The association between Helicobacter pylori infection and inflammatory bowel disease based on meta-analysis.

BACKGROUND: In humans there are epidemiological data suggesting a protective effect of Helicobacter pylori (H. pylori) infection against the development of autoimmune diseases and in addition, there are laboratory data illustrating H. pylori's ability to induce immune tolerance and limit inflammatory responses. Thus, numerous observational studies have examined the association between H. pylori infection and inflammatory bowel disease (IBD) with various results. OBJECTIVE: We performed a meta-analysis of available studies to better define the association of H. pylori infection and IBD. METHODS: Medical literature searches for human studies were performed through September 2014, using suitable keywords. In each study the risk ratio (RR) of H. pylori infection in IBD patients vs controls was calculated and pooled estimates were obtained using fixed- or random-effects models as appropriate. Heterogeneity between studies was evaluated using Cochran Q test and I(2) statistics, whereas the likelihood of publication bias was assessed by constructing funnel plots. RESULTS: Thirty-three studies were eligible for meta-analysis, including 4400 IBD patients and 4763 controls. Overall 26.5% of IBD patients were positive for H. pylori infection, compared to 44.7% of individuals in the control group. There was significant heterogeneity in the included studies (Q = 137.2, df (Q) =32, I(2) ( )= 77%, p < 0.001) and therefore the random-effects model of meta-analysis was used. The obtained pool RR estimation was 0.62 (95% confidence interval (CI) 0.55-0.71, test for overall effect Z = -7.04, p < 0.001). There was no evidence of publication bias. CONCLUSION: The results of this meta-analysis showed a significant negative association between H. pylori infection and IBD that supports a possible protective benefit of H. pylori infection against the development of IBD.

The gastrointestinal manifestation of constitutional mismatch repair deficiency syndrome: from a single adenoma to polyposis-like phenotype and early onset cancer.

Data on the clinical presentation of constitutional mismatch repair deficiency syndrome (CMMRD) is accumulating. However, as the extraintestinal manifestations are often fatal and occur at early age, data on the systematic evaluation of the gastrointestinal tract is scarce. Here we describe 11 subjects with verified biallelic carriage and who underwent colonoscopy, upper endoscopy and small bowel evaluation. Five subjects were symptomatic and in six subjects the findings were screen detected. Two subjects had colorectal cancer and few adenomatous polyps (19, 20 years), three subjects had polyposis-like phenotype (13, 14, 16 years), four subjects had few adenomatous polyps (8, 12-14 years) and two subjects had no polyps (both at age 6). Of the three subjects in the polyposis-like group, two subjects had already developed high-grade dysplasia or cancer and one subject had atypical juvenile polyps suggesting juvenile polyposis. Three out of the five subjects that underwent repeated exams had significant findings during short interval. The gastrointestinal manifestations of CMMRD are highly dependent upon age of examination and highly variable. The polyps may also resemble juvenile polyposis. Intensive surveillance according to current guidelines is mandatory.

Validation of the Capsule Endoscopy Crohn's Disease Activity Index (CECDAI or Niv score): a multicenter prospective study.

