February 2012

Volume 142Issue 2p191-414, e1-e33

Covering the Cover

  • Covering the Cover

    • Anson W. Lowe,
    • Richard H. Moseley
    Published online: December 19, 2011
    Tobacco remains the most preventable cause of death in the world. Evidence supporting a carcinogenic role for tobacco has now expanded to 18 cancers. In this issue of Gastroenterology, 2 studies provide evidence that tobacco use, mainly in the form of cigarette smoking, increases the risk of colorectal adenoma formation in patients with the Lynch syndrome, and the development of high-grade dysplasia and cancer among patients with Barrett's esophagus. The 2 studies indicate that lifestyle changes such as abstention from tobacco use can affect predisposed individuals.

Comment From the Editor

  • How Good Is Your Dentist? How Good Is Your Endoscopist? The Quality Imperative

    • David Lieberman
    Published online: December 19, 2011
    Recently, I polled my GI friends to determine how they selected their dentist, and whether their dentist practiced “high-quality” dentistry. Most had received recommendations from friends, and selected a dentist based on convenience of location. I asked if they were happy with their dentist, and if the dentist was “above average,” “average,” or “below average” in terms of dental skills and expertise. Every dentist who takes care of my friends and colleagues is “above average.” Apparently, dentistry is like Lake Wobegon, where “all of the children are above average.” Then, I asked, “How do you know if your dentist is above average?” Did the dentist use low-dose digital imaging to reduce radiation; monitor and report rates of infection; report the frequency of repeat fillings or crowns, root-canal experience, overall rates of complications, instrument sterilization, and more? Not one of my quality-conscious friends had considered these elements when selecting their dentist.

Mentoring, Education, and Training Corner

  • Writing and Publishing Scientific Papers

    • Hashem B. El–Serag
    Published online: December 19, 2011
    Published scientific papers are essential to disseminate research findings, and publications are a measure of academic productivity assessed for promotion and grant application. However, these are not perhaps the most important benefits of writing. As M. J. Mahoney once commented, “I would urge you to write not because it is a good thing, not because it is nice to see your name in print, but rather because you will really get to know a field only if you contribute to it” (Mahoney MJ, Psychology of the Scientist 1979).
  • AGA Gastroenterology Training Exam (GTE): A Progress Report

    • Gregory S. Sayuk,
    • Ikuo Hirano,
    • James T. Fitzgerald,
    • ...
    • Joy Akinyi,
    • Charles E. Willis
    • AGA Institute's GTE Subcommittee
    Published online: December 19, 2011
    Subspecialty fellowship program directors (PDs) are keenly interested in monitoring and enhancing their trainees' academic progress throughout their fellowship experience. In addition to assessing trainee clinical acumen and knowledge base, PDs are required to demonstrate growth in clinical performance to validate advancement to subsequent training years, for which training programs have been confronted with increasing requirements by the Accreditation Council for Graduate Medical Education (ACGME).
    Online ExtraAdditional Online Content Available


  • Diverticulosis and Dietary Fiber: Rethinking the Relationship

    • Lisa L. Strate
    Published online: December 19, 2011
    For more than a half century, the development of diverticulosis has been largely attributed to insufficient fiber intake and aging. In seminal work, Painter and Burkitt described marked differences in the prevalence of diverticular disease in Africa and Asia compared with Western countries, as well as pre- and postindustrialization in Europe and the United States.1 Western diets tended to be lower in fiber than African and Asian diets, and, in the West, the steady decline in fiber consumption mirrored the increase in diverticular disease.
  • Outcomes Among Living Liver Donors

    • James F. Trotter,
    • James E. Everhart
    Published online: December 26, 2011
    Management of donor risk is the most important consideration in the decision to perform a living donor liver transplantation (LDLT). Counseling potential donors on operative morbidity and mortality requires a comprehensive understanding of the available data on outcomes. Ideally, an individual potential living donor should be informed of the potential complications based on an objective analysis of a center’s own results. At present, this ideal has not been obtained. Instead, potential donors and their physicians must rely on outcome data from numerous single-center and a few multicenter studies.

