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Crypt region localization of intestinal stem cells in adults

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World Journal of Gastroenterology 2008年第47期14卷 7160-7162页

作者： Hugh James freeman Department of Medicine(Gastroen-terology) University of British ColumbiaVancouver V6T 1W5Canada

The intestinal epithelial lining plays a central role in the digestion and absorption of nutrients,but exists in a harsh luminal environment that necessitates continual *** renewal process involves epithelial cell proliferation in the crypt base and later cell migration from the crypt base to the luminal *** process is dependent on multi-potent progenitor cells,or stem cells,located in each *** are about 4 to 6 stem cells per crypt,and these stem cells are believed to generate distinct end-differentiated epithelial cell types,including absorptive cells,goblet cells,enteroendocrine cells and Paneth cells,while also maintaining their own progenitor cell *** studies suggested that intestinal stem cells were located either in the crypt base interspersed between the Paneth cells [*** base columnar(CBC) cell model] or at an average position of 4 cells from the crypt base [***-retaining cells(LRC +4) model].Recent studies have employed biomarkers in the in vivo mammalian state to more precisely evaluate the location of these progenitor cells in the intestinal *** notable of these novel markers are Lgr5,a gene that encodes a G-protein-coupled receptor with expression restricted to CBC cells,and Bmi 1,which encodes a chromatin remodeling protein expressed by *** studies raise the possibility that there may be separate stem cell lines or different states of stem cell activation involved in the renewal of normal mammalian intestinal tract.

关键词： Crypt base columnar cells Intestinal epithelial cell renewal Lgr5 gene Polycomb bmil protein Progenitor cells Stem cells +4 stem cellmodel

Adult eosinophilic gastroenteritis and hypereosinophilic syndromes

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World Journal of Gastroenterology 2008年第44期14卷 6771-6773页

作者： Hugh James freeman Department of Medicine (Gastroen-terology) University of British ColumbiaVancouver V6T 1W5Canada

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.

关键词： Eosinophils Eosinophilic gastroenteritis Eosinophilic gastritis Eosinophilic enteritis

Adult autoimmune enteropathy

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World Journal of Gastroenterology 2008年第8期14卷 1156-1158页

作者： Hugh James freeman Department of Medicine (Gastroenterology) University of British Columbia Vancouver BC Canada

Recent reports have suggested that autoimmune enteropathy involving the small bowel may occur in adults as well as in children. Apparently, the endoscopic and histological changes are similar to celiac disease before treatment, but these are not altered by any form of dietary restriction, including a gluten-free diet. As in celiac disease, histologic changes in gastric and colonic biopsies have also been recorded. Anti-enterocyte antibodies detected with immunofluorescent methods have been reported by a few laboratories, but these antibodies appear not to be specific and may simply represent epiphenomena. A widely available, reproducible and quantitative anti-enterocyte antibody assay is needed that could be applied in small bowel disorders that have the histological appearance of celiac disease, but fail to respond to a gluten-free diet.

关键词： Celiac disease Autoimmune enteropathy Anti-enterocyte antibodies Anti-goblet cell antibodies Antibodies in celiac disease

Long-term natural history of Crohn’s disease

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World Journal of Gastroenterology 2009年第11期15卷 1315-1318页

作者： Hugh James freeman Department of Medicine (Gastroen-terology) University of British Columbia Vancouver V6T 1W5 Canada

Crohn’s disease is a chronic inflammatory granulomatous process that usually involves different sites in the intestinal tract. Genetic and environmental factors are thought to play a role in its etiology and pathogenesis. The disorder has a heterogeneous clinical expression and data from tertiary care settings have documented its female predominance, occasional familial nature, and high rate of stricture formation and penetrating disease. It may appear from early childhood to late adulthood, although over 80% are currently diagnosed before age 40 years, usually with terminal ileal and colonic involvement. Several studies have now shown differences in phenotypic clinical expression depending on the initial age at diagnosis, with pediatric-onset disease being more severe and more extensive with more involvement of the upper gastrointestinal tract compared to adult-onset disease. In addition, long- term studies from these tertiary care settings have documented that the disorder may evolve with time into a more complex disease with stricture formation and penetrating disease complications (i.e. fistula and abscess). Although prolonged remission with no evidence of inflammatory disease may occur, discrete periods of symptomatic and active granulomatous inflammatory disease may re-appear over many decades. Long-term studies on the natural history have also suggested that discrete events (or agents) may precipitate this granulomatous inflammatory process.

