Amitabh Chak, Associate Professor
Case Western Reserve University 10900 Euclid Ave Cleveland, Oh 44106
Grant 5R01DK070863-03 from National Institute Of Diabetes And Digestive And Kidney Diseases IRG: CIGP
Abstract: Barrett s esophagus is the precursor of esophageal adenocarcinoma. Both Barrett s esophagus and esophageal adenocarcinoma are closely associated with gastroesophageal reflux. Screening endoscopy is therefore recommended for the evaluation of chronic gastroesophageal reflux symptoms. Endoscopic surveillance, performed in those identified with Barrett s esophagus, detects cancer at an early stage. However, the large majority of these cancers occur in previously undiagnosed Barrett s esophagus and nearly half of these persons have no history of gastroesophageal reflux symptoms. Identification of genetic risk factors would lead to more effective screening programs and improved understanding of the molecular pathogenesis of these diseases. Our prior case control study demonstrated familial aggregation of Barrett s esophagus and its associated cancers, which we termed Familial Barrett s Esophagus. We have since developed family recruitment and endoscopic screening methods to identify Familial Barrett s Esophagus. Recent molecular genetic studies have identified one putative locus and suggest the existence of at least one other locus linked to these diseases. These family recruitment, endoscopic screening, and genetic analysis methods will now be used to test the following central hypothesis Familial Barrett Esophagus has a genetic basis. The specific aims of this proposal are (1) To recruit and screen family members of esophageal adenocarcinoma patients, comparing age of cancer onset between probands classified as familial with those classified as apparently sporadic; (2) To perform endoscopic screening and measure the recurrence risk of Barrett s esophagus in siblings of probands with Barrett s esophagus and esophageal adenocarcinoma; and (3) To identify loci and map susceptibility genes associated with Familial Barrett s Esophagus. Using the multidisciplinary approach of our collaborative team of investigators, these aims will result in new information regarding a genetic predisposition to the development of Barrett s esophagus and esophageal adenocarcinoma.
Keywords: Barretts esophagus, cancer risk, esophagus neoplasm, family genetics, genetic susceptibility, adenocarcinoma, disease /disorder onset, genetic mapping, neoplasm /cancer genetics, preneoplastic state, clinical research, endoscopy, genetic screening, human subject
Project start date: 2005-09-30
Project end date: 2010-08-31
5R01DK070863-03 (2007): $748683
Sponsored Links Excellgen http://Excellgen.com
Amitabh Chak, Associate Professor
Case Western Reserve University 10900 Euclid Ave Cleveland, Oh 44106
Grant 5R01DK070863-02 from National Institute Of Diabetes And Digestive And Kidney Diseases IRG: CIGP
Abstract: Barrett s esophagus is the precursor of esophageal adenocarcinoma. Both Barrett s esophagus and esophageal adenocarcinoma are closely associated with gastroesophageal reflux. Screening endoscopy is therefore recommended for the evaluation of chronic gastroesophageal reflux symptoms. Endoscopic surveillance, performed in those identified with Barrett s esophagus, detects cancer at an early stage. However, the large majority of these cancers occur in previously undiagnosed Barrett s esophagus and nearly half of these persons have no history of gastroesophageal reflux symptoms. Identification of genetic risk factors would lead to more effective screening programs and improved understanding of the molecular pathogenesis of these diseases. Our prior case control study demonstrated familial aggregation of Barrett s esophagus and its associated cancers, which we termed Familial Barrett s Esophagus. We have since developed family recruitment and endoscopic screening methods to identify Familial Barrett s Esophagus. Recent molecular genetic studies have identified one putative locus and suggest the existence of at least one other locus linked to these diseases. These family recruitment, endoscopic screening, and genetic analysis methods will now be used to test the following central hypothesis Familial Barrett Esophagus has a genetic basis. The specific aims of this proposal are (1) To recruit and screen family members of esophageal adenocarcinoma patients, comparing age of cancer onset between probands classified as familial with those classified as apparently sporadic; (2) To perform endoscopic screening and measure the recurrence risk of Barrett s esophagus in siblings of probands with Barrett s esophagus and esophageal adenocarcinoma; and (3) To identify loci and map susceptibility genes associated with Familial Barrett s Esophagus. Using the multidisciplinary approach of our collaborative team of investigators, these aims will result in new information regarding a genetic predisposition to the development of Barrett s esophagus and esophageal adenocarcinoma.
