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| 1 | Celiac disease:Prevalence,diagnosis,pathogenesis and treatment显示文摘Celiac disease(CD) is one of the most common diseases,resulting from both environmental(gluten) and genetic factors [human leukocyte antigen(HLA) and nonHLA genes].The prevalence of CD has been estimated to approximate 0.5%-1% in different parts of the world.However,the population with diabetes,autoimmune disorder or relatives of CD individuals have even higher risk for the development of CD,at least in part,because of shared HLA typing.Gliadin gains access to the basal surface of the epithelium,and interact directly with the immune system,via both trans-and para-cellular routes.From a diagnostic perspective,symptoms may be viewed as either 'typical' or 'atypical'.In both positive serological screening results suggestive of CD,should lead to small bowel biopsy followed by a favourable clinical and serological response to the gluten-free diet(GFD) to confirm the diagnosis.Positive anti-tissue transglutaminase antibody or antiendomysial antibody during the clinical course helps to confirm the diagnosis of CD because of their over 99% specificities when small bowel villous atrophy is present on biopsy.Currently,the only treatment available for CD individuals is a strict life-long GFD.A greater understanding of the pathogenesis of CD allows alternative future CD treatments to hydrolyse toxic gliadin peptide,prevent toxic gliadin peptide absorption,blockage of selective deamidation of specific glutamine residues by tissue,restore immune tolerance towards gluten,modulation of immune response to dietary gliadin,and restoration of intestinal architecture. | Naiyana Gujral Hugh J Freeman Alan BR Thomson | 2012 | World Journal of Gastroenterology2012，18，42： | 19 |
| 2 | Adult eosinophilic gastroenteritis and hypereosinophilic syndromes显示文摘Eosinophilic gastroenteritis (EGE) in the adult is a distinctive pathologically-based disorder characterized by an eosinophil-predominant mucosal inflammatory process. Most often,the disorder is detected during endoscopic investigation for abdominal pain or diarrhea. Other causes of gastric and intestinal mucosal eosinophilia require exclusion,including parasitic infections and drug-induced causes. Occasionally,the muscle wall or serosal surface may be involved. EGE appears to be more readily recognized,in large part,due to an evolution in the imaging methods used to evaluate abdominal pain and diarrhea,in particular,endoscopic imaging and mucosal biopsies. Def inition of EGE,however,may be diffi cult,as the normal ranges of eosinophil numbers in normal and abnormal gastric and intestinal mucosa are not well standardized. Also,the eosinophilic inflammatory process may be either patchy or diffuse and the detection of the eosinophilic infiltrates may vary depending on the method of biopsy fixation. Treatment has traditionally focused on resolution of symptoms,and,in some instances,eosinophil quantification in pre-treatment and post-treatment biopsies. Future evaluation and treatment of EGE may depend on precise serological biomarkers to aid in defi nition of the long-term natural history of the disorder and its response to pharmacological or biological forms of therapy. | Hugh James Freeman | 2008 | World Journal of Gastroenterology2008，14，44： | 14 |
| 3 | Intestinal lymphangiectasia in adults显示文摘Intestinal lymphangiectasia in the adult may be characterized as a disorder with dilated intestinal lacteals causing loss of lymph into the lumen of the small intestine and resultant hypoproteinemia, hypogamma-globulinemia, hypoalbuminemia and reduced number of circulating lymphocytes or lymphopenia. Most often, intestinal lymphangiectasia has been recorded in children, often in neonates, usually with other congenital abnormalities but initial def inition in adults including the elderly has become increasingly more common. Shared clinical features with the pediatric population such as bilateral lower limb edema, sometimes with lymphedema, pleural effusion and chylous ascites may occur but these reflect the severe end of the clinical spectrum. In some, diarrhea occurs with steatorrhea along with increased fecal loss of protein, reflected in increased fe- cal alpha-1-antitrypsin levels, while others may present with iron def iciency anemia, sometimes associated with occult small intestinal bleeding. Most lymphangiectasia in adults detected in recent years, however, appears