Clinical Challenges and Images in GI

  • A Ghost Pancreas

    • Arnaud Galbois,
    • Fabien Stenard,
    • Dimitri Margetis
    Published online: December 21, 2011
    Question: A 73-year-old man without medical history was admitted to the Intensive Care Unit (ICU) for shock. The day before ICU admission, he suddenly experienced nausea and abdominal pain, and vomited twice. On admission, core temperature was 37.9°C, heart rate was 86 beats/min, and blood pressure was 70/36 mmHg. Painful abdominal distension without occlusion was noticed. Arterial blood gases on room air showed: pH, 7.19; HCO3, 9 mmol/L; PaCO2, 24 mmHg; PaO2, 105 mmHg; lactate, 9.3 mmol/L. Blood work showed: glycemia, 21.4 mmol/L; creatininemia, 306 μmol/L; hemoglobin, 16 g/dL; leukocytes, 9.4 g/L; platelets, 153 g/L; alanine aminotransferase, 412 IU/L; aspartate aminotransferase, 204 IU/L; lactate dehydrogenase, 1586 IU/L; alkaline phosphatase, 111 IU/L; total bilirubin, 42 μmol/L, and lipase, 1502 IU/L.
  • An Unusual Cause of Upper Gastrointestinal Bleeding

    • Ahmad ALHarbi,
    • Majid Almadi,
    • Andrew Szilagyi
    Published online: December 21, 2011
    Question: A 45-year-old man presented to the hospital with coffee ground emesis, melena, and syncope. Initial evaluation revealed signs of hemodynamic instability with a heart rate of 120 beats/min and a blood pressure of 88/62 mmHg. Initial laboratory investigations were normal except for a decreased hemoglobin level of 7.8 g/dL (normal, 13.0–17.0). After resuscitation, an evaluation for suspected upper gastrointestinal bleeding using an esophagogastroduodenoscope was performed; a focal area of mucosal erythema was noticed in the fundus with enlarged mucosal folds, no blood or active bleeding was seen.
  • The Way to a Man's Stomach Is Through His Heart

    • Luc Biedermann,
    • Ariana Gaspert,
    • Christoph Gubler
    Published online: December 21, 2011
    Question: A 74-year-old man underwent gastroscopy owing to severe nausea, vomitus, and fluctuating mild epigastric discomfort of 2 months’ duration. He had known chronic renal failure with a creatinine clearance of 32 mL/min (Modification of Diet in Renal Disease formula), diabetes mellitus, and coronary heart disease with a history of myocardial infarction. The patient reported initiation of his current gastrointestinal (GI) symptoms within several hours after a coronary angiography with stent implantation in the right coronary artery owing to worsening chest pain.
  • Emphysematous Changes of the Liver

    • Yang–Sheng Lin,
    • Wei–Sheng Wang,
    • Ming–Jen Chen
    Published online: December 21, 2011
    Question: A 59-year-old woman presented to the emergency department with nausea and epigastric pain for 2 days preceded by 2 weeks of anorexia. Several years ago, she was diagnosed as glucose intolerant, but did not receive regular follow-up. On examination, her temperature was 34.8°C and her blood pressure was 81/53 mm Hg. She had icteric sclera, palpated tenderness in the upper right quadrant of the abdomen, and hepatomegaly (liver span of 14 cm at the midclavicular line). Blood tests showed a leukocyte count of 5700/mm3, (55% neutrophils; 19% lymphocytes), a glucose level of 347 mg/100 mL, an aspartate aminotransferase of 10,920 U/L, an alanine aminotransferase level of 3651 U/L, a total bilirubin of 4.8 mg/dL, and a creatinine level of 3.4 mg/100 mL.

Electronic Clinical Challenges and Images in GI

  • To Snare a Snare, or Not to Snare?

    • Stijn J.B. Van Weyenberg
    Published online: December 22, 2011
    Question: A 79-year-old man presented with a 1-year history of intermittent colicky abdominal pain, without rectal blood loss or fever. On physical examination, the abdomen was not distended, there were normal bowel sounds and no rebound tenderness or peritoneal guarding. The laboratory results were all normal. Colonoscopy revealed mild diverticulosis of the sigmoid colon. Additionally, we observed a thin, stalk-like lesion, the distal end of which seemed to be trapped in a peristaltic wave, resulting in considerable strain to the tissue, not unlike a stretched snare (Figure A).
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  • An Uncommon Cause of Epigastric Pain and Emesis