Keywords: Barretts esophagus, cancer risk, esophagus neoplasm, family genetics, genetic susceptibility, adenocarcinoma, disease /disorder onset, genetic mapping, neoplasm /cancer genetics, preneoplastic state, clinical research, endoscopy, genetic screening, human subject
Project start date: 2005-09-30
Project end date: 2010-08-31
5R01DK070863-02 (2006): $745169
Amitabh Chak, Associate Professor
Medicinecase Western Reserve University
10900 Euclid Ave
cleveland, Oh 441064919
Grant 5R01DK070863-04 from National Institute Of Diabetes And Digestive And Kidney Diseases IRG: CIGP
Abstract: Barrett´s esophagus is the precursor of esophageal adenocarcinoma. Both Barrett´s esophagus and esophageal adenocarcinoma are closely associated with gastroesophageal reflux. Screening endoscopy is therefore recommended for the evaluation of chronic gastroesophageal reflux symptoms. Endoscopic surveillance, performed in those identified with Barrett´s esophagus, detects cancer at an early stage. However, the large majority of these cancers occur in previously undiagnosed Barrett´s esophagus and nearly half of these persons have no history of gastroesophageal reflux symptoms. Identification of genetic risk factors would lead to more effective screening programs and improved understanding of the molecular pathogenesis of these diseases. Our prior case control study demonstrated familial aggregation of Barrett´s esophagus and its associated cancers, which we termed Familial Barrett´s Esophagus. We have since developed family recruitment and endoscopic screening methods to identify Familial Barrett´s Esophagus. Recent molecular genetic studies have identified one putative locus and suggest the existence of at least one other locus linked to these diseases. These family recruitment, endoscopic screening, and genetic analysis methods will now be used to test the following central hypothesis Familial Barrett Esophagus has a genetic basis. The specific aims of this proposal are (1) To recruit and screen family members of esophageal adenocarcinoma patients, comparing age of cancer onset between probands classified as familial with those classified as apparently sporadic; (2) To perform endoscopic screening and measure the recurrence risk of Barrett´s esophagus in siblings of probands with Barrett´s esophagus and esophageal adenocarcinoma; and (3) To identify loci and map susceptibility genes associated with Familial Barrett´s Esophagus. Using the multidisciplinary approach of our collaborative team of investigators, these aims will result in new information regarding a genetic predisposition to the development of Barrett´s esophagus and esophageal adenocarcinoma
Keywords: Barretts esophagus, cancer risk, esophagus neoplasm, family genetics, genetic susceptibility adenocarcinoma, disease /disorder onset, genetic mapping, neoplasm /cancer genetics, preneoplastic state clinical research, endoscopy, genetic screening, human subject
Project start date: 2005-09-30
Project end date: 2010-08-31
5R01DK070863-04 (2008): $755466
Grants awarded to Amitabh Chak
CONSORTIUM TO IDENTIFY GENES FOR BARRETT´S ESOPHAGUS
Amitabh Chak, Professor
Case Western Reserve University, 10900 Euclid Ave, Cleveland, Oh 44106-7015
Abstract: This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Adenocarcinomas of the esophagus and adenocarcinomas of the gastroesophageal junction are postulated to be complex genetic diseases. Combined influences of environmental factors and genetic susceptibility likely influence the age at which these cancers develop. Initially we determined whether familiality and other recognized risk factors are associated with the development of these cancers at an earlier age. A structured validated questionnaire was utilized to collect self reported data on gastroesophageal reflux symptoms, risk factors for Barrett´s esophagus (BE) and family history, including age of cancer diagnosis in affected relatives from probands with BE, adenocarcinoma of the esophagus, or adenocarcinoma of the gastro-esophageal junction, at five tertiary care academic hospitals. Medical records of all relatives reported to be affected were requested from hospitals providing this cancer care to confirm family histories. Familiality of BE/cancer, obesity (defined as body mass index > 30), gastro-esophageal reflux symptoms, and other risk factors were assessed for association with a young age of cancer diagnosis. There were no significant differences in symptoms of gastroesophageal reflux, body mass index, race, gender, and smoking history between familial and non-familial cancers. However, mean age of cancer diagnosis was significantly younger comparing those who were obese one year prior to diagnosis with those who were non-obese, mean age 58.99 yrs vs. 63.6 yrs, p = 0.008. Multivariable modeling of age at cancer diagnosis showed that obesity 1 year before diagnosis was associated with a younger age of cancer diagnosis (p=0.005) after adjustment for heartburn and regurgitation duration
Keywords: Adenocarcinoma; Adenocarcinoma of the Cardioesophageal junction; Adenocarcinoma of the Esophagus; Adenocarcinoma of the Gastroesophageal Junction; Adenoma, Malignant; Affect; Age; BMI percentile; BMI z-score; Barrett Esophagus; Barrett Syndrome; Barrett Ulcer; Body mass index; CRISP; Cancer of the Esophagus; Cancers; Columnar Epithelial-Lined Lower Esophagus; Columnar-Lined Esophagus; Complex; Computer Retrieval of Information on Scientific Projects Database; Data; Development; Diagnosis; Environmental Factor; Environmental Risk Factor; Epidemiology, Family Medical History; Esophageal; Esophageal Adenocarcinoma; Esophageal Cancer; Esophageal Reflux; Esophagus; Esophagus Cancer; Familiar Malignant Neoplasm; Family Medical History; Family history of; Funding; GERD; Gastro-oesophageal Reflux; Gastroesophageal Reflux; Gastroesophageal reflux disease; Gastrointestinal Tract, Esophagus; Gender; Genes; Genetic Condition; Genetic Diseases; Genetic Predisposition; Genetic Predisposition to Disease; Genetic Susceptibility; Genetic analyses; Grant; HOSP; Heartburn; Hereditary Cancer; Hereditary Disease; Hereditary Malignant Neoplasm; Hospitals; Human Genetics; Inherited Predisposition; Inherited Susceptibility; Institution; Investigators; Malignant Esophageal Neoplasm; Malignant Esophageal Tumor; Malignant Neoplasms; Malignant Tumor; Malignant Tumor of the Esophagus; Malignant neoplasm of esophagus; Medical Records; Modeling; Molecular Disease; NIH; National Institutes of Health; National Institutes of Health (U.S.); Non obese; Nonobese; Obesity; Patient Self-Report; Pyrosis; Questionnaires; Quetelet index; Race; Racial Group; Relative; Relative (related person); Reporting; Research; Research Personnel; Research Resources; Researchers; Resources; Risk Factors; Self-Report; Smoking History; Source; Stocks, Racial; Structure; Symptoms; United States National Institutes of Health; adiposity; cancer care; cancer diagnosis; corpulence; corpulency; corpulentia; environmental risk; familial cancer; gastroesophageal junction adenocarcinoma; genetic analysis; genetic disorder; genetic etiology; genetic mechanism of disease; genetic vulnerability; hereditary disorder; malignancy; neoplasm/cancer; obese; obese people; obese person; obese population; proband; tertiary care
Project start date: 2009-08-01
Project end date: 2010-07-31
Budget start date: 1-AUG-2009
Budget end date: 31-JUL-2010
5P41RR003655-24_6728 (2009): $9697
ACUTE PANCREATITIS--A DIAGNOSTIC DILEMMA
Amitabh Chak, Associate Professor
Case Western Reserve University 10900 Euclid Ave Cleveland, Oh 44106
Grant 5M01RR000080-360880 from National Center For Research Resources
Abstract: The purpose of this study is to determine the usefulness of a rapid urine amylase test in the diagnosis of acute pancreatitis. The specific aim is to determine the concordance of the rapid urine amylase test in patients with post-ERCP induced hyperamylasemia compared to standard tests in the diagnosis of acute chemical pancreatitis. Results to date indicate that the Rapignost test has high specificity and sensitivity in diagnosing acute pancreatitis in the post-ERCP model of hyperamylasemia.