to have few or no clinical features of malabsorption. Diagnosis remains dependent on endoscopic changes confirmed by small bowel biopsy showing histological evidence of intestinal lymphangiectasia. In some, video capsule endoscopy and enteroscopy have revealed moreextensive changes along the length of the small intes- tine. A critical diagnostic element in adults with lym- phangiectasia is the exclusion of entities (e.g. malignancies including lymphoma) that might lead to obstruction of the lymphatic system and 'secondary' changes in the small bowel biopsy. In addition, occult infectious (e.g. Whipple's disease from Tropheryma whipplei) or in? am- matory disorders (e.g. Crohn's disease) may also present with profound changes in intestinal permeability and protein-losing enteropathy that also require exclusion. Conversely, rare B-cell type lymphomas have also been described even decades following initial diagnosis of intestinal lymphangiectasia. Treatment has been historically def ined to include a low fat diet with medium-chain triglyceride supplementation that leads to portal venous rather than lacteal uptake. A number of other pharma- cological measures have been reported or proposed but these are largely anecdotal. Finally, rare reports of localized surgical resection of involved areas of small intestine have been described but follow-up in these cases is often limited. 2011 Baishideng. All rights reserved. | Hugh James Freeman Michael Nimmo | 2011 | World Journal of Gastrointestinal Oncology2011，3，2： | 13 |
| 4 | “Melanosis” in the small and large intestine显示文摘Deposition of pigment in the intestinal mucosa is commonly observed by the endoscopist, especially within the colon, and particularly during investigations for constipation. Pigment may also be detected in the small intestine. Although labeled as melanosis, electron microscopy and X-ray analytical methods have provided evidence that this pigment is not melanin at all, but lipofuscin. Often, herbal remedies or anthracene containing laxatives are often historically implicated, and experimental studies in both humans and animal models have also confirmed the intimate relationship with these pharmacological or pseudo-pharmacological remedies. The appearance of melanosis coli during colonoscopy is largely due to pigment granule deposition in macrophages located in the colonic mucosa. The pigment intensity is not uniform, being more intense in the cecum and proximal colon compared to the distal colon. Possibly, this reflects higher luminal concentrations of an offending agent in the proximal compared to distal colon, differential absorption along the length of the colon, or finally, differences in macrophage distribution within the colon. Mucosal lymphoid aggregates normally display a distinct absence of pigment producing a 'starry sky' appearance, especially in the rectosigmoid region. Interestingly, some focal, usually sessile, colonic mucosal neoplastic lesions, rather than submucosal lesions, may be better appreciated as pigment deposition may be absent or limited. If detected, removal and further histopathologic analysis of the polyp may be facilitated. | Hugh James Freeman | 2008 | World Journal of Gastroenterology2008，14，27： | 10 |
| 5 | Natural history and long-term clinical course of Crohn's disease显示文摘Crohn’s disease is a chronic inflammatory disease process involving different sites in the gastrointestinal tract.Occasionally,so-called metastatic disease occurs in extra-intestinal sites.Granulomatous inflammation may be detected in endoscopic biopsies or resected tissues.Genetic,epigenetic and environmental factors appear to play a role.Multiple susceptibility genes have been described in both familial and non-familial forms while the disease is phenotypically heterogeneous with a female predominance.The disorder occurs over a broad age spectrum,from early childhood to late adulthood.More than 80%are diagnosed before age 40 years usually with terminal ileal and colonic involvement.Pediatric-onset disease is more severe and more extensive,usually with a higher chance of upper gastrointestinal tract disease,compared to adult-onset disease.Long-term studies have shown that the disorder may evolve with time into more complex disease with stricture formation and penetrating disease complications(i.e.,fistula,abscess).Although prolonged remission may occur,discrete periods of symptomatic disease may re-appear over many decades suggesting