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Introduction: Two tumors having different histopathologies at anatomically distinct sites giving the picture of dual primary malignancies. Here we presented a case of two possible primary tumors and one secondary mass. Case Report: A 74-year-old female, active smoker, without personal or family cancer history presented with early satiety and weakness for two months. Systems review was positive for a “raw” feeling in stomach, alleviated with antacids. Vital signs were stable with a negative abdominal exam. Lab showed leukocytosis 24.8 K/uL (3.5–10.8 K/uL) with left shift, microcytic anemia with hemoglobin 6.1 g/dL (12.0–16.0 g/dL), and reactive thrombocytosis 477 K/uL (130–400 K/uL). Contrast-enhanced computed tomography (CT) showed right upper lobe necrotizing cavitating lesion with reactive mediastinal and right hilar lymphadenopathy, two irregular hypodense lesions in pancreatic head and tail without ductal dilation with two irregular hypodense liver lesions. Immunohistochemistry of lung and pancreatic lesions were biopsied through endoscopic ultrasound (EUS), consistent with poorly differentiated squamous cell carcinoma (SCC) with extensive necrosis, which indicates pancreatic masses are likely metastases from the lung. Liver lesion biopsy exhibited high-grade neuroendocrine tumor (NET) with focal necrosis. Next gene sequencing was pursued. Given poor functional status, palliative immunotherapy was offered; however, the patient succumbed to respiratory failure. Conclusion: Given the morphology and immunoprofile, differential diagnosis includes dual primary cancers with one metastasis, or primary SCC with metastasis with neuroendocrine differentiation. Despite having different histopathology and immunophenotype, both lung and liver tumors harbor the same molecular profile even at the variants of unknown significance that show identical mutations. As a result, they are directly related. TP53, RB1, MYCL1, and MEK1 mutations are more prevalent in SCC than NET. Tumor mutation burden values may vary as the tumor clonal structure varies between primary and metastatic sites, with higher rates of monoclonal structure recorded in metastases due to clonal selection, leading to a reduction in overall genetic diversity (“bottlenecking”). This raises the suspicion that the liver tumor is a SCC with neuroendocrine differentiation. The paucity of the specimen and rapid clinical course limited further investigation. Germline testing would have been useful to determine whether these findings are somatic or germline.

Various studies have shown the interplay between the intestinal microbiome, environmental factors, and genetic changes in colorectal cancer (CRC) development. In this review, we highlight the various gut and oral microbiota associated with CRC and colorectal adenomas, and their proposed molecular mechanisms in relation to the processes of "the hallmarks of cancer", and differences in microbial diversity and abundance between race/ethnicity. Patients with CRC showed increased levels of

Patients with end-stage renal disease (ESRD) on hemodialysis are considered to be at higher risk of gastrointestinal bleeding (GIB) as compared with those without renal disease (NRD). We conducted a population-based study using the National Inpatient Sample (NIS) database to study the outcomes of GIB in ESRD.Patients admitted with GIB (upper and lower) from 2005 to 2013 were extracted from the NIS database using ICD-9 codes. Patients were divided into NRD and ESRD groups, and a 1:1 propensity matched analysis was performed. Various outcomes were compared in both groups, and subgroup analysis based on the timing of endoscopy was also performed.A total of 218 032 patients were included in the study. There was an increase in inpatient admissions among ESRD patients with GIB with significant reduction in mortality (P 0.001). In-hospital mortality, length of stay, and total costs were significantly higher in ESRD patients as compared with NRD. ESRD patients were less likely to undergo endoscopic evaluation compared with NRD (P 0.001). Late endoscopy ( 48 h) was associated with increased need for transfusion and health-care utilization but without a significant difference in mortality as compared with early endoscopy. On multivariate analysis, endoscopy was associated with significantly lower rate of mortality in ESRD patients with GIB (odds ratio 0.28, P 0.0001).End-stage renal disease patients with GIB had a significantly higher rate of mortality and a higher health-care utilization with a lower rate of endoscopic evaluation. Endoscopy was associated with a lower mortality rate on multivariate analysis.

