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ObjectiveVaccines against antigens expressed on adenomas could prevent new adenoma formation. We assessed whether a MUC1 peptide vaccine produces an immune response and prevents subsequent colonic adenoma formation.DesignMulticenter, double blind, placebo-controlled randomized trial in individuals age 40-70 with diagnosis of an advanced adenoma ≤1 year from randomization. Vaccine was administered at 0, 2, and 10 weeks with a booster injection at week 53. Adenoma recurrence was assessed ≥1 year from randomization. The primary endpoint was vaccine immunogenicity at 12 weeks defined by anti-MUC1 ratio ≥2.0.Results53 participants received the MUC1 vaccine and 50 placebo. 13/52 (25%) of MUC1 vaccine recipients had a ≥2-fold increase in MUC1 IgG (range 2.9-17.3) at week 12 vs. 0/50 placebo recipients (1-sided Fisher’s exact PConclusionAn immune response was observed only in vaccine recipients. Overall adenoma recurrence was not different than placebo, but a 38% absolute reduction in adenoma recurrence was observed in immune responders.ClinicalTrials.gov Identifier: NCT02134925.https://clinicaltrials.gov/ct2/show/NCT02134925Key PointsWhat is already knownAntigens expressed on colonic adenomas are potential targets for immunopreventive vaccines. An effective vaccine could prevent subsequent adenoma formation.What this Study AddsIn this multicenter, double blind, placebo-controlled randomized trial, MUC1 vaccine recipients developed an immune response. Overall adenoma recurrence was not different than placebo, but a 38% absolute reduction in adenoma recurrence was observed in immune responders.How this study might affect research, practice or policyVaccine immunoprevention is a potential new frontier to colorectal cancer prevention.

Barrett’s esophagus (BE) refers to the mucosal transition from normal squamous mucosa to a genetically unstable specialized columnar-type intestinal metaplasia in the esophagus. Recent sophisticated studies using orthogonal techniques of molecular and computational biology strongly support that BE is the predominant pathway to esophageal adenocarcinoma (EAC). In this treatise, we review the risk of BE transforming to EAC and the latest developments in risk assessment of BE progression to EAC. The progression rate of BE to EAC can vary from one study to another depending on the region of origin, definition of BE, and variations in data capture. Overall, the published studies suggest that the risk of BE transforming to EAC is less than 0.5% per year and that to high-grade dysplasia (HGD) or EAC is less than 1% per year. Clinical tools to predict risk such as the Progression in Barrett’s (PIB) have been developed but will need further validation. p53 is the biomarker for risk stratification and has stood the test of time but is still not being widely used due to incomplete correlation between the mutational status and protein expression. Molecular studies using genomics and proteomics approaches are being evaluated but need to demonstrate good clinical accuracy before being translated into practice.

Purpose The present in vivo study aimed to estimate the prevalence and variation in anterior loop of inferior alveolar nerve (IAN) in relation to mental foramen to assess the safe zone in anterior part of mandible for implant placement with cone-beam computed tomography (CBCT) in North Indian population. Materials and Methodology To conduct this study, 70 patients were selected and radiographically evaluated. All CBCT scans were made from Genoray Papaya 3D Plus. CBCTs were evaluated in CDSee software for anterior loop and height measurement anterior to mental foramen. Four parameters of prevalence of loop length and height anterior to mental foramen on right and left side each and four parameters of variation in loop length and height on right and left side each were recorded with the help of descriptive statistical analyses (mean, median, mode, and range) and paired t-test. Level of significance (p) was also calculated. Result Paired t-test value for comparison on both the right and left sides for loop length of IAN anterior to mental foramen was 0.140 and paired t-test value for loop height was 0.384. The p-values for loop length and height were 0.8891 and 0.7019, respectively. Conclusion Within the limitation of the study, it was observed that the anterior loop has a wide range of prevalence and variation in terms of loop length and loop height suggesting that it is difficult to get a defined measurement of loop length for a given population and surgical procedures cannot be performed based on the given data for IAN loop anatomy.

