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1.  Corrigendum 
PMCID: PMC3472916
2.  CAG News Page 
PMCID: PMC3299232
4.  Clinical significance of autoantibodies to p53 protein in patients with autoimmune liver diseases 
Mutations in the p53 gene leading to conformational changes in the p53 protein have been well established in many human cancers. Conformational changes and/or cellular accumulation of the protein may induce an immune response, resulting in circulating autoantibodies to p53, which have been documented in several types of cancers. Although rarely associated with autoimmune disease, a few reports have documented titres of anti-p53 autoantibodies in patients with autoimmune hepatitis and primary biliary cirrhosis. The clinical relevance of circulating autoantibodies to p53, therefore, remains unclear. Accordingly, this study aimed to examine the prevalence and clinical relevance of anti-p53 autoantibodies in patients with selected autoimmune liver diseases.
BACKGROUND:
Autoantibodies to p53 (anti-p53) are rarely present in the sera of patients with autoimmune diseases or the sera of patients with malignancies.
OBJECTIVE:
To examine the prevalence of anti-p53 in patients with autoimmune liver disease including autoimmune hepatitis (AIH), primary biliary cirrhosis (PBC), AIH/PBC overlap syndrome (AIH/PBC OS) and primary sclerosing cholangitis (PSC), and to determine the clinical significance of anti-p53 in autoimmune liver diseases.
METHODS:
Forty patients with AIH, 41 patients with PBC, eight patients with AIH/PBC OS and five patients with PSC were enrolled. Anti-p53 and antibodies to double-stranded DNA (anti-ds-DNA) were analyzed using commercially available ELISA kits. Demographic, laboratory and histological data were compared between the AIH groups seropositive and seronegative for anti-p53.
RESULTS:
Six of 40 (15.0%) patients with AIH and four of eight (50.0%) patients with AIH/PBC OS were positive for anti-p53. One of 41 (2.4%) patients with PBC was also positive for anti-p53, but all five patients with PSC were negative, indicating a significantly higher prevalence of anti-p53 in patients with AIH or AIH/PBC OS compared with patients with PBC. None of the AIH patients positive for anti-p53 progressed to hepatic failure or relapsed after immunosuppressive treatment. Titres of anti-ds-DNA in patients with AIH and AIH/PBC OS significantly correlated with titres of anti-p53 (r=0.511; P=0.0213).
CONCLUSION:
The emergence of anti-p53 is likely to be useful for discriminating AIH or AIH/PBC OS from PBC and helpful for predicting favourable prognoses in patients with AIH. DNA damage may trigger the production of anti-p53 in patients with AIH or AIH/PBC OS.
PMCID: PMC3299234  PMID: 22408762
Antibodies to ds-DNA; Antibodies to p53; Autoimmune hepatitis; Primary biliary cirrhosis
5.  FIT to be tried 
PMCID: PMC3299235  PMID: 22408763
6.  Fecal immunochemical tests compared with guaiac fecal occult blood tests for population-based colorectal cancer screening 
More than 10% of cancer deaths in Canadian men and women are attributed to colorectal cancer. Moreover, the incidence and mortality rates of CRC in Canada are among the highest in the world. Evidence gained from randomized controlled trials conducted over the past two decades has supported screening as the best tool to decrease the burden of disease. Since 2008, Ontario’s ColonCancerCheck Program has used a test kit based on the guaiac fecal occult blood test (gFOBT). At the time the gFOBT was approved for use, however, the fecal immunochemical test (FIT) was undergoing evaluation in various settings. In 2010, Cancer Care Ontario’s FIT Guidelines Expert Panel was convened to evaluate the current evidence concerning FIT to inform the decision on how to replace the gFOBT with the FIT in Ontario’s ColonCancerCheck Program. The focus of this article is on the 13 FIT kits currently approved in Canada for processing in a laboratory setting.