An endoscopist’s adenoma detection rate (ADR) is inversely related to interval colorectal cancer risk and cancer mortality. Previous studies evaluating the impact of gastroenterology fellow participation in colonoscopy on ADR have generated conflicting results. We aimed to determine the impact of fellow participation, duration of fellowship training, and physician sex on ADR and advanced ADR (AADR). We retrospectively analyzed average-risk patients undergoing screening colonoscopy at Veterans Affairs New York Harbor Healthcare System Brooklyn Campus and Kings County Hospital Center. Review of colonoscopy and pathology reports were performed to obtain adenoma-specific details, including the presence of advanced adenoma and adenoma location (right vs. left colon). There were 893 colonoscopies performed by attending only and 502 performed with fellow participation. Fellow participation improved overall ADR (44.6% vs. 35.4%, p

Background: Only about 50% of acute gallstone pancreatitis admissions undergo index cholecystectomy.Aims: We aimed to analyze the national trends in acute gallstone pancreatitis management: the proportion and optimal timing of cholecystectomy. Methods: Adult admissions with acute gallstone pancreatitis and associated procedures were extracted from National Inpatient Sample (2005-2014yy). Patients with index cholecystectomy were identified and divided into early and delayed intervention groups. Trends, complications, mortality, and hospital resource utilization were analyzed. Results: In 991,476 acute gallstone pancreatitis hospitalizations, the rate of index cholecystectomy remained low at 53-55%. Analysis of cholecystectomy complications and resource utilization demonstrated the safest and most cost-effective strategy is to perform cholecystectomy during 24-72 hours of admission. A risk difference of 12.6% in the complication rate was observed between early (72hrs) cholecystectomy groups. Delay in cholecystectomy to day five or beyond was associated with significantly higher morbidity, mortality, and resource utilization. Conclusion: The rate of index cholecystectomies to prevent recurrent acute gallstone pancreatitis remains significantly low nationally (53-55%). Our analysis demonstrates that cholecystectomy should be avoided in the first 24 hours, and optimal timing for intervention is from 24 to 72 hours of acute gallstone pancreatitis hospitalization. Careful patient selection and timing of definitive operative management are important to ensure the best clinical outcomes and avoid unnecessary healthcare expenses.

Background and study aims Patients with pancreatic cancer often have locally advanced or metastatic disease and are not candidates for curative surgery. Polymer-based microparticles (MPs) represent a drug delivery system that offers sustained release of a chemotherapeutic drug after intralesional injection for local tumor management. The aim of this study was to determine the feasibility of endoscopic ultrasound-guided fine-needle injection (EUS-FNI) of drug-loaded MPs tagged with a fluorophore and fiducial markers for locating the injection site. Secondary aims were to determine the tissue-specific effects of MPs. Methods Five pigs underwent EUS with selection of an injection site within the pancreas that was marked by placing fiducial markers prior to the MPs injection. EUS-FNI of either blank microparticles (BMPs), containing no drug, or gemcitabine-loaded microparticles (GMPs) was performed. A saline flush containing Spot Endoscopic Marker was used to expel any residual MPs in the needle shaft and tattoo the injection site. Results A green fluorescent protein flashlight was used to successfully identify the site of MP injection sites in the dissected pancreas. Frozen sections of pig pancreas demonstrated a defined deposit, confirming the delivery of the MPs. Finally, fluorescence microscopy showed activation of caspase-mediated cell death in pancreases of animals that received injections of GMPs. Conclusions This pilot study demonstrated that fiducial marker placement and pancreatic EUS-FNI of MPs was successful in all pigs with no animals demonstrating pancreatitis. Further studies are needed to determine the role for intralesional injection of drug-loaded MPs in borderline resectable or unresectable pancreatic cancer.