Purpose To compare between values of condylar inclination obtained by protrusive interocclusal records using extraoral Gothic arch tracing with cone-beam computed tomography (CBCT) scan, and cephalometric and panoramic radiographs in edentulous patients. Materials and Methods Horizontal condylar guidance angle (HCGA) was measured using the extraoral Gothic arch tracing, CBCT, lateral cephalogram, and orthopantomogram (OPG) in 20 patients aged between 40 and 75 years. HCGAs were determined clinically using protrusive interocclusal records and semi-adjustable articulator after extraoral Gothic arch tracing. Radiographically, Frankfort horizontal plane was marked and a straight line joining the superior-most point and the inferior-most point of posterior slope of the articular eminence (AE) was drawn till the two lines met at an intersection. The angle at this intersection depicted the AE inclination and the angle was measured. Statistical analysis was done using analysis of variance test, multiple comparison was done using Tukey test, and the Pearson correlation coefficient was compiled for different study parameters. Result A significant difference in condylar guidance was observed among different methods (p-value Conclusion It was concluded that horizontal condylar guidance (HCG) values with the radiographic technique were higher than the clinical method. It was observed that mean HCG values were higher by 6.4 degrees in CBCT, 6.7 degrees in OPG, and 9.9 degrees in lateral cephalogram as compared with the clinical value. It was also observed that there was a variation of condylar guidance up to 5 degrees between right and left sides.

Introduction Obtaining an appropriate impression of the implant position and surrounding soft and hard tissues is paramount to fabricating an esthetically and biologically functional definitive restoration. Materials and Methods An edentulous maxillary acrylic master model was chosen. Four dummy implants were drilled into this model from the first premolar to first premolar region at equal distance using a dental surveyor to ensure parallel placement of the implants. Ten samples, each made for open tray (Group A), closed tray direct (Group B), and closed tray indirect (Group C) techniques using polyvinylsiloxane, were poured in type IV dental stone and 30 samples were hence obtained. The linear distance between the four implants were measured using the profile projector for each of the cast. The data obtained were analyzed using ANOVA and Tukey's HSD test. Observation and Results Inter-implant and inter-abutment linear distances were measured (in mm) for the master model and the samples for 1 to 2, 2 to 3, 3 to 4, 1 to 3, 2 to 4, and 1 to 4, and the maximum deviation was found in Group B. Conclusion The dimensional accuracy of casts obtained from closed tray indirect impression technique was the highest with linear distance values closest to the implant master model followed by open tray, and the least accuracy was found for closed tray direct impression technique.

The aim of this article is to present the clinical application of leukocyte-platelet-rich fibrin (L-PRF) at immediately extracted site after the implant placement. A 37-year-old male patient reported to the Department of Prosthodontics, Bhojia Dental college Budh Baddi Dist Solan Himachal Pradesh 173205 with the chief complaint of decayed teeth in the posterior region and wants a fixed prosthesis. On the day of surgery, implants were placed in freshly extracted sockets along with the bone graft and L-PRF membrane. After 6 months of healing period, implant level impressions were made and final porcelain fused to metal crowns were given to the patient.

Search is one of the more common strategies used by problem-solving agents. For many hard problems, a backtracking search can be the most effective approach for finding a solution. Logic programming languages provide, as a core feature of the language, the mechanics for the search behind the scenes without requiring the user to specify the algorithm. However, this functionality has been generally left out of the core features of imperative programming languages. In this work, we propose integrating a search agent into an imperative programming language through a search construct in the syntax. By doing so, our intention is that the user may apply a declarative approach to problem solving. We extend the Go programming language with this search construct and develop an agent to perform the search. The algorithm behind the search is implicitly handled by the agent. We demonstrate the effectiveness of this search construct through solutions to an exhaustive search over a file-system, the NQueens problem, and the monkey and the bananas problem. To evaluate the performance of our agent, we compare its runtime performance against two of the common Prolog implementations, SWI-Prolog and GNU Prolog.