Keywords: acute disease /disorder, amylase, diagnosis design /evaluation, pancreatitis, urinalysis, cholangiography, diagnosis quality /standard, diagnostic test, pancreas visualization, rapid diagnosis, clinical research, human subject
Project start date: 1997-12-01
Project end date: 1998-11-30
Insulin/IGF-1 Pathway In Barrett´s Esophagus
Amitabh Chak, Associate Professor
Medicinecase Western Reserve University
10900 Euclid Ave
cleveland, Oh 441064919
Grant 1R21CA135692-01A1 from National Cancer Institute IRG: ZRG1
Abstract: The alarming rise in esophageal adenocarcinoma incidence over the past 3 decades coupled with a poor prognosis make this cancer an important national public health issue. Adenocarcinoma of the esophagus arises in Barrett´s esophagus, a pre- neoplastic metaplastic transformation of the squamous epithelium that is closely associated with gastroesophageal reflux. We, and others, have found that Barrett´s esophagus and esophageal adenocarcinoma are independently linked to obesity. The increased incidence of these diseases is partially attributable to a pandemic of obesity in this country. Increased levels of insulin and the Type 1 insulin growth factor are postulated to be a key mechanistic link between obesity, the Western diet, and carcinogenesis in other cancers. Our central hypothesis is that "hyperinsulinemia and high levels of Type 1 insulin growth factor (IGF-1) possibly related to the Western diet in susceptible individuals contribute to genetic and epigenetic changes in the esophageal epithelium that are key to the development of Barrett´s esophagus and its subsequent progression to esophageal adenocarcinoma". Components of this complex hypothesis will be explored in this case control study whose aims are -- to 1. Calculate insulin resistance and measure free IGF-1; 2. Assay phosphorylated insulin receptor substrate- 1 (phos-IRS-1) immunostaining; and 3. Assess for aberrant methylation of selected candidate genes in Barrett´s esophagus patients and control subjects. Successful conduct of this pilot study will enable future studies which are a) examining the interaction of the insulin/IGF proliferative pathway with gastreoesophageal reflux in esophageal carcinogenesis; b) studies to identify important dietary factors in the development of Barrett´s esophagus; c) risk stratification of Barrett´s esophagus based on biomarkers; and d) trials of potential therapeutic agents based on the insulin/IGF pathway. The research proposed in this application will determine whether increased level of the hormones, insulin and insulin growth factor-1, explain the link between obesity and adenocarcinoma of the esophagus. It will also enable studies to identify factors in the Western diet that might predispose to the development of Barrett´s esophagus and cancer. Furthermore, this research will identify biomarkers that may lead to methods for identifying people with Barrett´s esophagus who are at risk for developing cancer and lead to treatments aimed at halting or reversing this process
Project start date: 2008-07-21
Project end date: 2010-06-30
1R21CA135692-01A1 (2008): $195150
PATIENT ORIENTED RESEARCH IN BARRETT S ESOPHAGUS
Amitabh Chak, Associate Professor
Case Western Reserve University 10900 Euclid Ave Cleveland, Oh 44106
Grant 2K24DK002800-06 from National Institute Of Diabetes And Digestive And Kidney Diseases IRG: DDK
Abstract: Patient oriented research (POR) must translate advances in basic and technical sciences into an increased understanding of disease processes and novel clinical applications that improve patient care. The investigator s long-term career goals are to - 1) encourage POR in gastroenterology; 2) attract and mentor young trainees in POR; and 3) continually enhance his personal POR skills. The K24 mechanism has been instrumental in developing a POR program with a focus on Barrett s esophagus (BE) and esophageal adenocarcinoma (EAC). Successful mentored research projects developed novel low cost methods for BE screening that were subsequently used to demonstrate familial aggregation of BE and EAC. K24 support has also allowed the investigator to mentor nine fellows and seven residents in numerous projects. Many have begun productive academic careers or gastroenterology fellowships. Enrollment in epidemiological and genetic courses has further enhanced the investigator s personal skills in POR. A new R01 project aimed at characterizing familial BE and the identification of the heritable genetic mutation(s) that determine susceptibility to Barrett s esophagus form the major basis of the investigator s ongoing POR program. Novel research investigating a potential link between obesity and BE through the insulin/IGF-1 pathway is proposed in this application. Renewed support will allow the investigator to meet his career goals by - 1) directing and growing POR activities within his division; 2) continuing to attract and mentor residents, fellows, and advanced fellows in his expanding research program; and 3) continuing coursework in statistical genetics and cancer biology.
