搜索结果：Therapeutic advances in gastroenterology

1. OVERVIEW The field of pediatric gastroenterology, hepatology, and nutrition (referred to subsequently as pediatric gastroenterology) continues to expand and evolve and is far different from 1999, when the previous guidelines on fellowship training in this field were published (1). Although still a relatively young field, this subspecialty is increasingly recognized and accepted throughout the world (2), albeit with varying degrees of medical resources and access to care. Tremendous medical advances, especially in the fields of genetics, infectious disease, pharmacology, and immunology, have changed our fundamental understanding of pathophysiology, and along with technological innovations, such as wireless imaging technology and intraesophageal impedance monitoring, have affected the way we diagnose and manage disease. At the same time, economic factors have become increasingly important in discussions of health care and graduate medical education (3). With rapidly escalating health care costs, care must be demonstrated to be not only high in quality but also cost-effective. Moreover, in response to pressure from the public to ensure practitioners are competent, accrediting agencies are imposing new and increasingly complex constructs for assessing the competency of our trainees. These factors demand that the training of pediatric gastroenterology fellows be continuously revised and reevaluated. It is not sufficient to focus exclusively on the clinical aspects of training, however. Although the primary mission of fellowship programs is to create competent clinicians, ensuring the health of future generations requires a broader training mission that recognizes that some of our trainees will choose careers as researchers and medical educators. Fellowship training, therefore, must provide individuals with the opportunity to pursue other essential career pathways. The necessity of providing this more inclusive training must be reconciled with evolving lifestyle expectations of trainees (4) and duty hour restrictions (5). In response to these enumerated factors, the Executive Council of the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition (NASPGHAN) charged its Training Committee with the task of updating the 1999 fellowship training guidelines. The goals outlined by the Steering Committee were to consider existing guidelines and seek consistency where possible; specifically incorporate the Accreditation Council for Graduate Medical Education (ACGME) competencies; create a framework that would permit consistent updating; reflect the unique aspects of pediatric gastroenterology, including the breadth of the field and unique nature of the patients, especially the changing presentation of disease as children develop; and respond to the practical needs of pediatric gastroenterology program directors. In addition to the original NASGPHAN guidelines, other existing guidelines were reviewed in the preparation of this document. Table 1 provides a list of the primary guidelines and the means to access them. ACGME's Residency Review Committee issues standards for fellowship training in pediatric gastroenterology and updates them every 5 years, with the most recent update in 2009 (6,7). ACGME establishes detailed training program requirements that are not included in these NASPGHAN guidelines. Requirements for training as a pediatric gastroenterologist in Canada are enumerated by the Royal College of Physicians and Surgeons in Canada (RCPSC) (8,9). The European Society for Pediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN) reviewed training issues and developed a curriculum for fellows in 2002 (2). The task force also reviewed the gastroenterology core curriculum generated by 4 adult gastroenterology societies that was updated in 2007 (10) and the recent guidelines for fellowship training in pediatric cardiology, a subspecialty with similar training issues, including procedure training and advanced training opportunities (11).TABLE 1: Guide to existing guidelinesUnique Characteristics of a Pediatric Gastroenterologist A pediatric gastroenterologist is expected to be an expert in the anatomy and physiology of a large segment of the human body that includes the esophagus, stomach, intestines, liver, biliary tree, and pancreas, as well as the diverse array of acute, subacute, and chronic illnesses that may affect these organs. Trainees must have the ability to analyze and integrate the clinical data, instead of limiting their thought processes to a particular organ or segment of the gastrointestinal (GI) tract. In pediatric gastroenterology, an assessment of growth and nutrition is an especially integral part of any patient's evaluation and care. Diseases of the digestive system can negatively affect the nutritional status of the child; conversely, the nutritional status of the child can profoundly affect the diagnostic evaluation of the patient. In addition, the practitioner must possess exemplary interpersonal and communication skills, because the field of pediatric gastroenterology is truly multidisciplinary and requires routine consultations and collaborations with myriad allied providers, including endoscopy suite and operating room personnel, nurses, dietitians, pharmacists, social workers, surgeons, intensivists, radiologists, pathologists, psychologists, and psychiatrists. Many of the diseases encountered by a pediatric gastroenterologist also are of relevance to other subspecialties, including endocrinology, rheumatology, pulmonology, and metabolism/genetics, necessitating collaborative relationships with these experts. A pediatric gastroenterologist, unlike an adult gastroenterologist, interacts extensively with both the patient and the patient's care provider(s). As such, it is imperative that the care not only be evidence-based and cost-effective but also be delivered in a compassionate manner that respects patients’ families and their cultures. The fiscal aspects of health care, especially in the United States, are undergoing seismic modifications and it is anticipated that events in the next 5 years will be characterized by vastly different reimbursement models and accountability in medicine. A pediatric gastroenterologist will need to be adept at demonstrating added value to health care dollars and strive for continuous quality enhancement of care. Knowledge of the dollar footprint of care will be imperative, especially as the subspecialist will have increasing access to an ever-expanding array of technological tools and diagnostic modalities, including medical genetic and pharmacogenetic testing. Furthermore, it is likely that as medical homes are established, pediatric subspecialists will need to develop new relationships with primary care providers. The other trend affecting fellowship programs is the juxtaposition of personal lifestyle choices and career choices. A subset of pediatric gastroenterologists works part-time for a variety of reasons, including needs for childcare, personal (or family) health issues, or other personal obligations or pursuits. Because these needs affect the training years, programs have increasingly adapted to trainee lifestyle requests. In the early years of this subspecialty, the majority of practitioners entered academic institutions, and this later expanded to private practice options. Presently, graduating trainees also consider hybrid practices in which they have an academic appointment with some role in trainee education, but otherwise maintain an independent practice. In summary, the field of pediatric gastroenterology is undergoing rapid transformation and these updated guidelines aim to address the changes occurring in the training of this subspecialty during the last decade and, more important, to prepare us for the future. Competencies ACGME was established in 1981 with a goal of developing a uniform set of guidelines that could be applied to ensure and improve the quality of resident and fellow education. As part of its Outcome Project, 6 core competencies that could serve as focal points in the development of residency and fellowship training program curricula were identified in 1999 and became part of program requirements in 2002 (12). Similarly, the RCPSC developed a set of core competencies that are an integral part of fellowship training program curricula (Canadian Medical Education Directives for Specialists, or CanMEDS competencies) (13). Although the CanMEDS competencies are not identical to those of the ACGME, their goals are similar (Table 2). Application of these core competencies and implementation of assessment tools by program directors of pediatric gastroenterology fellowship training are required for program certification by the ACGME and the RCPSC. Table 3 indicates how the ACGME competencies are presented in this guideline document.TABLE 2: ACGME and CanMEDS core competenciesTABLE 3: Mapping ACGME competencies to guidelinesThe competency of medical knowledge (CanMEDS Medical Expert and Scholar) requires that fellows demonstrate knowledge of relevant biomedical, clinical, epidemiological, and sociobehavioral sciences and their application to patient care. Areas that are particularly applicable to understanding the clinical manifestations and treatment of GI disease include developmental biology, pharmacology, host/microbial interactions, immunology, and genetics. Fellows should develop an understanding of the pathophysiology underlying the disorders that are encountered in ambulatory and inpatient settings. Medical knowledge should be obtained through didactic conferences, self-directed learning, and in the course of supervised clinical care. Concepts important for training in pediatric gastroenterology are included in the individual content areas. The competency of patient care (CanMEDS Medical Expert and Manager) is directed at ensuring that fellows are able to provide competent and compassionate care to their patients. They must be able to gather appropriate information via the performance of a complete clinical history and comprehensive physical examination, review of medical records, and appraisal of up-to-date scientific evidence. They must be able to develop and implement patient management plans, taking into consideration patient/family preferences. They must be able to interpret diagnostic and therapeutic interventions and develop the clinical judgment necessary to make informed decisions. Fellows also are expected to develop technical competency in the performance of GI procedures that are considered essential for the practice of pediatric gastroenterology and should understand the indications, benefits, risks, and limitations of all procedures commonly used in the evaluation of children with GI disorders. Enumeration of the patient care experiences required for training in pediatric gastroenterology is included in the individual patient content areas of this document. Recommendations for procedural training are reviewed in a separate section of this overview and in more detail in the final section of these guidelines. The competency of practice-based learning and improvement (CanMEDS Scholar) emphasizes lifelong learning. Instruction in this competency should help fellows to develop a set of skills that will empower them to serially assess and reflect upon their perceived strengths and weaknesses as clinicians, and to develop strategies and realistic goals to improve their clinical practice. This includes the ability to incorporate constructive feedback provided by supervisors, colleagues, other health care providers, administrative staff, and patients. In addition, this process of continuous improvement requires the ability to use information technology to support their education and an understanding of the principles and application of evidence-based medicine. Fellows must perform practice-based improvement, which involves obtaining information about their own population of patients, instituting a change, and assessing the effect using a systematic methodology. This competency also includes the development of specific teaching skills that will permit fellows to effectively educate patients and families, students, residents, other fellows, and consulting physicians. The competency of interpersonal and communication skills (CanMEDS Communicator) encompasses more than the performance of specific tasks or behaviors. Fellows should demonstrate interpersonal skills such as the ability to be present in the moment; awareness of the importance of the relationships among physician, patient, and family members; respect for others and treating others as one would like to be treated; and the capacity to adjust interpersonal skills based on the needs of different patients and families (14). Fellows must be able to create and sustain therapeutic and ethically sound relationships with patients, use effective listening skills to facilitate relationships, and work effectively with others as a member or leader of a health care team. Physician providers must be able to communicate across cultural and socioeconomic boundaries. In addition, fellows should begin to learn the skills necessary to communicate their findings and experiences with colleagues and other health care providers, both orally and in the form of written reports, manuscripts, and case series. Such skills are critical in practicing medicine effectively in a multidisciplinary setting. The competency of professionalism (CanMEDS Professional) includes training to ensure that fellows will be able to provide compassionate care to their patients in a manner that is sensitive to language, age, culture, sex/sexual orientation, religious persuasion, and disabilities. Professionalism is realized through partnership between a patient and doctor, based on mutual respect, individual responsibility, and appropriate accountability. It should include such areas as honesty and integrity, self-awareness and knowledge of limits, reliability, respect for others, compassion, altruism and advocacy, continuous self-improvement, collaboration, and working in partnership with members of the health care team (15). Moral reasoning and judgment also are essential components of professional behavior. Fellows should receive formal training in bioethics to equip them in addressing complex problems, such as parental or to provide care for their The content areas of this include of the specific application of this competency to disorders encountered in the course of pediatric gastroenterology practice. The competency of practice (CanMEDS and fellows to their clinical in a manner that is of high and cost-effective. This requires that fellows understand different of medical practice and Fellows must learn skills that will them to for their patients and to from throughout the health care of training, the fellow should be able to demonstrate or understanding of the of members of a multidisciplinary team and how to a multidisciplinary that management of complex such as disease or The content areas of this also include of the specific application of this competency to disorders encountered in the course of pediatric gastroenterology practice. A of can be used to fellow and specific competencies may be through the application of different Medical knowledge may be with tools such as written or competencies are using a variety of including patient clinical patient and Although the particular of evaluation may from to it is essential that all pediatric gastroenterology fellowship training programs develop a process that the of and of constructive feedback to fellows in a manner that is and most likely to to their personal and career development is to the of these and to an effective feedback At are expert in these areas A fundamental in assessing trainees based on the ACGME competencies is that are to this the of clinical care and knowledge of the development of trainees A to this is the of professional to and are part of the essential professional must and to recognized of professional be and be and in its process and of a in pediatric gastroenterology is the medical management of the patient. provide a clinical in which to a in of the 6 areas by In this competency in practice could be in or ability to work on a multidisciplinary team and the competency in communication in or ability to provide compassionate and to the patient and and that one could create a specific on 1 and the ACGME competencies that could to the on training, would the of a set by all of the relevant program directors in the application of ACGME the content areas of this include the development of that in specific to appropriate In the guidelines for training in pediatric gastroenterology may be based on a of ACGME and the American of a to the competencies and improve the assessment of The and a of developmental for Application of the to subspecialty training must and Training ACGME requirements for subspecialty training in pediatric gastroenterology that the training program should be 3 years in and ensure trainee as by their 6 competencies in the treatment of and with diseases of the GI the pancreas, the and RCPSC guidelines only years of fellowship for certification in pediatric gastroenterology all of the enumerated for a training in Canada could an of fellowship or training their the increasing of pediatric gastroenterology practice and the ACGME we that at should be to clinical training in inpatient and ambulatory (Table This of clinical training would still permit the fellow to be by training that clinical a clinical the majority of fellowship training in the inpatient