recurrence or re-activation of this inflammatory process.Eventual development of a cure will likely depend on identification of an etiologic cause and a fundamental understanding of its pathogenesis.Until now,treatment has focused on removing risk factors,particularly cigarette smoking,and improving symptoms.In clinical trials,clinical remission is largely defined as improved numerical and endoscopic indices for'mucosal healing'.'Deep remission'is a conceptual,more'extended'goal that may or may not alter the long-term natural history of the disease in selected patients,albeit at a significant risk for treatment complications,including serious and unusual opportunistic infections. | Hugh James Freeman | 2014 | World Journal of Gastroenterology2014，20，1： | 10 |
| 6 | Early stage colon cancer显示文摘Evidence has now accumulated that colonoscopy and removal of polyps,especially during screening and surveillance programs,is effective in overall risk reduction for colon cancer.After resection of malignant pedunculated colon polyps or early stage colon cancers,long-term repeated surveillance programs can also lead to detection and removal of asymptomatic high risk advanced adenomas and new early stage metachronous cancers.Early stage colon cancer can be defined as disease that appears to have been completely resected with no subsequent evidence of involvement of adjacent organs,lymph nodes or distant sites.This differs from the clinical setting of an apparent'curative'resection later pathologically upstaged following detection of malignant cells extending into adjacent organs,peritoneum,lymph nodes or other distant sites,including liver.This highly selected early stage colon cancer group remains at high risk for subsequent colon polyps and metachronous colon cancer.Precise staging is important,not only for assessing the need for adjuvant chemotherapy,but also for patient selection for continued surveillance.With advanced stages of colon cancer and a more guarded outlook,repeated surveillance should be limited.In future,novel imaging technologies(e.g.,confocal endomicroscopy),coupled with increased pathological recognition of high risk markers for lymph node involvement(e.g.,'tumor budding')should lead to improved staging and clinical care. | Hugh James Freeman | 2013 | World Journal of Gastroenterology2013，19，46： | 8 |
| 7 | Proton pump inhibitors and an emerging epidemic of gastric fundic gland polyposis显示文摘Fundic gland polyps are now commonly recognized during endoscopy. These polyps are benign, often multiple and usually detected in the gastric body and fundus. In the past, these polyps were sometimes associated with familial adenomatous polyposis. In recent years, it has become evident that increasing numbers of these polyps are being detected during endoscopic studies, particularly in patients treated with proton pump inhibitors for prolonged periods. In some, dysplastic changes in these polyps have also been reported. Recent studies have suggested that there may be no increase in risk of colon cancer with long-term proton pump inhibitor therapy. While temporarily reassuring, ongoing vigilance, particularly in those genetically predisposed to colon cancer, is still warranted. | Hugh James Freeman | 2008 | World Journal of Gastroenterology2008，14，9： | 7 |
| 8 | Intraductal papillary mucinous neoplasms and other pancreatic cystic lesions显示文摘Pancreatic cystic neoplasms are being increasingly recognized, even in the absence of symptoms, in large part, due to markedly improved imaging modalities such as magnetic resonance imaging (MRI)/magnetic resonance cholangio pancreatography (MRCP) and computer tomography (CT) scanning. During the past 2 decades, better imaging of these cystic lesions has resulted in definition of different types, including pancreatic intraductal papillary mucinous neoplasms (IPMN). While IPMN represent only a distinct minority of all pancreatic cancers, they appear to be a relatively frequent neoplastic form of pancreatic cystic neoplasm. Moreover, IPMN have a much better outcome and prognosis compared to pancreatic ductal adenocarcinomas. Therefore, recognition of this entity is exceedingly important for the clinician involved in diagnosis and further evaluation of a potentially curable form of pancreatic cancer. | Hugh James Freeman | 2008 | World Journal of Gastroenterology2008，14，19： | 7 |