Keywords: Barretts esophagus, insulin, insulinlike growth factor, obesity, mentoring /mentor, clinical research, human subject, patient oriented research
Project start date: 1999-12-01
Project end date: 2011-06-30
2K24DK002800-06 (2006): $179933
PATIENT ORIENTED RESEARCH IN BARRETT´S ESOPHAGUS
Amitabh Chak, Professor
Case Western Reserve University, 10900 Euclid Ave, Cleveland, Oh 44106-7015
Grant 5K24DK002800-10 from National Institute Of Diabetes And Digestive And Kidney Diseases
Abstract: Patient oriented research (POR) must translate advances in basic and technical sciences into an increased understanding of disease processes and novel clinical applications that improve patient care. The investigator´s long-term career goals are to - 1) encourage POR in gastroenterology; 2) attract and mentor young trainees in POR; and 3) continually enhance his personal POR skills. The K24 mechanism has been instrumental in developing a POR program with a focus on Barrett´s esophagus (BE) and esophageal adenocarcinoma (EAC). Successful mentored research projects developed novel low cost methods for BE screening that were subsequently used to demonstrate familial aggregation of BE and EAC. K24 support has also allowed the investigator to mentor nine fellows and seven residents in numerous projects. Many have begun productive academic careers or gastroenterology fellowships. Enrollment in epidemiological and genetic courses has further enhanced the investigator´s personal skills in POR. A new R01 project aimed at characterizing familial BE and the identification of the heritable genetic mutation(s) that determine susceptibility to Barrett´s esophagus form the major basis of the investigator´s ongoing POR program. Novel research investigating a potential link between obesity and BE through the insulin/IGF-1 pathway is proposed in this application. Renewed support will allow the investigator to meet his career goals by - 1) directing and growing POR activities within his division; 2) continuing to attract and mentor residents, fellows, and advanced fellows in his expanding research program; and 3) continuing coursework in statistical genetics and cancer biology
Keywords: Adenocarcinoma of the Esophagus; Affect; Age; Barrett Esophagus; Barrett Syndrome; Barrett Ulcer; Cancer Biology; Cancers; Chronic; Columnar Epithelial-Lined Lower Esophagus; Columnar-Lined Esophagus; Complex; Cross-Product Ratio; DNA Alteration; DNA mutation; Development; Disease; Disorder; Enrollment; Epidemiology; Esophageal Adenocarcinoma; Esophageal Reflux; Family; Fellowship; First Degree Relative; GERD; Gastro-oesophageal Reflux; Gastroenterology; Gastroesophageal Reflux; Gastroesophageal reflux disease; Gene Alteration; Gene Mutation; Generations; Genetic; Genetic Predisposition; Genetic Predisposition to Disease; Genetic Susceptibility; Genetic mutation; Germ Lines; Goals; Hereditary; Humulin R; Incidence; Individual; Inherited; Inherited Predisposition; Inherited Susceptibility; Insulin; Insulin (ox), 8A-L-threonine-10A-L-isoleucine-30B-L-threonine-; Insulin, Regular; Interdisciplinary Research; Interdisciplinary Study; Investigators; K24 Mechanism; K24 Program; Link; Linkage (Genetics); Malignant Neoplasms; Malignant Tumor; Maps; Mentors; Metaplasia; Metaplastic Change; Methods; Midcareer Investigator Award in Patient-Oriented Research; Midcareer Investigator Award in Patient-Oriented Research (K24); Multidisciplinary Collaboration; Multidisciplinary Research; Novolin R; Obesity; Odds Ratio; Pathway interactions; Patient Care; Patient Care Delivery; Patients; Pedigree; Predisposition; Predisposition gene; Process; Programs (PT); Programs [Publication Type]; R01 Mechanism; R01 Program; RPG; Recurrence; Recurrent; Relative Odds; Reporting; Research; Research Activity; Research Grants; Research Personnel; Research Project Grants; Research Projects; Research Projects, R-Series; Researchers; Risk Ratio; Science; Screening procedure; Sequence Alteration; Siblings; Somatic Mutation; Study, Interdisciplinary; Susceptibility; Susceptibility Gene; Testing; Translating; Translatings; adiposity; base; career; clinical applicability; clinical application; corpulence; corpulency; corpulentia; cost; design; designing; disease/disorder; enroll; experiment; experimental research; experimental study; genetic etiology; genetic linkage; genetic mechanism of disease; genetic pedigree; genetic vulnerability; improved; language translation; male; malignancy; meetings; member; neoplasm/cancer; novel; obese; obese people; obese person; obese population; pathway; patient oriented research; patient oriented study; pedigree structure; predisposing gene; proband; programs; research study; screening; screenings; skills
Project start date: 1999-12-01
Project end date: 2011-06-30
Budget start date: 1-JUL-2010
Budget end date: 30-JUN-2011
PFA/PA: PA-04-107
5K24DK002800-10 (2010): $178853
5K24DK002800-09 (2009): $178853
5K24DK002800-08 (2008): $178853
5K24DK002800-07 (2007): $178853
TRANSNASAL ESOPHAGOSCOPY VS. ESOPHAGEAL CAPSULE ENDOSCOPY FOR BARRETT´S SCREENING
Amitabh Chak
Case Western Reserve University, 10900 Euclid Ave, Cleveland, Oh 44106-7015
Grant 1RC4DK090645-01 from National Institute Of Diabetes And Digestive And Kidney Diseases
Abstract: Metaplastic transformation of the esophagus, termed Barrett´s esophagus (BE) is a premalignant condition with a 1 per 200 patient-years risk of malignant progression to esophageal adenocarcinoma. The incidence of esophageal adenocarcinoma has increased dramatically, over three fold in the past three decades, while the prognosis of this cancer has remained poor. Detection of early cancers within a BE surveillance program is currently the only hope for improving prognosis. BE is associated with chronic gastroesophageal reflux, however, screening endoscopy for BE in these patients cannot be recommended because it is expensive and there is insufficient evidence to support its efficacy. Since endoscopy is not performed in most individuals with gastroesophageal reflux symptoms and 4 in 10 patients with BE are also asymptomatic, current medical practice in the United States detects only a minority of BE cases. Clearly we need more effective methods for BE screening. Esophageal capsule endoscopy and transnasal esophagoscopy are two novel unsedated endoscopic methods for esophageal examination. Capsule endoscopy is more expensive and likely not as sensitive as TNE. However, it may be more acceptable than TNE as