that clinical pediatric gastroenterology is an consideration should be to providing a of training in the ambulatory setting. A care opportunity of at should be provided during the 3 years of the training duty should to the guidelines by ACGME and be of training fellow should increasing for clinical care and demonstrate increasing both in the inpatient and ambulatory during the course of the Fellows also should demonstrate increasing in the performance of routine diagnostic and therapeutic GI Fellows have career goals that may affect their The of training should trainees with specific to clinical training, including training in such as and therapeutic or liver, and the required of clinical a fellow to formal in areas such as or management of training, to during the could be to this such training could of the pediatric gastroenterology as a separate or in a clinical practice. Such training should not with of the work on the also should permit fellows are in academic careers to pursue advanced such as a in public health or clinical Trainees in a career in or would receive training during their fellows and programs should that the to as an commonly requires that at 4 to 5 years of training is to equip a fellow to work as an in or of this career is included as an 1 to years as a trainee or as on and of to support training, and the individual needs of trainees. Table 5 of training for pediatric gastroenterologists different career training for different career and are an integral part of the practice of pediatric gastroenterology, and trainees are expected to demonstrate competency in the performance of a array of and such as and are in a of as a of technological in changes in other diagnostic and in the health care it important to guidelines for pediatric gastroenterology training programs that trainees are to in the most core principles of procedure training will important of the of specific Trainees must understand the appropriate indications, risks, benefits, and of both diagnostic and therapeutic program must have formal for and development of skills in the performance of procedure on a trainees should maintain a procedures and This will facilitate the feedback that must be to trainees throughout their training as to their of and they are expectations for their of Trainees are not expected goals should be constructive in how to the necessary of for their of training and the of procedures to competency for procedure are in the endoscopy and procedure guideline for training that trainee not have to in all of the procedures but it is important that trainee become with every procedure and understand its and competency is recognized as a As such, it is recognized that some trainees will procedural competency at a of procedures because of and other factors that procedural others will more or to the same of Although that procedural competency than is the more appropriate review of the published for of that should be procedures Trainees are expected to in the procedures that they to perform of At of training, trainees have not procedural in a procedure that they to perform will by an such as procedural competency an essential of all training programs is to ensure that trainee is to relevant which include diagnostic and therapeutic GI diagnostic and therapeutic of the endoscopy and and impedance monitoring, and the of the 1999 North American Society for Pediatric and Nutrition training guidelines the 2009 ACGME update procedures from the list to the the including and This was by the that some of the procedures are increasingly by These will to affect the training of pediatric gastroenterologists and certification As a guidelines for procedure training will to the of the care of children with and nutritional disorders is the of disease and the development of new diagnostic and therapeutic In addition, a understanding of the and processes the development and of the GI liver, and is essential to in disease and health during The of these requires the of individuals with training in clinical, and medical education, health and health in the subspecialty of pediatric gastroenterology must understand the of the field and be to assess the of new information on clinical care and practice evidence-based medicine. with ACGME and guidelines subspecialty training in pediatric gastroenterology must fellows must receive formal training in and in clinical, or or The of of other than recognizes the importance of all for the of the field of pediatric in this can be as 4 of academic The of encompasses the in original and clinical The of education involves the development of and assessment tools for the communication of knowledge to and the The of is with among diverse such as the use of communication technology in in or in patient care. The of application involves the use of knowledge to of individuals and The of work by this include clinical and Many are included the of and Trainees need to knowledge in all aspects of through a of and in a with appropriate The must begin during the and throughout the of The requirements for the nature of the and its but it not the of that must be to this the goals established by the at of fellowship training should be to some such as a a at some of will be for of the these of the should be to Trainees must in a formal core curriculum in The curriculum should be presented in a that learning through the use of diverse modalities, including and The curriculum should provide trainees with the opportunity to an understanding of clinical and critical of data, collaborative in social responsibility, human and application of to clinical and evidence-based medicine. The curriculum also should include principles of teaching and adult learning, curriculum and assessment of Trainees should the necessary skills to information in and written prepare for and of clinical and and complete and for Furthermore, the trainees should develop as effective of individuals and of in clinical and requirements all fellows are to complete a supervised This must be to the field of pediatric gastroenterology, hepatology, or with the to prepare trainees to become effective subspecialists and to to the of in the in the should to the development of skills to analyze the work of gather and analyze new and and from a body of from and into written and The may include clinical, and medical education, health and health include clinical, and or systematic review of the critical of health or and curriculum The must be or have and requires and of information or Trainees must and comprehensive knowledge of all aspects of their Trainees should practice during the performance of the by about the the of others, and to The is to to a work for which trainees are for a of its of an work are a a formal extensively a or complex a and a Fellowship training in is to be in a and Trainees must have the opportunity to and analyze present their work in conferences, and with other trainees and in a variety of provide an appropriate of the program must include with established skills in in different areas of clinical health health and education. Trainees should a member to provide during their The is fundamental to the training process and must to support trainees during the of their The should have an established of in have in a field to pediatric gastroenterology, and be of the opportunities for trainees to for in conferences, and with others in the subspecialty of pediatric The must ensure that the and required for the of the specific are to the fellow and must or and provide trainee is to have a by written guidelines The in with the and program is for the of trainees through the of the and for the assessment of a specific and the of that the guidelines for The as by the is to at 3 individuals the with 1 member from the subspecialty of pediatric The program can serve as a and in but or is not a member of the The is to on a during the of training, at The is to trainees in the development of a course of to knowledge and skills those provided by the core curriculum to ensure of the The will in the specific of the and of the of the at its The will the program on during the training and the was and to the program and guidelines. Training the of knowledge and some pediatric gastroenterologists have their practices to clinical areas. to practice in these areas may training to develop the medical knowledge and clinical and technological skills necessary to At the field of pediatric includes areas of and guidelines for training in of these were published in As the of pediatric gastroenterology it is likely that new will develop and others will The goal of advanced training in pediatric gastroenterology is to provide clinical for subspecialty trainees would be expected in a fellowship training of areas in which advanced training can be appropriate include but are not to pediatric hepatology, and therapeutic and and Such training could be obtained in 1 of 3 the of a all of the requirements for clinical training and are during an of fellowship or in the course of practice. The only for obtaining advanced training in pediatric gastroenterology is that which for pediatric a of added in this subspecialty requires the of an of fellowship training in pediatric and a examination, by the and the American of Although the original NASPGHAN guidelines requirements for advanced training in other areas of subspecialty pediatric gastroenterology for advanced fellowship training not and, therefore, for this training were not included in this document. Furthermore, it is that the will be able to the expected of that NASPGHAN consider the requirements for programs that may advanced training in areas other than pediatric and for fellowship training in these areas. of the Areas to the medical knowledge and clinical skills that trainees must develop to a field have in and detailed of specific In such have by program directors and of practical The Steering Committee established a of principles for the development of content areas. the that to be the of the content areas should be by and than In the of medical of all relevant is and learning, on a is an essential part of practice and should be goal was to create a that could be updated in response to changes in medical knowledge and practice. a to the ACGME competencies for content was thought to be important to help all aspects of trainee development that are necessary to both professional and of practice. The Steering Committee identified areas of content that the breadth of pediatric gastroenterology in disease, of the GI GI GI and and GI nutritional and of these content were to task and they in to serve on these task The of content the role of the competencies in fellowship The of the content areas and the of the to the competencies are in Table The last section of Table 6 emphasizes the importance of the developmental in understanding the field of pediatric of the content The the role of the and especially the task force and members for their work in the content areas. and in the document. and the NASPGHAN with The also the NASPGHAN members reviewed the and provided critical

Reviews20 December 2005New Concepts in the Pathophysiology of Inflammatory Bowel DiseaseGiorgos Bamias, MD, Mark R. Nyce, MD, Sarah A. De La Rue, PhD, and Fabio Cominelli, MD, PhDGiorgos Bamias, MDFrom University of Virginia, Charlottesville, Virginia., Mark R. Nyce, MDFrom University of Virginia, Charlottesville, Virginia., Sarah A. De La Rue, PhDFrom University of Virginia, Charlottesville, Virginia., and Fabio Cominelli, MD, PhDFrom University of Virginia, Charlottesville, Virginia.Author, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-143-12-200512200-00007 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Clinical PrinciplesThe inflammatory bowel diseases (IBDs), that is, Crohn disease and ulcerative colitis, affect approximately 1 million persons in North America and several million persons worldwide.Approximately 30% of patients present between 10 and 30 years of age.Current therapeutic options are limited and include nonspecific anti-inflammatory and immunosuppresive medications.Surgery is required for 50% to 80% of patients with Crohn disease, while only 20% of patients with ulcerative colitis have surgery.Novel biological therapeutics have greatly improved the quality of life of patients with IBD.Pathophysiologic PrinciplesBoth genetic and environmental factors play important roles in disease pathogenesis.New hypotheses implicate the innate immune system and ...References1. 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Sutton CL, Kim J, Yamane A, Dalwadi H, Wei B, Landers C, et al. Identification of a novel bacterial sequence associated with Crohn's disease. Gastroenterology. 2000;119:23-31. [PMID: 10889151] CrossrefMedlineGoogle Scholar62. Mow WS, Vasiliauskas EA, Lin YC, Fleshner PR, Papadakis KA, Taylor KD, et al. Association of antibody responses to microbial antigens and complications of small bowel Crohn's disease. Gastroenterology. 2004;126:414-24. [PMID: 14762777] CrossrefMedlineGoogle Scholar63. Arnott ID, Landers CJ, Nimmo EJ, Drummond HE, Smith BK, Targan SR, et al. Sero-reactivity to microbial components in Crohn's disease is associated with disease severity and progression, but not NOD2/CARD15 genotype. Am J Gastroenterol. 2004;99:2376-84. [PMID: 15571586] CrossrefMedlineGoogle Scholar64. Mow WS, Landers CJ, Steinhart AH, Feagan BG, Croitoru K, Seidman E, et al. High-level serum antibodies to bacterial antigens are associated with antibiotic-induced clinical remission in Crohn's disease: a pilot study. Dig Dis Sci. 2004;49:1280-6. [PMID: 15387358] CrossrefMedlineGoogle Scholar Author, Article, and Disclosure InformationAffiliations: From University of Virginia, Charlottesville, Virginia.Acknowledgments: The authors thank the entire personnel of the Digestive Health Center of Excellence at the University of Virginia.Grant Support: By the United States Public Health Service/National Institutes of Health grants DK-42195, DK-44540, and DK-55812 to Fabio Cominelli and The UVa Digestive Health Research Center (P30 DK-67629).Disclosures: Honoraria: F. Cominelli (UCB Pharmaceuticals, Inc., Centocor, Elan, Sigma-Tau).Corresponding Author: Fabio Cominelli, MD, PhD, Division of Gastroenterology and Hepatology, P.O. Box 800708, University of Virginia Health System, Charlottesville, VA 22908; e-mail, [email protected]edu.Current Author Addresses: Drs. Bamias, Nyce, De La Rue, and Cominelli: Digestive Health Center of Excellence, University of Virginia, P.O. Box 800708, Charlottesville, VA 22908-0708. 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PREAMBLE The guidelines for the diagnosis, surveillance and therapy of Barrett's esophagus were originally published by the American College of Gastroenterology in 1998 and updated in 2002. These and other guidelines undergo periodic review. Significant advances have occurred in the area of Barrett's esophagus over the past four years leading to another revision of the prior guidelines. These advances include the potential use of esophageal capsule endoscopy for the diagnosis and screening of Barrett's esophagus, data regarding the outcome of low-grade dysplasia, the treatment of high-grade dysplasia using photodynamic therapy, and the development of new ablation techniques such as radiofrequency ablation. These guidelines are intended to be applied by physicians who see Barrett's esophagus patients and are intended to indicate a preferred, but certainly not the only, acceptable approach. Physicians need to choose the course best suited to the individual patient and to the variables that exist at the time of decision making. The guidelines are for adult patients with the diagnosis of Barrett's esophagus, as defined herein. Both these and the original guidelines were developed under auspices of the American College of Gastroenterology and the Practice Parameters Committee and approved by the Board of Trustees. The world literature was reviewed extensively for the original guidelines and once again reviewed using the National Library of Medicine database. Search terms used included Barrett's esophagus, esophageal neoplasm, esophagus, intestinal metaplasia, esophageal diseases, and adenocarcinoma, all appropriate studies and any additional ones found in reference to these papers were obtained and reviewed. Evidence was available from a hierarchy of trials and randomized controlled trials were given the greatest weight. Abstracts presented at national and international meetings were only used when unique data from ongoing trials were presented. When scientific data were lacking, recommendations are based on expert opinion. The recommendations made are based on the level of evidence found. Grade A recommendations imply that there is consistent level 1 evidence (randomized controlled trials), Grade B indicates that the evidence would be level 2 or 3 which are cohort studies or case control studies. Grade C recommendations are based on level 4 studies meaning case series or poor quality cohort studies, and Grade D recommendations are based on level 5 evidence meaning expert opinion. SIGNIFICANCE OF BARRETT'S ESOPHAGUS Barrett's esophagus continues to be increasingly recognized in the United States and is believed to be the major risk factor for the development of esophageal adenocarcinoma. The incidence of adenocarcinoma of the esophagus continues to rise rapidly. The rate of rise is alarming and is widespread in Western countries. In a review by the epidemiologists of the National Cancer Institute of cancer incidences normalized to the year 1975, esophageal adenocarcinoma