Colorectal cancer (CRC) is the second most common cause of cancer deaths in Canadian men and women – accounting for almost 12% of all cancer deaths. In Ontario, it is estimated that 8100 persons were diagnosed with CRC in 2011, and 3250 died from the disease. CRC incidence and mortality rates in Ontario are among the highest in the world. Screening offers the best opportunity to reduce this burden of disease. The present report describes the findings and recommendations of Cancer Care Ontario’s Fecal Immunochemical Tests (FIT) Guidelines Expert Panel, which was convened in September 2010 by the Program in Evidence-Based Care. The purpose of the present guideline is to evaluate the existing evidence concerning FIT to inform the decision on how to replace the current guaiac fecal occult blood test with FIT in the Ontario ColonCancerCheck Program. Eleven articles were included in the present guideline, comprising two systematic reviews, five articles reporting on three randomized controlled trials and reports of four other studies. Additionally, one laboratory study was obtained that reported on several parameters of FIT tests that helped to inform the present recommendation. The performance of FIT is superior to the standard guaiac fecal occult blood test in terms of screening participation rates and the detection of CRC and advanced adenoma. Given greater specimen instability with the use of FIT, a pilot study should be undertaken to determine how to implement the FIT in Ontario.
PMCID: PMC3299236  PMID: 22408764
Cancer Care Ontario; Colorectal cancer screening; Fecal immunochemical tests; Guaiac fecal occult blood test
7.  Reassessing the role for lamivudine in chronic hepatitis B infection: A four-year cohort analysis 
The data supporting the use of antiviral agents other than lamivudine in the management of patients with hepatitis B virus (HBV) infection are based on highly selected clinical trial populations that may not be representative of typical HBV-infected populations encountered in many clinics. Despite its limitations, however, lamivudine is relatively inexpensive and widely available and, in carefully selected patients, can still be successfully used to achieve long-term HBV suppression. This study investigated the long-term effectiveness of lamivudine in an adherent, frequently monitored, noninvestigational HBV-infected cohort.
BACKGROUND/OBJECTIVES:
Lamivudine is readily available and inexpensive. Guidelines recommend other antiviral medications because they achieve superior virological suppression with less resistance. These data are based on clinical trial populations and may not be representative of typical hepatitis B virus (HBV) populations. The authors assessed lamivudine in maintaining long-term viral suppression in an adherent, frequently monitored, noninvestigational HBV-infected population.
METHODS:
All HBV patients (n=369) between 2000 and 2010 were evaluated in a retrospective, single-centre study. Virological response was defined by complete suppression of HBV DNA (<400 copies/mL) and was assessed at six to 12 month intervals over four years. Enzymatic and serological outcomes, as well as treatment failures were assessed.
RESULTS:
Forty-seven patients (36 men; mean age 44 years, mean alanine aminotransferase level 123 U/L; METAVIR stage 3/4 [n=21], treatment naive [n=41]) received lamivudine 100 mg to 300 mg daily. The mean pretreatment viremia was 5.19 log10 copies/mL, and was above the limit of detection (>6.91 log10 copies/mL) in 11 patients (23%). The mean (± SD) dosing duration was 32±22 months. Virological suppression was achieved in 45 (96%) patients. Mean viremia declined to 3.06 log10 copies/mL (n=27) and 2.68 log10 copies/mL (n=18) at 12 and 48 months, respectively, with 78% and 88% with undetectable viremia at these time points, respectively. The mean alanine aminotransferase level declined to 31 U/L and 36 U/L at 12 and 48 months, respectively. Seven of 13 (54%) hepatitis B e antigen-positive patients seroconverted. The treatment failure rate was 11%.
CONCLUSIONS:
In a selected group of HBV patients, successful long-term viremia suppression was achieved with low treatment failure rates. With strict dosing adherence and monitoring for virological breakthrough, sustained virological suppression can be reliably achieved with lamivudine in carefully selected patients.
PMCID: PMC3299237  PMID: 22408765
3TC; Antivirals; HBV; Heptovir; Lamivudine; Viremia
8.  Safety of esophagogastroduodenoscopy within 30 days of myocardial infarction: A retrospective cohort study from a Canadian tertiary centre 
Patients who experience gastrointestinal bleeding after myocardial infarction (MI) often have comorbidities that could place them at increased risk of complications if evaluative endoscopy were to be performed. Although esophagogastroduodenoscopy is considered to be generally safe in high-risk individuals, some post-MI patients may be more susceptible to a variety of cardiopulmonary complications. This cohort study examined cardiopulmonary safety in post-MI patients and evaluated specific predictors of complications of post-MI endoscopy.