BACKGROUND AND STUDY AIMS: The Capsule Endoscopy Crohn's Disease Activity Index (CECDAI or Niv score) was devised to measure mucosal disease activity using video capsule endoscopy (VCE). The aim of the current study was to prospectively validate the use of the scoring system in daily practice. METHODS: This was a multicenter, double-blind, prospective, controlled study of VCE videos from 62 consecutive patients with isolated small-bowel Crohn's disease. The CECDAI was designed to evaluate three main parameters of Crohn's disease: inflammation (A), extent of disease (B), and stricture (C), in both the proximal and distal segments of the small bowel. The final score was calculated by adding the two segmental scores: CECDAI = ([A1 × B1] + C1) + ([A2 × B2] + C2). Each examiner in every site interpreted 6 - 10 videos and calculated the CECDAI. The de-identified CD-ROMs were then coded and sent to the principal investigator for CECDAI calculation. RESULTS: The cecum was reached in 72 % and 86 % of examinations, and proximal small-bowel involvement was found in 56 % and 62 % of the patients, according to the site investigators and principal investigator, respectively. Significant correlation was demonstrated between the calculation of the CECDAI by the individual site investigators and that performed by the principal investigator. Overall correlation between endoscopists from the different study centers was good, with r = 0.767 (range 0.717 - 0.985; Kappa 0.66; P < 0.001). There was no correlation between the CECDAI and the Crohn's Disease Activity Index or the Inflammatory Bowel Disease Quality of Life Questionnaire or any of their components. CONCLUSION: A new scoring system of mucosal injury in Crohn's disease of the small intestine, the CECDAI, was validated. Its use in controlled trials and/or regular follow-up of these patients is advocated.

Appropriateness of gastrointestinal consultations for hospitalized patients in an academic medical center.

BACKGROUND: Consultation of experts in the internal medicine or surgery subspecialties is needed in the hospitalized population according to decisions of the house staff. Sometimes the referrals are not justified, consuming time and money without a significant change in the patient outcome. OBJECTIVES: The aim of our retrospective study was to evaluate justification of consecutive referrals of hospitalized patients for gastroenterology consultation. MATERIALS AND METHODS: Request for consultation was deemed not justified when at least one of the following parameters was found: No contribution to case management, discharge before consultation, cancellation at the last minute, and a recommendation for ambulatory management or surgery. RESULTS: In August-September 2006, there were 232 requests for gastroenterology consultations. Of them 127 (54.7%) were men. The average age was 64.13+/-20.33 years. Ninety-four (40.2%) of the cases had been hospitalized because of other reasons than the consultation issue. Consultation was not justified in 60 patients (25.9%). Ambulatory management was a possibility in 151 cases (65.0%). Request for colonoscopy and gastrointestinal background disease were the only significant predictive factors for justification of consultation, P < 0.0001 for both. CONCLUSIONS: In one fourth of the cases, gastroenterology consultation was not justified according to our strict criteria.

European Society of Gastrointestinal Endoscopy (ESGE): recommendations (2009) on clinical use of video capsule endoscopy to investigate small-bowel, esophageal and colonic diseases.

These recommendations on video capsule endoscopy, an emerging technology with an impact on the practice of endoscopy, were developed by the European Society of Gastrointestinal Endoscopy (ESGE) Guidelines Committee. The first draft of each section was prepared by one or two members of the writing team, who were selected as experts on the content of that section on the basis of their published work. They used evidence-based methodology, performing MEDLINE and PubMed literature searches to identify relevant clinical studies. Abstracts from scientific meetings were included only if there was no published full paper on a particular topic. If there was disagreement, the first author of the Guideline made the final decision. Recommendations were graded according to the strength of the supporting evidence. The draft guideline was critically reviewed by all authors and submitted to the ESGE councillors for their critical review before approval of the final document. The ESGE Guidelines Committee acknowledges that this document is based on a critical review of the data available at the time of preparation and that further studies may be needed to clarify some aspects. Moreover, this Guideline may be revised as necessary to account for changes in technology, new data, or other aspects of clinical practice. This document should be regarded as supplying recommendations only to gastroenterologists in providing care to their patients. It is not a set of rules and should not be construed as establishing a legal standard of care, or as encouraging, advocating, requiring, or discouraging any particular treatment. These recommendations must be interpreted according to the clinician's knowledge, expertise, and clinical judgment in the management of individual patients and, if necessary, a course of action that varies from recommendations must be undertaken.

Can patients at high risk for significant colorectal neoplasms and having normal quantitative faecal occult blood test postpone elective colonoscopy?