incidence rates were found to outpace even those of melanoma, breast cancer and prostate cancer in terms of the rapidity of rise (1). These epidemiologists also found there was no concomitant decrease in diagnoses of gastric cancers or more proximal cancers, making a classification change unlikely to be responsible for this increase in adenocarcinoma. In the Danish Cancer Registry, adenocarcinoma incidence rates actually decrease in patients older than 85 (14.14/100,00 (80–84 yr) decreasing to 7.2/100,000 (85+ yr) unlike squamous cancer rates suggesting that this rise in adenocarcinoma incidence may be truly a recent phenomenon as evidenced by this age cohort effect (2). DEFINITION OF BARRETT'S ESOPHAGUS Barrett's esophagus is a change in the distal esophageal epithelium of any length that can be recognized as columnar type mucosa at endoscopy and is confirmed to have intestinal metaplasia by biopsy of the tubular esophagus. (Grade B recommendation). This working definition of Barrett's esophagus has changed little over the last 10 years. A recent "critical review of the diagnosis" of Barrett's esophagus concluded that "the working definition of BE is displacement of the squamocolumnar junction proximal to the gastroesophageal junction" and "endoscopy with multiple systematic biopsies is needed to establish the diagnosis of Barrett's esophagus" (3). This definition does not distinguish between short and long segment Barrett's esophagus and implies that only columnar lined esophagus should be biopsied. Although intestinal metaplasia is not specifically mentioned in this definition, clearly the reason to do multiple biopsies in the columnar appearing esophagus is to identify the presence of intestinal metaplasia, the premalignant lesion for esophageal adenocarcinoma (EAC). The vast majority of adenocarcinomas of the esophagus are accompanied by intestinal metaplasia in multiple cohort studies (4–8) and many adenocarcinomas of the esophagogastric junction are also associated with esophageal intestinal metaplasia (9–11). The incidence of adenocarcinoma of the esophagus has continued to rise in the United States, at least until the year 2002 (12). Supporting the primary role of BE as the premalignant lesion for EAC is the unmasking of underlying BE by chemotherapy of adenocarcinoma of the distal esophagus. A retrospective study reviewed 79 patients with locally advanced EAC who had preoperative chemotherapy and had restaging endoscopy and biopsy prior to resection. Pre-therapy endoscopy showed BE in 75%, whereas 97% had documented BE on post-chemotherapy biopsy or in the resected specimen (13). This suggests that the cancer overgrows the fertile field of BE so that at presentation of the patient with EAC, BE may no longer be detectable. Esophagitis might also mask Barrett's esophagus. In a recent study of 172 patients with erosive esophagitis, a full 12% were found to have Barrett's metaplasia after healing of the esophagitis (14). There is not universal agreement on the inclusion of intestinal metaplasia as a criterion for BE. The British Society of Gastroenterology has excluded the need for IM from the diagnosis of BE (15). It is well recognized that the yield of IM decreases as the segment of columnar lining shortens and fewer biopsies are taken. Repeat endoscopy and biopsy are often necessary to establish the presence of IM (16, 17). In patients with >1cm of columnar lined esophagus at endoscopy, multiple biopsies may be necessary to confidently detect intestinal metaplasia. Based on a recent retrospective study, eight biopsies may provide an adequate assessment of the presence of intestinal metaplasia (18). The issue becomes when to label a patient as having BE and having an increased risk for EAC compared to someone lacking BE. Because of the implication of the label of BE in the United States for obtaining health insurance and the increased cost of life insurance in the United States (19), it seems appropriate to establish the presence of IM before committing the patient to the diagnosis of BE and to surveillance endoscopy. There are no data on the risk of EAC in columnar lined esophagus lacking IM. Another new development in the endoscopic standardization of Barrett's esophagus is the Prague classification system of circumferential (CM) and maximal length (M). This system identifies the landmarks of the squamocolumnar junction, the gastroesophageal junction, the extent of circumferential columnar lining and the most proximal extension of the columnar mucosa excluding islands to determine the length of Barrett's esophagus. Twenty-nine endoscopists scored 29 videos with centimeter intervals marked on the image (20). The reliability coefficients (RC) for C 0.95, M 0.94, the gastroesophageal junction 0.88 and the location of the hiatus 0.85 were excellent. The overall RC for the endoscopic recognition of BE ≥1cm was 0.72. However, for less than 1cm of columnar lining the coefficient was only 0.22. In an era of growing endoscopic therapy for neoplastic BE, this standardization is important. Unfortunately, proximal islands of columnar lining and ultra-short BE <1cm are not included in this schema. In summary, a strategy to decrease the recent rise in esophageal cancer would be earlier diagnosis of Barrett's esophagus. The diagnosis should be made with endoscopy and biopsy of columnar lined esophagus only (Grade B Recommendation). Histological changes of intestinal metaplasia (goblet cells) are needed for the diagnosis prior to recommendations of surveillance. Ideally, erosive esophagitis should be healed prior to biopsy to increase the yield and avoid missing short segments of columnar lining (Grade B Recommendation). Endoscopic descriptions of a Barrett's esophagus should be precise and ideally follow established classification systems (Grade D Recommendation). SCREENING Screening for Barrett's esophagus remains controversial because of the lack of documented impact on mortality from EAC. The large number of patients that lack reflux symptoms but have Barrett's esophagus provides a diagnosis challenge. The highest yield for Barrett's is in older (age 50 or more) Caucasian males with longstanding heartburn. Patients with the highest likelihood of BE are older Caucasian males with chronic reflux symptoms. The challenges to screening for BE include the inability to predict who has BE prior to endoscopy, the lack of evidence based criteria, the invasiveness and expense of endoscopy, and the increasing documentation of a subgroup of patients with BE who lack reflux symptoms. Investigators have attempted to predict BE with clinical and demographic features comparing documented BE patients to patients with GERD lacking BE. Predictors included age >40 (21), heartburn (21–23), long duration GERD symptoms (more than 13 years) (23), and male gender (22). Yet the only consistent correlation in most studies was heartburn and the sensitivity was poor. With the nation's increasing obesity problems, it is not surprising that increased body mass index is correlated with Barrett's esophagus, particularly visceral adiposity characterized by CT scan of the abdomen (24). The emerging data on the potential mechanistic role of cytokines from increasing visceral fat will bear watching. The epidemiology of EAC in the United States identifies risk factors of male gender and Caucasian ethnicity: the annual incidence of EAC in Caucasian men is 3.6/100,000 compared to 0.8 in African American men and 0.3 in Caucasian women (12). The precise magnitude of risk for gender, ethnicity and age are not defined. Esophageal capsule endoscopy is a new technique that has the potential to provide a noninvasive diagnosis of suspected BE, i.e. a columnar lined esophagus. Early studies of small numbers of patients showing high sensitivity have been followed by data sets in abstract form documenting substantially lower sensitivity (25, 26). Although intriguing, this technique cannot be recommended in the screening setting at this time (Grade B Recommendation). It is anticipated that the cost of the capsule and its accuracy will be barriers to lowering the threshold for screening for BE. A more definitive estimate of the population prevalence of BE −1.6% - provides evidence of asymptomatic BE. Forty-four percent of the BE patients from a random sample of adults in 2 communities in Sweden lacked "troublesome heartburn and/or regurgitation over the past 3 months" (27). The inability to distinguish these patients' poses a major problem in developing an effective screening strategy for BE based upon symptoms. There are no current risk factors recognized to identify asymptomatic patients with BE. Such identification will be necessary before screening can be expected to effectively detect the majority of patients with BE. The natural history of asymptomatic BE is undefined. In summary, screening for Barrett's esophagus in the general population cannot be recommended at this time. (Grade B recommendation) The use of screening in selective populations at higher risk remains to be established (Grade D recommendation) and therefore should be individualized. SURVEILLANCE OF BARRETT'S ESOPHAGUS The grade of dysplasia determines the appropriate surveillance interval. Any grade of dysplasia by histology should be confirmed by an expert pathologist. Surveillance endoscopy remains controversial because of the lack of randomized trials supporting its value. Critical analysis of the literature does suggest a survival advantage of endoscopic surveillance. Multiple retrospective studies have been published, all of which indicate that survival is statistically enhanced if the cancers are detected by endoscopic surveillance rather than presenting with symptoms (Table 1). In a California community-based population, surveillance detected cancer had lower staging with better survival (28). A larger SEER/Medicare database documented that an EGD 1 year prior to the diagnosis of EAC was associated with earlier stage and improved survival (29).Table 1: Retrospective Surgical Series of Survival for EAC Based on Surveillance StatusSurveillance is practiced by the vast majority of endoscopists in the US (30, 31). The strongest rationale for early case detection of EAC is the poor 5 year survival of EAC of 13% even with contemporary therapy (32). A patient with documented BE needs to be assessed as a candidate for surveillance. It is recommended that patients be advised of the benefits and risks of surveillance endoscopy. Consideration for beginning a surveillance program should include age, likelihood of survival over the next five years, patient's understanding of the process and its limitations for detection of cancer, and the willingness of the patient to adhere to the recommendations (Grade B Recommendation). Surveillance endoscopy should be performed in patients whose reflux symptoms are controlled with proton pump inhibitor therapy. The goal is healing the esophagitis to reduce the likelihood of the inflammatory process interfering with the visual recognition of BE (14) and contributing to cellular changes confusing the reading of dysplasia. Four quadrant biopsies every 2cm of the Barrett's mucosa sample only a small fraction of the lining but offer the possibility of recognizing dysplasia. Ideally the biopsies from a given segment of Barrett's esophagus should be submitted to pathology in a separate container to enable the focusing of subsequent biopsies on the area if dysplasia is identified. Cost effectiveness studies are needed to evaluate this approach. Even if the initial two endoscopies within one year lack dysplasia, there is no guarantee of the subsequent lack of neoplasia, but may allow an interval of three years for surveillance (Table 2). A combined cohort of BE patients documented that half of patients who developed HGD/EAC had no dysplasia on their first two endoscopies (33).Table 2: Dysplasia Grade and Surveillance IntervalThe finding of low grade dysplasia (LGD) warrants a follow-up endoscopy within six months to ensure that no higher grade of dysplasia is present in the esophagus. If none is found, then yearly endoscopy is warranted until no dysplasia is present on two consecutive annual endoscopies. LGD should be confirmed by an expert GI pathologist because of the problem of reading variability (34). When two pathologists agree on the diagnosis of LGD, the patient has a greater likelihood of neoplastic progression percent of biopsies the recognition of LGD will be (20). of patients with LGD had no dysplasia after a follow-up of 4 years. The finding of high grade dysplasia in mucosa should to by an expert GI pathologist and a subsequent endoscopy within three with should undergo endoscopic resection. Although the natural history of is there is a five year risk of EAC excluding in the first It is because of the high risk of cancers that these patients are often as if cancer is with endoscopic CT and even have been performed there is not evidence to their Patients with confirmed high grade dysplasia, even if should be regarding their or would use as a threshold for or surveillance. who to have their dysplasia on surveillance should be to the highest of dysplasia found. This is based upon the problem of on subsequent of intestinal metaplasia mucosa can also with short segments of columnar so the patient should undergo periodic surveillance. If therapy has been patients should be followed and in the area of prior Barrett's mucosa at intervals appropriate for their prior grade of dysplasia until there is of ablation is documented on at least three consecutive endoscopies. (Grade D recommendation) surveillance is recommended Barrett's mucosa has been to recommendations regarding these intervals are not made given the of data of intestinal metaplasia but case series have established that the phenomenon does In summary, the surveillance of Barrett's esophagus does have evidence suggesting The more advanced the in terms of dysplasia, the more surveillance is However, using evidence of dysplasia as the primary to establish surveillance is There are with and need for endoscopies which this an that will need Surveillance is recommended but is a Grade C as long controlled studies are not OF grade dysplasia expert pathologist and more endoscopy and grade dysplasia also by an expert pathologist and a threshold for A more biopsy is necessary to the presence of concomitant adenocarcinoma. Any such as or is best assessed with endoscopic for a more and of of patients with high grade dysplasia is on endoscopic and and the patient's age, and is no longer the necessary treatment to have that for high-grade dysplasia the of four quadrant biopsies should be every 1 because larger intervals to a greater rates of cancer In any within the Barrett's if high-grade dysplasia has been found, should undergo endoscopic to adequate for more has been to be associated with a higher of and with to endoscopic may be these are The use of large has been in the setting of high-grade dysplasia, to biopsy have not been in terms of changes in patient The endoscopic technique to be used to yield is a which should the mucosa in to the biopsy Endoscopic has also been used surveillance of Barrett's esophagus in the that increased to sample the might to better diagnoses are as to additional can be obtained from However, the use of new such as in may be in increasing the clinical of ablation therapy has also been to decrease the risk of development of cancer within Barrett's esophagus. This is in with which to be a The of has not been established However, all studies on ablation therapy have been in with at least and most often proton pump inhibitor therapy. therapy has been the only therapy in a randomized control to decrease cancer risk in Barrett's esophagus In this study, patients were randomized to photodynamic therapy or with the primary of therapy using and was to decrease the risk of by but not the development of cancer after at least months of follow The therapy was also to high-grade dysplasia in of patients of patients in the control also high-grade dysplasia These were if high-grade dysplasia at any subsequent endoscopy. ablation techniques were originally for the treatment of Barrett's esophagus lacking dysplasia. The initial were that The of ablation was first with these ablation has been with or which to have based upon recent small randomized trials at high has been in case series to be to high-grade dysplasia and even small cancers, follow-up is not available has been used to low-grade dysplasia and rates of the Barrett's mucosa are in the with multiple of the of the have been in small of patients followed over short of time. therapy with an with has been in It is in high-grade dysplasia and early EAC in case series It does have of and even patient ablation using a based system has been to be of in of Barrett's esophagus in months after of treatment a radiofrequency on the has treatment of with this This was to the of the esophagus with high radiofrequency and esophageal have been Endoscopic of has also been to Barrett's esophagus, there is data its Surgical has been a of therapy for Barrett's esophagus with high grade dysplasia based upon that endoscopic surveillance may not detect early cancers in to of patients and the for prior to development of cancer may be the of EAC at in patients with at biopsy has been as low as recent studies have that the risk of cancer in the setting of is low at if there is no evidence of cancers detected in the presence of prior high grade dysplasia are early stage This has to changes in the is performed in these can be performed with