD were identified (Male: 15, Female: 10, mean age: 60). Five patients had a confirmed history of FAP (mean age: 36), 9 had a high probability of FAP based on family or personal GI history (mean age: 61), 3 had no indication of FAP (such as family or personal history of colon cancer or polyps) (mean age: 63), and in 8 patients the family or personal history was not recorded (mean age: 62). Seventeen patients (68%) were on a protein pump inhibitor (PPI). The mean age of FGPD patients with FAP is significantly lower than patients without FAP (p< 0.001). The 26 patients with FGPND included 10 males and 16 females (mean age: 60). None of the patients had a history of FAP, 12 had a high probability of FAP based on family or personal GI history (mean age: 61), 6 had no indication of FAP (mean age: 59), and in 8 patients the family or personal history was not recorded (mean age: 55). Eighteen patients (69%) were on a PPI. There were no ethnic/racial differences between the two groups of patients. Of all biopsies from patients with FGPD, 88% of all fragments were smaller than 5 mm2 and 5% were greater than10 mm2. In contrast, of all the biopsies from patients with FGPND, 68% of all fragments were smaller than 5 mm2 and 20% were greater than 10 mm2. These data show no correlation between PPI use and the presence of low grade dysplasia in FGP. FGPND tended to result in larger biopsy fragments than FGPD; however there was no significant difference in the number of polyps described endoscopically between the two groups. Patients who have low-grade dysplasia in FGP are more likely to have FAP or a high probability of FAP than those without dysplasia. Low grade dysplasia in FGP is seen at a younger age in patients with FAP than in those without FAP. Finding low grade dysplasia in FGP, particularly in patients younger than 40 years, should raise a suspicion for FAP.

Barrett's oesophagus: Evidence from the current meta-analyses.

Guidelines have been published regarding the management of Barrett's oesophagus (columnar-lined oesophagus). These have examined the role of surveillance in an effort to detect dysplasia and early cancer. The guidelines have provided criteria for enrolment into surveillance and some risk stratification with regard to surveillance interval. The research basis for the decisions reached with regard to cancer risk is weak and this manuscript has examined the available data published from meta-analyses up to 25(th) April 2013 (much of which has been published since the guidelines and their most recent updates have been written). There were 9 meta-analyses comparing patients with Barrett's oesophagus to control populations. These have demonstrated that Barrett's oesophagus is more common in males than females, in subjects who have ever smoked, in subjects with obesity, in subjects with prolonged symptoms of gastro-oesophageal reflux disease, in subjects who do not have infection with Helicobacter pylori and in subjects with hiatus hernia. These findings should inform public health measures in reducing the risk of Barrett's oesophagus and subsequent surveillance burden and cancer risk. There were 8 meta-analyses comparing different groups of patients with Barrett's oesophagus with regard to cancer risk. These have demonstrated that there was no statistically significant benefit of antireflux surgery over medical therapy, that endoscopic ablative therapy was effective in reducing cancer risk that there was similar cancer risk in patients with Barrett's oesophagus independent of geographic origin, that the adenocarcinoma incidence in males is twice the rate in females, that the cancer risk in long segment disease showed a trend to be higher than in short segment disease, that there was a trend for higher cancer risk in low-grade dysplasia over non-dysplastic Barrett's oesophagus, that there is a lower risk in patients with Helicobacter pylori infection and that there is a significant protective effect of aspirin and statins. There were no meta-analyses examining the role of intestinal metaplasia. These results demonstrate that guidance regarding surveillance based on the presence of intestinal metaplasia, segment length and the presence of low-grade dysplasia has a weak basis, and further consideration should be given to gender and helicobacter status, ablation of the metaplastic segment as well as the chemoprotective role of aspirin and statins.

INCIDENCE AND ENDOSCOPIC FOLLOW-UP OF PATIENTS WITH ULCERATIVE COLITIS

INTRODUCTION : Ulcerative colitis (UC) is an idiopathic inflammatory bowel disease, which is characterized by a chronic recurrent inflammation of the intestinal mucosa. Patients with UC have a high risk of developing colorectal cancer (CRC). In the UC, malignization is produced by dysplasia. THE PURPOSE OF THE STUDY was to establish the incidence of adenomatous polyps, stenoses, dysplasia and CRC in patients with UC who were being monitored at Mures County Clinical Hospital. MATERIAL AND METHOD : We have performed an observational prospective study on a batch of 47 patients who were being monitored at our clinic in the period January 2007 – December 2011. The UC diagnosis was established based on symptomatology, colonoscopy and by histopathological analysis. The data were processed by means of statistic instruments in Excel (Microsoft Excel 2003). RESULTS : In the period January 2007 – December 2011 there were 160 patients with UC under our clinic monitoring. According to the disease evolution, 99 patients (62%) had a < 5 years evolution, 48 patients (30%) between 5 and 10 years, and 13 patients (8%) over 10 years. From the total of 160 patients in the study were included 47. About 27 (57%) were men and 20 (43%) women, with an average age of 47,193 years. The presence of low-grade dysplasia was identified in 2 patients (4.25%), high-grade dysplasia was identified in 1 patient (2.12%) and CRC was identified in 2 patients (4.25%). For these patients the therapeutic indication was surgical intervention. Conclusions : The correct approach in preventing CRC in UC should cover a clinical follow-up with regular visits, an intensive control of the activity of the disease by medical treatment associated with endoscopic monitoring of biopsy sampling. The purpose of the colonoscopic monitoring consists in detecting the preneoplasic lesions before the malign transformation. Thus, the detection and management of dysplastic lesions is a crucial element in reducing death rate by CRC. Keywords: Ulcerative colitis, Low-grade dysplasia, High-grade dysplasia, Colorectal cancer, Endoscopy, Colectomy.

Covering the Cover

Covering the Cover