Background and study aims Pancreatic neuroendocrine tumors (P-NENs) are rare tumors with malignant potential. Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) has been shown to be superior to other imaging methods in preoperative localization and diagnosis of P-NENs. The objective of this study was to describe the EUS features of non-metastatic cystic and non-cystic P-NENs seen at a referral center and to evaluate the performance of EUS-FNA in diagnosis of P-NENs. Patients and methods All patients with histologically confirmed, non-metastatic P-NENs, which underwent EUS-FNA prior to surgical resection at the Moffitt Cancer Center between Jan 2005 and Dec 2012 were included. Clinical, endoscopic and pathologic information was abstracted from electronic medical records. Results Thirty-nine patients, all with non-functional P-NENs, were included in this study. Thirteen tumors were cystic and 26 were solid. Among the cystic tumors, 50 % were partly cystic and partly solid, and 50 % were fully cystic. The cystic tumors were more commonly seen at the body/tail, and the solid tumors were more uniformly distributed. Fluid could be aspirated from 50 % of the cystic tumors, all with a carcinoembryonic antigen level Conclusions EUS-FNA is much more sensitive in diagnosing solid P-NENs than cystic PNETs. Our results indicate that EUS-FNA may have higher sensitivity for diagnosis of cystic P-NENs than the reported sensitivity of EUS-FNA for all pancreatic cystic tumors.

Biospecimen donation is essential for studies of cancer prevention, early detection, and treatment. Donations from minority groups, for whom the cancer burden is high, are infrequent and inadequate for research purposes. The obstacles to donation of biospecimens by African Americans and other minority groups must be identified. Patients aged 18-85 years were surveyed based on the clinic visited (group A: GI/primary care and group B: oncology with confirmed cancer diagnosis) and analyzed as separate groups. The validated biobanking attitudes and knowledge survey (BANKS) as well as pancreatic cancer questions were used. In group A, 278/292 surveys were completed (5/6 patients participated). In group B, 54/59 surveys were completed (4/5 patients participated). There were low mean scores on the BANKS knowledge sections, specifically in regard to specimen ownership and the separation of research and medical records. Also, two major concerns limited donation: (1) fear that personal, medical, and family medical information may be stolen from the biobank; and (2) mistrust that biospecimens could be used for unintended purposes. Low knowledge about biospecimen acquisition, added to mistrust, warrant community-based, and patient education in an effort to improve attitudes, increase participation, and regain healthy therapeutic alliances.

Endoscopic ultrasound guided brachytherapy (EGBT) has been reported to be useful in certain malignancies including esophageal and pancreatic cancers. Percutaneous or surgical placement of radioactive seeds into the liver secondaries (brachytherapy) has been done successfully, however, the utility of EGBT in liver metastasis remains largely unclear. In this case report, we demonstrate the safety, efficacy and feasibility of EUS guided brachytherapy (EGBT) in liver metastasis secondary to leiomyosarcoma.

Background & study aims Corona virus disease-19 (COVID-19) pandemic has markedly impacted routine medical services including gastrointestinal (GI) endoscopy. We aim to report the real-life performance in high volume GI endoscopy units during the pandemic. Patients and methods A web-based survey covering all aspects of daily performance in GI endoscopy units was sent to endoscopy units worldwide. Responses were collected and data were analyzed to reveal the effect of COVID-19 pandemic on endoscopy practice. Results Participants from 48 countries (n = 163) responded to the survey with response rate of 67.35%. The majority (85%) decreased procedure volume by over 50%, and four endoscopy units (2.45%) completely stopped. The top three indications for procedures included upper GI bleeding (89.6%), lower GI bleeding (65.6%) and cholangitis (62.6%). The majority (93.9%) triaged patients for COVID-19 prior to procedure. N95 masks were used in (57.1%), isolation gowns in (74.2%) and head covers in (78.5%). Most centers (65%) did not extend use of N95 masks, however 50.9% of centers reused N95 masks. Almost all (91.4%) centers used standard endoscopic decontamination and most (69%) had no negative pressure rooms. Forty-two centers (25.8%) reported positive cases of SARS-CoV-2 infection among patients and 50 (30.7%) centers reported positive cases of SARS-CoV-2 infection among their healthcare workers. Conclusions Most GI endoscopy centers had a significant reduction in their volume and most procedures performed were urgent. Most centers used the recommended personal protective equipment (PPE) by GI societies however there is still a possibility of transmission of SARS-CoV-2 infection in GI endoscopy units.