| 9 | Multifocal stenosing ulceration of the small intestine显示文摘Several reports have described an apparently uncommon clinicopathological disorder that is characterized by multifocal stenosing small-intestinal ulceration.Compared to Crohn's disease,the ulcers are not transmural and typically remain shallow,and involve only the mucosa and submucosa.The disorder seems to be localized in the jejunum and proximal ileum only,and not the distal ileum or colon.Only nonspecif ic inflammatory changes are present without giant cells or other typical features of granulomatous inflammation.Most patients present clinically with recurrent obstructive events that usually respond to steroids,surgical resection,or both.With the development of newer imaging modalities to visualize the small-intestinal mucosa,such as double-balloon enteroscopy,improved understanding of the long-term natural history of this apparently distinctive disorder should emerge. | Hugh James Freeman | 2009 | World Journal of Gastroenterology2009，15，39： | 5 |
| 10 | Recent advances in small bowel diseases:Part Ⅰ显示文摘As is the case in all parts of gastroenterology and hepatology,there have been many advances in our knowledge and understanding of small intestinal diseases.Over 1000 publications were reviewed for 2008 and 2009,and the important advances in basic science as well as clinical applications were considered.In Part Ⅰ of this Editorial Review,seven topics are considered:intestinal development;proliferation and repair;intestinal permeability;microbiotica,infectious diarrhea and probiotics;diarrhea;salt and water absorption;necrotizing enterocolitis;and immunology/allergy.These topics were chosen because of their importance to the practicing physician. | Alan BR Thomson Angeli Chopra Michael Tom Clandinin Hugh Freeman | 2012 | World Journal of Gastroenterology2012，18，26： | 5 |
| 11 | Recent advances in celiac disease显示文摘Celiac disease now affects about one person in a hundred in Europe and North America. In this review, we consider a number of important and exciting recent developments, such as clinical associations, HLA-DQ2 and HLA-DQ8 predispositions, the concept of potential celiac disease, the use of new imaging/endoscopy techniques, and the development of refractory disease. This review will be of use to all internists, pediatricians and gastroenterologists. | Hugh James Freeman Angeli Chopra Michael Tom Clandinin Alan BR Thomson | 2011 | World Journal of Gastroenterology2011，17，18： | 3 |
| 12 | Tropheryma whipplei infection显示文摘Whipple's disease was initially described in 1907. Over the next century, the clinical and pathological features of this disorder have been better appreciated. Most often, weight loss, diarrhea, abdominal and joint pain occur. Occasionally, other sites of involvement have been documented, including isolated neurological disease, changes in the eyes and culture-negative endocarditis. In the past decade, the responsible organism Tropheryma whipplei has been cultivated, its genome sequenced and its antibiotic susceptibility defined. Although rare, it is a systemic infection that may mimic a wide spectrum of clinical disorders and may have a fatal outcome. If recognized, prolonged antibiotic therapy may be a very successful form of treatment. | Hugh James Freeman | 2009 | World Journal of Gastroenterology2009，15，17： | 3 |
| 13 | Use of the Crohn's disease activity index in clinical trials of biological agents显示文摘The Crohn's disease activity index(CDAI) has been commonly used to assess the effects of treatment with different agents in Crohn's disease(CD).However these studies may be compromised,if the results compared to a placebo or standard therapy group(in the absence of a placebo) substantially differ from the expected response.In addition,significan concerns have been raised regarding the reliability and validity of the CDAI.Reproducibility of the CDAI may be limited as significant inter-observer error has been recorded,even if measurements are done by experienced clinicians with expertise in the diagnosis and treatment of CD.Finally,many CDAI endpoints are open to subjective interpretation and have the potential for manipulation.This is worrisome as there is the potential for significant financial gain if the results of a clinical trial appear to provide a positive result.Physicians caring for patients should be concerned about the positive results in clinica trials that are sponsored by industry,even if the trials involve respected centers and the results appear in highly ranked medical journals. | Hugh James Freeman | 2008 | World Journal of Gastroenterology2008，14，26： | 3 |