Purpose:To assess whether MUC1 peptide vaccine produces an immune response and prevents subsequent colon adenoma formation.Patients and Methods:Multicenter, double-blind, placebo-controlled randomized trial in individuals age 40 to 70 with diagnosis of an advanced adenoma ≤1 year from randomization. Vaccine was administered at 0, 2, and 10 weeks with a booster injection at week 53. Adenoma recurrence was assessed ≥1 year from randomization. The primary endpoint was vaccine immunogenicity at 12 weeks defined by anti-MUC1 ratio ≥2.0.Results:Fifty-three participants received the MUC1 vaccine and 50 placebo. Thirteen of 52 (25%) MUC1 vaccine recipients had a ≥2-fold increase in MUC1 IgG (range, 2.9–17.3) at week 12 versus 0/50 placebo recipients (one-sided Fisher exact P < 0.0001). Of 13 responders at week 12, 11 (84.6%) responded to a booster injection at week 52 with a ≥2-fold increase in MUC1 IgG measured at week 55. Recurrent adenoma was observed in 31 of 47 (66.0%) in the placebo group versus 27 of 48 (56.3%) in the MUC1 group [adjusted relative risk (aRR), 0.83; 95% confidence interval (CI), 0.60–1.14; P = 0.25]. Adenoma recurrence occurred in 3/11 (27.3%) immune responders at week 12 and week 55 (aRR, 0.41; 95% CI, 0.15–1.11; P = 0.08 compared with placebo). There was no difference in serious adverse events.Conclusions:An immune response was observed only in vaccine recipients. Adenoma recurrence was not different than placebo, but a 38% absolute reduction in adenoma recurrence compared with placebo was observed in participants who had an immune response at week 12 and with the booster injection.

Background Information on Advanced Adenoma

supplementary methods: Detailed laboratory methods

Endpoint titers of plasma antibodies at week 12 amongst vaccine responders

Germline variants in CDH1 are associated with elevated risks of diffuse gastric cancer and lobular breast cancer. It is uncertain whether there is an increased risk of colorectal neoplasia.This was a retrospective analysis of colonoscopy outcomes in patients with germline CDH1 pathogenic/likely pathogenic variants.Eighty-five patients were included with a mean age of 46.9 years. Initial colonoscopy found adenomatous polyps in 30 patients (35.3%), including advanced adenomas in 9 (10.6%). No colorectal cancers were identified on index or subsequent colonoscopies (when available).CDH1 carriers have colorectal neoplasia identified at similar rates as in the general population. Despite potential difficulties after gastrectomy, colorectal cancer screening remains important in this population.

The CAPP2 trial investigated the long-term effects of aspirin and resistant starch on cancer incidence in Lynch syndrome (LS) patients. Participants with LS were randomised double-blind to 30g resistant starch (RS) daily or placebo for up to 4 years. We present long-term cancer outcomes based on the planned 10 year follow up from recruitment, supplemented by national cancer registry data to 20 years in England, Wales and Finland. Overall, 463 participants received RS and 455 placebo. After up to 20 years follow-up, there was no difference in colorectal cancer (CRC) incidence (n=52 diagnosed with CRC among those randomised to RS against n=53 on placebo) but fewer participants had non-colorectal LS cancers in those randomised to RS (n=27) compared with placebo (n=48); intention-to-treat (ITT) analysis (Hazard Ratio (HR) 0.54 (95%CI 0.33-0.86), p=0.010)). In ITT analysis allowing for multiple primary cancer diagnoses among participants by calculating Incidence Rate Ratios (IRR) confirmed the protective effect of RS against non-CRC LS cancers (IRR 0.52 (95%CI 0.32- 0.84), p=0.0075). These effects are particularly pronounced for cancers of the upper GI tract; 5 diagnoses in those on RS versus 21 diagnoses on placebo. The reduction in non-CRC LS cancers was detectable in the first 10 years and continued in the next decade. For CRC, ITT analysis showed no effect of RS on CRC risk (HR 0.92 (95%CI (0.62-1.34)), p=0.63). There was no interaction between aspirin and RS treatments. In conclusion, 30g daily RS appears to have a substantial protective effect against non-CRC cancers for LS patients.