BACKGROUND:
Patients who experience myocardial infarction (MI) are at risk of gastrointestinal (GI) bleeding complications. Endoscopic evaluation may lead to cardiopulmonary complications. Guidelines and studies regarding the safety of endoscopy in this population are limited.
OBJECTIVE:
To evaluate the safety of endoscopy in a retrospective cohort of post-MI patients at a Canadian tertiary centre.
METHODS:
Using hospital diagnostic/procedure codes, the charts of patients meeting the inclusion criteria of having ST elevation MI or non-ST elevation MI, and GI bleeding detected at endoscopy were reviewed. The information retrieved included demographics, medical history, medications, endoscopy details and cardiopulmonary/GI events.
RESULTS:
A total of 121 patients experienced an MI and underwent endoscopy within 30 days. However, only 44 met the inclusion criteria and were reviewed. The mean age of the patients was 75 years, and 55% were female. The mean hemoglobin level was 86 g/L, and 38 of 44 patients required a transfusion. Comorbidities included hypertension (82%), diabetes (46%), heart failure (55%), stroke (21%), lung disease (27%), previous MI (46%), cardiac bypass surgery (30%), history of GI bleed (25%), history of ulcer (18%) and ejection fraction <50% (48%). The median number of days to endoscopy after MI was three. Complications included seven patients with acute coronary syndrome, one with arrhythmia, one with respiratory failure, one with aspiration pneumonia and two with perforation. Age, hemoglobin level or timing of endoscopy did not significantly predict a complication.
CONCLUSIONS:
Patients with GI bleeding after MI often have comorbidities and are on antiplatelet agents. Endoscopy is a valuable tool in the diagnosis and management of bleeding complications, but must be weighed against the potential risk of other complications, which in the present study occurred in more than 25% of procedures.
PMCID: PMC3299238  PMID: 22408766
Acute myocardial infarction; Complication; Gastrointestinal endoscopy; Safety
9.  The utility of Xenon-133 liver scan in the diagnosis and management of nonalcoholic fatty liver disease 
Nonalcoholic fatty liver disease (NAFLD) encompasses a wide spectrum of liver damage and is the most common cause of chronic liver diseases in Western countries. Although a relatively common condition affecting approximately 20% of the general population, NAFLD is especially prevalent in obese individuals, a figure likely to rise as obesity rates in Western countries continue to increase. Liver biopsy remains the gold standard diagnostic method; however, its invasive nature, among other factors, has prompted the need to develop less invasive, alternative methods to quantify hepatic fat and determine disease severity. Xenon-133 liver scanning is one such method that has been in use for more than 10 years in the evaluation of patients with suspected NAFLD. This study compared Xenon-133 liver scan with other currently used, invasive and noninvasive methods of liver assessment.
BACKGROUND:
Nonalcoholic fatty liver disease (NAFLD) is an important and common condition affecting approximately 20% of the general population. Given the limitation of radiological investigations, diagnosis often requires a liver biopsy.
OBJECTIVE:
To compare Xenon-133 (Xe-133) liver scanning with ultrasonography in the diagnosis of NAFLD.
METHODS:
From January 2003 to February 2007, 258 consecutive patients with suspected NAFLD underwent Xe-133 liver scanning at Royal Victoria Hospital (Montreal, Quebec). Of these, 43 patients underwent ultrasonography and liver biopsy for the evaluation of NAFLD. Patients with other liver diseases and significant alcohol consumption were excluded. Two nuclear medicine physicians assessed liver Xe-133 uptake and measured the grade of steatosis using a standardized protocol. The degree of steatosis was determined from biopsy specimens assessed by two hepatopathologists.