a screening examination. To determine which is preferable for BE screening we propose research comparing the effectiveness of these two new modalities with the following Specific Aims - 1) train physician extenders at a VA in the performance of both procedures; 2) compare acceptability when the two procedures are used for BE screening in primary care clinics at a VA; and 3) measure and compare patient satisfaction with the two procedures. This research will identify which of the two unsedated procedure should be implemented in BE screening. Cancer of the esophagus has a poor prognosis unless it is detected early. Barrett´s esophagus is a pre- cancerous condition that is diagnosed by endoscopy, however most individuals with Barrett´s esophagus remain undetected. The proposed research will compare two new techniques, a wireless video capsule and an ultraslim endoscope, for detecting Barrett´s esophagus. The results will define whether these techniques are accepted and well tolerated by veterans at a Veterans Affairs hospital and determine how satisfied they are with screening examinations performed by nurse practitioners and physician assistants. Ultimately, this study will lead to more effective screening programs for Barrett´s esophagus
Keywords: 21+ years old; Adenocarcinoma; Adenocarcinoma of the Esophagus; Adenoma, Malignant; Adopted; Adult; Barrett Esophagus; Barrett Syndrome; Barrett Ulcer; CAPS; Cancer Prognosis; Cancer Screening for Patients; Cancer Staging; Cancerous; Cancers; Capsules; Characteristics; Chronic; Client satisfaction; Clinic; Columnar Epithelial-Lined Lower Esophagus; Columnar-Lined Esophagus; Data; Development; Diagnosis; Diagnostic Neoplasm Staging; Doctor`s Assistants; Dysplasia; Early Diagnosis; Endoscopes; Endoscopy; Epidemiology / Surveillance; Esophageal; Esophageal Adenocarcinoma; Esophageal Reflux; Esophagoscopy; Esophagus; Forecast of outcome; GERD; Gastro-oesophageal Reflux; Gastroesophageal Reflux; Gastroesophageal reflux disease; Gastrointestinal Tract, Esophagus; HOSP; Hospitals; Human, Adult; Incidence; Individual; Insurance; Investigation; Investigators; Lead; Malignant; Malignant - descriptor; Malignant Neoplasms; Malignant Tumor; Measures; Medical; Medical Surveillance; Metaplastic; Methods; Methods and Techniques; Methods, Other; Minority; Modality; Neoplasm Staging; Nurse Practitioners; Patient Satisfaction; Patients; Pb element; Performance; Physician Assistants; Physicians; Physicians` Extenders; Population; Populations at Risk; Pre-Malignant; Precancerous Conditions; Premalignant; Premalignant Condition; Premalignant State; Primary Care; Primary Health Care; Primary Healthcare; Procedures; Prognosis; Programs (PT); Programs [Publication Type]; Randomized; Randomized Controlled Trials; Research; Research Personnel; Research Proposals; Researchers; Risk; Risk Estimate; Screening for cancer; Screening procedure; Sedation procedure; Surveillance; Surveillance Program; Survey Instrument; Surveys; Symptoms; Techniques; Testing; Training; Tumor Staging; United States; Veterans; Wireless Technology; adult human (21+); capsule (pharmacologic); cost; disease diagnosis; dyscrasia; early cancer detection; early detection; gastrointestinal; heavy metal Pb; heavy metal lead; improved; male; malignancy; minimally invasive; neoplasm/cancer; novel; outcome forecast; precancerous; precancerous state; programs; randomisation; randomization; randomized controlled study; randomly assigned; screening; screenings; sedation; wireless
Relevance: Cancer of the esophagus has a poor prognosis unless it is detected early. Barrett´s esophagus is a pre- cancerous condition that is diagnosed by endoscopy, however most individuals with Barrett´s esophagus remain undetected. The proposed research will compare two new techniques, a wireless video capsule and an ultraslim endoscope, for detecting Barrett´s esophagus. The results will define whether these techniques are accepted and well tolerated by veterans at a Veterans Affairs hospital and determine how satisfied they are with screening examinations performed by nurse practitioners and physician assistants. Ultimately, this study will lead to more effective screening programs for Barrett´s esophagus
Project start date: 2010-09-30
Project end date: 2012-08-31
Budget start date: 30-SEP-2010
Budget end date: 31-AUG-2012
PFA/PA: RFA-OD-10-008
1RC4DK090645-01 (2010): $805318
FAMILIAL BARRETT´S ESOPHAGUS SUMMIT
Amitabh Chak, Professor
Case Western Reserve University, 10900 Euclid Ave, Cleveland, Oh 44106-7015
Grant 1R13CA144432-01 from National Cancer Institute
Abstract: Introduction and Background Familial Barrett´s Esophagus (FBE), the familial aggregation of Barrett´s esophagus (BE), esophageal adenocarcinoma, and esophagogastric junctional adenocarcinoma, is a complex genetic trait, likely caused by genetic variants that predispose to disease susceptibility. Various family based and population based study designs, each with its own unique strengths and weaknesses, are utilized in the research of complex genetic diseases like FBE. Successful gene searches require a team approach that combines clinicians, epidemiologists, statisticians, pathologists, and molecular biologists in large collaborative accrual networks. Aim The proposed FBE Summit will bring national and international investigators interested in the genetic susceptibility to Barrett´s esophagus and esophageal adenocarcinoma together to - 1) determine a common definition of the FBE phenotype/trait; 2) develop mutual transfer agreements for sharing samples; 3) select common genotyping platforms for data sharing; 4) define the most promising joint study designs for identifying susceptibility genes; 5) develop joint collaborative proposals; and 6) identify project managers who will ensure the success of these research teams. Previous Work The FBE Summit is an outgrowth of our annual FBE consortium meeting, which began in 2002. These annual meetings have helped us grow our familial research to investigators at 7 institutions, publish 7 manuscripts on various epidemiological aspects of FBE, and create a joint bio-repository from identified FBE pedigrees. Plan for Meeting and Expected Products The organizing committee identified six important issues -- trait definition, accrual, bio-banking, study design, genotyping, and team research that need to be addressed to advance FBE research. The format of the previously successful NCI sponsored Barrett´s Esophagus