techniques that the use of and However, the invasiveness of the one large series of patients the major rates time in and time of to be to that from which the of the esophagus the mucosa and with has also been in to decrease the after This has been to but has not been by the because of the need for the Patients need to be to a higher for the best A recent analysis of the literature has there needs to be at least a year at an to decrease mortality to or less A recent retrospective study comparing the mortality of patients with high-grade dysplasia with photodynamic therapy and endoscopic compared with found between the two at months of patients in had an esophageal cancer In summary, high-grade dysplasia is associated with a risk of cancer needs to be with of endoscopic ablation therapy, and presented to the patient based on their for these and the available to provide the current it as if surveillance with endoscopic techniques a of or may in retrospective cohort studies from expert The of which of these be and will on the available in the patient's the patient's and the (Grade B recommendation). BARRETT'S ESOPHAGUS Barrett's esophagus has been the of new It is not surprising the esophagus is using and the of mucosa to be is There have been to image Barrett's esophagus. The most available technique is a of the to two major and which are actually more by in the mucosa and These the to the mucosa better in with a high This has been the has been or A can be performed after image and has been by another The is based on with of by the Both of these can be applied to Barrett's esophagus In one study of patients with Barrett's esophagus with of had high grade dysplasia, the sensitivity of detection for a was with a of However, studies regarding the in of these has not been has also been used in to of dysplasia in Barrett's esophagus. This to detect from cellular in the esophagus. of dysplasia do not have as as and This may be more for screening larger of In Barrett's esophagus, one study has found that was for of high grade dysplasia in patients but had a rate have been used to image the esophagus with to the mucosa of of intestinal metaplasia but will not if there is high grade dysplasia or cancer The by which is applied and the of performed prior to of the this technique have had and studies have not found a advantage to in to random four quadrant biopsies in detection of dysplasia such as and have also been to the detection of in Barrett's esophagus in with high endoscopy There is in these it is the identification of will be in clinical The can the other techniques have been developed that small mucosa that might be on these These include and which can the mucosa and actually image cellular studies are in in Barrett's esophagus. in patients had an accuracy of for detection of which in a more to but using to also has for the detection of intestinal metaplasia at the gastric junction prior studies have not been in dysplasia can the from the mucosa and its to determine the of dysplasia that is that can such as and have been combined to allow improved of the mucosa the present of these is to in an and Although there is not evidence at this time to the use of these systems on a clinical BARRETT'S ESOPHAGUS Multiple have been but have actually been There is in the use of such as and in biopsy in cancer as well as of of such as and In recent studies that of and as well as demographic of the patients and BE length are of cancer or is for clinical There is a large cohort of patients that has been followed with the in the This has been using of that have been by to a of Based on these studies, there is no risk of cancer development for five years if there is no evidence of increased than or However, if was there was an increased risk of cancer whereas evidence of increased risk However, these have been to clinical because of the number of biopsies in the needed to In the in has at of as a using to detect of of and these are of cancer with a increased risk of cancer if of is detected However, these techniques have only been applied to that have been of these in a study is needed before it can be recommended for In a recent an of from patients who had developed cancer compared to case who had not found that of three and in their once again to predict cancer These be on which is an advantage over the mentioned However, these studies have only been on patient and have not been applied in a large that have been over time include of of and Although multiple have been to be in small of none of these has been in studies. The for the detection of GERD patients who will to BE would be noninvasive i.e. and or The to risk patients with BE would be noninvasive and the focusing of surveillance endoscopy on this high risk for EAC. This would identify patients with BE who will to EAC early for even the appropriate therapy. A low risk also be which might not cost effective surveillance would be this that can be performed on a clinical for widespread use are not BARRETT'S ESOPHAGUS a in the stage of esophageal adenocarcinoma by Barrett's esophagus seems Unfortunately, evidence that any treatment cancer and more cancer in this setting is The best evidence for any with that have been in multiple studies to be associated with a risk of cancer with an of interval This risk has also been with the that such as and were also with Unfortunately, in a randomized not its patient was not more effective than in patients with BE and dysplasia in the of the change of the of biopsies with dysplasia studies have risk of cancer in given trials are the use of and low and high proton pump inhibitor therapy in Barrett's esophagus but these will years to from two retrospective cohort studies suggest that therapy the likelihood of developing dysplasia This provides a rationale to even asymptomatic BE patients with The of therapy as a of cancer has not been documented can be made to use these as BARRETT'S ESOPHAGUS patients with Barrett's esophagus, the goal of with such as the proton pump is to control reflux symptoms. symptoms can be controlled in most patients with proton pump inhibitor therapy. a may be necessary in a subgroup of Retrospective studies have a decrease in development of dysplasia in patients with or proton pump have that of esophageal may decrease of there are no data that the use of high therapy to or the development of EAC. Patients who are for may These include patients lacking major and whose reflux symptoms are controlled with therapy. are with a rate at 5 years The vast majority of data do not provide that EAC detection of It is anticipated that in the short may available that identify Barrett's mucosa based on high or A randomized impact of surveillance endoscopy. A randomized controlled of surveillance is needed to determine the of this recognition of techniques are available that can distinguish of dysplasia. These from and to such as and or more of these will definition of risk of dysplasia. in the of endoscopic ablation of the most recent radiofrequency ablation is is beginning clinical trials and older are more photodynamic therapy with the development of new of the and duration of the surveillance after endoscopic ablation therapy of a to risk BE There are many potential but clinical trials that their This will change given the many for

Potential conflict of interest: Dr. Chalasani consults for and received grants from Eli Lilly. He consults for NuSirt, AbbVie, Afimmune, Tobira, Madrigal, Shire, Cempra, Ardelyx, Axovant, and Amarin. He received grants from Intercept, Gilead, Galectin, and Cumberland. Dr. Younossi consults for Bristol‐Myers Squibb, Gilead, Intercept, Allergan, and GlaxoSmithKline. He advises for Vertex and Janssen. Dr. Brunt advises for Gilead. Dr. Charlton consults for and received grants from Gilead, Intercept, NGM Bio, Genfit, and Novartis. He received grants from Conatus. Dr. Cusi consults for and received grants from Novo Nordisk. He consults for Tobira. He received grants from Cirius, Novartis, Janssen, Zydus, Nordic, and Lilly. Dr. Rinella consults for Intercept, Gilead, Genfit, Novartis, NGM Bio, and Nusirt. She advises for Fibrogen, Immuron, Enanta, and AbbVie. Dr. Harrison consults for Madrigal, NGM Bio, Genfit, Echosens, Prometheus, Cirius, Perspectum, and HistoIndex. He advises for Garland, Intercept, Novartis, and Pfizer. He is on the speakers' bureau for AbbVie, Gilead, and Alexion. Dr. Sanyal consults for and received grants from Salix, Conatus, Galectin, Gilead, malinckrodt, Echosens‐Sandhill, Novartis, and Sequana. He consults for and is employed by Sanyal Bio. He consults for and owns stock in GenFit, Hemoshear, Durect, and Indalo. He consults for Immuron, Intercept, Pfizer, Boehringer Ingleheim, Nimbus, Nitto Denko, Lilly, Novo Nordisk, Fractyl, Allergan, Chemomab, Affimmune, Teva, and Ardelyx. He received grants from Bristol‐Myers Squibb and Merck. He received royalties from UptoDate. He owns stock in Exhalenz, Arkana, and NewCo LLC. The funding for the development of this Practice Guidance was provided by the American Association for the Study of Liver Diseases. This practice guidance was approved by the American Association for the Study of Liver Diseases on June 15, 2017. Preamble This guidance provides a data‐supported approach to the diagnostic, therapeutic, and preventive aspects of nonalcoholic fatty liver disease (NAFLD) care. A “Guidance” document is different from a “Guideline.” Guidelines are developed by a multidisciplinary panel of experts and rate the quality (level) of the evidence and the strength of each recommendation using the Grading of Recommendations, Assessment Development, and Evaluation system. A guidance document is developed by a panel of experts in the topic, and guidance statements, not recommendations, are put forward to help clinicians understand and implement the most recent evidence. This Practice Guidance was commissioned by the American Association for the Study of Liver Diseases (AASLD) and is an update to the Practice Guideline published in 2012 in conjunction with the American Gastroenterology Association and the American College of Gastroenterology (ACG).1 Sections where there have been no notable newer publications are not modified, so some paragraphs remain unchanged. This narrative review and guidance statements are based on the following: (1) a formal review and analysis of the recently published world literature on the topic (Medline search up to August 2016); (2) the American College of Physicians' Manual for Assessing Health Practices and Designing Practice Guidelines2; (3) guideline policies of the AASLD; and (4) the experience of the authors and independent reviewers with regard to NAFLD. This practice guidance is intended for use by physicians and other health professionals. As clinically appropriate, guidance statements should be tailored for individual patients. Specific guidance statements are evidence based whenever possible, and, when such evidence is not available or is inconsistent, guidance statements are made based on the consensus opinion of the authors.3 This is a practice guidance for clinicians rather than a review article, and interested readers can refer to several recent comprehensive reviews.4 Because this guidance document is lengthy, to make it easier for the reader, a list of all guidance statements and recommendations are provided in a tabular form there be (1) evidence of by or and (2) of of such use of a or the of is with such and can be nonalcoholic fatty liver or nonalcoholic is the of evidence of in the form of is the of and with with or this guidance document be to or or of fatty liver of of and the of in from fatty liver to to of evidence of in the form of of the or evidence of The of to and liver is of with and with or This can to liver and liver of with or evidence of or of with no with are with such and of and is a to in liver in with in is A of and and of in the is a of the of in the A have of from are a for of by was a of for of by was the of using and was to be a of for an of of developed by to an rate of The for in the of are A from using of an rate for of the of such this most the of A from an rate of A recent the of from to be the rate from the is to be to the there is a of publications the of in the are in a recent of the of The the of by is The of is from the and the rate is from As the for a liver liver is not in of the there is no of the or of there have been some to the of by The the of in the are in the The of liver for a is to be The of liver a for is from to the of in the and of in of are not in with of the of This and of been this provides a list of the and and and independent of are with and is the most and for NAFLD. the of from to and is with NAFLD. this the of with have is a of in with some have to of have is to the of and this and can in a the of in with or the of in with NAFLD. this and and are in with NAFLD. The of in with been to be a a the based on to and to The rate of was the rate for with the to and to was the rate in the with the was and The of to and the of and of liver disease to with Association of the of or of the (1) than in or than in (2) or (3) than in and than in (4) or or or and or been a for NAFLD. the of in is than in The of and on have the to have a of have a of the of and to be to be is most of the recent the for be by the to the the of the from to and of the have the of with is evidence with with some of are for such and have the following: with have to The most of in with is disease independent of other is the of in the it is the or of with is the of in with with have an a recent and and to be and and and The for and for to be and The most of with is to or are of is the of in the to the of with the the of the of been to a with are have a have and are to from liver than other of from a of from the not have other was with in the of This of in is to most with have is This of with have a of and with the with or in the of in of the for liver disease is of the recent in with a rate of the of in to with a rate of and in with to with a recent of with and a of an of rate not different from with This is with of with with or liver is the of and the of in the are with As of liver disease is the development of The rate was to be of with of the to to liver to and to it is the for in is the of with the and of the of evidence for or recent of of the of in with is A consensus for be in and in a liver to the on and a is of the of in published literature been Guidance or recent on in and on in is a for when with NAFLD. Evaluation of and for other than liver or A recent of with be for based on the the and and for this have not been Guidance with on have or to liver disease or have liver should be have and up with on or and have liver should be for or and for such or for in and can be there should be for with or not with have of the available evidence of and of there are in the and of NAFLD. A analysis using a for in with is not of with available liver can be in with not be to liver or are is experts recently have for for liver disease in with not Guidance for in or is not this of and with of to and of should be a of for and in with such or or can be to or for or of of a of with have a a of with and for and the of liver was and fatty liver was in of of with in the of and the of have been from no in a to in a of an of in using to and and not and, the of and was and Guidance of for is not Evaluation of the The of (1) there is by or (2) there is no (3) there are no for and (4) there are no of of are disease and a with it is to for liver and liver can in with not the of liver of this are and is a of not it can disease the are of was with in a of and are in a with should be in the with in with and the is Liver should be in the of and a to the or of and to in a with NAFLD. of and are in with and are to be an of no liver to a of from the in or in and not with disease or other are should be for the of or and Guidance a with it is to for and with and in the of or a liver should be of in with other of liver disease or to should a for liver of with should the of such or and Assessment of and in The of is is can to liver and liver Liver is the most approach for the of and in with it is is by and and and such and not the of liver in with NAFLD. there been in and for in with is the of this practice of the of and and the and of in with by or by is an for and is in The use of to is a for in an the of in with in is The of is a for the of in with is with of the of an of such and to the of liver with and such and are the for of have been for the of in with This is not available in a The for the of in to Liver and or and The is based on available and and is using the published a of of the an the of for with or A and to a and to the of is an based on and with are with are to have A recent and liver and (1) than other such and and (2) for in with The panel of of of and an of with and for or This panel been recently approved for use in is not available for use in the liver was recently approved by the and for use in and with liver recent the of in with using an on the of in with from the The liver for was with and The for was in of the the on the of using an with in with The rate for in this was The for for and was The recently experience with in with in the using a with an or rate for a liver was is for of in with the by than for or in or for and and have several with and in with for in is not Guidance with the of and can be to for a liver or are clinically for with of or or are clinically for in with NAFLD. to a Liver in Liver the for liver in with NAFLD. is for and some and it should be in the