ObjectiveThere is a lack of literature on postendoscopic retrograde cholangiopancreatography (ERCP) complications in predominantly black urban populations of low socioeconomic status. The aim of this study was to determine the incidence and predictors of post-ERCP complications in this patient population.DesignRetrospective review of ERCP cases performed at two hospitals from 2007 to 2017 was performed. The categories of complications evaluated were overall complications, severe or fatal complications, pancreatitis, bleeding, infection, perforation and cardiopulmonary events. Predictors of complications were determined by univariate analysis.ResultsA total of 1079 ERCP procedures were reviewed. There were 106 complications (9.8%). Twenty-one were severe (1.9%) and 20 were fatal (1.9%). Both post-ERCP pancreatitis (PEP) and post-ERCP bleeding occurred in 18 patients (1.7%) each. Risk factors for overall complications were male sex (OR 1.54), ASA grade IV or V (OR 2.19), prior history of PEP (OR 6.98) and pancreatic duct stent placement (OR 2.75). Those who were ASA grade III or lower (OR 0.4) or who underwent biliary stone extraction (OR 0.62) had fewer complications. PEP was more likely in those with a prior history of PEP (OR 37.6). Those with a suspected or known biliary duct stone had less frequent pancreatitis (OR 0.32). Post-ERCP bleeding was more likely in the presence of cholangitis (OR 8.72).ConclusionOutcomes of ERCP in a predominantly black urban population demonstrate a lower incidence of PEP and all-cause mortality compared with historical data reported in the general population. Potential risk factors for post-ERCP complications were identified but require larger studies for validation.

Background and Aims Pancreatic cancer organoids are tumor models of individualized human pancreatic ductal adenocarcinoma (PDA), created from surgical specimens and used for personalized treatment strategies. Unfortunately, most patients with PDA are not operative candidates. Creation of human PDA organoids at the time of initial tumor diagnosis is therefore critical. Our aim was to assess the feasibility of creating human PDA organoids by EUS fine-needle biopsy (EUS-FNB) sampling in patients with PDA. Methods In this prospective clinical trial in patients referred to evaluate a pancreatic mass, EUS-FNA was performed for initial onsite diagnosis. Two additional needle passes were performed with a 22-gauge FNB needle for organoid creation. Primary outcome was successful isolation of organoids within 2 weeks of EUS-FNB sampling (P0, no passages), confirmed by organoid morphology and positive genotyping. Results Thirty-seven patients with 38 PDA tumors were enrolled. Successful isolation of organoids (P0) was achieved in 33 of 38 tumors (87%). Establishment of PDA organoid lines for ≥5 passages of growth (P5, five passages) was reached in 25 of 38 tumors (66%). In the single patient with successful P5 FNB sampling–derived and P5 surgically derived organoids, there was identical matching of specimens. There were no serious adverse events. Two patients developed bleeding at the EUS-FNB puncture site requiring hemostasis clips. Conclusions Pancreatic cancer organoids can be successfully and rapidly created by means of EUS-FNB sampling using a 22-gauge needle at the time of initial diagnosis. Successful organoid generation is essential for precision medicine in patients with pancreatic cancer in whom most are not surgically resectable. (Clinical trial registration number: NCT03140592.)

We assessed the association of metformin use with survival in colorectal cancer in a population consists mostly of African-American and Afro-Caribbean patients. We identified 585 colorectal cancer patients, 167 (28.6%) and 418 (71.5%) were as diabetic (DM) and nondiabetic, respectively. The diagnosis of diabetes did not impact cancer survival or extent of disease. Overall, DMs with metformin use (D+M+) have better overall survival than both DMs without metformin use (D+M∼) and nondiabetics (D∼M∼), with a mean survival of 109.9 months compared with 95.7 and 106.1 months, respectively (log-rank p < 0.05). The use of metformin shows significant reduction of risk of mortality compared with nonusers (hazard ratio: 0.34; 95% CI: 0.15–0.81; p = 0.01). Use of insulin and status of diabetes did not have a significant impact on overall cancer survival.