    • Doerthe Kuester,
    • Christian Schulz,
    • Peter Malfertheiner
    Published online: December 22, 2011
    Question: A 35-year-old man presented to our gastrointestinal clinic with a 4-week history of sudden onset emesis and upper abdominal pain in the right epigastrium. Alarming symptoms, such as dysphagia, weight loss, vomiting, or gastrointestinal bleeding, were not reported. Physical examination revealed no abnormalities. Initial laboratory investigations showed elevation of alanine transaminase (54.6 U/L), alkaline phosphatase (147.6 U/L), and lactate dehydrogenase (353.4 U/L) levels. Upper gastrointestinal endoscopy revealed multiple nodular polypoid dark lesions of the esophagus (Figure A), the gastric antrum and corpus (Figure C), and the bulbus duodeni.
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  • A Rare but Important Cause of Acute Abdomen

    • Wan-Ling Miriam Wu,
    • I-Ha Lao
    Published online: December 22, 2011
    Question: A 33-year-old man with history of right inguinal hernia presented with progressive abdominal pain for 1 week. On examination he had a soft right inguinal mass with diffuse peritonitis, and laboratory tests revealed an elevated white cell count (13 × 109/L). Abdominal computed tomography demonstrated a pathognomonic whirling fatty mass in the omentum (Figure A, black arrow) with diffuse abdominal/pelvic fatty infiltration (Figure B, arrowhead) extending into right inguinal canal next to the hernia (Figure C, D, white arrow).
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  • Upper Gastrointestinal Bleeding in a Patient With Multiple Myeloma

    • Sumanth R. Daram,
    • Elizabeth R. Paine,
    • Amanda F. Swingley
    Published online: December 22, 2011
    Question: A 53-year-old African American woman was diagnosed with κ-light chain multiple myeloma in 2005. She underwent chemotherapy previously, and stem cell transplantation 4 months before the current hospitalization. She presented with acute upper gastrointestinal (GI) bleeding in the form of hematemesis. The patient underwent emergent esophagogastroduodenoscopy. There was no evidence of active bleeding. A multilobulated, submucosal mass, about 4 × 4 cm, with an overlying ulceration measuring about 10 mm was seen, occupying the proximal corpus along the greater curvature (Figure A).
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  • Large Tumor of the Liver and Hypoglycemic Shock in an 85-Year-Old Patient

    • Sonia Radunz,
    • Hideo A. Baba,
    • Georgios C. Sotiropoulos
    Published online: December 23, 2011
    Question: An 85-year-old woman was referred to our institution with a palpable mass in the upper abdomen. Her past medical history was unremarkable except for arterial hypertension and coronary artery disease. Lately, she had experienced frequent episodes of drenching sweats. On physical examination, a large mass was palpated in the upper abdomen. Computed tomography showed a large, heterogenous liver tumor of the left lobe measuring 17 cm in diameter (Figure A). The liver showed no signs of cirrhosis and no other lesions or pathologic findings were observed in the abdomen or the thorax.
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  • Vague Abdominal Discomfort for 5 Years and a Large Upper Abdominal Mass in a 45-Year-Old Woman

    • Jiann–Hwa Chen,
    • Chung–Tai Yue,
    • Chieh–Wen Lai
    Published online: December 26, 2011
    Question: A 45-year-old woman with a history of a gastric ulcer 10 years ago presented to the outpatient department with vague upper abdominal discomfort for 5 years. She had no history of abdominal surgery. She denied having poor appetite and weight loss. Physical examination showed a moderately nourished lady, not anemic in appearance; a firm, large, nontender mass was distinguished in the left upper abdominal quadrant. All blood tests were normal, including tumors markers (carcinoembryonic antigen, alfa-fetoprotein, carbohydrate antigen 19-9, and carbohydrate antigen 125).
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  • Transient Ischemic Attack in a Patient With Cirrhosis

    • Jagrati Mathur,
    • David Limsui
    Published online: December 23, 2011
    Question: A 63-year-old man presented with acute onset of slurred of speech that resolved within a few hours. He was recently diagnosed with cirrhosis secondary to hepatitis C and alcohol. He had lost 10 kg over the past year. He appeared thin and frail and was afebrile with normal vitals. Jaundice, hepatosplenomegaly, and ascites were not present. The abdomen was nondistended and nontender. His cardiac examination was normal, and he had no lymphadenopathy. Neurologic examination was normal with no asterixis.
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  • A Common Disease With an Unusual Complication of Acute Abdomen