RESULTS:
NAFLD was identified by liver biopsy in 35 of 43 patients (81.4%). Xe-133 scan demonstrated 94.3% sensitivity (95% CI 81.4% to 98.4%) and 87.5% specificity (95% CI 52.9% to 99.4%) for the presence of NAFLD. The positive and negative predictive values for detection of steatosis by Xe-133 scan were 97.1% (95% CI 85.1% to 99.8%) and 77.8% (95% CI 45.3% to 93.7%), respectively. The positive and negative likelihood ratios were 7.54 (95% CI 1.20 to 47.26) and 0.07 (95% CI 0.02 to 0.26), respectively. Two patients with NAFLD (5.7%) who had a negative Xe-133 scan result had histologically mild steatosis (<10%). The grade of steatosis on liver biopsy was highly correlated with the results of the Xe-133 scan (r=0.87; P<0.001). The sensitivity and specificity of ultrasound in diagnosing steatosis were 62.9% and 75%, respectively.
CONCLUSION:
Xe-133 liver scan proved to be a safe, reliable, non-invasive method for diagnosing and quantifying hepatic steatosis, and was superior to ultrasound.
PMCID: PMC3299239  PMID: 22408767
Nonalcoholic fatty liver disease; Ultrasonography; Xenon-133 liver scan
11.  An era of safety culture 
PMCID: PMC3275407  PMID: 22312604
12.  Indicators of safety compromise in gastrointestinal endoscopy 
The growth in the use of endoscopy to diagnose and treat many gastointestinal disorders, and its central role in cancer screening programs, has led to a significant increase in the number of procedures performed. This growth, however, has also led to many variations in, among others, the provision of services, the choice of sedative medications and the training of providers. The recognition of the significance of quality in endoscopy has prompted several countries, including Canada, to initiate efforts to adopt nationwide quality improvement programs. The Canadian Association of Gastroenterology formed a committee to review endoscopy and quality with the aim of stimulating improvement. This article focuses specifically on patient safety indicators that were developed at a consensus conference aimed at generating a broad range of recommendations for selected endoscopic procedures, which if adopted, could lead to significant changes in how endoscopy services are provided.
INTRODUCTION:
The importance of quality indicators has become increasingly recognized in gastrointestinal endoscopy. Patient safety requires the identification and monitoring of occurrences associated with harm or the potential for harm. The identification of relevant indicators of safety compromise is, therefore, a critical element that is key to the effective implementation of endoscopy quality improvement programs.
OBJECTIVE:
To identify key indicators of safety compromise in gastrointestinal endoscopy.
METHODS:
The Canadian Association of Gastroenterology Safety and Quality Indicators in Endoscopy Consensus Group was formed to address issues of quality in endoscopy. A subcommittee was formed to identify key safety indicators. A systematic literature review was undertaken, and articles pertinent to safety in endoscopy were identified and reviewed. All complications and measures used to document safety were recorded. From this, a preliminary list of 16 indicators was compiled and presented to the 35-person consensus group during a three-day meeting. A revised list of 20 items was subsequently put to the consensus group for vote for inclusion on the final list of safety indicators. Items were retained only if the consensus group highly agreed on their importance.
RESULTS:
A total of 19 indicators of safety compromise were retained and grouped into the three following categories: medication-related – the need for CPR, use of reversal agents, hypoxia, hypotension, hypertension, sedation doses in patients older than 70 years of age, allergic reactions and laryngospasm/bronchospasm; procedure-related early – perforation, immediate postpolypectomy bleeding, need for hospital admission or transfer to emergency department from the gastroenterology unit, instrument impaction, severe persistent abdominal pain requiring evaluation proven to not be perforation; and procedure-related delayed – death within 30 days of procedure, 14-day unplanned hospitalization, 14-day unplanned contact with a health provider, gastrointestinal bleeding within 14 days of procedure, infection or symptomatic metabolic complications.
CONCLUSIONS:
The 19 indicators of safety compromise in endoscopy, identified by a rigorous, evidence-based consensus process, provide clear outcomes to be recorded by all facilities as part of their continuing quality improvement programs.
