Gastroenterology RSS feed: Current Issue. Gastroenterology is the most prominent journal in the field of gastrointestinal disease. As the official journal of the AGA Institute , Gastroenterology delivers up-to-date and authoritative coverage of both basic and clinical gastroenterology. Regular features include articles by leading authorities and reports on the latest treatments for diseases. Original research is organized by clinical and basic-translational content, as well as by alimentary tract, liver, pancreas, and biliary content. Gastroenterology also bridges the gap between basic and clinical science by publishing comprehensive reviews and perspectives on important topics such as pancreatitis and liver disease. Additional features include Covering the Cover; Mentoring, Training, and Education Corner; Press Highlights; Imaging and Advanced Technology; Clinical Challenges and Images in GI; Selected Summaries; Print and Digital Media Reviews; Continuing Medical Education Activities; Editorials; and Correspondence. Multimedia offerings include images, video abstracts, and podcasts. Gastroenterology also provides updates and commentary via Facebook, Twitter, LinkedIn, and its research blog ?The AGA Journals Blog?. Gastroenterology is recommended for initial purchase in the Brandon-Hill study, Selected List of Books and Journals for the Small Medical Library. Gastroenterology is ranked 1st of 74 journals in the Gastroenterology and Hepatology category on the 2012 Journal Citation Reports®, published by Thomson Reuters, and has an Impact Factor of 11.68. Its immediacy index, which is a measure of how topical and urgent work published Gastroenterology is, is 2.995, the highest in the field. On average, authors receive decisions on their manuscripts within three weeks. Gastroenterology is circulated to 19,000 individuals and institutions worldwide. http://www.gastrojournal.org/?rss=yesElsevier Inc.en © 2013 Published by Elsevier Inc. All rights reserved. Gastroenterology0016-50851446May 2013 © 2013 Published by Elsevier Inc. All rights reserved. healthpermissions@elsevier.comhttp://www.gastrojournal.org/article/PIIS0016508513004629/abstract?rss=yesCover 110.1053/S0016-5085(13)00462-9Gastroenterology 144, 6 (2013)2013-05-01Gastroenterology2013-05-011446S0016-5085(13)X0005-8OFCOFChttp://www.gastrojournal.org/article/PIIS0016508513003533/abstract?rss=yes Every May, Gastroenterology publishes a supplementary issue, the “13th Issue”, that is devoted to a specific theme. In 2011, the theme was inflammatory bowel disease and last year's was viral hepatitis. This year the board of editors unanimously decided that it was necessary to devote the 13th Issue to the exocrine pancreas and its disorders. Because of the rapid pace of developing new information on mechanisms of the diseases of the exocrine pancreas in the recent past, and the fact that we are approaching a crossroads of converting this mechanistic understanding into new treatments for patients with these diseases, it was an ideal choice. For these reasons, we had the privilege to recruit leading authorities in both the basic and clinical sciences to update our readers in topics of importance in both domains. Also, we will outline the challenges that lie ahead, as well as the approaches that may be utilized to advance the care of patients with pancreatic disease. We anticipate that this juxtaposition of topics will spur innovations and lead to critical new treatments. We have divided the issue into 2 sections. The first section includes topics of basic investigation related to biology and disease mechanisms; the second is focused on clinical manifestations and management of pancreatic disorders.The Pancreas: Biology, Diseases, and TherapyDiane M. Simeone, Stephen J. Pandol10.1053/j.gastro.2013.03.009Gastroenterology 144, 6 (2013)2013-05-01Gastroenterology2013-05-011446S0016-5085(13)X0005-8Introduction11631165http://www.gastrojournal.org/article/PIIS0016508513003004/abstract?rss=yes For everyone interested in the pancreas, it is truly a noble organ. Known to the ancient Greeks, its name in Greek “pan kreas” translates as “all flesh.” Aristotle believed its function was to protect the great vessels and 4 centuries later Galen claimed it to be a cushion for the stomach. The Renaissance anatomists, beginning with Vesalius, defined its structure with its ducts, first shown by Johann Wirsung in 1642, to empty into the intestine. Regnier de Graaf, of the Graafian follicle, was the first to study pancreatic secretion in 1664, using a goose quill inserted into the duct. In the 19th century, Claude