    • Jui-Shan Hsu,
    • I-Hui Wu,
    • Kao-Lang Liu
    Published online: December 22, 2011
    Question: A previously healthy 64-year-old man presented to the emergency department with a 4-day duration of progressive and diffuse abdominal pain. The pain, seemingly unrelated to meals or postural change, began with intermittent cramps and progressed to a steady, constant ache. Physical examination revealed marked lower quadrant tenderness, diffuse peritoneal sign, and reduced bowel sounds. Deep tenderness at McBurney's point was not obvious. Laboratory investigation disclosed leukocytosis with a left shift, and the remaining tests were unremarkable.
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  • Dysphagia in an HIV Patient: A Rare Culprit

    • Ana Gonçalves,
    • Teresa Antunes
    Published online: December 22, 2011
    Question: A 37-year-old Caucasian woman sought medical attention for intermittent dysphagia for both liquids and solids, loss of appetite, and a 5-kg weight loss in the past 3 months. She denied other symptoms such as fever, productive cough, or diarrhea. The patient history was significant for HIV-1; infection was diagnosed 15 years previously. She was noncompliant with medical follow-up or antiretroviral therapy for the last 5 years. On physical examination, the patient was visibly malnourished, with a body mass index of 15 kg/m2.
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  • Bleeding Polyps?

    • Martin Wilhelmi,
    • Pablo Munoz,
    • Maria-Anna Ortner
    Published online: December 23, 2011
    Question: A 60-year-old Caucasian woman presented with melena of 3 days’ duration. It was the second episode of gastrointestinal (GI) bleeding. Fourteen days ago, colonoscopy done in another hospital revealed diverticulosis and 3 small polypoid lesions in the cecum without signs of acute bleeding. Biopsies of the lesions have been taken. Gastroscopy was normal. At admission to our hospital, the patient was hemodynamically stable. Laboratory findings showed hemoglobin level of 80 g/L (normal limits, 121–154 g/L) and thrombocytes of 34 g/L (normal limits, 140–380 g/L).
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  • An Extremely Unusual and Large Cause of Anemia

    • Javier G. Castillo,
    • Dana Telem,
    • Tomas M. Heimann
    Published online: December 22, 2011
    Question: A 63-year-old man with a long-standing medical history of anemia presented to the gastroenterology outpatient clinic with diffuse abdominal pain, progressive dragging sensation in the left upper quadrant, and marked dizziness. Other prominent clinical symptoms included a weight loss of 15 lbs over 2 months, anorexia, and intermittent constipation. Clinical examination revealed tenderness in the left upper quadrant and massive splenomegaly. On further palpation, the spleen extended to the umbilicus, and had a smooth surface and a very firm consistency.
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Reviews and Perspectives

    Imaging and Advanced Technology

    • Myc Target miRs and Liver Cancer: Small Molecules to Get Myc Sick

      • Marie–Annick Buendia,
      • Ludovic Bourre,
      • Stefano Cairo
      Published online: December 19, 2011
      Primary liver cancer is a disease arising from malignant transformation of hepatocytes, which account for up to 80% of the liver tissue. In infants, the most common form of liver tumor is hepatoblastoma (HB), a rare childhood tumor that mostly affects kids <3 years old. In adults, hepatocellular carcinoma (HCC) is by far the most common form of liver malignancy.

    Reviews in Basic and Clinical Gastroenterology and Hepatology

    • Dysregulation of Wnt/β-Catenin Signaling in Gastrointestinal Cancers

      • Bryan D. White,
      • Andy J. Chien,
      • David W. Dawson
      Published online: December 09, 2011
      Aberrant Wnt/β-catenin signaling is widely implicated in numerous malignancies, including cancers of the gastrointestinal tract. Dysregulation of signaling is traditionally attributed to mutations in Axin, adenomatous polyposis coli, and β-catenin that lead to constitutive hyperactivation of the pathway. However, Wnt/β-catenin signaling is also modulated through various other mechanisms in cancer, including cross talk with other altered signaling pathways. A more complex view of Wnt/β-catenin signaling and its role in gastrointestinal cancers is now emerging as divergent phenotypic outcomes are found to be dictated by temporospatial context and relative levels of pathway activation.
      Additional Online Content Available