| 14 | Use of the tumor necrosis factor-blockers for Crohn's disease显示文摘The use of anti-tumor necrosis factor-therapy for inflammatory bowel disease represents the most important advance in the care of these patients since the publication of the National Co-operative Crohn's disease study thirty years ago.The recommendations of numerous consensus groups worldwide are now supported by a wealth of clinical trials and several meta-analyses.In general,it is suggested that tumor necrosis factor-blockers(TNFBs) are indicated(1) for persons with moderately-severe Crohn's disease or ulcerative colitis(UC) who have failed two or more causes of glucocorticosteroids and an acceptably long cause(8 wk to 12 wk) of an immune modulator such as azathioprine or methotrexate;(2) non-responsive perianal disease;and(3) severe UC not responding to a 3-d to 5-d course of steroids.Once TNFBs have been introduced and the patient is responsive,therapy given by the IV and SC rate must be continued.It remains open to definitive evidence if concomitant immune modulators are required with TNFB maintenance therapy,and when or if TNFB may be weaned and discontinued.The supportive evidence from a single study on the role of early versus later introduction of TNFB in the course of a patient's illness needs to be confirmed.The risk/benefit profile of TNFB appears to be acceptable as long as the patient is immunized and tested for tuberculosis and viral hepatitis before the initiation of TNFB,and as long as the long-term adverse effects on the development of lymphoma and other tumors do not prone to be problematic.Because the rates of benefits to TNFB are modest from a population perspective and the cost of therapy is very high,the ultimate application of use of TNFBs will likely be established by cost/benefit studies. | Alan BR Thomson Milli Gupta Hugh J Freeman | 2012 | World Journal of Gastroenterology2012，18，35： | 3 |
| 15 | Risk factors in familial forms of celiac disease显示文摘Celiac disease has been reported in up to 2% of some European populations. A similar risk has been identified in the America and Australia where immigration of Eu-ropeans has occurred. Moreover, an increasing number of celiac disease patients are being identified in many Asian countries, including China and India. Finally, celiac disease has also been detected in Asian immigrants and their descendants to other countries, such as Canada. Within these so-called 'general' celiac populations, however, there are specific high risk groups that have an even higher prevalence of celiac disease. Indeed, the single most important risk factor for celiac disease is having a first-degree relative with already-defined celiac disease, particularly a sibling. A rate up to 20% or more has been noted. Risk is even greater if a specific family has 2 siblings affected, particularly if a male carries the human leukocyte antigen-DQ2. Both structural changes in the small bowel architecture occur along with func-tional changes in permeability, even in asymptomatic first-degree relatives. Even if celiac disease is not evident, the risk of other autoimmune disorders seems significantly increased in first-degree relatives as well as intestinal lymphoma. Identification of celiac disease is important since recent long-term studies have shown that the mortality of celiac disease is increased, if it is unrecognized and untreated. | Hugh James Freeman | 2010 | World Journal of Gastroenterology2010，16，15： | 3 |
| 16 | Colitis associated with biological agents显示文摘In the past,there has been considerable focus on a host of drugs and chemicals that may produce colonic toxicity.Now,a variety of new biological monoclonal antibody agents,usually administered by infusion,have appeared in the clinical realm over the last decade or so to treat different chronic inflammatory or malignant disorders.For some of these agents,adverse effects have been documented,including apparently new forms of immune-mediated inflammatory bowel disease.In some,only limited symptoms have been recorded,but in others,severe colitis with serious complications,such as bowel perforation has been recorded.In others,adverse effects may have a direct vascular or ischemic basis,while other intestinal effects may be related to a superimposed infection.Some new onset cases of ulcerative colitis or Crohn's disease may also be attributed to the same agents used to treat