PMCID: PMC3275408  PMID: 22312605
Digestive system; Endoscopy; Health care; Quality assurance; Surgical complications; Safety
13.  Awareness of postpolypectomy surveillance guidelines: A nationwide survey of colonoscopists in Canada 
Several studies have demonstrated that screening asymptomatic, average-risk individuals and those at increased risk can reduce colorectal cancer mortality. Adherence to postpolypectomy surveillance guidelines becomes increasingly important amid the increasing demands for colonoscopy because suboptimal compliance can lead to unnecessary risks and the ineffective use of resources. However, performing too many surveillance colonoscopies, or at intervals that are too short, may hinder access to endoscopic procedures and decrease the cost effectiveness of colorectal cancer screening programs. Two reasons appear to be primarily responsible for nonadherence to postpolypectomy guidelines: lack of awareness or familiarity, and disagreement with the guidelines. Accordingly, this study aimed to determine the awareness of postpolypectomy guidelines among members of the Canadian Association of Gastroenterology, and the factors associated with physicians’ choices to deviate from them.
INTRODUCTION:
Due to the increasing demand for colonoscopy, adherence to postpolypectomy surveillance guidelines is important. Suboptimal compliance can lead to unnecessary risks and ineffective use of resources.
OBJECTIVE:
To determine the awareness of and adherence to postpolypectomy surveillance guidelines among members of the Canadian Association of Gastroenterology (CAG).
METHODS:
A survey describing 14 clinical cases was mailed to all physician members (n=411) of the CAG. Respondents were required to recommend a surveillance interval and a reason for his or her choice.
RESULTS:
A total of 150 colonoscopists (37%) completed the survey. Adherence to the guidelines varied from 23% to 96% per clinical scenario (median 63%). Recommended surveillance intervals were too short in 0% to 60% of the different cases (median 8%). The recommended interval was most often (60%) too short for a patient with one tubular adenoma with high-grade dysplasia. Surveillance intervals were too long in 4% to 75% of the cases (median 9%). The recommended interval was most often too long in a patient with a villous adenoma 15 mm in size and removed piecemeal (75%). Most often, recommendations were reported to be based on guidelines (median 74%; range 31% to 94%). However, in nine of 14 cases, more than 10% (median 18%; range 12% to 38%) of the respondents stated that their recommendation was based on guidelines, but did not provide the appropriate surveillance interval.
CONCLUSIONS:
Compliance to colonoscopy surveillance guidelines is suboptimal and reflects both overuse and underuse. The results show that awareness about the content of guidelines needs to be raised and strategies implemented to increase adherence.
PMCID: PMC3275409  PMID: 22312606
Adenomatous polyps; Cancer prevention; Colonoscopy; Guidelines; Surveillance
14.  Antibiotic prophylaxis in transarterial therapy of hepatocellular carcinoma: A meta-analysis 
Transarterial therapies, either alone or in conjunction with adjuvant therapies, have been demonstrated to improve survival rates in patients with hepatocellular carcinoma (HCC). Although generally well tolerated and widely used for more than two decades, transarterial procedures have been reported to be associated with several infectious complications when performed in patients with HCC. However, the question of whether antibiotic prophylaxis is necessary for patients undergoing transarterial procedures for HCC remains controversial. Accordingly, this meta-analysis examined clinical trial evidence regarding the effects of prophylactic antibiotic therapy versus no prophylactic treatment with respect to infectious complications in patients undergoing transarterial therapy for HCC.
BACKGROUND:
The use of prophylactic antibiotics against postprocedure infection in patients undergoing transarterial therapy for hepatocellular carcinoma is controversial.
AIM:
To compare the effects of prophylactic antibiotic treatment and no prophylactic antibiotic treatment on infectious complications following transarterial procedures.
METHODS:
Clinical trials fulfilling predefined selection criteria were identified by searching several bibliographic databases; a meta-analysis was performed where appropriate.
RESULTS:
Four trials of inadequate quality consisting of 210 patients were included in the analysis. Only one case of possible postprocedure infection in each group was reported. The rate of patients developing fever (RR 0.91 [95% CI 0.61 to 1.35]), changes in peripheral white blood cell count or serum C-reactive protein levels, and the mean length of hospital stay (mean difference 0.20 [95% CI 0.75 to 1.14]) showed no significant intergroup differences between antibiotic and no antibiotic treatment. Furthermore, the results of the present study indicated that the incidence of bacteremia, septicemia, sepsis or hepatic abscess after transarterial therapy was rare.