Bernard in Paris, and others, showed the digestive capabilities of pancreatic juice for fat, carbohydrate, and protein. Paul Langerhans, a medical student in Berlin, described the eponymous islets in 1869 and in 1889, Miring and Minkowski described experimental diabetes in the dog after pancreatectomy. In addition to understanding the anatomy and physiology of the exocrine pancreas, Hans Chiari had described the autodigestion of the pancreas that accompanies pancreatitis in 1896. By 1900, the histology and general understanding of the function of the pancreas was in place. The 20th century was to be occupied first with understanding the control of pancreatic secretion and then the understanding of specific cell types of the pancreas as molecular machines evolved to carry out specific functions. A timeline for this increase in understanding of the pancreas and its diseases is shown in . More detailed coverage of the last 160 years is shown in .The Nobel Pancreas: A Historical PerspectiveJohn A. Williams10.1053/j.gastro.2012.10.056Gastroenterology 144, 6 (2013)2013-05-01Gastroenterology2013-05-011446S0016-5085(13)X0005-8Commentary11661169http://www.gastrojournal.org/article/PIIS0016508513001947/abstract?rss=yes The endocrine and exocrine cells in the adult pancreas are not static, but can change their differentiation state in response to injury or stress. This concept of cells in flux means that there may be ways to generate certain types of cells (such as insulin-producing β-cells) and prevent formation of others (such as transformed neoplastic cells). We review different aspects of cell identity in the pancreas, discussing how cells achieve their identity during embryonic development and maturation, and how this identity remains plastic, even in the adult pancreas. Control of Cell Identity in Pancreas Development and RegenerationBen Z. Stanger, Matthias Hebrok10.1053/j.gastro.2013.01.074Gastroenterology 144, 6 (2013)2013-05-01Gastroenterology2013-05-011446S0016-5085(13)X0005-8Review11701179http://www.gastrojournal.org/article/PIIS0016508513001984/abstract?rss=yes Animal models of acute and chronic pancreatitis have been created to examine mechanisms of pathogenesis, test therapeutic interventions, and study the influence of inflammation on the development of pancreatic cancer. In vitro models can be used to study early stage, short-term processes that involve acinar cell responses. Rodent models reproducibly develop mild or severe disease. One of the most commonly used pancreatitis models is created by administration of supraphysiologic concentrations of caerulein, an ortholog of cholecystokinin. Induction of chronic pancreatitis with factors thought to have a role in human disease, such as combinations of lipopolysaccharide and chronic ethanol feeding, might be relevant to human disease. Models of autoimmune chronic pancreatitis have also been developed. Most models, particularly of chronic pancreatitis, require further characterization to determine which features of human disease they include. Models of Acute and Chronic PancreatitisMarkus M. Lerch, Fred S. Gorelick10.1053/j.gastro.2012.12.043Gastroenterology 144, 6 (2013)2013-05-01Gastroenterology2013-05-011446S0016-5085(13)X0005-8Review11801193http://www.gastrojournal.org/article/PIIS001650851300190X/abstract?rss=yes Our understanding of the pathogenesis of pancreatic cancer and pancreatitis has advanced so greatly in recent years that it would hardly be an exaggeration to refer to the present time as the Pancreatic Renaissance. Unfortunately, the tangible benefits to patients have not been commensurate with the theoretical advances. In seeking to explain this disparity, most investigators view with suspicion the relevance of the models thus far used. For novel therapies to emerge, it is necessary that the animal models recapitulate the human disease with precision. This realization has engendered a vigorous search for better models, especially genetically engineered models. The key to progress lies in a sound understanding of the strengths, weaknesses, and applicability of the models in the investigator's repertoire.Relevance of Animal Models of Pancreatic Cancer and Pancreatitis to Human DiseaseAshok K. Saluja, Vikas Dudeja10.1053/j.gastro.2013.01.070Gastroenterology 144, 6 (2013)2013-05-01Gastroenterology2013-05-011446S0016-5085(13)X0005-8Commentary11941198http://www.gastrojournal.org/article/PIIS0016508513002187/abstract?rss=yes Inflammation and autophagy are cellular defense mechanisms. When these processes are deregulated (deficient or overactivated) they produce pathologic