Original Research

    Clinical-Alimentary Tract

    • Tobacco Smoking Increases the Risk of High-Grade Dysplasia and Cancer Among Patients With Barrett's Esophagus

      • Helen G. Coleman,
      • Shivaram Bhat,
      • Brian T. Johnston,
      • Damian McManus,
      • Anna T. Gavin,
      • Liam J. Murray
      Published online: November 07, 2011
      Esophageal adenocarcinoma arises from Barrett's esophagus (BE); patients with this cancer have a poor prognosis. Identification of modifiable lifestyle factors that affect the risk of progression from BE to esophageal adenocarcinoma might prevent its development. We investigated associations among body size, smoking, and alcohol use with progression of BE to neoplasia.
    • Smoking Increases the Risk for Colorectal Adenomas in Patients With Lynch Syndrome

      • Renate M. Winkels,
      • Akke Botma,
      • Fränzel J.B. Van Duijnhoven,
      • ...
      • Jan H. Kleibeuker,
      • Hans F.A. Vasen,
      • Ellen Kampman
      Published online: November 07, 2011
      Individuals with Lynch syndrome have a high risk of developing colorectal carcinomas and adenomas at a young age, due to inherited mutations in mismatch repair genes. We investigated whether modifiable lifestyle factors, such as smoking and alcohol intake, increase this risk.
    • Next-Generation Stool DNA Test Accurately Detects Colorectal Cancer and Large Adenomas

      • David A. Ahlquist,
      • Hongzhi Zou,
      • Michael Domanico,
      • ...
      • Henrik Toft Sørensen,
      • Barry M. Berger,
      • Graham P. Lidgard
      Published online: November 07, 2011
      Technical advances have led to stool DNA (sDNA) tests that might accurately detect neoplasms on both sides of the colorectum. We assessed colorectal neoplasm detection by a next-generation sDNA test and effects of covariates on test performance.
      PodcastVideo AbstractCME QuizAdditional Online Content Available
    • Adalimumab Induces and Maintains Clinical Remission in Patients With Moderate-to-Severe Ulcerative Colitis

      • William J. Sandborn,
      • Gert van Assche,
      • Walter Reinisch,
      • ...
      • Mary Beth Tighe,
      • Andreas Lazar,
      • Roopal B. Thakkar
      Published online: November 07, 2011
      Adalimumab is a fully human monoclonal antibody that binds tumor necrosis factor (TNF)-α. Its efficacy as maintenance therapy for patients with ulcerative colitis has not been studied in a controlled, double-blind trial.
      Online ExtraAdditional Online Content Available
    • A High-Fiber Diet Does Not Protect Against Asymptomatic Diverticulosis

      • Anne F. Peery,
      • Patrick R. Barrett,
      • Doyun Park,
      • ...
      • Joseph A. Galanko,
      • Christopher F. Martin,
      • Robert S. Sandler
      Published online: November 07, 2011
      The complications of diverticulosis cause considerable morbidity in the United States; health care expenditures for this disorder are estimated to be $2.5 billion per year. Many physicians and patients believe that a high-fiber diet and frequent bowel movements prevent the development of diverticulosis. Evidence for these associations is poor. We sought to determine whether low-fiber or high-fat diets, diets that include large quantities of red meat, constipation, or physical inactivity increase risk for asymptomatic diverticulosis.
      Online ExtraEditorial Accompanies ArticleAdditional Online Content Available


    Basic and Translational-Alimentary Tract

    • Helicobacter pylori Infection Recruits Bone Marrow−Derived Cells That Participate in Gastric Preneoplasia in Mice

      • Christine Varon,
      • Pierre Dubus,
      • Frédéric Mazurier,
      • ...
      • Nathalie Senant–Dugot,
      • Martina Carlotti,
      • Francis Mégraud
      Published online: November 07, 2011
      Studies in animal models have shown that bone marrow−derived cells (BMDC) could be involved in the formation of carcinomas of the upper gastrointestinal tract, including gastric carcinoma. Most gastric carcinomas in humans have been associated with chronic infection with Helicobacter pylori; we investigated the bacteria’s potential to induce premalignant lesions in mice and studied the kinetics of BMDC settlement in the gastric epithelium.
      Additional Online Content Available
    • Deficiency of Claudin-18 Causes Paracellular H+ Leakage, Up-regulation of Interleukin-1β, and Atrophic Gastritis in Mice