most from and Guidance Liver should be in with are of The of or or liver by or be for are for Liver should be in with in for and the of be a liver of The of are of with the of not by The for of liver in a with or the and on of the is the to from on of and The for have been by the by not with or and or not all for with of or in or and and of have no or of up to is or is and is with and is of in from in in be or in and and be in is readers refer to other recent publications for of of fatty liver disease in and are for of in from the and from the Liver of the and for The was developed a of in from a the the for for use in and from with the of and in with other of liver there is a for and for with based and to the of in and and The by a of was with in and when a a Guidance should a with and with and and A on or be Specific such be The or of should be a to and is of The of should of liver disease the such and with or have from a liver liver disease should be to with and Guidance liver disease should be to with and of and been to with NAFLD. The to is the to in the of a of with to of in was with have been by a recent with liver in this a was the the of the the in such was with in all of and it is to or in of the of to a in this with a the is with of liver and in The of the to to be than the of in are by a of and by or by in in and The in fatty been in to a for and, there was no in in in the with are recommendations to can be The of are in and this been with an of and the of on in are a recent an in with no in The and of than or by than have in independent of This is by a of of a a or for was with the in of development or in independent of the The of on are from a of of or was not with in or recommendations have in of the recommendations was to have a on and are for with to the of and on are on in a analysis of in a than on a review of and in liver liver with of the to of a recommendations to in a of to in and Guidance by or in conjunction with A of a by and is to the of of of to a is to the of the of in with or to other aspects of liver the of on liver in with several have an in and not liver published not liver in with and Guidance is not for in patients. are for the with on and on and The of to and in and have to in with an in not of or is no available in most and in the of of an in no was an review of all evidence by the an an of in with and or and and The with in to of and there was a in to a recent Cusi with or with a from and or for by an with The was a of in the different of with the and of and of no different was with and a of is of in with an with or for in with not to and the for the of with a in with to or for The was an in by with in and in the or and no in the This was in in the to in the and in the Because this of and a of was to be a there with this not the of a was in a of than and and there no in other is the most with from and from to in of to been a with or for up to and no and use of or of in with Guidance liver in with and with it be to patients. and should be with each and should not be to been an in the of in with and a recently published of with for was with of and of As was with Guidance is to to liver disease in with or is a of and disease in with is an and been a for is of for the different of and of the use of other or other and to most and not or of for it can be (1) the use of is with a in in with (2) in in in and and of in a of with and (3) not have an on the the form of was a of for The was in a of to to the of Liver in or in with of was in with than in with recent with in with are the of of with this been several with and A and other such not A analysis of with the of the by in in the in A and from to not a and a published in a of was and with a in the of of of and this be by or with Guidance a of liver in with and be for this and should be with each is not to in liver or all is in for is in all of most is to and to or disease in most and and from and the most of in there are no of in to be in the there are several and and with liver and with liver of and and in with and in and to there was a in the and of and and with or there was a in and and of or and with no in liver and a in was the to this of and there is no clinically in can be to the a on with with the of and of in to in of a of available in the of to or the of and by a by in the of The and of in with is not analysis from the and for with and to was in with and in with A recent review of in with A and is with with Guidance can be in with or is to an to The and of in with to are not with or be on a by an have and to and in with and liver in with have been with of a no in with fatty approved in the to have been to in and in a review of the published literature in evidence to the use of fatty in with to liver the of was by and recently to for fatty in with or than a other have been in and is the of this Guidance is not for the of or fatty should not be a of or be to in with NAFLD. in and is a for and should be by with and or than on or than in or than on or in several have a of than on the or by and of a recent analysis of from the of by are are no the of on disease or of or The of on the and have not been in with NAFLD. Guidance with should not of are to make recommendations with regard to of by with NAFLD. is a and of and for the and a and to and of is there are and of the and and of are not and with have a by and to a of with to be by and the of rather than by the of have evidence of the of with of in with or and A recent analysis of the The and Evaluation and in with to analysis of the The and a of in with in to it is to in with based on to use in with or and several have the of in with liver disease of in liver the of is not in with are not in liver from is in of for are and have with liver or not all and on when this was not a of in liver or liver Guidance with are for and of should be in all with NAFLD. with or are not for liver from can be to in with and be in with should be in with and are are in a a and a in a this was with and This was recently approved by the for with are to in a up to in a recently an for a this was with there was a in Guidance and available in with should not be to and and are and, in is on a to the most for in the with is with an of and to an analysis of the for a of and and with the of when for not to an of or The of on and in the of the of a in of or for not been for and been in a of with been in and and in for The of an to of all to the is is with been an independent of and Because of the of and with and a of is with some of and have all been to be in this As is with a of with is in with with to when is or is with an of disease and in the most for liver in the Because of the of with rate of or of with the is than of are from are for with and and are to other The of is an of and in evidence of is or by for is in of by the of the a rate is than for other than with for than and is in of by the A recent experience of to this from and recommendations for are to for other with and and a and are in the of is by and is in with a of are some to the of patients. and and Guidance with have of should be to clinically or the Guidance to Practice with should be for to the and practice with of should be for to the practice evidence not and for in with evidence not a liver in with or this be on a of Specific to and in be to or to with of in be most for or The of and in are the in with are and with of of in for the in based the of or the for and the and of the A of in and using a of to using the of liver to from The was when for and A recent the of to be in from and in based on This the of in to with with a of with with and with the of was to be with of to in with and or in with so use of the of liver a of with and from of of on the of was in of with liver other than in was the most and was in of the with NAFLD. with the a of and a of of been in of with The of and to was in to a with than to to an and NAFLD. A the of in for of of the and of The the on with received with of the liver developed the was to and the or in of and in not to be and with are on of to the of in is in of of or of by health than of with for with not be and for of by As in with of such and are for and of with of of for in health in for and there are no to with in this the of an for liver disease with and in with and with in the with other the to the of in of fatty or and in are in a of with and, on some liver is to and the of use or is in and for are the no panel of or can and in Guidance with fatty liver are or not should be for of such fatty and in to for of are in with in with or to should a liver to and Because of a of a formal recommendation be made with regard to for in with and A The to a liver in a to the of be the with and the the with an of than or of to of there is an in or of all with to a liver it be to are to have or to with for liver on in of and of have been to for The of the to of with based on of As in development of or to for or disease is of and are can be to in with a of and with is in in with an of of the or of with of a liver a with and the Guidance Liver in with should be in in the is or in there is of or A liver to a of should be on for of with can from in some in of and there is a in This is by or and in the of The and to be different in with Guidance liver should the in with to NAFLD. for are by a of and on to The is to a quality of and and liver and of should be made to from Because most have this is the in with in in and by in most with NAFLD. of the to this using and Because liver not the of the the of on liver not be with to or and not liver in in and the of with and in an or in to on of or the of to aspects of in is are to the of for should with a to quality of and of of American Association and in As in for or have in or liver on and A using in a the of or to in to with the of of was not different the there in and of with to this a no on liver or liver The from the of to this the in of or of was not the a in on to been some to fatty to in a of and to in for in in Guidance and liver in with and should be the of no to with and should not be to or The of a is not to some with of in is be to in and should be with each in

Brief Communications15 October 1994Treatment of Achalasia with Intrasphincteric Injection of Botulinum Toxin: A Pilot TrialPankaj J. Pasricha, MD, William J. Ravich, MD, Thomas R. Hendrix, MD, Samuel Sostre, MD, Bronwyn Jones, MD, and Anthony N. Kalloo, MDPankaj J. Pasricha, MD, William J. Ravich, MD, Thomas R. Hendrix, MD, Samuel Sostre, MD, Bronwyn Jones, MD, and Anthony N. Kalloo, MDAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-121-8-199410150-00006 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Achalasia is a disorder characterized by a failure of the lower esophageal sphincter to relax with swallowing and by a lack of esophageal peristalsis. The sphincteric abnormalities in achalasia are thought to be caused by a selective loss of inhibitory neurons in the myenteric plexus, resulting in the relatively unopposed excitation of the smooth muscle by acetylcholine and other mediators. Our previous studies in animals [1] have shown that locally injected botulinum toxin, a potent inhibitor of acetylcholine release, can reduce lower esophageal sphincter tone. We report our initial experience with this agent for the treatment of achalasia in humans.... References1. Pasricha PJ, Ravich WJ, Kalloo AN. Effects of intrasphincteric botulinum toxin on the lower esophageal sphincter in piglets. Gastroenterology. 1993; 105:1045-9. Google Scholar2. Eckardt VF, Aignherr C, Bernhard G. Predictors of outcome in patients with achalasia treated with pneumatic dilation. Gastroenterology. 1992; 103:1732-8. Google Scholar3. Wong RK, Maydonovitch CL. Achalasia. In: Castell DO, ed. The Esophagus. Boston: Little, Brown; 1992:233. Google Scholar4. Stuart RC, Hennessy TP. Primary disorders of oesophageal motility. Br J Surg. 1989; 76:1111-20. Google Scholar5. Richter JE. Motility disorders of the esophagus. In: Yamada T, ed. Textbook of Gastroenterology. Philadelphia: J.B. Lippincott; 1991:1083. Google Scholar6. Csendes A, Braghetto I, Henriquez A, Cortes C. Late results of a prospective randomized comparing forceful dilatation and esophagomyotomy in patients with achalasia. Gut. 1989; 30:299-304. Google Scholar7. Vantrappen G, Hellemans J. Treatment of achalasia and related motor disorders. Gastroenterology. 1980; 79:144-54. Google Scholar8. Coccia G, Bortolotti M, Michetti P, Dodero M. Prospective clinical and manometric study comparing pneumatic dilatation and sublingual nifedipine in the treatment of oesophageal achalasia. Gut. 1991; 32:604-6. Google Scholar9. Robertson CS, Hardy JG, Atkinson M. Quantitative assessment of the response to therapy in achalasia of the cardia. Gut. 1989; 30:768-73. Google Scholar10. Janckovic J, Brin MF. Therapeutic uses of botulinum toxin. N Engl J Med. 1991; 324:1186-94. Google Scholar Author, Article, and Disclosure InformationAuthors: Pankaj J. Pasricha, MD; William J. Ravich, MD; Thomas R. Hendrix, MD; Samuel Sostre, MD; Bronwyn Jones, MD; Anthony N. Kalloo, MDFrom Johns Hopkins Hospital, Baltimore, Maryland.\\\Corresponding Author: Pankaj J. Pasricha, MD, Johns Hopkins Hospital, 600 North Wolfe Street, Blalock 4, Baltimore, MD 21287-4461. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byAchalasia Treatment: From the Whale Bone to POEMThe Limited Role for Botox in Achalasia: A Gastroenterologist's PerspectiveEsophageal AchalasiaAdverse Events Associated With Botox as Reported in a Food and Drug Administration DatabaseThe Endoscopic Treatment of Esophageal Motility DisordersASGE guideline on the management of achalasiaComparison of Different Treatment Modalities and Treatment Algorithm for Esophageal AchalasiaBotulinum Toxin Treatment in Gastrointestinal DisordersAcalasia, una visión actualEsophageal Achalasia: Endoluminal TherapyEndoscopic Management of Achalasia: Botulinum Toxin and Pneumatic DilationEsophageal Motility DisordersBridging therapy for achalasia in a second trimester pregnant patientManagement of Achalasia: Expert Consensus StatementsThe 2018 ISDE achalasia guidelinesManagement of achalasia cardia: Expert consensus statementsClinical and Translational Aspects of Normal and Abnormal Motility in the Esophagus, Small Intestine and ColonEsophageal AchalasiaHeller Myotomy Is Superior to Balloon Dilatation or Botulinum Injection in Children with Achalasia: A Two-Center ReviewPharmakologische und endoskopische Therapie bei ÖsophagusmotilitätsstörungenAlteraciones motoras esofágicasIdiopathic (primary) achalasia: a reviewMotility Disorders of the EsophagusBotulinum neurotoxin: Progress in negating its neurotoxicity; and in extending its therapeutic utility via molecular engineering. MiniReviewAssessment and Management of Primary Esophageal Motility Disorders: Achalasia and Distal Esophageal SpasmPharmacotherapy for the management of achalasia: Current status, challenges and future directionsEndoscopic pneumatic dilation versus botulinum toxin injection in the management of primary achalasiaAchalasia – advances in treatmentEndoscopic botulinum toxin injection: Benefit and limitationBotulinum neurotoxin in the gastrointestinal tractClinical Use of Botulinum Neurotoxin: Autonomic ConditionsBotulinum toxin and pneumatic dilation in the treatment of achalasiaTools for endoscopic stricture dilationComparison Between Botulinum Injection and Removable Covered Self-Expanding Metal Stents for the Treatment of AchalasiaThe role of Botulinum toxin injection in the management of achalasiaBotulinum Toxin for LES Spastic DisordersEsophageal Motor Disorders: Achalasia, Diffuse Esophageal Spasm, Nonspecific Motor Disorders, Eosinophilic EsophagitisPerspectives on Esophageal SurgeryEndoscopic approach to achalasiaOesophageal achalasiaLaparoscopic stapled cardioplasty for failed treatment of achalasiaAchalasiaTherapeutische EndoskopieBotulinum toxin in the treatment of diffuse esophageal spasmAchalasia: Update on the Disease and Its TreatmentPatología digestiva superior: trastornos de la degluciónAchalasia: A review of Western and Iranian experiencesFour Hundred Laparoscopic Myotomies for Esophageal AchalasiaLong-lasting effect of a single botulinum toxin injection in the treatment of oropharyngeal dysphagia secondary to upper esophageal sphincter dysfunction: A pilot studyIdiopathic (primary) achalasiaAchalasiaIntragastric Injection of Botulinum Toxin A for the Treatment of ObesityEndoscopic pneumatic dilation versus botulinum toxin injection in the management of primary achalasiaBotulinum Toxin Type A for Poststroke Cricopharyngeal Muscle DysfunctionReview article: the management of achalasia – a comparison of different treatment modalities1Effect of botulinum toxin antral injection on gastric emptying and weight reduction in obese patients: a pilot studyFeline lower esophageal sphincter sling and circular muscles have different functional inhibitory neuronal responsesNon-surgical treatment of esophageal achalasiaEndoscopic balloon dilatation versus botulinum toxin injection in the management of primary achalasiaTreatment with botulinum neurotoxin of gastrointestinal smooth muscles and sphincters spasmsCurrent and future treatment of chest pain of presumed esophageal originRandomized Controlled Trial of Botulinum Toxin Versus Laparoscopic Heller Myotomy for Esophageal AchalasiaLong-term outcome of esophageal myotomy for achalasiaTube digestif et toxine botuliqueBotulinum toxin in the therapy of gastrointestinal motility disordersBotulinum toxin for spastic GI disorders: a systematic reviewTreatment of achalasia: the short-term response to