effects, such as oxidative stress, metabolic impairments, and cell death. Unresolved inflammation and disrupted regulation of autophagy are common features of pancreatitis and pancreatic cancer. Furthermore, obesity, a risk factor for pancreatitis and pancreatic cancer, promotes inflammation and inhibits or deregulates autophagy, creating an environment that facilitates the induction and progression of pancreatic diseases. However, little is known about how inflammation, autophagy, and obesity interact to promote exocrine pancreatic disorders. We review the roles of inflammation and autophagy, and their deregulation by obesity, in pancreatic diseases. We discuss the connections among disordered pathways and important areas for future research. Inflammation, Autophagy, and Obesity: Common Features in the Pathogenesis of Pancreatitis and Pancreatic CancerIlya Gukovsky, Ning Li, Jelena Todoric, Anna Gukovskaya, Michael Karin10.1053/j.gastro.2013.02.007Gastroenterology 144, 6 (2013)2013-05-01Gastroenterology2013-05-011446S0016-5085(13)X0005-8Review11991209.e4http://www.gastrojournal.org/article/PIIS0016508513001960/abstract?rss=yes Pancreatic ductal adenocarcinoma is a devastating disease, and patient outcomes have not improved in decades. Treatments that target tumor cells have largely failed. This could be because research has focused on cancer cells and the influence of the stroma on tumor progression has been largely ignored. The focus of pancreatic cancer research began to change with the identification of pancreatic stellate cells, which produce the pancreatic tumor stroma. There is compelling in vitro and in vivo evidence for the influence of pancreatic stellate cells on pancreatic cancer development; several recent preclinical studies have reported encouraging results with approaches designed to target pancreatic stellate cells and the stroma. We review the background and recent advances in these areas, along with important areas of future research that could improve therapy. A Starring Role for Stellate Cells in the Pancreatic Cancer MicroenvironmentMinoti V. Apte, Jeremy S. Wilson, Aurelia Lugea, Stephen J. Pandol10.1053/j.gastro.2012.11.037Gastroenterology 144, 6 (2013)2013-05-01Gastroenterology2013-05-011446S0016-5085(13)X0005-8Review12101219http://www.gastrojournal.org/article/PIIS0016508513001911/abstract?rss=yes The Kras gene is mutated to an oncogenic form in most pancreatic tumors. However, early attempts to use this molecule as a specific biomarker of the disease, or inhibit its activity as a cancer therapy, failed. This left a situation in which everyone was aware of the association between this important oncogene and pancreatic cancer, but no one knew what to do about it. Recent findings have changed this picture—many assumptions made about KRAS and its role in pancreatic cancer were found to be incorrect. Several factors have contributed to increased understanding of the activities of KRAS, including creation of genetically engineered mouse models, which have allowed for detailed analyses of pancreatic carcinogenesis in an intact animal with a competent immune system. Cancer genome sequencing projects have increased our understanding of the heterogeneity of individual tumors. We also have a better understanding of which oncogenes are important for tumor maintenance and are therefore called “drivers.” We review the advances and limitations of our knowledge about the role of Kras in development of pancreatic cancers and the important areas for future research. Roles for KRAS in Pancreatic Tumor Development and ProgressionMarina Pasca di Magliano, Craig D. Logsdon10.1053/j.gastro.2013.01.071Gastroenterology 144, 6 (2013)2013-05-01Gastroenterology2013-05-011446S0016-5085(13)X0005-8Review12201229http://www.gastrojournal.org/article/PIIS0016508513001972/abstract?rss=yes Immune cells are important in the pathogenesis of acute pancreatitis and determine disease severity. Results from cytokine-based clinical trials for acute pancreatitis have been disappointing, so strategies that target and alter the behavior of infiltrating immune cells require consideration. Recurrent acute pancreatitis can progress to chronic pancreatitis, which is a well-described risk factor for pancreatic ductal adenocarcinoma (PDA). However, most patients with chronic pancreatitis do not develop PDA, and most patients with PDA do not have a history of pancreatitis. Interestingly, chronic pancreatitis and PDA tissues have similarities in their desmoplasia and inflammatory infiltrates, indicating overlapping inflammatory responses. Further studies are needed