CONCLUSION:
Antibiotic prophylaxis in patients undergoing transarterial therapy for hepatocellular carcinoma may not be routinely necessary. However, a more judicious use of antibiotics is recommended for patients who are at an increased risk of infection. Nevertheless, prospective trials on a larger scale are clearly needed.
PMCID: PMC3275410  PMID: 22312607
Antibiotic prophylaxis; Hepatocellular carcinoma; Infection; Meta-analysis; Transarterial therapy
15.  Current considerations in direct percutaneous endoscopic jejunostomy 
For patients who are unable to meet their nutritional needs orally, enteral feeding via a percutaneous approach has become the mainstay of therapy. However, traditional enteral feeding methods, such as percutaneous endoscopic gastrostomy, may not be viable options for patients with severe gastroparesis or gastric outlet obstruction. Direct percutaneous endoscopic jejunostomy (DPEJ) is an enteral access method that was first described more than 20 years ago and has gained popularity among gastroenterologists. This review discusses the indications for and contraindications to DPEJ, the procedure, the application of DPEJ in specific subsets of patients with gastrointestinal disorders, and presents a brief tabular summary of complications and success rates of DPEJ in case series published since 2000.
BACKGROUND:
Direct percutaneous endoscopic jejunostomy (DPEJ) is a well-known approach to deliver postpyloric enteral nutritional support to individuals who cannot tolerate gastric feeding. However, it is technically difficult, and some case series have reported significant procedural failure rates. The present article describes current indications, successes and complications of DPEJ placement
METHODS:
A MEDLINE database search was performed to identify relevant articles using the key words “direct percutaneous endoscopic jejunostomy”, “percutaneous endoscopic gastrostomy”, and “percutaneous endoscopic gastrostomy with a jejunal extension tube”. Additional articles were identified by a manual search of the references cited in the key articles obtained in the primary search.
RESULTS:
DPEJ is gradually becoming more common in the treatment of patients who cannot tolerate gastric feeding. Differences in patient selection and technique modifications may contribute to the various success rates reported. Failure is most often due to inadequate transillumination or gastroduodenal obstruction. Currently, there are limited data to evaluate the safety and effectiveness of DPEJ.
CONCLUSION:
The clinical use of DPEJ is increasing. With appropriate care and expertise, DPEJ may prove to be reliable and safe.
PMCID: PMC3275411  PMID: 22312608
Adverse events; Application; Direct percutaneous endoscopic jejunostomy; Percutaneous endoscopic gastrostomy
16.  Helicobacter pylori in First Nations and recent immigrant populations in Canada 
Despite the decreasing prevalence of Helicobacter pylori infection among most of the Canadian population, it remains high among Aboriginals and recent immigrants. Given the health risks and complications associated with H pylori infection, measures aimed at eradicating H pylori are especially useful, particularly in vulnerable groups, and even more so if they lead to a reduction in the conditions that predispose individuals to gastric cancer. Following a brief discussion on the pathogenic role of H pylori, the prevalence and epidemiology of H pylori infection, and the associated health consequences, this article reviews a conference held by the Canadian Helicobacter Study Group in October 2010, which gathered a panel of experts in several fields to address the health risks of H pylori infection in at-risk populations and the potential benefits of adopting an eradication strategy.
The diminishing prevalence of Helicobacter pylori infection among most segments of the Canadian population has led to changes in the etiologies and patterns of associated upper gastrointestinal diseases, including fewer peptic ulcers and their complications. Canadian Aboriginals and recent immigrants are among populations in which the prevalence of H pylori infection remains high and, therefore, the health risks imposed by H pylori remain a significant concern. Population-based strategies for H pylori eradication in groups with a low prevalence of infection are unlikely to be cost effective, but such measures are attractive in groups in which the prevalence rates of infection remain substantial. In addition to a lower prevalence of peptic ulcers and dyspepsia, the public health value of eradication may be particularly important if this leads to a reduction in the prevalence of gastric cancer in high prevalence groups. Therefore The Canadian Helicobacter Study Group held a conference that brought together experts in the field to address these issues, the results of which are reviewed in the present article. Canadians with the highest prevalence of H pylori infection are an appropriate focus for considering the health advantages of eradicating persistent infection. In Canadian communities with a high prevalence of both H pylori and gastric cancer, there remains an opportunity to test the hypothesis that H pylori infection is a treatable risk factor for malignancy.