Background and Aims Gastroenterology fellowships need to ensure that trainees achieve competence in upper endoscopy (EGD) and colonoscopy. Because the impact of structured feedback remains unknown in endoscopy training, this study compared the effect of structured feedback with standard feedback on trainee learning curves for EGD and colonoscopy. Methods In this multicenter, cluster, randomized controlled trial, trainees received either individualized quarterly learning curves or feedback standard to their fellowship. Assessment was performed in all trainees using the Assessment of Competency in Endoscopy tool on 5 consecutive procedures after every 25 EGDs and colonoscopies. Individual learning curves were created using cumulative sum (CUSUM) analysis. The primary outcome was the mean CUSUM score in overall technical and overall cognitive skills. Results In all, 13 programs including 132 trainees participated. The intervention arm (6 programs, 51 trainees) contributed 558 EGD and 600 colonoscopy assessments. The control arm (7 programs, 81 trainees) provided 305 EGD and 468 colonoscopy assessments. For EGD, the intervention arm (–.7 [standard deviation {SD}, 1.3]) had a superior mean CUSUM score in overall cognitive skills compared with the control arm (1.6 [SD, .8], P = .03) but not in overall technical skills (intervention, –.26 [SD, 1.4]; control, 1.76 [SD, .7]; P = .06). For colonoscopy, no differences were found between the 2 arms in overall cognitive skills (intervention, –.7 [SD, 1.3]; control, .7 [SD, 1.3]; P = .95) or overall technical skills (intervention, .1 [SD, 1.5]; control, –.1 [SD, 1.5]; P = .77). Conclusions Quarterly feedback in the form of individualized learning curves did not affect learning curves for EGD and colonoscopy in a clinically meaningful manner. (Clinical trial registration number: NCT02891304.)

Purpose The Next Accreditation System requires training programs to demonstrate competence among trainees. Within gastroenterology (GI), there are limited data describing learning curves and structured assessment of competence in esophagogastroduodenoscopy (EGD) and colonoscopy. In this study, the authors aimed to demonstrate the feasibility of a centralized feedback system to assess endoscopy learning curves among GI trainees in EGD and colonoscopy. Method During academic year 2016-2017, the authors performed a prospective multicenter cohort study, inviting participants from multiple GI training programs. Trainee technical and cognitive skills were assessed using a validated competence assessment tool. An integrated, comprehensive data collection and reporting system was created to apply cumulative sum analysis to generate learning curves that were shared with program directors and trainees on a quarterly basis. Results Out of 183 fellowships invited, 129 trainees from 12 GI fellowships participated, with an overall trainee participation rate of 72.1% (93/129); the highest participation level was among first-year trainees (90.9%; 80/88), and the lowest was among third-year trainees (51.2%; 27/53). In all, 1,385 EGDs and 1,293 colonoscopies were assessed. On aggregate learning curve analysis, third-year trainees achieved competence in overall technical and cognitive skills, while first- and second-year trainees demonstrated the need for ongoing supervision and training in the majority of technical and cognitive skills. Conclusions This study demonstrated the feasibility of using a centralized feedback system for the evaluation and documentation of trainee performance in EGD and colonoscopy. Furthermore, third-year trainees achieved competence in both endoscopic procedures, validating the effectiveness of current training programs.

Background and Aims: The incidence and mortality of colorectal cancer is persistently highest in Black/African-Americans in the United States. While access to care, barriers to screening, and poverty might explain these findings, there in increased interest in examining biological factors that impact the colonic environment. Our group is examining biologic factors that contribute to disparities in development of adenomas prospectively. In preparation for this and to characterize a potential patient population, we conducted a retrospective review of initial screening colonoscopies in a cohort of patients. Methods: A retrospective review was performed on initial average risk screening colonoscopies on patients (age 45 - 75 years) during 2012 at three institutions. Descriptive statistics and multivariable logistic regression models were used to examine the relationship between potential risk factors and the detection of adenomas. Results: Of the 2225 initial screening colonoscopies 1495 (67.2%) were performed on Black/African-Americans and 566 (25.4%) on Caucasians. Multivariable logistic regression revealed that older age, male sex, current smoking and teaching gastroenterologists were associated with higher detection of adenomas and these were less prevalent among Black/African-Americas except for age. Neither race, ethnicity, BMI, diabetes mellitus, HIV nor insurance was associated with adenoma detection. Conclusion: In this sample, there was no association between race and adenoma detection. While this may be due to a lower prevalence of risk factors for adenomas in this sample, our findings were confounded by a lower detection rate by consultant gastroenterologists at one institution. The study allowed us to rectify the problem and characterize patients for future trials.