The prosthodontic management of a patient with long-term edentulism is challenging. Conventional dentures have been the traditional standard of care for the longest time. However, most patients experience difficulty in adapting to their mandibular dentures due to lack of stability and retention. From the past two decades, implant-supported overdentures have been offering numerous advantages over the traditional complete dentures and removable partial dentures with predictably good clinical results. These advantages include increased oral function, decreased bone resorption, decreased prosthesis movement, better aesthetics, and maintenance of occlusal vertical dimension. This article presents a case report of fabrication of two-implant overdenture in mandibular knife edge ridge in the anterior mandible opposing conventional maxillary complete denture.

Introduction This study was undertaken to evaluate the pattern of stress distribution in implant body and surrounding bone with and without splinting of implant prostheses when subjected to occlusal loading, using the finite element analysis. Methods The geometric models of implant and mandibular bone were generated. Two models were created in accordance with the need of the study. The first model was given a two implant in the first mandibular molar and second premolar with splinted prosthesis. Then, second model was given two such implants in the same region but without splinting the prosthesis. Forces of 100 N and 50 N were applied axially and buccolingually, respectively. Results The maximum von Mises stress values with axial force of the implant splinted prosthesis were observed to be 4.21 MPa for cortical bone, 0.88 MPa for cancellous bone, and 10.592 MPa for implant body. The maximum von Mises stress values with buccolingual force of the implant splinted prosthesis were observed to be 9.08 MPa for cortical bone, 1.33 MPa for cancellous bone, and 30.08 MPa for implant body. The maximum von Mises stress values with axial force of the implant nonsplinted prosthesis were observed to be 4.51 MPa for cortical bone, 0.91 MPa for cancellous bone, 13.18 MPa for implant body. The maximum von Mises stress values with buccolingual force of the implant nonsplinted prosthesis were observed to be 9.52 MPa for cortical bone, 1.91 MPa for cancellous bone, 35.04 MPa for implant body. Conclusion The maximum stresses were transferred more to the implant body than to the bone in both the splinted and nonsplinted implant prostheses. The maximum von Mises stresses were observed on nonsplinted implant prostheses, so splinting implant prostheses led to lower stress in the implant body and surrounding bone.

The aim of this article is to present the clinical application of implant placement in the aesthetic zone using bone graft and leukocyte-platelet-rich fibrin to obtain desirable results. A 27-year-old male patient reported with a chief complaint of missing tooth in the anterior region due to trauma and wants to replace it with a fixed prosthesis. The patient had been undergoing orthodontic treatment for the last 3 years. After proper treatment planning, endo-osseous implant followed by alloplastic bone graft was placed and platelet-rich fibrin membrane was placed on the labial bony surface as the labial plate was thin. After 6 months, the prosthetic procedure was done.

Aim and Objective The main aim of this study was to evaluate the effect of three different types of pattern materials on the vertical marginal accuracy of complete cast crown. Material and Methods Three groups of 20 specimens each were made based on three pattern materials, that is, blue inlay wax, autopolymerizing acrylic resin, and light cure pattern resin. Castings were made and examined using stereo microscope for vertical marginal discrepancy. Results The result showed that the highest mean gap was noticed in the castings fabricated using inlay type B pattern wax followed by the castings fabricated using autopolymerizing resin and the least mean gap was observed in the castings fabricated using light cure modeling material. Conclusion It was concluded from this study that the use of light cure modeling material to make patterns for casting with lost wax technique is best recommended than inlay type B pattern and autopolymerizing resin.

Dental implants are fixtures that constitute for the replacements of the root of a missing natural tooth. Dental implant therapy has been widely used for the restoration of partially and fully edentulous patients. The implant literature emphasizes the importance of a passively fitting prosthesis to prevent prosthodontic complications or even loss of fixture integration. Failure to achieve a passively fitting prosthesis and force tightening of superstructure may result in complications such as abutment, framework, and gold screw loosening or fracture. Various materials that can be used for making an implant impression are polyether, polyvinylsiloxane, condensation silicone, polysulfide, irreversible hydrocolloid material, and various others. There are various studies in relation to the accuracy of these impression materials out of which various scientists concluded different results with most studies stating polyether with the maximum amount of dimensional accuracy in comparison to other materials. An accurate implant impression plays a significant role and serves as a starting point in the process of producing good working casts. Thus, the accuracy of impression techniques becomes a significant issue in consideration of passive fit. Reproduction of intraoral relationship of implants through impression procedures is the first step in achieving accurate fit prosthesis. This transference is still complicated by the number, angulation, depth, and position of implants. The advent of computer-aided design/computer-assisted manufacturing technology improved the framework fabrication procedures and has increased the precision of fit of implant prosthesis.