关键词： Natural history Crohn's disease Age-dependent phenotypes Clinical behavior Granulomatous inflammation

“Melanosis” in the small and large intestine

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World Journal of Gastroenterology 2008年第27期14卷 4296-4299页

作者： Hugh James freeman Department of Medicine (Gastroen- terology) University of British Columbia

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.

关键词： Melanosis Lipofuscin Melanosis coli Constipation Hemosiderin Melanosis ilei Melanosisduodeni Anthraquinones

Colitis associated with biological agents

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World Journal of Gastroenterology 2012年第16期18卷 1871-1874页

作者： Hugh James freeman Division of Gastroenterology Department of MedicineUniversity of British Columbia HospitalVancouverBCV6T 1W5Canada

In the past,there has been considerable focus on a host of drugs and chemicals that may produce colonic ***,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 *** some of these agents,adverse effects have been documented,including apparently new forms of immune-mediated inflammatory bowel *** some,only limited symptoms have been recorded,but in others,severe colitis with serious complications,such as bowel perforation has been *** others,adverse effects may have a direct vascular or ischemic basis,while other intestinal effects may be related to a superimposed *** 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 *** 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 *** agent has frequently been used in the treatment of different malignancies,notably,malignant *** effects with this agent occur in up to 40% and these are believed to be largely *** of these is a form of enterocolitis that may be severe,and occa-sionally,*** 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.

关键词： Biological agents Colitis Crohn's disease Inflammatory bowel disease Infliximab Ipilimumab Rituximab Ulcerative colitis

Heterogeneity of colorectal adenomas, the serrated adenoma, and implications for screening and surveillance

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World Journal of Gastroenterology 2008年第22期14卷 3461-3463页

作者： Hugh James freeman Department of Medicine (Gastroen-terology) University of British Columbia Vancouver V6T 1W5 Canada

Current algorithms for screening and surveillance for colon cancer are valuable, but may be limited by the underlying nature of the targeted neoplastic lesions. Although part of the success of adenoma removal relates to interruption of so-called "adenoma-carcinoma sequence", an alternate serrated pathway to colon cancer may pose difficulties with the ultimate results achieved by traditional colonoscopic methods. The endpoint carcinoma in this unique pathway may be derived from a dysplastic serrated adenoma. These tend to be located primarily in the right colon, especially in females, and are frequently associated with co-existent colon cancer. Unfortunately, however, there are few, if any, other identifiable risk factors, including age or family history of colon polyps or colon cancer. Moreover, this alternate serrated pathway may itself also be quite biologically heterogeneous as reflected in sessile serrated adenomas (SSA) with virtually exclusive molecular signatures defined by the presence of either BRAF or KRAS mutations. Screening algorithms in the future may need to be modified and individualized, depending on new information that likely will emerge on the natural history of these biologically heterogeneous lesions that differs from traditional adenomatous polyps.

关键词： Colorectal adenomas Serrated polyps Polyp Heterogeneity Colonoscopy Screening Colorectal Cancer

Intraductal papillary mucinous neoplasms and other pancreatic cystic lesions

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World Journal of Gastroenterology 2008年第19期14卷 2977-2979页

作者： Hugh James freeman Department of Medicine (Gastroen-terology) University of British Columbia

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.

关键词： Pancreatic cancer Pancreatic intraductal papillary mucinous neoplasms Mucinous cystic neoplasm of pancreas Serous cystadenoma Pancreatic cysticlesions

The spirit of Henry Norman Bethune and gastroenterology

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World Journal of Gastroenterology 2008年第2期14卷 174-179页

作者： Hugh J freeman Department of Medicine University of British Columbia Vancouver BC Canada

Henry Norman Bethune was a physician and surgeon from Canada. He had a highly impressive medical career in Montreal but did his most important work in China where he cared for soldiers on the battlefield. He died in 1939 and was recognized as a hero, but only much later received recognition in Canada. He was a skilled doctor, both as a physician and as a surgeon. However, he was much more and will serve as an inspiration for this series. He was an innovator, an idealist and a perfectionist. It is hoped that this series will gather expert commentaries on a range of issues critical to the subspecialty from fundamental science to clinical care so that future directions can be defined.

关键词： Bethune Gastroenterology China Canada Battlefield surgery