Translational Research (BETR) Working Group meeting was adopted for this meeting. Invited speakers will cover these six important issues during a full day FBE Summit meeting on May 1, 2010 in Cleveland. Talks will be followed by breakout sessions, chaired by members of the organizing committee. Specific goals of the breakout sessions will include the development of mechanisms for creating national and international consortia and facilitating specimen and data sharing. Subsequent publication of the invited lectures and the action items from the breakout sessions will enable the formation of collaborative research teams and large scale study proposals that are essential for progress in complex genetic diseases such as Barrett´s esophagus and esophageal adenocarcinoma. The FBE Summit meeting would promote Familial Barrett´s Esophagus research. The ultimate goal of this research is to identify inherited genetic mutations that make individuals susceptible to developing Barrett´s esophagus and cancers. Genetic blood tests could then be developed to improve endoscopic screening efforts in high risk groups. Furthermore, the identification of these genes would provide mechanistic insights into these diseases and also provide targets for developing novel therapeutic strategies
Keywords: Address; Adenocarcinoma; Adenocarcinoma of the Esophagus; Adenoma, Malignant; Adopted; Articulation; Barrett Esophagus; Barrett Syndrome; Barrett Ulcer; Blood Tests; Cancer of the Esophagus; Columnar Epithelial-Lined Lower Esophagus; Columnar-Lined Esophagus; Complex; Complex Genetic Trait; DNA Alteration; DNA mutation; Development; Diathesis; Disease; Disease susceptibility; Disorder; Ensure; Epidemiologist; Epidemiology; Esophageal Adenocarcinoma; Esophageal Cancer; Esophagus Cancer; Family; Gene Alteration; Gene Mutation; Genes; Genetic; Genetic Condition; Genetic Diseases; Genetic Predisposition; Genetic Predisposition to Disease; Genetic Susceptibility; Genetic mutation; Genotype; Goals; Group Meetings; Hematologic Tests; Hematological Tests; Hematology Testing; Hereditary; Hereditary Disease; Individual; Inherited; Inherited Predisposition; Inherited Susceptibility; Institution; International; Investigators; Joints; Lectures; Lectures (PT); Lectures [Publication Type]; Malignant Esophageal Neoplasm; Malignant Esophageal Tumor; Malignant Tumor of the Esophagus; Malignant neoplasm of esophagus; Manuscripts; Meetings, Group; Molecular; Molecular Disease; Pathologist; Pedigree; Phenotype; Predisposition gene; Publications; Publishing; Research; Research Design; Research Personnel; Research Specimen; Researchers; Sampling; Scientific Publication; Screening procedure; Sequence Alteration; Specimen; Study Type; Susceptibility Gene; Transfer Agreement; Translational Research Working Group; Work; base; disease/disorder; disease/disorder proneness/risk; genetic disorder; genetic etiology; genetic mechanism of disease; genetic pedigree; genetic variant; genetic vulnerability; hereditary disorder; high risk; improved; insight; interest; lectures; liability to disease; meetings; member; new therapeutics; next generation therapeutics; novel therapeutics; pedigree structure; population based; predisposing gene; public health relevance; repository; screening; screenings; sharing data; study design; success; trait
Relevance: PUBLIC HEALTH RELEVANCE The FBE Summit meeting would promote Familial Barrett´s Esophagus research. The ultimate goal of this research is to identify inherited genetic mutations that make individuals susceptible to developing Barrett´s esophagus and cancers. Genetic blood tests could then be developed to improve endoscopic screening efforts in high risk groups. Furthermore, the identification of these genes would provide mechanistic insights into these diseases and also provide targets for developing novel therapeutic strategies
Project start date: 2010-04-05
Project end date: 2011-03-31
Budget start date: 5-APR-2010
Budget end date: 31-MAR-2011
PFA/PA: PA-08-149
1R13CA144432-01 (2010): $10000
Sponsored Links Excellgen http://Excellgen.com
Familial Aggregation Of Barrett s Esophagus
Amitabh Chak, Associate Professor
University Hospitals Of Cleveland Lksd 1400 Cleveland, Oh 441065000
Grant 5R03DK061426-02 from National Institute Of Diabetes And Digestive And Kidney Diseases IRG: ZDK1
Abstract: Esophageal adenocarcinoma is associated with a very poor prognosis. More effective screening, surveillance, and treatment strategies are required. The overall aim of this pilot proposal is to develop methodologies that will facilitate future multicenter studies aimed at assessing the familial aggregation of Barrett s esophagus and esophageal adenocarcinoma. Three specific methodologies will be developed 1. A multicenter network will be established at five different institutions to enable the measurement of the prevalence of familial Barrett s esophagus. Familial Barrett s esophagus will be identified by administration of a questionnaire that has already been tested at University Hospitals of Cleveland. 2. Methodology will be developed to screen symptomatic first degree relatives of index patients with Barrett s esophagus and esophageal adenocarcinoma. Relatives with gastroesophageal reflux disease who have already been identified at University Hospitals of Cleveland through the study questionnaire will be recruited for screening endoscopy via mailings and phone calls. 3.Methodology will also be developed to recruit and screen asymptomatic or mildly symptomatic first degree using a new battery powered ultrathin endoscope. Successful conduct of this research proposal will result in the creation of a multi-center network, the identification of families with aggregation of Barrett s esophagus and esophageal adenocarcinoma, and the development of methodology for detecting Barrett s esophagus in previously undiagnosed family members. These three achievements will permit future full-scale multi-center epidemiologic and genetic linkage studies with the ultimate goals of measuring the familial risk of Barrett s esophagus and the identification of susceptibility gene(s) that predispose individuals to the development of Barrett s esophagus. The results of these future investigations will aid the development of lower cost, more effective screening and surveillance programs for Barrett s esophagus. They will also define a population at risk in whom interventions to prevent or eradicate Barrett s esophagus can be applied.