botulinum toxin injection seems to be independent of any kind of pretreatmentEsophagogastroduodendoscopy in pediatric patients including biopsy techniques and dilatationLong-term effects of myotomy and partial fundoplication for esophageal achalasia*Treatment of Chest Pain in Patients With Noncardiac, Nonreflux, Nonachalasia Spastic Esophageal Motor Disorders Using Botulinum Toxin Injection Into The Gastroesophageal JunctionTreatment of Idiopathic Gastroparesis With Injection of Botulinum Toxin Into The Pyloric Sphincter MuscleAchalasia: A review of therapeutic options and outcomesTreatment of Achalasia with Botulinum A ToxinLong-term follow-up of achalasia patients treated with botulinum toxinTreatment of symptomatic diffuse esophageal spasm by endoscopic injections of botulinum toxin: A prospective study with long-term follow-upRandomized controlled trial of intrasphincteric botulinum toxin a injection versus balloon dilatation in treatment of achalasia cardiaDiagnosis and treatment of achalasiaIndications and efficacy of botulinum toxin in disorders of the gastrointestinal tractPharmacologic Therapy in Treating AchalasiaStrategies for Treating Severe Refractory DysphagiaEtiology and Treatment of Achalasia in the Pediatric Age GroupADVANCES IN DIAGNOSTIC AND THERAPEUTIC ENDOSCOPYPharmacotherapy with Botulinum Toxin: Harnessing Nature's Most Potent NeurotoxinLong-term follow-up of achalasic patients treated with botulinum toxinInvited comment: 'Long-term follow-up of achalasia patients'Evaluation of the Use of Botulinum Toxin in Children With AchalasiaEndoscopic practice at the start of the new millenniumAchalasia: Pathophysiology, Diagnosis, and Nonoperative TreatmentAcalasia esofágica. Revisión de sus aspectos clínicos, diagnósticos y terapéuticosEndoscopy of the Upper Gastrointestinal TractEsophageal pharmacology and treatment of primary motility disordersLong-Term Efficacy of Botulinum Toxin in Classical Achalasia: A Prospective StudyReview article: pharmacological options in achalasiaAchalasia: Willis or Heller?AGA technical review on treatment of patients with dysphagia caused by benign disorders of the distal esophagusTreatment of AchalasiaBotox injection for achalasia: a modified techniqueBOTULINUM TOXIN INJECTIONS FOR ACHALASIA SYMPTOMSBotulinum Toxin Injections for Achalasia Symptoms Can Approximate The Short Term Efficacy of A Single Pneumatic Dilation: A Survival Analysis ApproachSelektive Denervierung durch Botulinus-Toxin als therapeutisches Prinzip im GastrointestinaltraktBiomedical aspects of Botulinum ToxinNITROGLYCERIN—IS IT GOOD FOR MORE THAN HEARTS?Successful treatment of esophageal achalasia with laparoscopic Heller myotomy and Toupet fundoplicationBruxism after brain injury: Successful treatment with botulinum toxin-APATHOPHYSIOLOGY AND ENDOSCOPIC/BALLOON TREATMENT OF ESOPHAGEAL MOTILITY DISORDERSRecent Advances in the Treatment of AchalasiaEditorialsBotulinum toxin injection for an esophageal muscular A-ringKonservative TherapieTreatment of achalasia by injection of botulinum toxin under endoscopic ultrasound guidanceTreatment of symptomatic nonachalasia esophageal motor disorders with botulinum toxin injection at the lower esophageal sphincterUse of high-resolution endoscopic ultrasonography to assess esophageal wall damage after pneumatic dilation and botulinum toxin injection to treat achalasiaTraitement de l'achalasie par injection de toxine botulinique sous contrôle échoendoscopiqueThe Use of High Frequency Endoscopic Ultrasonography Probes in the Evaluation of AchalasiaIntrasphincteric Botulinum Toxin for the Treatment of AchalasiaTreatment of Achalasia — From Whalebone to Botulinum ToxinMechanismen des zellulären ProteintransportsMolekular- und zellbiologische Aspekte neuroendokriner Tumorerkrankungen des gastroenteropankreatischen SystemsGastrointestinal ApplicationsTherapeutische Endoskopie 15 October 1994Volume 121, Issue 8Page: 590-591KeywordsAcetylcholineBotulinum toxinEndoscopyIschemiaNeuronsRadionuclide imagingSkeletal musclesSmooth musclesSurgerySwallowing ePublished: 15 August 2000 Issue Published: 15 October 1994 Copyright & PermissionsCopyright © 1994 by American College of Physicians. 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Article1 August 1963Family Occurrences of Ulcerative Colitis, Regional Enteritis, and IleocolitisJOSEPH B. KIRSNER, M.D., F.A.C.P., JEAN A. SPENCER, M.D.JOSEPH B. KIRSNER, M.D., F.A.C.P., JEAN A. SPENCER, M.D.Author, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-59-2-133 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptDespite the genetic heterogeneity of man, surveys of disease among population groups and families are important in the search for possible etiologic mechanisms in obscure diseases. Whereas ulcerative colitis and regional enteritis hitherto had been regarded as characteristically limited to one member of a family, recent observations suggest a more than casual family incidence of these diseases.Spriggs (1) in 1934, noted ulcerative colitis in 2 brothers and a sister. Moltke (2) recorded 5 families with multiple instances of the disease (mother, daughter, 2; brother, sister, 2; and father, daughter, one). Jackman and Bargen (3) in 1942, described occurrences in...References1. SPRIGGS EI: Chronic ulceration of the colon. Quart. J. Med. 27: 549, 1934. CrossrefGoogle Scholar2a. MOLTKE O: Familial occurrences of non-specific suppurative coloproctitis. Acta. Med. Scand., Supp. 77, 78: 426, 1936. Google Scholar2b. MOLTKE O: Ueber das Familiar Auftreten der Chronischen Suppurative Koloproctitis. Klin. Wschr. 15: 124, 1936. CrossrefGoogle Scholar3. JACKMANBARGEN RFJA: Familial occurrence of chronic ulcerative colitis. Amer. J. Dig. Dis. 9: 147, 1942. CrossrefGoogle Scholar4. SLOANBARGENGAGE WPJARP: Life histories of patients with chronic ulcerative colitis: a review of 2,000 cases. Gastroenterology 16: 25, 1950. CrossrefMedlineGoogle Scholar5. PAULSON ME: "Nonspecific or indeterminate colitis," in Diseases of the Digestive System, Lea & Febiger, Philadelphia, 1953, p. 783. Google Scholar6. KIRSNERPALMER JBWL: Clinical course of non-specific ulcerative colitis. JAMA 137: 922, 1948. CrossrefMedlineGoogle Scholar7. PARISHÉRAUD JM: Familial hemorrhagic rectocolitis. Arch. Mal. Appar. Dig. 50: 370, 1961. MedlineGoogle Scholar8. BARKER WF: Familial history of patients with ulcerative colitis. Amer. J. Surg. 103: 25, 1962. CrossrefGoogle Scholar9. HOUGHTONNAISH EAJM: Familial ulcerative colitis and ileitis. Gastroenterologia 88: 65, 1958. CrossrefGoogle Scholar10. BACON HE: Ulcerative colitis. J. B. Lippincott Co., Philadelphia, 1958. Google Scholar11. SCHLESINGERPLATT BJ: Ulcerative colitis in childhood and a follow up study. Proc. Royal Soc. Med. 51: 733, 1958. CrossrefMedlineGoogle Scholar12. CORNESSTREHER JSM: Primary Crohn's disease of the colon and rectum. Gut 2: 189, 1961. CrossrefMedlineGoogle Scholar13. WIGLEYMACLAURIN RDBP: A study of ulcerative colitis in New Zealand, showing a low incidence in maoris. Brit. Med. J. 2: 228, 1962. CrossrefMedlineGoogle Scholar14. CROHN BB: Personal communication. December, 1962. Google Scholar15. BARGEN JA: Personal communication. December, 1962. Google Scholar16 HAMMERLEMMANS MAM: Familial colitis gravis. Nederl. T. Geneesk. 80: 5131, 1936. Google Scholar17. FEDER IA: Chronic ulcerative colitis. An analysis of 88 cases. Amer. J. Dig. Dis. 5: 239, 1938. CrossrefGoogle Scholar18. JULIEN-MARIE L: Rectocolite Hemmorhagique Chez un Enfant. Carostese Familial de l'Affection. Arch. Mal. Appar. Dig. 31: 76, 1942. Google Scholar19. PAULLEY JW: Ulcerative colitis. Gastroenterology 16: 566, 1950. CrossrefMedlineGoogle Scholar20. TIDRICK RT Personal communication, 1962. Google Scholar21. LYONSPOSTLETHWAIT CRRW: Chronic ulcerative colitis in twins. Gastroenterology 10: 545, 1948. MedlineGoogle Scholar22. WEBB LR: The occurrence of ulcerative colitis in twin males. Gastroenterology 15: 523, 1950. CrossrefMedlineGoogle Scholar23. CROHNYARNIS BBH: Regional ileitis. Grune & Stratton, New York, 1958. Google Scholar24. STEIGMANNSHAPIRO FS: Familial regional enteritis. Gastroenterology 40: 215, 1961. CrossrefGoogle Scholar25. SHERLOCKBELLSTEINBERGALMY PBMHTP: Familial occurrences of regional enteritis. Presented at the Annual Meeting American Gastroenterological Association, April, 1962. Google Scholar26. FREYSZHAEMMERLIKARTAGENER HAM: Ileitis regionalis bei einem Weiblichen Zwillingspaar. Gastroenterologia 89: 75, 1958. CrossrefMedlineGoogle Scholar27. LEWISOHN R: Segmental enteritis. Surg. Gynec. Obstet. 66: 215, 1938. Google Scholar28. BROWNSCHEIFFLEY PWCH: Chronic regional enteritis occurring in three siblings. Amer. J. Dig. Dis. 6: 257, 1939. CrossrefGoogle Scholar29. BOCKUS HL: "Chronic stenosing regional enteritis and enterocolitis." in Gastroenterology, Vol. 2, W. B. Saunders Company, Philadelphia, 1946. p. 1620. Google Scholar30. KIRSNEROWENSHUMPHREYS JBFMEM: Regional enteritis in father and son. Gastroenterology 10: 883, 1948. MedlineGoogle Scholar31. REICH H, cited by J. B. Kirsner (30). Google Scholar32. ARMITAGEWILSON GM: Crohn's disease: survey of literature and report on thirty-four cases. Brit. J. Surg. 38: 182, 1950. CrossrefMedlineGoogle Scholar33. EDWARDS HC: Recent Advances in Surgery, 4th ed. J. & A. Churchill, Ltd. London, 1954. Google Scholar34. EUDELVIGNIE FR: Les Formes Caecales de la Maladie de Crohn. Presse Méd. 63: 1846, 1955. MedlineGoogle Scholar35. HEARDJOHN GEEL: Medical memorandum; regional ileitis in mother and son. Brit. Med. J. 2: 85, 1956. CrossrefMedlineGoogle Scholar36. METZGERFROBESE HNAS: Terminal ileitis in a fifteen year old boy and in the mother nineteen years previously. Gastroenterology 31: 439, 1956. CrossrefMedlineGoogle Scholar37. NIEDERLE MB: Regional ileitis in monozygous female twins. Arch. Mal. Appar. Dig. 50: 1245, 1961. MedlineGoogle Scholar38. FELSENWOLARSKY JW: Familial incidence of ulcerative colitis and ileitis. Gastroenterogy 28: 412, 1955. CrossrefMedlineGoogle Scholar39. MELROSE AG: The geographical incidence of chronic ulcerative colitis in Britain. Gastroenterology 29: 1055, 1955. CrossrefMedlineGoogle Scholar40. MELROSE AG: Observations on the European incidence of chronic ulcerative colitis. Gastroenterologia 86: 626, 1956. CrossrefMedlineGoogle Scholar41. WINSTONEHENDERSONBROOKE WEAJBN: Blood groups and secretor status in ulcerative colitis. Lancet 2: 64, 1960. CrossrefMedlineGoogle Scholar42. SMITHTRUELOVE RSSC: Blood groups and secretor status in ulcerative colitis. Brit. Med. J. 1: 870, 1961. CrossrefMedlineGoogle Scholar43. BOYDHEISLEROROWAN WCME: Rh blood groups in ulcerative colitis. Nature (London) 190: 1123, 1961. CrossrefGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: From the Department of Medicine, University of Chicago, Chicago, Illinois.This study was supported in part by grant A-2133 from the National Institute of Arthritis and Metabolic Diseases, National Institutes of Health, Bethesda, Maryland.Presented in part at the Midwest regional meeting of the American College of Physicians, October 20, 1962, and at the Chicago Society of Internal Medicine, January 28, 1963.Requests for reprints should be addressed to Joseph B. Kirsner, M.D., Department of Medicine, University of Chicago, Chicago, Illinois. 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KIRSNER, M.D., PH.D. 1 August 1963Volume 59, Issue 2Page: 133-144KeywordsArthritisColitisEnteritisGenetic diseasesMetabolic disordersPopulation geneticsUlcerative colitis Issue Published: 1 August 1963 CopyrightCopyright ©, 1963, by The American College of PhysiciansPDF DownloadLoading ...

OBJECTIVE: To provide health care providers, patients, and the general public with a responsible assessment of currently available data regarding the management and treatment of hepatitis C. PARTICIPANTS: A non-Federal, nonadvocate, 12-member panel representing the fields of infectious diseases, gastroenterology, medical oncology, molecular genetics, geriatrics, internal medicine, and the public. In addition, experts in these same fields presented data to the panel and to a conference audience of approximately 300. EVIDENCE: Presentations by experts; a systematic review of the medical literature provided by the Agency for Healthcare Research and Quality; and an extensive bibliography of hepatitis C research papers, prepared by the National Library of Medicine. Scientific evidence was given precedence over clinical anecdotal experience. CONFERENCE PROCESS: Answering predefined questions, the panel drafted a statement based on the scientific evidence presented in open forum and the scientific literature. The draft statement was read in its entirety on the final day of the conference and circulated to the experts and the audience for comment. The panel then met in executive session to consider these comments and released a revised statement at the end of the conference. The statement was made available on the World Wide Web at http://consensus.nih.gov immediately after the conference. This statement is an independent report of the panel and is not a policy statement of the NIH or the Federal Government. CONCLUSIONS: The incidence of newly acquired hepatitis C infection has diminished in the United States. This decline is largely due to a decrease in cases among IDUs for reasons that are unclear and, to a lesser extent, to testing of blood donors for HCV. The virus is transmitted by blood and such transmission now occurs primarily through injection drug use, sex with an infected partner or multiple partners, and occupational exposure. The majority of infections become chronic, and therefore the prevalence of HCV infections is high, with about 3 million Americans now estimated to be chronically infected. HCV is a leading cause of cirrhosis, a common cause of HCC and the leading cause of liver transplantation in the United States. The disease spectrum associated with HCV infection varies greatly. Various studies have suggested that 3 to 20 percent of chronically infected patients will develop cirrhosis over a 20-year period, and these patients are at risk for HCC. Persons who are older at the time of infection, patients with continuous exposure to alcohol, and those co-infected with HIV or HBV demonstrate accelerated progression to more advanced liver disease. Conversely, individuals infected at a younger age have little or no disease progression over several decades. The diagnosis of chronic hepatitis C infection is often suggested by abnormalities in ALT levels and is established by EIA followed by confirmatory determination of HCV RNA. Several sensitive and specific assays are now partly automated for the purposes of detecting HCV RNA and quantifying the viral level. Although there is little correlation between viral level and disease manifestations, these assays have proven useful in identifying those patients who are more likely to benefit from treatment and, particularly, in demonstrating successful response to treatment as defined by an SVR. Liver biopsy is useful in defining baseline abnormalities of liver disease and in enabling patients and healthcare providers to reach a decision regarding antiviral therapy. Noninvasive tests do not currently provide the information that can be obtained through liver biopsy. Information on the genotype of the virus is important to guide treatment decisions. Genotype 1, most commonly found in the United States, is less amenable to treatment than genotypes 2 or 3. Therefore, clinical trials of antiviral therapies require genotyping information for appropriate stratification of subjects. Recent therapeutic trials in defined, selected populations have clearly shown that combinations of interferons and ribavirin are more effective than monotherapy. Moreover, trials using pegylated interferons have yielded improved SVR rates with similar toxicity profiles. However, results continue to show that the SVR rate is less common in patients with genotype 1 infections, higher HCV RNA levels, or more advanced stages of fibrosis. Genotype 1 infections require therapy for 48 weeks, whereas shorter treatment is feasible in genotype 2 and 3 infections. In genotype 1, the lack of an early virologic response (< 2 log decrease in HCV RNA) is associated with failure to achieve an SVR. The SVR is lower in patients with advanced liver disease than in patients without cirrhosis. Ongoing trials are exploring the usefulness of combination therapy in various populations. Preliminary experience in IDUs, individuals co-infected with HIV, children, and other special groups suggests similar responses are achievable in these populations. Patients with acute hepatitis C may be treated, but specific recommendations for antiviral treatment must await further evaluation of the rate of spontaneous clearance of the virus and determination of the optimal time to initiate treatment. Preventive measures beyond blood-banking practices include prompt identification of infected individuals, awareness of the potential for perinatal transmission, implementation of safe-injection practices, linkage of drug users to drug treatment programs, and implementation of community-based education and support programs to modify risk behavior. Some of these measures have been successfully implemented in the control of HIV infections, and it stands to reason that they would be valuable for reducing HCV transmission. Future advances in the diagnosis and management of hepatitis C require continued vigilance concerning the transmission of this infection, extending treatment to populations not previously evaluated in treatment trials, and the introduction of more effective therapies.