PMCID: PMC3275412  PMID: 22312609
Gastric cancer; Helicobacter pylori; Immigrants; Native Canadians
17.  Discovery and verification of gelsolin as a potential biomarker of colorectal adenocarcinoma in a Chinese population: Examining differential protein expression using an iTRAQ labelling-based proteomics approach 
Despite the wide range of available colorectal cancer (CRC) screening tests, less than 50% of cases are detected at early stages. However, the identification of differentially expressed proteins or novel protein biomarkers in CRC may have some utility and, ultimately, improve patient care and survival. Proteomics combined with mass spectroscopy and liquid chromatography are emerging as powerful tools that have led to the discovery of potential markers in cancer biomarker discovery in several types of cancers. This article describes a novel technology that uses isotopic reagents to tag selected proteins that show a consistent pattern of differential expression in CRC.
OBJECTIVE:
To identify and validate potential biomarkers of colorectal adenocarcinoma using a proteomic approach.
METHODS:
Multidimensional liquid chromatography/mass spectrometry was used to analyze biological samples labelled with isobaric mass tags for relative and absolute quantitation to identify differentially expressed proteins in human colorectal adenocarcinoma and paired normal mucosa for the discovery of cancerous biomarkers. Cancerous and noncancerous samples were compared using online and offline separation. Protein identification was performed using mass spectrometry. The downregulation of gelsolin protein in colorectal adenocarcinoma samples was confirmed by Western blot analysis and validated using immunohistochemistry.
RESULTS:
A total of 802 nonredundant proteins were identified in colorectal adenocarcinoma samples, 82 of which fell outside the expression range of 0.8 to 1.2, and were considered to be potential cancer-specific proteins. Immunohistochemistry revealed a complete absence of gelsolin expression in 86.89% of samples and a reduction of expression in 13.11% of samples, yielding a sensitivity of 86.89% and a specificity of 100% for distinguishing colorectal adenocarcinoma from normal tissue.
CONCLUSIONS:
These findings suggest that decreased expression of gelsolin is a potential biomarker of colorectal adenocarcinoma.
PMCID: PMC3275404  PMID: 22288069
Biomarker; Colorectal cancer; Gelsolin; Proteomic
21.  Canadian Association of Gastroenterology consensus guidelines on safety and quality indicators in endoscopy 
Several organizations worldwide have developed procedure-based guidelines and/or position statements regarding various aspects of quality and safety indicators, and credentialing for endoscopy. Although important, they do not specifically address patient needs or provide a framework for their adoption in the context of endoscopy services. The consensus guidelines reported in this article, however, aimed to identify processes and indicators relevant to the provision of high-quality endoscopy services that will support ongoing quality improvement across many jurisdictions, specifically in the areas of ethics, facility standards and policies, quality assurance, training and education, reporting standards and patient perceptions.
BACKGROUND:
Increasing use of gastrointestinal endoscopy, particularly for colorectal cancer screening, and increasing emphasis on health care quality, highlight the need for clearly defined, evidence-based processes to support quality improvement in endoscopy.
OBJECTIVE:
To identify processes and indicators of quality and safety relevant to high-quality endoscopy service delivery.
METHODS:
A multidisciplinary group of 35 voting participants developed recommendation statements and performance indicators. Systematic literature searches generated 50 initial statements that were revised iteratively following a modified Delphi approach using a web-based evaluation and voting tool. Statement development and evidence evaluation followed the AGREE (Appraisal of Guidelines, REsearch and Evaluation) and GRADE (Grading of Recommendations, Assessment, Development and Evaluation) guidelines. At the consensus conference, participants voted anonymously on all statements using a 6-point scale. Subsequent web-based voting evaluated recommendations for specific, individual quality indicators, safety indicators and mandatory endoscopy reporting fields. Consensus was defined a priori as agreement by 80% of participants.