Keywords: Barretts esophagus, adenocarcinoma, cancer prevention, cancer risk, carcinogenesis, esophagus neoplasm, family genetics, genetic susceptibility, neoplasm /cancer epidemiology, biomedical equipment development, clinical biomedical equipment, cooperative study, diagnosis design /evaluation, diagnostic test, endoscopy, neoplasm /cancer diagnosis, histopathology, human genetic material tag, human subject, patient oriented research, questionnaire, statistics /biometry
Project start date: 2002-05-01
Project end date: 2005-04-30
5R03DK061426-02 (2003): $119890
Amitabh Chak, Associate Professor
Case Western Reserve University 10900 Euclid Ave Cleveland, Oh 44106
Grant 1R01DK070863-01 from National Institute Of Diabetes And Digestive And Kidney Diseases IRG: CIGP
Abstract: Barrett s esophagus is the precursor of esophageal adenocarcinoma. Both Barrett s esophagus and esophageal adenocarcinoma are closely associated with gastroesophageal reflux. Screening endoscopy is therefore recommended for the evaluation of chronic gastroesophageal reflux symptoms. Endoscopic surveillance, performed in those identified with Barrett s esophagus, detects cancer at an early stage. However, the large majority of these cancers occur in previously undiagnosed Barrett s esophagus and nearly half of these persons have no history of gastroesophageal reflux symptoms. Identification of genetic risk factors would lead to more effective screening programs and improved understanding of the molecular pathogenesis of these diseases. Our prior case control study demonstrated familial aggregation of Barrett s esophagus and its associated cancers, which we termed Familial Barrett s Esophagus. We have since developed family recruitment and endoscopic screening methods to identify Familial Barrett s Esophagus. Recent molecular genetic studies have identified one putative locus and suggest the existence of at least one other locus linked to these diseases. These family recruitment, endoscopic screening, and genetic analysis methods will now be used to test the following central hypothesis Familial Barrett Esophagus has a genetic basis. The specific aims of this proposal are (1) To recruit and screen family members of esophageal adenocarcinoma patients, comparing age of cancer onset between probands classified as familial with those classified as apparently sporadic; (2) To perform endoscopic screening and measure the recurrence risk of Barrett s esophagus in siblings of probands with Barrett s esophagus and esophageal adenocarcinoma; and (3) To identify loci and map susceptibility genes associated with Familial Barrett s Esophagus. Using the multidisciplinary approach of our collaborative team of investigators, these aims will result in new information regarding a genetic predisposition to the development of Barrett s esophagus and esophageal adenocarcinoma.
Keywords: Barretts esophagus, cancer risk, esophagus neoplasm, family genetics, genetic susceptibility, adenocarcinoma, disease /disorder onset, genetic mapping, neoplasm /cancer genetics, preneoplastic state, clinical research, endoscopy, genetic screening, human subject
Project start date: 2005-09-30
Project end date: 2010-08-31
1R01DK070863-01 (2005): $756367
Amitabh Chak, Associate Professor
Medicinecase Western Reserve University
10900 Euclid Ave
cleveland, Oh 441064919
Grant 3R01DK070863-04S1 from National Institute Of Diabetes And Digestive And Kidney Diseases IRG: CIGP
Abstract: Barrett´s esophagus is the precursor of esophageal adenocarcinoma. Both Barrett´s esophagus and esophageal adenocarcinoma are closely associated with gastroesophageal reflux. Screening endoscopy is therefore recommended for the evaluation of chronic gastroesophageal reflux symptoms. Endoscopic surveillance, performed in those identified with Barrett´s esophagus, detects cancer at an early stage. However, the large majority of these cancers occur in previously undiagnosed Barrett´s esophagus and nearly half of these persons have no history of gastroesophageal reflux symptoms. Identification of genetic risk factors would lead to more effective screening programs and improved understanding of the molecular pathogenesis of these diseases. Our prior case control study demonstrated familial aggregation of Barrett´s esophagus and its associated cancers, which we termed Familial Barrett´s Esophagus. We have since developed family recruitment and endoscopic screening methods to identify Familial Barrett´s Esophagus. Recent molecular genetic studies have identified one putative locus and suggest the existence of at least one other locus linked to these diseases. These family recruitment, endoscopic screening, and genetic analysis methods will now be used to test the following central hypothesis Familial Barrett Esophagus has a genetic basis. The specific aims of this proposal are (1) To recruit and screen family members of esophageal adenocarcinoma patients, comparing age of cancer onset between probands classified as familial with those classified as apparently sporadic; (2) To perform endoscopic screening and measure the recurrence risk of Barrett´s esophagus in siblings of probands with Barrett´s esophagus and esophageal adenocarcinoma; and (3) To identify loci and map susceptibility genes associated with Familial Barrett´s Esophagus. Using the multidisciplinary approach of our collaborative team of investigators, these aims will result in new information regarding a genetic predisposition to the development of Barrett´s esophagus and esophageal adenocarcinoma
Project start date: 2005-09-30
Project end date: 2010-08-31
3R01DK070863-04S1 (2008): $39995
FAMILIAL FACTORS IN BARRETT S ESOPHAGUS
Amitabh Chak, Associate Professor
Case Western Reserve University 10900 Euclid Ave Cleveland, Oh 44106
Grant 5K24DK002800-04 from National Institute Of Diabetes And Digestive And Kidney Diseases IRG: DDK
Abstract: Advances in basic sciences often translate into an increased understanding of disease processes. Similarly, advances in endoscopic engineering also produce new technology with novel applications in clinical gastroenterology. I believe that patient-oriented researchers in gastrointestinal diseases and gastrointestinal endoscopy must translate advances in basic sciences and engineering technology to improved methods for patient care. Using my previous experience in basic research and training in advanced endoscopy, I have initiated and successfully implemented investigations that address this goal. My research objectives have been furthered by the opportunity to mentor several advanced gastroenterology fellows in the performance of specialized endoscopic procedures and patient-oriented research projects. These trainees are now productive clinical investigators in the field of gastrointestinal endoscopy. Protected time provided by this award will permit me to develop a meaningful research program that focuses on applying new endoscopic techniques and advances in human genetics to the evaluation of Barrett s esophagus and esophageal adenocarcinoma. The award will also further my education in two areas in which it is slightly deficient, viz., biostatistics and human genetics. Educational courses in these subjects and collaborations with experts in these fields will strengthen the development of my research program. Lastly, the award will allow me to teach advanced endoscopy to new trainees and mentor them in the development of their own research projects within my program. Esophageal adenocarcinoma is associated with a very poor prognosis. More effective screening, surveillance, and treatment strategies are required. The aim of the current proposal is to identify familial factors involved in the development of Barrett s esophagus and esophageal adenocarcinoma. The ultimate goal of this research program is to help identify the heritable genetic mutation(s) that determine susceptibility to Barrett s esophagus in order to improve screening and surveillance strategies for this disease.