Article1 August 1954ULCERATIVE COLITIS: THERAPEUTIC EFFECTS OF CORTICOTROPIN (ACTH) AND CORTISONE IN 120 PATIENTSJOSEPH B. KIRSNER, M.D., Ph.D., F.A.C.P., WALTER L. PALMER, M.D., Ph.D., F.A.C.P.JOSEPH B. KIRSNER, M.D., Ph.D., F.A.C.P., WALTER L. PALMER, M.D., Ph.D., F.A.C.P.Author, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-41-2-232 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptINTRODUCTIONThe effects of corticotropin (ACTH) and cortisone in ulcerative colitis have been characterized as beneficial,1-5 indifferent6-8 and unfavorable.9-14 Numerous studies also have emphasized the complications of therapy and the recurrences.15-20 The observation of 40 patients in 19511 indicated that, while ACTH and cortisone do not cure ulcerative colitis, they may be useful adjuncts, initiating rapid and occasionally dramatic clinical improvement. The present report summarizes our experience with corticotropin and cortisone in 120 patients with ulcerative colitis observed during the past four years.PATIENTS STUDIEDGeneral Data:The series includes 65 females and 55 males; the majority were between 20...Bibliography1. KirsnerPalmerKlotz JBWLAP (a) : ACTH and cortisone in chronic ulcerative colitis. A comparison of clinical effects, J. Lab. and Clin. Med. 36: 846, 1950. (b) Kirsner, J. B., and Palmer, W. L.: ACTH in ulcerative colitis. Report of progress, Gastroenterology 18: 143, 1951. (c) Kirsner, J. B.: Discussion of "ACTH in chronic ulcerative colitis," Proc. Second Clinical ACTH Conference, 1951, The Blakiston Co., Philadelphia, p. 500. (d) Kirsner, J. B., and Palmer, W. L.: Effect of corticotropin (ACTH) in chronic ulcerative colitis. Observations in forty patients, J. A. M. A. 147: 541, 1951. MedlineGoogle Scholar2. 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Report of case, New England J. Med. 233: 87, 1945. (b) Jobb, E., and Finkelstein, A.: Interesting x-ray findings in a case of acute fulminating ulcerative colitis, Gastroenterology 8: 213, 1947. (c) Griffiths, L. L., and Gilchrist, L.: Fatal case of acute ulcerative colitis with multiple perforations, Brit. M. J. 1: 1366, 1951. (d) McEwen, K. L., and Lodwell, E. A.: Acute fulminating idiopathic ulcerative colitis, Radiology 59: 185, 1952. CrossrefGoogle Scholar33. JankelsonMcClureSweetsir IRCWF: Idiopathic ulcerative colitis. Perforation of the bowel, Rev. Gastroenterol. 12: 31, 1945. Google Scholar34. SalassaKeatingSprague RMFRRG: Clinical aspects of suppression of adrenal cortical function after use of cortisone, Proc. Staff Meet., Mayo Clin. 28: 662, 1953. MedlineGoogle Scholar35. Blanco HG: Considerations on the pathogenesis of ulcerative colitis: its treatment with ACTH and cortisone, Ap. de la des. Clinica No. 3-15, 1953. Google Scholar36. KirsnerPalmerMaimonRicketts JBWLSNWE: Clinical course of chronic non-specific ulcerative colitis, J. A. M. A. 137: 922, 1948. CrossrefMedlineGoogle Scholar37. LevineKirsnerKlotz MJBAP: A new concept of the pathogenesis of ulcerative colitis, Science 144: 552, 1951. CrossrefGoogle Scholar38. Machella TE: Problems in ulcerative colitis, Am. J. Med. 13: 760, 1952. CrossrefMedlineGoogle Scholar39. KirsnerPalmer JBWL: Ulcerative colitis: consideration of its etiology and treatment, J. A. M. A. 155: 341, 1954. CrossrefMedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Chicago, Illinois*Received for publication February 23, 1954. (Presented at Midwest Regional Meeting, American College of Physicians, Milwaukee, Wisconsin, November 21, 1953.)From the Department of Medicine, University of Chicago.†This study was supported in part by the Wallach Fund for Gastrointestinal Research.Dr. David Klein, of Wilson Laboratories, Chicago, Illinois, very generously supplied much of the corticotropin (ACTH).Merck and Company provided a portion of the cortisone. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byInflammatory bowel disease part II: Clinical and therapeutic aspectsBlood eosinophilia and ulcerative colitis--influence of ethnic origin.Clinical Observations on Inflammatory Bowel DiseaseThe Treabnent of Ulcerative ColitisChronic ulcerative colitis in elderly patientsEosinophilia in Peripheral Blood and Inflammatory Exudate in Non-specific ProctocolitisImmediate and Prolonged Therapeutic Effects of Corticotrophin and Adrenal Steroids in Ulcerative ColitisEOSINOPHIL LEUCOCYTES IN ULCERATIVE COLITISCORTICOTROPIN (ACTH) AND THE ADRENAL STEROIDS IN THE MANAGEMENT OF ULCERATIVE COLITIS: OBSERVATIONS IN 240 PATIENTS*†JOSEPH B. KIRSNER, M.D., F.A.C.P., WALTER L. PALMER, M.D., F.A.C.P., JEAN A. SPENCER, M.D., RICHARD O. BICKS, M.D., CHARLES F. JOHNSON, M.D.Response to Drugs and PsychiatryGeneralized scleroderma associated with chronic ulcerative colitisSteroid hormones in the management of chronic ulcerative colitisThe Use of ACTH and Adrenocorticosteroids in Diseases of the Digestive SystemThe Role of Acth and Adrenal Steroids in Perforation of the Colon in Ulcerative Colitis a Clinical-Pathologic StudyUlcerative Colitis; Observations on Its Etiology, Course and ManagementThe Use of the Adrenocorticosteroids in GastroenterologyThe use of ACTH, cortisone, hydrocortisone and related compounds in the management of ulcerative colitisGastroenterologyToxic Psychosis Under Cortisone and CorticotrophinObservations on the Influence of Corticotropins upon the Course of Chronic Ulcerative ColitisTHE PRESENT STATUS OF ACTH AND ADRENAL STEROID THERAPY IN MEDICINE*J. C. BECK, M.D., F.R.C.P.(C)THE RÔLE OF ACTH, CORTISONE AND HYDROCORTISONE IN SURGERY*†WILLIAM E. ABBOTT, M.D., HARVEY KRIEGER, M.D., STANLEY LEVEY, Ph.D.THE USE OF HYDROCORTISONE IN ULCERATIVE COLITIS: PRELIMINARY OBSERVATIONS 1 August 1954Volume 41, Issue 2Page: 232-250KeywordsAdrenocorticotropic hormoneResearch fundingUlcerative colitis Issue Published: 1 August 1954 PDF downloadLoading ...

The World Gastroenterology Organization (WGO) is a federation of more than 100 national societies that represents over 52,000 practitioners around the world. As the only global society for gastroenterology professionals, WGO has been bringing together the world's leading minds in this field for over 50 years. The WGO works to improve the standards of training, education, and practice of gastroenterology and hepatology worldwide with a focus on low-resource nations.1 It is WGO's mission to promote, to the general public and health care professionals alike, an awareness of the worldwide prevalence and optimal care of digestive and liver disorders through the provision of high-quality, accessible, and independent education and training. What isn't as well known is that the WGO Foundation was created in 2007 to serve as the philanthropic arm of the WGO and to act as the primary mechanism to secure philanthropic funds for these goals. The powerful calling of the WGO—to assist low-resource countries in critical need of training and education and to position them to help themselves—has attracted some of the leading minds and voices of the gastroenterology profession from around the world. The Foundation is led by a volunteer Board composed of both physicians and business professionals who are committed to charting an important course of making philanthropy a vitally important part of the culture of change the WGO is striving to create. The Foundation seeks to be the catalytic agent for this change—a change that has and will continue to improve the lives of those confronting digestive and liver disorders every day in every part of the world. TRANSFORMATION OF OUR MISSION: NEEDS OF HIGH-RESOURCE VERSUS LOW-RESOURCE NATIONS Over the past 10 years, the WGO has transformed from focusing solely on the developed or “high-resource” world to providing training and educational offerings to the developing or “low-resource” nations around the globe. There are many, many global health care issues that need time, money, and attention, but digestive and liver disorders have not received a proportionate share of funding or garnered the same level of attention as other diseases, such as HIV/AIDS, malaria, and tuberculosis. In addition to the prevention, diagnosis, and treatment of digestive and liver disorders, there have also been many advances in our understanding of the etiology and the pathogenesis of these diseases. Unfortunately, these breakthroughs and the related benefits from their discovery have not been felt equally in every part of the world, especially in the regions facing the greatest need. To diminish the significant financial burden placed on the national healthcare budgets of many low-resource nations as a result of preventable and treatable digestive disorders, the WGO has positioned itself in a key leadership role. As the “global guardians of digestive health,” WGO strives to provide the resources, tools, education, advocacy, and training needed to address these challenges and create sustainable, enduring change on many levels through the hard work and dedication of its volunteer members. Consistent with this honorable and altruistic approach, the WGO maintains its role as the leading global gastroenterologic organization with the charge of promoting the highest standards of education, training, and practice within an ethical and principled framework.2 WGO PROGRAMS The WGO has a portfolio of training and education programs to fulfill its mission including: Training Centers; Train the Trainers; Global Guidelines; Outreach Program; Cancer Education & Advocacy; and Public Awareness. These programs represent an unprecedented level of collaboration between WGO, its member national societies, industry, and local government through financial support, donation of equipment and supplies, curriculum development, and general awareness. PROGRAM OBJECTIVES Each WGO program is thoughtfully designed to address specific areas of need in the practice of gastroenterology. Individual sessions or programs are further customized to meet the unique requirements and challenges of the settings in which they are delivered. The following high-impact strategies are how WGO and its partners promote progress and change around the world: WGO Training Centers—To elevate the level of practice and help retain highly skilled doctors and other related health professionals in low-resource nations by expanding the reach of and opportunities offered through this flagship program. WGO has trained over 1600 professionals at these 14 training centers since 2005; WGO Train the Trainers—To enhance the educational and training skills of clinician-educators by bringing together trainers from across the globe in intensive 4-day sessions. This forum developed by WGO enables interaction between world leaders in education for the sharing of experience and the discussion of common problems with over 400 participating to date; WGO Global Guidelines—To provide locally relevant treatment options through wider dissemination and adoption of these practical tools that use cascades that can be adapted to available resources and infrastructure, 20 of which have been developed to date3; WGO Outreach Program—To equip WGO Training Centers for primary and enhanced training and home institutions of WGO trainees with endoscopic instruments; and Advocacy and Public Awareness—To enhance the understanding of digestive disorders among practitioners, the public, and governments alike through programs, such as World Digestive Health Day (WDHD), a yearlong, worldwide public health campaign that focuses on an important topic in the area of digestive health. In 2009, we focused on Irritable Bowel Syndrome with the topic of Inflammatory Bowel Disease for 2010. VISION FOR THE FUTURE WGO seeks to create a Global Education & Training Network leveraging the strength of the existing WGO programs. This network will expand each program's impact and reach to maximize resources and training efficiency. The long-term outcomes of this initiative include: Increased access to high-quality patient care; and Retention of skilled healthcare providers locally. Although many organizations seek to advance the profession of gastroenterology, the reach and influence of the WGO is wider. We are the only organization that is truly global as reflected in the breadth of our member national societies and their member professionals. WGO also differs in the way it goes about its mission. We are the only one that seeks to expand the overall practice of the specialty within both fully developed countries with unlimited access to technology and modern techniques and low-resource nations where basic infrastructure, such as electricity and sanitation sometimes scarcely exist. Our programs provide applicable knowledge and skills to in-country gastroenterologic professionals through scalable global guidelines and locally relevant training to educate them along with the local population in ways to prevent and treat common digestive and liver disorders. The end result is that practitioners are better able to care for their fellow citizens through their enhanced skills, tools, and expertise while expanding the specialty of gastroenterology and hepatology by training their peers. We recognize the critical role that research plays in developing optimal preventive, diagnostic and therapeutic strategies for digestive diseases world-wide and the paucity of clinical research on digestive problems in emerging nations. Through the Train the Trainers program WGO promotes the inclusion of instruction on research methods in gastroenterology training programs by including modules on evidence-based medicine, trial design, and critical evaluation. An advanced version of TTT has been developed, which focuses entirely on trial design and the performance of clinical trials in gastroenterology. To further promote clinical research in low- resource regions, the Research Methodology Group of the Education and Training committee has developed a tool-kit of materials to assist the clinical investigator. We are eager to partner with our friends from industry, academia, private practice, the public sector around the world to deliver on our important mission. We will post announcements and updates of our accomplishments on this important mission in the coming months on both of our websites, www.worldgastroenterology.org and www.wgofoundation.org.