With technological advancements, the availability of low-cost smartphones and internet connectivity, the online retail industry has gained traction. A pandemic-related lockdown has fuelled the fire. Consequently, it becomes important to identify the factors defining online retail service quality (ORSQ), which affect customer satisfaction and customer engagement behaviour. First, a qualitative study was conducted to identify ORSQ factors and reliability, ease of use, customer-friendly policies, problem handling and security were found to be the most vital ones for Indian consumers. Further, a quantitative study was attempted to determine the impact of ORSQ factors on consumer satisfaction and customer engagement behaviour. While testing these relationships, website familiarity was considered as a moderating variable between ORSQ factors and customer satisfaction. The findings of the study suggest that the identified ORSQ factors influence customer satisfaction and customer engagement behaviour in turn. The moderating effect of website familiarity was also established on customer satisfaction. For the analysis, Smart PLS 3.0 was used.

The pathogenesis of subsquamous intestinal metaplasia (SSIM), in which glands of Barrett’s esophagus (BE) are buried under esophageal squamous epithelium, is unknown. In a rat model of reflux esophagitis, we found that columnar-lined esophagus developed via a wound-healing process involving epithelial-mesenchymal plasticity (EMP) that buried glands under ulcerated squamous epithelium. To explore a role for reflux-induced EMP in BE, we established and characterized human Barrett’s organoids and sought evidence of EMP after treatment with acidic bile salts (AB). We optimized media to grow human BE organoids from immortalized human Barrett’s cells and from BE biopsies from seven patients, and we characterized histological, morphological, and molecular features of organoid development. Features and markers of EMP were explored following organoid exposure to AB, with and without a collagen I (COL1) matrix to simulate a wound-healing environment. All media successfully initiated organoid growth, but advanced DMEM/F12 (aDMEM) was best at sustaining organoid viability. Using aDMEM, organoids comprising nongoblet and goblet columnar cells that expressed gastric and intestinal cell markers were generated from BE biopsies of all seven patients. After AB treatment, early-stage Barrett’s organoids exhibited EMP with loss of membranous E-cadherin and increased protrusive cell migration, events significantly enhanced by COL1. Using human BE biopsies, we have established Barrett’s organoids that recapitulate key histological and molecular features of BE to serve as high-fidelity BE models. Our findings suggest that reflux can induce EMP in human BE, potentially enabling Barrett’s cells to migrate under adjacent squamous epithelium to form SSIM. NEW & NOTEWORTHY Using Barrett’s esophagus (BE) biopsies, we established organoids recapitulating key BE features. During early stages of organoid development, a GERD-like wound environment-induced features of epithelial-mesenchymal plasticity (EMP) in Barrett’s progenitor cells, suggesting that reflux-induced EMP can enable Barrett’s cells to migrate underneath squamous epithelium to form subsquamous intestinal metaplasia, a condition that may underlie Barrett’s cancers that escape detection by endoscopic surveillance, and recurrences of Barrett’s metaplasia following endoscopic eradication therapy.

In this paper, we bring together our efforts in identifying and understanding nonequilibrium phase segregation driven by active processes in the living cell, with special focus on the segregation of cell membrane components driven by active contractile stresses arising from cortical actomyosin. This also has implications for active segregation dynamics in membraneless regions within the cytoplasm and nucleus (3d). We formulate an active version of the Flory-Huggins theory that incorporates a contribution from fluctuating active stresses. Apart from knitting together some of our past theoretical work in a comprehensive narrative, we highlight some new results, and establish a correspondence with recent studies on Active Model B/B+. We point to the many unusual aspects of the dynamics of active phase segregation, such as (i) anomalous growth dynamics, (ii) coarsening accompanied by propulsion and coalescence of domains that exhibit nonreciprocal effects, (iii) segregation into mesoscale domains, (iv) emergence of a nonequilibrium phase segregated steady state characterised by strong macroscopic fluctuations (fluctuation dominated phase ordering (FDPO)), and (v) mesoscale segregation even above the equilibrium Tc. Apart from its implications for actively driven segregation of binary fluids, these ideas are at the heart of an Active Emulsion description of the lateral organisation of molecules on the plasma membrane of living cells, whose full molecular elaboration appears elsewhere.