to determine the differences and similarities of these responses, improve our understanding of PDA pathogenesis, and develop specific immune-based therapies. Immune cells in PDA produce immunosuppressive signals that allow tumors to evade the immune response. Unlike single therapeutic agent studies that block immunosuppressive mechanisms, studies of combination therapies that include therapeutic vaccines have provided promising results. Role of Immune Cells and Immune-Based Therapies in Pancreatitis and Pancreatic Ductal AdenocarcinomaLei Zheng, Jing Xue, Elizabeth M. Jaffee, Aida Habtezion10.1053/j.gastro.2012.12.042Gastroenterology 144, 6 (2013)2013-05-01Gastroenterology2013-05-011446S0016-5085(13)X0005-8Review12301240http://www.gastrojournal.org/article/PIIS0016508513001923/abstract?rss=yes Pancreatic ductal adenocarcinomas comprise a hierarchy of tumor cells that develop around a population of cancer stem cells. The cancer stem cells promote tumor growth and progression through a number of mechanisms, including differentiation into bulk tumor cells, metastasis, alteration of adjacent stromal cells, and evasion of conventional therapies. As with other cancer stem cells, pancreatic cancer stem cells (PCSCs) can be distinguished from bulk tumor cells based on their expression of unique surface markers, abilities to form spheres under nonadherent conditions and tumors in mice, and self-renewal and differentiation capacities. We review the markers used to identify PCSCs, the signaling pathways that regulate PCSC functions, the complex interactions between PCSCs and stromal cells, and approaches to therapeutically target PCSCs and improve treatment of patients with pancreatic cancer. Biology and Clinical Applications of Pancreatic Cancer Stem CellsEthan V. Abel, Diane M. Simeone10.1053/j.gastro.2013.01.072Gastroenterology 144, 6 (2013)2013-05-01Gastroenterology2013-05-011446S0016-5085(13)X0005-8Review12411248http://www.gastrojournal.org/article/PIIS0016508513003545/abstract?rss=yes Some of the first glimpses into acute pancreatitis were by Reginald H. Fitz, pathologist, who described the clinical features of acute pancreatitis in 1889 and subtyped it into hemorrhagic, suppurative, and gangrenous pancreatitis. However, he believed pancreatitis was the result of gastroduodenitis. In 1896, Chiari put forth the premise that pancreatitis was the result of pancreatic autodigestion. Claude Bernard demonstrated that pancreatic secretion was involved in the digestion of protein, carbohydrate, and fat in dogs. The notion that pancreatic substances could be given to patients with pancreatitis to ameloriate their steatorrhea dates back to 1868. It would appear that the initial description of chronic pancreatitis and precipitating factors can be attributed to Comfort in 1946 ().A Historical Perspective on Clinical Advances in Pancreatic DiseasesAnil K. Rustgi10.1053/j.gastro.2013.03.010Gastroenterology 144, 6 (2013)2013-05-01Gastroenterology2013-05-011446S0016-5085(13)X0005-8Commentary12491251http://www.gastrojournal.org/article/PIIS0016508513001686/abstract?rss=yes Acute pancreatitis is one of the most frequent gastrointestinal causes of hospital admission in the United States. Chronic pancreatitis, although lower in incidence, significantly reduces patients' quality of life. Pancreatic cancer is associated with a high mortality rate and is one of the top 5 causes of death from cancer. The burden of pancreatic disorders is expected to increase over time. The risk and etiology of pancreatitis differ with age and sex, and all pancreatic disorders affect the black population more than any other race. Gallstones are the most common cause of acute pancreatitis, and early cholecystectomy eliminates the risk of future attacks. Alcohol continues to be the single most important risk factor for chronic pancreatitis. Smoking is an independent risk factor for acute and chronic pancreatitis, and its effects could synergize with those of alcohol. Significant risk factors for pancreatic cancer include smoking and non-O blood groups. Alcohol abstinence and smoking cessation can alter the progression of pancreatitis and reduce recurrence; smoking cessation is the most effective strategy to reduce the risk of pancreatic cancer. The Epidemiology of Pancreatitis and Pancreatic CancerDhiraj Yadav, Albert B. Lowenfels10.1053/j.gastro.2013.01.068Gastroenterology 144, 6 (2013)2013-05-01Gastroenterology2013-05-011446S0016-5085(13)X0005-8Review12521261http://www.gastrojournal.org/article/PIIS0016508513001996/abstract?rss=yes The prognosis is poor for most patients with