      • Daisuke Hayashi,
      • Atsushi Tamura,
      • Hiroo Tanaka,
      • ...
      • Hiromi Rakugi,
      • Yoshitaka Isaka,
      • Sachiko Tsukita
      Published online: November 11, 2011
      Although defects in tight junction (TJ) epithelial paracellular barrier function are believed to be a primary cause of inflammation, the mechanisms responsible remain largely unknown.
      Additional Online Content Available
    • Inflammation and Disruption of the Mucosal Architecture in Claudin-7–Deficient Mice

      • Lei Ding,
      • Zhe Lu,
      • Oded Foreman,
      • ...
      • Randall Renegar,
      • Jian Cao,
      • Yan–Hua Chen
      Published online: October 31, 2011
      Integrity of the intestinal epithelium is required for nutrition absorption and defense against pathogens. Claudins are cell adhesion molecules that localize at tight junctions (TJs); many are expressed in the intestinal tract, but little is known about their functions. Claudin-7 is unique in that it has a stronger basolateral membrane distribution than other claudins, which localize primarily to apical TJs in the intestinal epithelium. We investigated the basolateral functions of claudin-7 and assessed the effects of disruption of Cldn7 in intestines of mice.
      Additional Online Content Available
    • The Copolymer P(HEMA-co-SS) Binds Gluten and Reduces Immune Response in Gluten-Sensitized Mice and Human Tissues

      • Maud Pinier,
      • Gregor Fuhrmann,
      • Heather J. Galipeau,
      • ...
      • Ludmila Tuckova,
      • Jean–Christophe Leroux,
      • Elena F. Verdu
      Published online: November 11, 2011
      Copolymers of hydroxyethyl methacrylate and styrene sulfonate complex with isolated gliadin (the toxic fraction of gluten) and prevent damage to the intestinal barrier in HLA-HCD4/DQ8 mice. We studied the activity toward gluten and hordein digestion and biologic effects of poly(hydroxyethyl methacrylate-co-styrene sulfonate (P(HEMA-co-SS)). We also investigated the effect of gliadin complex formation in intestinal biopsy specimens from patients with celiac disease.
      Online ExtraAdditional Online Content Available
    • Dysregulation of CD1d-Restricted Type II Natural Killer T Cells Leads to Spontaneous Development of Colitis in Mice

      • Chia–Min Liao,
      • Michael I. Zimmer,
      • Sharmila Shanmuganad,
      • Hon–Tsen Yu,
      • Susanna L. Cardell,
      • Chyung–Ru Wang
      Published online: November 03, 2011
      CD1d-restricted natural killer (NK) T cells are a subset of immunoregulatory T cells that comprise type I (express the semi-invariant T-cell receptor [TCR] and can be detected using the α-galactosylceramide/CD1d tetramer) and type II (express diverse TCRs and cannot be directly identified). Studies in mouse models of inflammatory bowel disease revealed a complex role for type I NKT cells in the development of colitis. Type II NKT cells have been associated with intestinal inflammation in patients with ulcerative colitis.
      Online ExtraAdditional Online Content Available
    • CCL17 Promotes Intestinal Inflammation in Mice and Counteracts Regulatory T Cell–Mediated Protection From Colitis

      • Alexander F. Heiseke,
      • Antonia C. Faul,
      • Hans–Anton Lehr,
      • ...
      • Roland M. Schmid,
      • Anne B. Krug,
      • Wolfgang Reindl
      Published online: November 03, 2011
      Priming of T cells by dendritic cells (DCs) in the intestinal mucosa and associated lymphoid tissues helps maintain mucosal tolerance but also contributes to the development of chronic intestinal inflammation. Chemokines regulate the intestinal immune response and can contribute to pathogenesis of inflammatory bowel diseases. We investigated the role of the chemokine CCL17, which is expressed by conventional DCs in the intestine and is up-regulated during colitis.
      Additional Online Content Available
    • Severe Defects in Absorptive Ion Transport in Distal Colons of Mice That Lack ClC-2 Channels