Thirty years ago, responding to the growing interest, rapid expansion, and increase in research in pediatric gastroenterology and nutrition, we established the Journal of Pediatric Gastroenterology and Nutrition (JPGN). The editorial of the first edition began, quo vadis? (1). Thirty years later, we are asking the same question. What should the vision of JPGN be? It seems mandatory to provide the pediatric gastroenterologist with research and knowledge of gastrointestinal ontogenic function and malfunction during early life. It was hoped that the Journal would serve as an intellectual stimulus and an international forum for the presentation and discussion of advances and controversies within the discipline. The findings of differential timing of the expression of the genes controlling various small intestinal disaccharidases, pancreatic exocrine enzymes, and so on, led to a new practical paradigm on gut development (2). The paradigm included interaction of genetic endowment, gene expression, intrinsic biological clocks, endogenous regulatory mechanisms of the hypothalamic-hypophysial-thyroid-adrenal axis, gastrointestinal receptors and mediators, and environmental influences. The environmental influences affecting gut ontogeny included intrauterine growth retardation and malnutrition early in life (2). Barker (3) hypothesized that the effect of intrauterine growth retardation increases the risk of later-onset disease, particularly cardiovascular disease, hypertension, and type 2 diabetes mellitus in adults (3). The ontogeny of gut enzymes in early infancy and the recognition of pancreatic amylase deficiency and the early appearance of intestinal α-glucosidases and salivary amylase led to another ontogenic paradigm of alternate pathways of digestion and absorption in early infancy. The pragmatic outcome of ontogenic research was to use α-glucosides, such as sucrose, maltose, maltodextrins, and short polymers of glucose, during the neonatal period and for the compromised infant. Studies focused on the investigation and clinical applications of gastrointestinal ontogeny exemplify the early emphasis of JPGN. The potential for new therapeutic modalities attributable to age-related changes in the gut can stimulate clinical and basic research. The human genome project, the availability of stem cell biology, advances in molecular mechanisms of growth and development, and discoveries of mucosal growth factors and receptors that occurred as a result of the inception of JPGN have led to dramatic expansion of the basic, translational, and clinical studies in the Journal. We aspired to be one of the journals that publish original articles on gut ontogeny. In addition, we decided to invite ontogenic review articles that provided a basis for understanding the importance of gut ontogeny. Conversely, we were successful publishing age-related clinical studies in pediatric gastroenterology, with an emphasis on early life. An example of clinical disorders that we began to address successfully is celiac disease (CD). Clinical studies in CD emerged in the Journal, including global prevalence and high prevalence of silent preschool- and school-aged children, association with autoimmune disorders, Down syndrome, type 1 diabetes mellitus, and atypical presentations. Mechanistic studies of the effect of several genetic factors together with an environmental trigger were published. The genetic predisposition to CD was studied as a complex of HLA-DQA1*05/DQB1*02 and HLA-DQA*0301/DQB*0302 genes as major factors. Two strategies of genetic research—linkage and association studies—led to the discovery of several susceptibility loci and genes such as a region on 5q, MYO9B, and CTLA4. In addition, a genomewide association study identified 8 new risk regions, 7 of which harbour genes controlling the immune response. Again, we solicited review articles on genetic molecular biology research and the pathogenesis of CD. Another example for specific age-related clinical presentation and therapeutic considerations is failure to gain weight and short stature associated with pediatric inflammatory bowel disease (IBD). Pediatric IBD is different in some major aspects from adult IBD. Early-onset IBD has a distinct phenotype with disease manifestations that are primarily colonic with severe perianal disease and extragastrointestinal manifestations. Furthermore, early-onset IBD is unique in its association with metabolic diseases, neutrophil defects, immunodeficiency states, chronic granulomatous disease, and leukocyte adhesion defects. IBD is thought to result from a complex interplay of multiple genes and environmental factors. Large-scale genotyping techniques have resulted in identification of >30 IBD-associated genes. Pediatric IBD management must consider lifelong disease and treatment. Twenty-five percent of patients with IBD develop the disease in childhood and adolescence. Clinicians need to weigh the risks and benefits of selected therapies, particularly the effects of medications, such as steroids, on growth and development and lifetime of exposure. For the last 30 years, the Journal has published a significant number of articles addressing issues specifically focused on pediatric IBD. We realized that the greatest challenge facing JPGN was reaching out to the world in general and developing countries in particular. We solicited articles from developing countries and found worthwhile clinical observations, but we were challenged by the flaws of study design, such as inclusion and exclusion criteria, sample size, and statistical analyses; data presentation; results; and conclusions. We were confronted with English and grammatical mistakes, leading us to correct and rewrite articles, provided they had a sound scientific message for the pediatric gastroenterology community. A new dimension of the Journal was added when the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition started to develop and update clinical practice guidelines and recommendations (4,5). Overall, it is apparent that JPGN has evolved to become an important cornerstone for the discipline and a reference journal for the societies of pediatric gastroenterology, hepatology, and nutrition. My suggestion for the future is that the clinical research emphasizes acute and chronic gut diseases, all the while continuing to consider the effect of the ontogeny of the gut. In the quest to improve the knowledge of pediatric gastroenterology and nutrition, we should develop new areas of focus and analysis, perspectives, policy forums, and technical comments, similar to the journal Science. Presentation of the basic science news on the ontogeny of the gut, including cell biology, genetics, and immunology, should be a stimulus for inquiry and research to advance the frontiers of pediatric gastroenterology.

BACKGROUND: Over the past 30 years, nanotechnology has evolved dramatically. It has captured the interest of variety of fields from computing and electronics to biology and medicine. Recent discoveries have made invaluable changes to future prospects in nanomedicine; and introduced the concept of theranostics. This term offers a patient specific 'two in one' modality that comprises of diagnostic and therapeutic tools. Not only nanotechnology has shown great impact on improvements in drug delivery and imaging techniques, but also there have been several ground-breaking discoveries in regenerative medicine. AIM: Gastroenterology invites multidisciplinary approach owing to high complexity of gastrointestinal (GI) system; it includes physicians, surgeons, radiologists, pharmacologists and many more. In this article, we concentrate on current developments in nano-gastroenterology. METHODS: Literature search was performed using Web of Science and Pubmed search engines with terms--nanotechnology, nanomedicine and gastroenterology. Article search was concentrated on developments since 2005. RESULTS: We have described original and innovative approaches in gastrointestinal drug delivery, inflammatory disease and cancer-target treatments. Here, we have reviewed advances in GI imaging using nanoparticles as fluorescent contrast, and their potential for site-specific targeting. This review has also depicted various approaches and novel discoveries in GI regenerative medicine using nanomaterials for scaffold designs and induced pluripotent stem cells as cell source. CONCLUSIONS: Developments in nanotechnology have opened new range of possibilities to help our patients. This includes novel drug delivery vehicles, diagnostic tools for early and targeted disease detection and nanocomposite materials for tissue constructs to overcome cosmetic or physical disabilities.

BACKGROUND: The efficacy of vedolizumab, an α4β7 integrin antibody, in Crohn's disease is unknown. METHODS: In an integrated study with separate induction and maintenance trials, we assessed intravenous vedolizumab therapy (300 mg) in adults with active Crohn's disease. In the induction trial, 368 patients were randomly assigned to receive vedolizumab or placebo at weeks 0 and 2 (cohort 1), and 747 patients received open-label vedolizumab at weeks 0 and 2 (cohort 2); disease status was assessed at week 6. In the maintenance trial, 461 patients who had had a response to vedolizumab were randomly assigned to receive placebo or vedolizumab every 8 or 4 weeks until week 52. RESULTS: At week 6, a total of 14.5% of the patients in cohort 1 who received vedolizumab and 6.8% who received placebo were in clinical remission (i.e., had a score on the Crohn's Disease Activity Index [CDAI] of ≤150, with scores ranging from 0 to approximately 600 and higher scores indicating greater disease activity) (P=0.02); a total of 31.4% and 25.7% of the patients, respectively, had a CDAI-100 response (≥100-point decrease in the CDAI score) (P=0.23). Among patients in cohorts 1 and 2 who had a response to induction therapy, 39.0% and 36.4% of those assigned to vedolizumab every 8 weeks and every 4 weeks, respectively, were in clinical remission at week 52, as compared with 21.6% assigned to placebo (P<0.001 and P=0.004 for the two vedolizumab groups, respectively, vs. placebo). Antibodies against vedolizumab developed in 4.0% of the patients. Nasopharyngitis occurred more frequently, and headache and abdominal pain less frequently, in patients receiving vedolizumab than in patients receiving placebo. Vedolizumab, as compared with placebo, was associated with a higher rate of serious adverse events (24.4% vs. 15.3%), infections (44.1% vs. 40.2%), and serious infections (5.5% vs. 3.0%). CONCLUSIONS: Vedolizumab-treated patients with active Crohn's disease were more likely than patients receiving placebo to have a remission, but not a CDAI-100 response, at week 6; patients with a response to induction therapy who continued to receive vedolizumab (rather than switching to placebo) were more likely to be in remission at week 52. Adverse events were more common with vedolizumab. (Funded by Millennium Pharmaceuticals; GEMINI 2 ClinicalTrials.gov number, NCT00783692.).

Technological advances in artificial intelligence (AI) represent an enticing opportunity to benefit gastroenterological practice. Moreover, AI, through machine or deep learning, permits the ability to develop predictive models from large datasets. Possibilities of predictive model development in machine learning are numerous dependent on the clinical question. For example, binary classifiers aim to stratify allocation to a categorical outcome, such as the presence or absence of a gastrointestinal disease. In addition, continuous variable fitting techniques can be used to predict quantity of a therapeutic response, thus offering a tool to predict which therapeutic intervention may be most beneficial to the given patient. Namely, this permits an important opportunity for personalization of medicine, including a movement from guideline-specific treatment algorithms to patient-specific ones, providing both clinician and patient the capacity for data-driven decision making. Furthermore, such analyses could predict the development of GI disease prior to the manifestation of symptoms, raising the possibility of prevention or pre-treatment. In addition, computer vision additionally provides an exciting opportunity in endoscopy to automatically detect lesions. In this review, we overview the recent developments in healthcare-based AI and machine learning and describe promises and pitfalls for its application to gastroenterology.

OBJECTIVE: The qualitative research presented here is part of a larger project on the significance of medical clowning during invasive examinations in children in the Department of Gastroenterology and the Center for the Sexually Abused in a hospital in Israel. It investigated what makes up the essence of medical clowning, what skills and techniques are used by medical clowns, and whether their work contains therapeutic elements. METHODS: A total of 9 children undergoing invasive examinations and 9 of their accompanying parents participated in semistructured interviews, which were analyzed using a thematic analysis methodology assisted by an Atlas-ti software program. RESULTS: The interviews revealed that the medical clowning intervention during invasive examinations was essentially therapeutic, with the clown using theatrical and clowning tools to incorporate therapeutic elements such as empowerment, reversal of role, reframing, and building a therapeutic alliance. In addition, during the invasive examinations, the medical clowning followed the model of brief crisis intervention therapy. CONCLUSION: The study advances the need to incorporate medical clowns as an integral part of medical teams performing invasive procedures and to include clowns in all stages of the hospital visit when children undergo invasive examinations.

BACKGROUND: Gut-selective blockade of lymphocyte trafficking by vedolizumab may constitute effective treatment for ulcerative colitis. METHODS: We conducted two integrated randomized, double-blind, placebo-controlled trials of vedolizumab in patients with active disease. In the trial of induction therapy, 374 patients (cohort 1) received vedolizumab (at a dose of 300 mg) or placebo intravenously at weeks 0 and 2, and 521 patients (cohort 2) received open-label vedolizumab at weeks 0 and 2, with disease evaluation at week 6. In the trial of maintenance therapy, patients in either cohort who had a response to vedolizumab at week 6 were randomly assigned to continue receiving vedolizumab every 8 or 4 weeks or to switch to placebo for up to 52 weeks. A response was defined as a reduction in the Mayo Clinic score (range, 0 to 12, with higher scores indicating more active disease) of at least 3 points and a decrease of at least 30% from baseline, with an accompanying decrease in the rectal bleeding subscore of at least 1 point or an absolute rectal bleeding subscore of 0 or 1. RESULTS: Response rates at week 6 were 47.1% and 25.5% among patients in the vedolizumab group and placebo group, respectively (difference with adjustment for stratification factors, 21.7 percentage points; 95% confidence interval [CI], 11.6 to 31.7; P<0.001). At week 52, 41.8% of patients who continued to receive vedolizumab every 8 weeks and 44.8% of patients who continued to receive vedolizumab every 4 weeks were in clinical remission (Mayo Clinic score ≤2 and no subscore >1), as compared with 15.9% of patients who switched to placebo (adjusted difference, 26.1 percentage points for vedolizumab every 8 weeks vs. placebo [95% CI, 14.9 to 37.2; P<0.001] and 29.1 percentage points for vedolizumab every 4 weeks vs. placebo [95% CI, 17.9 to 40.4; P<0.001]). The frequency of adverse events was similar in the vedolizumab and placebo groups. CONCLUSIONS: Vedolizumab was more effective than placebo as induction and maintenance therapy for ulcerative colitis. (Funded by Millennium Pharmaceuticals; GEMINI 1 ClinicalTrials.gov number, NCT00783718.).