Introduction: The incidence of esophageal adenocarcinoma (EAC) has increased more than any other cancer in our lifetime. Barrett’s esophagus (BE) is the only known precursor to EAC. At present, HER-2 and anti-PD-L1 therapies are FDA-approved for EAC, and off-label use of EGFR-directed therapy has been reported. Our study aims to use liquid chromatography mass spectrometry (LC/MS) to measure the expression of oncoproteins that are currently approved-drug targets in EAC and explore new promising targets for drug development and diagnostic applications for EAC and BE. Methods: EAC patients who underwent esophagectomy without chemo-radiation were identified. BE patients with subsequent progression to EAC and those without progression for >10 years were identified. Normal esophageal mucosa tissues with no history of progression were analyzed for baseline expression. Tissue sections were microdissected to isolate pure EAC, BE and normal mucosal cells from stroma. These biopsies were solubilized for LC/MS-based quantification of 80+ clinically relevant tumor markers including novel markers which are believed to play a role in the disease progression from BE to EAC. The expression trends of these markers were scrutinized by immunofluorescence (IF) in a subset of specimens/biomarkers to confirm mass spec results. Results: A total of 159 tissues were analyzed via LC-MS. In 55 EAC tissues - HER2, PD-L1 and EGFR were overexpressed in 16.3%, 0%, and 0% of patients, respectively. New markers DAD1 and S100P were noted to have high (7,634.0 and 27,222.6 attomoles/ug) and consistent (98.1% and 94.5%) overexpression in EAC samples. Expression of HER2, S100P and DAD1 were significantly higher in EAC compared to 23 normal esophageal mucosa specimens. There was no statistical difference in the expression of PD-L1 and EGFR between EAC and healthy mucosal samples. 45 BE biopsies progressed to EAC within a mean of 380 days, while the remaining 36 BE specimens did not progress over a 10-year period. 8 novel biomarkers were expressed at a higher level in BE tissue that progressed to cancer when compared to esophageal tissue that remained stable over 10 years. The expression trends observed via LC/MS were confirmed via IF in DAD1, S100P and two other novel markers. Discussion: LC-MS revealed low prevalence of target proteins in currently approved EAC therapies and high levels of newly discovered disease drivers that should be explored as possible therapy targets or diagnostic markers. The differential overexpression of the novel markers in progressive and non-progressive BE tissues, as well as the consistent overexpression of these markers in EAC tumors, demonstrates the potential for early detection of esophageal carcinogenesis and/or reveals potential therapeutic programs for an indication that lacks highly efficacious targeted therapy options. Citation Format: Christopher Hartley, Ajay Bansal, Catherine Hagen, Olivia Driscoll, Seyun Oh, Joe Abdo, Sumeet K. Mittal. Mass spectrometry detects lower frequency of routine markers and consistent overexpression of novel disease drivers in Barrett's-related esophageal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2805.

Numerous researchers have examined various aspects of privacy concern and information-sharing behaviour for online social networking sites; few past researches stated that social media users' privacy concern behavior influenced by their demographic profile. This article attempts to analyse social networking users’ privacy concerns and information-sharing behaviours for urban and rural areas of India. It additionally investigates privacy concerns among users with distinctive levels of Internet addiction. It has been observed that are most of the respondents are susceptible to privacy infringement because of their online social media awareness. The examination finds that urban and rural users vary in their information-sharing practices and privacy adaption. Urbanites might be at more serious risk to privacy infringement and information sharing on account of their valuable data and their social media practices. Furthermore, social media users are dependent on the privacy alerts and settings available to them while sharing information on the various social media sites. Users with low social media awareness might be powerless against privacy infringement in the absence of such alerts from the site administrators. Potential implications of discoveries are given and advice for future research had been also discussed.