pancreatic cancer, chronic pancreatitis, or other pancreatic diseases. Advances in pancreatic imaging could help identify these diseases at earlier stages, when they are easier to treat. Radiographic imaging and endoscopic imaging of the pancreas have progressed from the abdominal roentogram and endoscopic retrograde pancreatography to multi-detector computed tomography, magnetic resonance cholangiopancreatography, endoscopic ultrasonography, and pancreatoscopy. These technologies have improved the diagnosis and treatment of benign disease but have not significantly increased our ability to detect early-stage disease or affect outcomes of patients with pancreatic cancer or chronic pancreatitis. Advances in endoscopic imaging and molecular-based radiographic tests could allow physicians to identify pancreatic lesions and their precursors at earlier stages. Furthermore, research studies that include these tools could improve our understanding of disease pathogenesis and identify diagnostic markers and therapeutic targets. We review endoscopic imaging modalities, focusing on new endoscopic and molecular-based radiographic imaging tests that have the potential to substantially improve diagnosis and treatment of pancreatic disease. Technologies for Imaging the Normal and Diseased PancreasGregory A. Coté, Jeffrey Smith, Stuart Sherman, Kimberly Kelly10.1053/j.gastro.2013.01.076Gastroenterology 144, 6 (2013)2013-05-01Gastroenterology2013-05-011446S0016-5085(13)X0005-8Review12621271.e1http://www.gastrojournal.org/article/PIIS0016508513001959/abstract?rss=yes Acute pancreatitis is the leading cause of hospitalization for gastrointestinal disorders in the United States. As rates of hospitalization for acute pancreatitis continue to increase, so does demand for effective management. We review approaches to best manage patients with acute pancreatitis, covering diagnosis, risk and prognostic factors, treatment, and complications, considering recommendations from current practice guidelines. Clinical Management of Patients With Acute PancreatitisBechien U. Wu, Peter A. Banks10.1053/j.gastro.2013.01.075Gastroenterology 144, 6 (2013)2013-05-01Gastroenterology2013-05-011446S0016-5085(13)X0005-8Review12721281http://www.gastrojournal.org/article/PIIS0016508513002199/abstract?rss=yes Advances in our understanding of chronic pancreatitis have improved our care of patients with this disease. Although our therapies are imperfect and many patients remain symptomatic, appropriate medical care improves the quality of life in these patients. Proper management requires an accurate diagnosis, recognition of the modifiable causes of disease, assessment of symptoms and complications, treatment of these symptoms and complications utilizing a multidisciplinary team, and ongoing monitoring for the effect of therapy and the occurrence of complications. Management of Chronic PancreatitisChristopher E. Forsmark10.1053/j.gastro.2013.02.008Gastroenterology 144, 6 (2013)2013-05-01Gastroenterology2013-05-011446S0016-5085(13)X0005-8Review12821291.e3http://www.gastrojournal.org/article/PIIS0016508513001893/abstract?rss=yes A combination of genetic, environmental, and metabolic factors contribute to the development and recurrence of acute and chronic pancreatitis; information on all of these is required to manage patients effectively. For example, variants that affect regulation of the protease, serine (PRSS)1-PRSS2, and claudin (CLDN)2 loci, rather than their coding sequences, interact with other genetic and environmental factors to affect disease development. New strategies are needed to use these data and determine their contribution to pathogenesis, because these variants differ from previously studied, rare variants in exons (coding regions) of genes such as PRSS1, SPINK1, cystic fibrosis transmembrane conductance regulator (CFTR), chymotrypsin (CTR)C, and calcium-sensing receptor (CASR). Learning how various genetic factors affect pancreatic cells and systems could lead to etiology-based therapies rather than treatment of symptoms. Genetic Risk Factors for Pancreatic DisordersDavid C. Whitcomb10.1053/j.gastro.2013.01.069Gastroenterology 144, 6 (2013)2013-05-01Gastroenterology2013-05-011446S0016-5085(13)X0005-8Review12921302http://www.gastrojournal.org/article/PIIS0016508513001935/abstract?rss=yes Approximately 10% of persons 70 years old or older are now diagnosed with pancreatic cysts, but it is not clear which ones require additional analysis, interventions, or follow-up. Primary care doctors rely on gastroenterologists for direction because no one wants to miss a diagnosis