      • Marcelo A. Catalán,
      • Carlos A. Flores,
      • Mireya González–Begne,
      • Yan Zhang,
      • Francisco V. Sepúlveda,
      • James E. Melvin
      Published online: November 11, 2011
      The fluid secretion model predicts that intestinal obstruction disorders can be alleviated by promoting epithelial Cl secretion. The adenosine 3′,5′-cyclic monophosphate (cAMP)-activated anion channel CFTR mediates Cl-dependent fluid secretion in the intestine. Although the role of the ClC-2 channel has not been determined in the intestine, this voltage-gated Cl channel might compensate for the secretory defects observed in patients with cystic fibrosis and other chronic constipation disorders.
      Additional Online Content Available

    Basic and Translational-Liver

    • Selective Activation of Nuclear Bile Acid Receptor FXR in the Intestine Protects Mice Against Cholestasis

      • Salvatore Modica,
      • Michele Petruzzelli,
      • Elena Bellafante,
      • ...
      • Emina Halilbasic,
      • Michael Trauner,
      • Antonio Moschetta
      Published online: November 03, 2011
      Cholestasis is a liver disorder characterized by impaired bile flow, reduction of bile acids (BAs) in the intestine, and retention of BAs in the liver. The farnesoid X receptor (FXR) is the transcriptional regulator of BA homeostasis. Activation of FXR by BAs reduces circulating BA levels in a feedback mechanism, repressing hepatic cholesterol 7α-hydroxylase (Cyp7a1), the rate-limiting enzyme for the conversion of cholesterol to BAs. This mechanism involves the hepatic nuclear receptor small heterodimer partner and the intestinal fibroblast growth factor (FGF) 19 and 15.
      Online ExtraAdditional Online Content Available
    • CCR9+ Macrophages Are Required for Acute Liver Inflammation in Mouse Models of Hepatitis

      • Nobuhiro Nakamoto,
      • Hirotoshi Ebinuma,
      • Takanori Kanai,
      • ...
      • Paul E. Love,
      • Hidetsugu Saito,
      • Toshifumi Hibi
      Published online: November 11, 2011
      Antigen-presenting cells (APCs) are involved in the induction of liver inflammation. We investigated the roles of specific APCs in the pathogenesis of acute liver injury in mice.
      Additional Online Content Available

    Basic and Translational-Pancreas

    • The Phosphatase PHLPP1 Regulates Akt2, Promotes Pancreatic Cancer Cell Death, and Inhibits Tumor Formation

      • Claudia Nitsche,
      • Mouad Edderkaoui,
      • Ryan M. Moore,
      • ...
      • Julia Mayerle,
      • Markus M. Lerch,
      • Anna S. Gukovskaya
      Published online: October 31, 2011
      The kinase Akt mediates resistance of pancreatic cancer (PaCa) cells to death and is constitutively active (phosphorylated) in cancer cells. Whereas the kinases that activate Akt are well characterized, less is known about phosphatases that dephosporylate and thereby inactivate it. We investigated regulation of Akt activity and cell death by the phosphatases PHLPP1 and PHLPP2 in PaCa cells, mouse models of PaCa, and human pancreatic ductal adenocarcinoma (PDAC).
      Online ExtraAdditional Online Content Available
    • Restricted Heterochromatin Formation Links NFATc2 Repressor Activity With Growth Promotion in Pancreatic Cancer

      • Sandra Baumgart,
      • Elisabeth Glesel,
      • Garima Singh,
      • ...
      • Thomas M. Gress,
      • Shiv K. Singh,
      • Volker Ellenrieder
      Published online: November 11, 2011
      Transcriptional silencing of the p15INK4b tumor suppressor pathway overcomes cellular protection against unrestrained proliferation in cancer. Here we show a novel pathway involving the oncogenic transcription factor nuclear factor of activated T cells (NFAT) c2 targeting a p15INK4b-mediated failsafe mechanism to promote pancreatic cancer tumor growth.
      Online ExtraAdditional Online Content Available

Continuing Medical Education (CME) Activity

Selected Summaries

  • The Microbiota and Bariatric Surgery: It's a Bug's Life

    • Eileen F. Murphy,
    • Eamonn M.M. Quigley
    Published online: December 21, 2011
    Li J, Ashrafian H, Bueter M, et al. Metabolic surgery profoundly influences gut microbial-host metabolic cross-talk. Gut 2011;60:1214–1223.
  • Reply