Keywords: Barretts esophagus, family genetics, genetic susceptibility, adenocarcinoma, longitudinal human study, endoscopy, human subject, patient oriented research
Project start date: 2001-08-15
Project end date: 2006-06-30
5K24DK002800-04 (2004): $132408
FAMILIAL FACTORS IN BARRETT´S ESOPHAGUS
Amitabh Chak, Associate Professor
Medicinecase Western Reserve University
10900 Euclid Ave
cleveland, Oh 44106
Grant 1K24DK002800-01A2 from National Institute Of Diabetes And Digestive And Kidney Diseases IRG: DDK
Abstract: Advances in basic sciences often translate into an increased understanding of disease processes. Similarly, advances in endoscopic engineering also produce new technology with novel applications in clinical gastroenterology. I believe that patient-oriented researchers in gastrointestinal diseases and gastrointestinal endoscopy must translate advances in basic sciences and engineering technology to improved methods for patient care. Using my previous experience in basic research and training in advanced endoscopy, I have initiated and successfully implemented investigations that address this goal. My research objectives have been furthered by the opportunity to mentor several advanced gastroenterology fellows in the performance of specialized endoscopic procedures and patient-oriented research projects. These trainees are now productive clinical investigators in the field of gastrointestinal endoscopy. Protected time provided by this award will permit me to develop a meaningful research program that focuses on applying new endoscopic techniques and advances in human genetics to the evaluation of Barrett´s esophagus and esophageal adenocarcinoma. The award will also further my education in two areas in which it is slightly deficient, viz., biostatistics and human genetics. Educational courses in these subjects and collaborations with experts in these fields will strengthen the development of my research program. Lastly, the award will allow me to teach advanced endoscopy to new trainees and mentor them in the development of their own research projects within my program. Esophageal adenocarcinoma is associated with a very poor prognosis. More effective screening, surveillance, and treatment strategies are required. The aim of the current proposal is to identify familial factors involved in the development of Barrett´s esophagus and esophageal adenocarcinoma. The ultimate goal of this research program is to help identify the heritable genetic mutation(s) that determine susceptibility to Barrett´s esophagus in order to improve screening and surveillance strategies for this disease
Keywords: Barretts esophagus, family genetics, genetic susceptibility adenocarcinoma, longitudinal human study endoscopy, human subject, patient oriented research
Project start date: 2001-08-15
Project end date: 2006-06-30
1K24DK002800-01A2 (2001): $132408
FAMILIAL FACTORS IN BARRETT S ESOPHAGUS
Amitabh Chak, Associate Professor
Case Western Reserve University 10900 Euclid Ave Cleveland, Oh 44106
Grant 5K24DK002800-05 from National Institute Of Diabetes And Digestive And Kidney Diseases IRG: DDK
Abstract: Advances in basic sciences often translate into an increased understanding of disease processes. Similarly, advances in endoscopic engineering also produce new technology with novel applications in clinical gastroenterology. I believe that patient-oriented researchers in gastrointestinal diseases and gastrointestinal endoscopy must translate advances in basic sciences and engineering technology to improved methods for patient care. Using my previous experience in basic research and training in advanced endoscopy, I have initiated and successfully implemented investigations that address this goal. My research objectives have been furthered by the opportunity to mentor several advanced gastroenterology fellows in the performance of specialized endoscopic procedures and patient-oriented research projects. These trainees are now productive clinical investigators in the field of gastrointestinal endoscopy. Protected time provided by this award will permit me to develop a meaningful research program that focuses on applying new endoscopic techniques and advances in human genetics to the evaluation of Barrett s esophagus and esophageal adenocarcinoma. The award will also further my education in two areas in which it is slightly deficient, viz., biostatistics and human genetics. Educational courses in these subjects and collaborations with experts in these fields will strengthen the development of my research program. Lastly, the award will allow me to teach advanced endoscopy to new trainees and mentor them in the development of their own research projects within my program. Esophageal adenocarcinoma is associated with a very poor prognosis. More effective screening, surveillance, and treatment strategies are required. The aim of the current proposal is to identify familial factors involved in the development of Barrett s esophagus and esophageal adenocarcinoma. The ultimate goal of this research program is to help identify the heritable genetic mutation(s) that determine susceptibility to Barrett s esophagus in order to improve screening and surveillance strategies for this disease.
Keywords: Barretts esophagus, family genetics, genetic susceptibility, adenocarcinoma, longitudinal human study, endoscopy, human subject, patient oriented research
Project start date: 2001-08-15
Project end date: 2006-06-30
5K24DK002800-05 (2005): $132408
5K24DK002800-03 (2003): $132408
Amitabh Chak, Associate Professor
Case Western Reserve University 10900 Euclid Ave Cleveland, Oh 44106
Grant 5P41RR003655-190078 from National Center For Research Resources IRG: ZRG1
Keywords: Barretts esophagus, biomedical facility, family genetics, genetics, clinical research
Project start date: 2004-08-01
Project end date: 2005-07-31