these diseases,or be responsible for disease exacerbation.Dramatic and well documented side effects have been observed with ipilimumab,a humanized monoclonal antibody developed to reduce and overcome cytotoxic T-lymphocyte antigen 4,a key negative feedback regulator of the T-cell anti-tumor response.This agent has frequently been used in the treatment of different malignancies,notably,malignant melanoma.Side effects with this agent occur in up to 40% and these are believed to be largely immune-mediated.One of these is a form of enterocolitis that may be severe,and occa-sionally,fatal.Other agents include rituximab(an antiCD20 monoclonal antibody),bevacizumab(a monoclonal antibody against the vascular endothelial growth factor) and anti-tumor necrosis factor agents,including infliximab,adalimumab and etanercept. | Hugh James Freeman | 2012 | World Journal of Gastroenterology2012，18，16： | 3 |
| 17 | Hepatobiliary and pancreatic disorders in celiac disease显示文摘许多肝并且胆道混乱可以复杂化乳糜泻的临床的功课。这些中的一些被假设了分享普通基因因素或有普通免疫致病,例如主要胆汁性肝硬变,主要致硬化的胆管炎或胆管炎。在乳糜泻的另外的肝的变化可以与营养不良源于损害滋养的吸收被联系,包括肝的脂肪变性。另外,乳糜泻可以与稀罕肝的复杂并发症被联系,例如肝的 T 房间淋巴瘤。最后,胰腺的外分泌功能可以在乳糜泻被损害并且代表处理失败的一个原因。 | Hugh James Freeman | 2006 | World Journal of Gastroenterology2006，12，10： | 2 |
| 18 | Endocrine manifestations in celiac disease显示文摘Celiac disease(CD) is an autoimmune small intestinal mucosal disorder that often presents with diarrhea, malabsorption and weight loss. Often, one or more associated endocrine disorders may be associated with CD. For this review, methods involved an extensive review of published English-language materials. In children and adolescents, prospective studies have demonstrated a significant relationship to insulindependent or type 1 diabetes, whereas in adults, autoimmune forms of thyroid disease, particularly hypothyroidism, may commonly co-exist. In some with CD, multiple glandular endocrinopathies may also occur and complicate the initial presentation of the intestinal disease. In others presenting with an apparent isolated endocrine disorder, serological screening for underlying subclinical CD may prove to be positive, particularly if type 1 diabetes, autoimmune thyroid or other autoimmune endocrine diseases, such as Addison's disease are first detected. A number of reports have also recorded hypoparathyroidism or hypopituitarism or ovarian failure in CD and these may be improved with a strict gluten-free diet. | Hugh James Freeman | 2016 | World Journal of Gastroenterology2016，22，38： | 2 |
| 19 | Pancreatic endocrine and exocrine changes in celiac disease显示文摘Although there is a great deal of information on celiac disease and associated involvement of other non-intestinal sites,data on concomitant changes in the structure and function of the pancreas is limited. The present review critically examines pancreatic endocrine changes that have been well documented in the literature,including insulin-dependent diabetes mellitus. Pancreatic exocrine alterations may also occur,and if severe,marked malnutrition with pancreatic failure and ductal calcification have been observed. Finally,other pancreatic disorders have been recorded with celiac disease. | Hugh J Freeman | 2007 | World Journal of Gastroenterology2007，13，47： | 2 |
| 20 | Adult celiac disease in the elderly显示文摘There is an increased awareness that celiac disease may occur in the elderly although presentations with either diarrhea, weight loss or both may be less common causing delays in diagnosis for prolonged periods. Higher detection rates also seem evident owing to active case screening, largely through serodiagnostic measures. In some elderly patients who are genetically predisposed, it has been hypothesized that celiac disease might be precipitated late in life by an antigen, possibly from an infectious agent. As a result, peptide mimicry or other poorly-defined mechanisms may precipitate an autoimmune gluten-dependent clinical state. Although diarrhea and weight loss occur, only isolated iron deficiency anemia may be present at the time of initial diagnosis. In addition, the risk of other autoimmune disorders, particularly autoimmune thyroiditis, and bone disease, are increased. Osteopenia may also be associated with an increased risk of fractures. Finally, elderly celiacs have an increased risk of malignant intestinal disease, especially lymphoma. | Hugh James Freeman | 2008 | World Journal of Gastroenterology2008，14，45： | 2 |
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