INTRODUCTION: SARS-CoV-2 has infected more than 2 12 million people in United States GI symptoms have frequently been reported in association with COVID-19 Studies have reported prevalence and impact of GI symptoms on COVID-19 outcomes with marked variability in different regions of the world We investigated the association of GI symptoms with clinical characteristics and mortality in COVID-19 in a diverse multiethnic population in Brooklyn, NY METHODS: We performed a retrospective study of patients who were positive for SARS-CoV2 and were admitted from 04/01/20 through 04/15/20 at four academic medical centers in Brooklyn We collected data on COVID-19 symptoms, medical comorbidities, clinical outcomes and GI symptoms at presentation including nausea, vomiting, diarrhea, abdominal pain, anorexia, and GI bleeding (Table 1) We compared length of hospital stay, ICU admission rate, and all-cause mortality in patients with GI symptoms at presentation (Group A) with patients who did not have any GI symptoms (Group B) Charlson Comorbidity Index (CCI) was used to account for comorbid conditions and CURB65 score for pneumonia severity Groups were compared with Wilcoxon Rank Sum, Chi-Square and Fisher's exact test Logistic regression was used to evaluate the association of GI symptom at presentation with all-cause mortality RESULTS: Of the total of 680 patients included, 48 9% were black, average age was 66 8 years, no significant difference in gender distribution, and mean BMI for the cohort was 30 27 kg/m2 Table 1) 36 02% of patients had at least one GI symptom at presentation Most common presenting GI symptom was anorexia (19 7%) followed by diarrhea (13%) and nausea (7 2%) Baseline mean CCI score for group A and B were 3 50 and 3 85 respectively (P = 0 11) CURB65 score at presentation was lower in Group A (mean 1 61) compared to Group B (mean 1 83) (P = 0 028) There was no significant difference in ICU care requirements between the groups (17 6% (A) vs 21 8% (B), P = 0 18) Group A had slightly longer mean length of hospital stay 8 85 vs 8 30 days (group B), (P = 0 07) When adjusted for age, BMI, ethnicity, sex and pneumonia severity index, presence of a GI symptom at presentation was not associated with mortality (OR 0 8;95% CI: 0 55, 1 16;P = 0 24 CONCLUSION: In hospitalized COVID-19 patients, presence of GI symptoms at presentation was not associated with higher mortality Patients without a GI symptom presented with higher pneumonia severity

INTRODUCTION: With the onset of the COVID-19 pandemic, hospitals have restructured criteria for endoscopic procedures in order to reduce the number of aerosol-generating procedures and to minimize exposure of consultation services and staff to the virus and to preserve personal protective equipment We aimed to evaluate outcomes of patients who were hospitalized for SARS-CoV-2 and experienced gastrointestinal bleeding (GIB) METHODS: We performed a retrospective review of patient charts with confirmed COVID-19 between 03/12 and 05/11/2020 across four hospitals for whom gastroenterology was consulted for GIB We evaluated demographics, past medical history, anticoagulation use, number of units transfused, and mortality of patients who had GIB during hospital stay Patients who underwent endoscopy and managed medically were compared with Wilcoxon Rank Sum, Chi-Square and Fisher's exact test as appropriate RESULTS: Of the total 68 patients with GIB, 14 underwent endoscopic evaluation (Group A) and 54 were managed medically (Group B) Only two patients underwent endoscopic hemostatic therapy Age, gender and ethnicity were not significantly different between the two groups ICU admissions accounted for 5 (35 7%) from Group A and 15 (27 8%) from the Group B In terms of respiratory status, 21% in Group A compared to 48 7% in Group B required mechanical ventilation, BiPAP or high flow nasal canula Patients who were not receiving any anticoagulation were more likely to undergo endoscopy, however this was not statistically significant (P = 0 069) In the medically managed group, 35 patients (64 8%) received packed red blood cell transfusion with a mean of 2 8 units whereas 11 (78 6%) patients in the endoscopically managed group received a mean of 4 2 units Patients who underwent endoscopy had a mean hospital stay of 13 9 days whereas those treated conservatively had a mean of 12 6 days Mortality was 21 4% (3/14) in the group receiving endoscopy and 42 6% (23/54) in the medically managed group (P = 0 22) CONCLUSION: Although not statistically significant, GIB patients who were medically managed had higher mortality rate than patients who underwent endoscopies This is likely due to the severity of COVID-19, which was indicated by the patient's oxygenation requirement, and less likely from blood loss due to the lower mean units of pack red blood cell transfusion