BACKGROUND: Common reasons for elective screening and surveillance colonoscopy, at predetermined intervals, are family or personal history of colorectal cancer (CRC) or advanced adenoma (AAP). Quantified, human haemoglobin (Hb)-specific, immunochemical faecal occult blood tests (I-FOBT) detect bleeding. AIM: To determine I-FOBT sensitivity for CRC or AAP before elective colonoscopy in patients at high-risk of cancer or advanced adenoma. METHODS: Prospective double-blind study of 1000 ambulatory asymptomatic high-risk patients (555 family history of CRC, 445 surveillance for past neoplasm), who prepared three I-FOBTs before elective colonoscopy. I-FOBTs quantified as ngHb/mL of buffer by OC-MICRO instrument and results >or=50 ngHb/mL considered positive. RESULTS: At colonoscopy, eight patients had CRC, 64 others had AAP. Sensitivity for CRC and/or AAP was the highest, 65.3% (95% CI 54.3, 76.3), when any of the three I-FOBTs was >or=50 ngHb (15.4%), with specificity of 87.5% (95% CI 86.4, 90.5) identifying all CRCs and 62% of AAPs. CONCLUSIONS: All cancers or an AAP were detected every third I-FOBT-positive colonoscopy (47/154), so colonoscopy was potentially not needed at this time in 84.6% (846 patients). I-FOBT screening might provide effective supervision of high-risk patients, delaying unnecessary elective colonoscopies. This favourable evaluation needs confirmation and cost-benefit study by risk-group.

Prospective multicenter performance evaluation of the second-generation colon capsule compared with colonoscopy.

BACKGROUND AND STUDY AIMS: A second-generation capsule endoscopy system, using the PillCam Colon 2, was developed to increase sensitivity for colorectal polyp detection compared with the first-generation system. The performance of this new system is reported. PATIENTS AND METHODS: In a five-center feasibility study, second-generation capsule endoscopy was prospectively compared with conventional colonoscopy as gold standard for the detection of colorectal polyps and other colonic disease, in a cohort of patients scheduled for colonoscopy and having known or suspected colonic disease. Colonoscopy was independently performed within 10 hours after capsule ingestion. Capsule-positive but colonoscopy-negative cases were counted as false-positive. RESULTS: 104 patients (mean age 49.8 years) were enrolled; data from 98 were analyzed. Patient rate for polyps of any size was 44 %, 53 % of these patients having adenomas. No adverse events related to either procedure were reported. The capsule sensitivity for the detection of patients with polyps >or= 6 mm was 89 % (95 % confidence interval [CI] 70 - 97) and for those with polyps >or= 10 mm it was 88 % (95 %CI 56 - 98), with specificities of 76 % (95 %CI 72 - 78) and 89 % (95 %CI 86 - 90), respectively. Both polyps missed by colonoscopy and mismatch in polyp size by study definition lowered specificity. Overall colon cleanliness for capsule endoscopy was adequate in 78 % of patients (95 %CI 68 - 86). CONCLUSIONS: The new second-generation colon capsule endoscopy is a safe and effective method for visualizing the colon and detecting colonic lesions. Sensitivity and specificity for detecting colorectal polyps appear to be very good, suggesting a potential for improved accuracy compared with the first-generation system. Further prospective and comparative studies are needed.

Factors associated with radiation exposure in patients with inflammatory bowel disease.

BACKGROUND: Inflammatory bowel disease (IBD) patients undergo multiple radiological evaluations. AIM: To estimate total and abdominal radiation exposure from diagnostic X-ray investigations in IBD patients and the associated risk factors. METHODS: Patients with Crohn's disease (CD) or ulcerative colitis (UC) treated in the IBD clinic were recruited. Clinical data were extracted from patient files and radiological data were obtained from the central HMO computer data base. RESULTS: A total of 199 CD and 125 UC patients were included. The mean cumulative estimated doses (CED) for CD and UC were 21.1 19.5 and 15.1 20.4 millisieverts (mSv) respectively (P < 0.001). Twenty-three patients (7.1%) had an estimated CED of > or =50 mSv. In multivariate analyses, predictors of increased CED were: surgery (OR 5.68, 95% CI: 2.73-11.8, P < 0.001), CD (OR 2.56, 95% CI: 1.29-5.07, P = 0.007), prednisone use (OR 2.0, 95% CI: 1.11-3.67, P = 0.02), first year of disease (OR 6.4, 95% CI: 1.3-32, P = 0.02) and age in the upper quartile(OR 3.26, 95% CI: 1.68-6.3, P = 0.001). CONCLUSIONS: Diagnosis of CD, IBD-related surgery, prednisone use, first year of diagnosis and age on the upper quartile are independent predictors of increased exposure in IBD patients. Alternative investigations which do not require radiation exposure should be considered for patients at risk for increased radiation exposure.