of pancreatic cancer, but meanwhile there is pressure to limit use of diagnostic tests and limit costs. We review the different cystic neoplasms of the pancreas and diagnostic strategies based on clinical features and imaging data. We discuss surgical and nonsurgical management of the most common cystic neoplasms, based on the recently revised Sendai guidelines. Intraductal papillary mucinous neoplasm (particularly the branch duct variant) is the lesion most frequently identified incidentally. We report what is known about its pathology, its risk of developing into pancreatic ductal adenocarcinoma, the pros and cons of current guidelines for management, and the potential role of endoscopic ultrasound in determining cancer risk. We also review surgical treatment and strategies for surveillance of pancreatic cysts. Pancreatic Cystic Neoplasms: Management and Unanswered QuestionsJames J. Farrell, Carlos Fernández-del Castillo10.1053/j.gastro.2013.01.073Gastroenterology 144, 6 (2013)2013-05-01Gastroenterology2013-05-011446S0016-5085(13)X0005-8Review13031315http://www.gastrojournal.org/article/PIIS0016508513002990/abstract?rss=yes Despite our improved understanding of pancreatic cancer biology and ability to perform more complex pancreatic cancer surgeries that produce better short-term outcomes, major progress toward increasing survival times has been painstakingly slow. Through the often-repeated, dismal survival statistics, it is easy to lose sight of real progress that has been made in pancreatic cancer therapy. It is particularly interesting to observe the extent to which these advances are interdependent and the effects they have had on practice. For example, during the past 5–10 years, we have seen widespread adoption of pancreatic imaging protocols that allow for objectively defined criteria of resectability. This has led to the definition of “borderline resectable pancreatic cancer”—a new clinical category that has affected the design of clinical trials. A major change in our surgical approach has been the move to minimally invasive pancreatectomy, which continues to gain broader acceptance and use, particularly for left-sided lesions. Although many new agents have been developed aimed at putative molecular targets, recent breakthroughs in therapy for advanced disease have arisen from our ability to safely give patients combination cytotoxic chemotherapy. We are now faced with the challenge of combining multidrug, cytotoxic chemotherapies with newer-generation agents. Ultimately, the hope is that drug combinations will be selected based on biomarkers, and strategies for pancreatic cancer therapy will be personalized, which could prolong patients' lives and reduce toxicity. We review the major advances in pancreatic cancer therapy during the last 5 years, and discuss how these have set the stage for greater progress in the near future. Therapeutic Advances in Pancreatic CancerAndrew Scott Paulson, Hop S. Tran Cao, Margaret A. Tempero, Andrew M. Lowy10.1053/j.gastro.2013.01.078Gastroenterology 144, 6 (2013)2013-05-01Gastroenterology2013-05-011446S0016-5085(13)X0005-8Review13161326http://www.gastrojournal.org/article/PIIS0016508513004642/abstract?rss=yesEditorial Board10.1053/S0016-5085(13)00464-2Gastroenterology 144, 6 (2013)2013-05-01Gastroenterology2013-05-011446S0016-5085(13)X0005-8FrontmatterA2A2http://www.gastrojournal.org/article/PIIS0016508513004654/abstract?rss=yesTable of Contents10.1053/S0016-5085(13)00465-4Gastroenterology 144, 6 (2013)2013-05-01Gastroenterology2013-05-011446S0016-5085(13)X0005-8FrontmatterA7A8http://www.gastrojournal.org/article/PIIS0016508513004666/abstract?rss=yesGastroenterology is the premiere journal in the field of gastrointestinal disease and is led by an internationally renowned board of editors. As the official journal of the AGA Institute, Gastroenterology delivers up-to-date and authoritative coverage of both basic and clinical gastroenterology and hepatology. Regular features include research and perspectives by leading authorities, reports on the latest technologies for diagnosing and treating digestive diseases, images illustrating important clinical findings, reviews of scholarly media, medical news, meeting summaries, video abstracts, and monthly podcasts. Gastroenterology also bridges the gap between basic and clinical science by publishing comprehensive reviews on important topics such as pancreatitis and liver disease.Information for Authors and Readers10.1053/S0016-5085(13)00466-6Gastroenterology 144, 6 (2013)2013-05-01Gastroenterology2013-05-011446S0016-5085(13)X0005-8FrontmatterA9A10