Early detection of colorectal cancer (CRC) is crucial for effective treatment. Among CRC screening techniques, optical colonoscopy is widely considered the gold standard. However, it is a costly and invasive procedure with a low rate of compliance. Our long-term goal is to develop molecular imaging agents for the non-invasive detection of CRC by molecular imaging-based colonoscopy using CT, MRI or fluorescence. To achieve this, cell surface targets must be identified and validated. Here, we report the discovery of cell-surface markers that distinguish CRC from surrounding tissues that could be used as molecular imaging targets. Profiling of mRNA expression microarray data from patient tissues including adenoma, adenocarcinoma, and normal gastrointestinal tissues was used to identify potential CRC specific cell-surface markers. Of the identified markers, six were selected for further validation (CLDN1, GPR56, GRM8, LY6G6D/F, SLCO1B3 and TLR4). Protein expression was confirmed by immunohistochemistry of patient tissues. Except for SLCO1B3, diffuse and low expression was observed for each marker in normal colon tissues. The three markers with the greatest protein overexpression were CLDN1, LY6G6D/F and TLR4, where at least one of these markers was overexpressed in 97% of the CRC samples. GPR56, LY6G6D/F and SLCO1B3 protein expression was significantly correlated with the proximal tumor location and with expression of mismatch repair genes. Marker expression was further validated in CRC cell lines. Hence, three cell-surface markers were discovered that distinguish CRC from surrounding normal tissues. These markers can be used to develop imaging or therapeutic agents targeted to the luminal surface of CRC.

Background: The incidence of colorectal cancer is persistently higher in Black/African Americans than other races in the United States. It is less clear whether Black/African Americans are at higher risk for colonic precancerous polyps, which represent an earlier stage in colorectal adenoma-carcinoma progression. Methods: A retrospective chart review was performed on initial average-risk screening colonoscopies on patients (age 45-75 years) during 2012 at 3 institutions. Multivariable logistic regression models were used to examine the relationship between potential risk factors and the detection of precancerous polyps. Results: Of the 2,225 initial screening colonoscopies, 1,495 (67.2%) were performed on Black/African Americans and 566 (25.4%) on Caucasian non-Hispanic patients. The mean age of initial colonoscopies was 57.1 y and 56.0 y for Black and Caucasian patients, respectively. Male patients represented 32.0% and 42.8% of the Black and Caucasian patients, respectively. Obese patients represented 41.4% and 31% of Black and Caucasian patients. A higher percentage (30%) of the Black patients were diagnosed with diabetes mellitus compared to Caucasians (11%). Multivariable logistic regression revealed that performance of the colonoscopy by academic gastroenterologists was associated with higher precancerous polyp detection compared to contractual nonacademic gastroenterologists (OR 1.69 95% CI 1.32-2.17, p Conclusions: It is imperative that metrics of polyp detection rates be routinely monitored to ensure that all patients have access to high-quality screening colonoscopies. A prospective observational cohort study will help further identify factors associated with precancerous polyp detection, now that variations in operator detection rates have been addressed. Citation Format: Yakira David, Lorenzo Ottaviano, Jihye Park, Sadat Iqbal, Michelle Likhtshteyn, Samir Kumar, Helen Lyo, Ayanna Lewis, Brandon Lung, Jesse Frye, Li Huang, Ellen Li, Jie Yang, Laura Martello, Shivakumar Vignesh, Joshua Miller, Evan Grossman. Factors contributing to precancerous polyp detection in initial screening colonoscopies [abstract]. In: Proceedings of the Eleventh AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2018 Nov 2-5; New Orleans, LA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl):Abstract nr B102.