    • Julian R. Marchesi,
    • Jia Li,
    • Elaine Holmes,
    • Hutan Ashrafian,
    • Thanos Athanasiou,
    • Ara Darzi,
    • Jeremy K. Nicholson
    Published online: December 19, 2011
    We welcome the authors’ comments in relation to our article published in Gut (2011;60:1214–1223) and wish to reiterate the point that referring to the role of gut microbiota as potentially being “mere epiphenomenon” needs to be strongly reconsidered. The whole field has moved beyond this notion and we should be thinking of where on the continuum of microbiome–host interactions this change in the composition falls. In the last 10 years, we have slowly begun to reintegrate the functions in the gut microbiome into host biology and there are many notable examples where they influence host; for example, bacterial glucuronidases impact chemotherapeutic treatments for colorectal cancer (Science 2010;330:831–835).
  • Stimulant Laxatives for the Treatment of Chronic Constipation: Is it Time to Change the Paradigm?

    • Darren M. Brenner
    Published online: December 21, 2011
    Kamm MA, Mueller-Lissner S, Wald A, et al. Oral bisacodyl is effective and well-tolerated in patients with chronic constipation. Clin Gastroenterol Hepatol 2011;9:577–583.
  • Inflammatory Bowel Disease and Thromboembolism: A C‘Lot’ to Worry About

    • Joshua Max,
    • Akbar K. Waljee
    Published online: December 21, 2011
    Kappelman MD, Horvath-Puho E, Sandler RS, et al. Thromboembolic risk among Danish children and adults with inflammatory bowel diseases: a population-based nationwide study. Gut 2011;60:937–943.
  • Irritable Bowel Syndrome: A Dysfunction of the Endocannabinoid System?

    • Martin Storr,
    • Hans–Dieter Allescher
    Published online: December 21, 2011
    Park JM, Choi MG, Cho YK. Cannabinoid receptor 1 gene polymorphism and irritable bowel syndrome in the Korean population: a hypothesis-generating study. J Clin Gastroenterol 2011;45:45–49.

Print and Digital Media Reviews

  • Controversies in Hepatology: The Experts Analyze Both Sides

    • Paul Y. Kwo
    Published online: December 22, 2011
    The field of hepatology has grown exponentially over the past 40 years both in the clinical and research arenas. This has accompanied the world-wide recognition of the burden of chronic liver disease including alcoholic liver disease, hepatitis B, hepatitis C, nonalcoholic liver disease, and end-stage liver disease and hepatocellular cancer. Major advances in our understanding of these diseases along with major therapeutic advances including treatments for viral hepatitis; autoimmune, cholestatic, and metabolic liver diseases; alcoholic hepatitis; end-stage liver disease; and the ultimate therapy for end-stage liver disease, liver transplantation, have allowed hepatologists to improve the lives of those with chronic liver disease while extending survival and in many instances, curing our patients of their ailment.
  • Endoscopic Ultrasound: An Introductory Manual and Atlas, 2nd edition

    • Michael J. Levy
    Published online: December 19, 2011
    Endoscopic ultrasound (EUS) has emerged as a valuable diagnostic imaging modality since its introduction >30 years ago. There remains a need for enhanced EUS training that is not fully met by dedicated EUS training programs. Although technical skills are most readily acquired within a formal EUS fellowship, the education is facilitated by having a thorough knowledge of normal and abnormal EUS anatomy and a clear understanding of the concepts that apply to therapeutic EUS. Such educational material also benefits persons completing training to allow skill maintenance and continued intellectual and procedural growth.
  • Curbside Consultation in GI Cancer for the Gastroenterologist: 49 Clinical Questions

    • Neil Gupta,
    • Sreenivasa Jonnalagadda
    Published online: December 22, 2011
    This is another issue of the successful “Curbside Consultation” textbook series published by SLACK Incorporated. This new addition to the series focuses on the area of gastrointestinal cancers and is a timely release considering the growing complexities and nuances related to the management of colorectal cancer, esophageal adenocarcinoma, pancreatic cancer, and hepatocellular cancer. Colorectal cancer is the third leading cause of cancer and second leading cause of cancer-related death, causing an estimated 50,000 deaths in 2011.
  • Correction

    Published online: January 09, 2012
    Polyak SJ, Morishima C, Scott JD, et al. A summary of the 18th international symposium on hepatitis C virus and related viruses. Gastroenterology 2012;142:e1–e5.