TPS209 Background: Lynch syndrome (LS) is the most common inherited colorectal cancer (CRC) syndrome and is responsible for about 3% of newly diagnosed CRC. It is caused by germline mutations in one of the DNA mismatch repair (MMR) genes, and patients with LS carry a lifetime risk of CRC ranging between 10% and 70%. The role of inflammation in driving this malignant transformation is now well established and retrospective studies have revealed a potential chemo-preventative role for omega-3 (ω-3) polyunsaturated fatty acids (PUFAs), possibly via inhibition of inflammatory pathways associated with the development of defective MMR CRC tumors. While patients with LS have the highest risk of developing CRC, the majority of chemoprevention trials are focused on sporadic CRC. Effective interventions to reduce the risk of developing CRC in this population are limited to close surveillance and surgical prophylaxis. There is an unmet need for safe, effective, and non-invasive chemo-preventive interventions in patients with LS. Methods: This pilot study is a single-arm, open-label, phase 2 clinical trial of omega-3 acid ethyl esters (generic Lovasa; 2 grams orally once daily) for adult patients (≥ 18 years of age) with confirmed LS (based on germline testing of the MMR genes panel: MLH1, MSH2, MSHS6, PMS2 or deletion in EPCAM gene). Patients who are not candidate for elective endoscopy and/or with prior history of right sided or pan-colectomy are excluded. Thirty-four patients are expected to enroll, with a primary objective to determine the feasibility (defined as 80% retention rate) of 12 months of treatment with 2 grams capsules of omega-3 acid ethyl esters daily. Secondary endpoints include safety and tolerability of the intervention. Correlative aims include pre and post treatment assessment of colon mucosal tissue proliferation (right sided colon specimens will be evaluated for markers of proliferation (Ki-67) and apoptosis (Caspase-3)), the effect of omega-3 acid ethyl esters on inflammatory markers in serum, urine and feces (PGE-2, COX-2, β-catenin levels, and EPA:AA ratios), and gene expression related to proliferation, apoptosis and cell survival in colon tissue (NF-κB/Wnt pathways). The impact of omega-3 acid ethyl esters on intestinal microbiota will also be assessed (16S rRNA-based profiling). Correlative Colon tissue, serum, urine and feces samples are collected at baseline and at 12 months. The study is actively enrolling with 20 patients enrolled at the time of submission. Clinical trial information: NCT03831698.

343 Background: Esophageal adenocarcinoma (EAC) continues to have extremely poor prognosis despite advances in surgical and oncological regimens. Targeted and immune therapy hold promise to improve outcomes in solid tumors including EAC. At present HER-2 and anti-PD-L1 therapies are approved by the FDA for EAC. Additionally, off-label use of EGFR directed therapy has been reported. The aim of this study is to measure expression of 80+ oncoproteins in EAC using multiplexed mass spectrometry to elucidate expression of currently approved-drug targets and explore promising new targets for drug development. Methods: After Institutional Review Board approval (Mayo Clinic and KUMC), EAC patients whose tumors were resected via esophagectomy before chemotherapy and/or radiation were identified. Normal esophageal mucosa samples with no history of EAC were also retrieved for analysis. Tissue sections were microdissected to exclude stroma from adenocarcinoma cells. Isolated EAC cells were solubilized for mass spectrometry-based quantitation of more than 80 clinically relevant tumor markers. Results: 55 EAC tissues were analyzed. HER2, PD-L1 and EGFR were overexpressed only in 16.3%, 0%, and 0% of patients, respectively. New oncoproteins #2 and #6 were noted to have high (7,634.0 and 27,222.6 attomoles/ug) and consistent (98.1% and 94.5%) overexpression in EAC samples. Expression of HER2, oncoproteins #2 and #6 were significantly higher in EAC compared to normal esophageal mucosa. There was no statistical difference in the expression of PD-L1 and EGFR between EAC and normal samples. Conclusions: Mass spectrometry revealed a very low prevalence of target oncoproteins in EAC for currently used drugs. Our study potentially reveals alternate markers which are near universally present at high levels and should be further explored for targeted treatment.[Table: see text]