RESULTS:
Consensus was reached on 23 recommendation statements addressing the following: ethics (statement 1: agreement 100%), facility standards and policies (statements 2 to 9: 90% to 100%), quality assurance (statements 10 to 13: 94% to 100%), training, education, competency and privileges (statements 14 to 19: 97% to 100%), endoscopy reporting standards (statements 20 and 21: 97% to 100%) and patient perceptions (statements 22 and 23: 100%). Additionally, 18 quality indicators (agreement 83% to 100%), 20 safety indicators (agreement 77% to 100%) and 23 recommended endoscopy-reporting elements (agreement 91% to 100%) were identified.
DISCUSSION:
The consensus process identified a clear need for high-quality clinical and outcomes research to support quality improvement in the delivery of endoscopy services.
CONCLUSIONS:
The guidelines support quality improvement in endoscopy by providing explicit recommendations on systematic monitoring, assessment and modification of endoscopy service delivery to yield benefits for all patients affected by the practice of gastrointestinal endoscopy.
PMCID: PMC3275402  PMID: 22308578
Digestive system; Endoscopy; Guideline; Health care; Quality assurance
22.  Losartan reduces trinitrobenzene sulphonic acid-induced colorectal fibrosis in rats 
Intestinal fibrosis – a chronic and progressive process mediated by several factors – occurs in several fibrostenosing enteropathies, but most frequently in patients with Crohn’s disease (CD). Despite the advances made in the understanding of CD and its management over the past 20 years, surgical intervention remains the only treatment strategy for patients with fibrostenosing CD. The results of several studies, however, have suggested that fibrosis may be a reversible and/or preventable phenomenon. Following an overview summarizing the contemporary knowledge regarding the cellular, cytokine and growth factor interactions that contribute to inflammation and the progression of fibrosis, this article describes an experimental animal model of colitis resembling human CD, which the authors used to investigate whether losartan, an angiotensin II receptor antagonist, could be used as a prophylactic agent to reduce the risk of intestinal fibrosis and strictures in patients with CD.
BACKGROUND:
Intestinal fibrosis is a challenging clinical condition in several fibrostenosing enteropathies, particularly Crohn’s disease. Currently, no effective preventive measures or medical therapies are available for intestinal fibrosis. Fibrosis, due to an abnormal accumulation of extracellular matrix proteins, is a chronic and progressive process mediated by cell/matrix/cytokine and growth factor interactions, but may be a reversible phenomenon. Of the several molecules regulating fibrogenesis, transforming growth factor-beta 1 (TGF-β1) appears to play a pivotal role; it is strongly induced by the local activation of angiotensin II. The levels of both TGF-β1 and angiotensin II are elevated in fibrostenosing Crohn’s disease.
AIMS:
To evaluate the in vivo effect of losartan – an angiotensin II receptor antagonist – on the course of chronic colitis-associated fibrosis and on TGF-β1 expression.
METHODS:
Colitis was induced by intrarectal instillation of trinitrobenzene sulphonic acid (TNBS) (15 mg/mL) while losartan was administered orally daily by gavage (7 mg/kg/day) for 21 days. Three groups of rats were evaluated: control (n=10); TNBS treated (n=10); and TNBS + losartan treated (n=10). Inflammation and fibrosis of the colon were evaluated by macro- and microscopic score analysis. Colonic TGF-β1 levels was measured using ELISA.
RESULTS:
Twenty-one days after induction, losartan significantly improved the macro- and microscopic scores of fibrosis in the colonic wall and reduced TGF-β1 concentration.
CONCLUSIONS:
Prophylactic oral administration of losartan reduces the colorectal fibrosis complicating the TNBS-induced chronic colitis, an effect that appears to be mediated by a downregulation of TGF-β1 expression.
PMCID: PMC3275403  PMID: 22288068
Angiotensin II receptor antagonist; Experimental colitis; Fibrosis; Inflammatory bowel disease; Losartan; TGF-β1; TNBS
23.  CAG News Page 
PMCID: PMC3266152  PMID: 22175051
25.  Letter to the Editor 
PMCID: PMC3266154  PMID: 22175053

Results 1-25 (736)