Identification of colorectal adenomas by a quantitative immunochemical faecal occult blood screening test depends on adenoma characteristics, development threshold used and number of tests performed.

BACKGROUND: Faecal occult blood tests (FOBT) are faulted by low sensitivity for advanced adenomatous polyps (AAP). Quantified, immunochemical, haemoglobin (Hb)-specific immunochemical FOBT (I-FOBT) measurements are now used for colorectal screening. AIMS: To correlate adenoma characteristics to amount of faecal Hb lost and to evaluate sensitivity and specificity for AAP by faecal Hb development threshold used and number of I-FOBTs collected. METHODS: Three daily I-FOBTs were collected and analysed in 1221 patients scheduled for colonoscopy. Faecal Hb was analysed as ngHb/mL of buffer and the highest result related to colonoscopy findings. RESULTS: In 1204 patients without cancer, colonoscopy identified adenomas in 294, 99 with AAPs. Adenoma patients had elevated faecal Hb increasing with advanced histology, size, pedunculated shape and multiplicity (P < 0.001 for all). At 50 ngHb/mL threshold, sensitivity and specificity for AAPs were 54.5% (95%CI 44.7, 64.7) and 88.1% (95%CI 86.2, 90.1) for three tests. At higher thresholds, sensitivity decreased, but was significantly higher with more samples collected. Conversely, specificity increased at higher thresholds, but decreased with more samples. CONCLUSIONS: Faecal Hb loss from adenomas is significantly associated with size, number and advanced features. Sensitivity and specificity for AAPs are determined by test threshold chosen and number of samples collected; these determine the number of colonoscopies needed for positive tests.

Quantitative colonoscopic evaluation of relative efficiencies of an immunochemical faecal occult blood test and a sensitive guaiac test for detecting significant colorectal neoplasms.

BACKGROUND: The guaiac faecal occult blood test (G-FOBT), HemoccultSENSA, is sensitive for significant neoplasms [colorectal cancer (CRC), advanced adenomatous polyps (AAP)], but faulted by non-specificity for human haemoglobin (Hb). Quantified, Hb- specific, immunochemical faecal occult blood tests (I-FOBT) are now used. AIMS: To (i) compare I-FOBT and G-FOBT efficacy in identifying significant neoplasms and colonoscopy needs for positive tests and (ii) examine number of I-FOBTs needed and test threshold to use for equivalent or better sensitivity than G-FOBT and fewest colonoscopies for positive tests. METHODS: Three daily G-FOBTs and I-FOBTs were collected and analysed in 330 patients scheduled for colonoscopy. RESULTS: Colonoscopy found significant neoplasms in 32 patients, 6 CRC, 26 AAP. G-FOBT, sensitivity and specificity were 53.1% (17 neoplasms) and 59.4%, resulting in 8.1 colonoscopies/neoplasm. One I-FOBT having >or=50 ngHb/mL of buffer provided equivalent sensitivity but 94.0% specificity, resulting in 2.1 colonoscopies/neoplasm. By analysing the higher of two I-FOBTs at 50 ngHb/mL threshold, sensitivity increased to 68.8% (22 neoplasms, P = 0.063), specificity fell to 91.9% (P < 0.001), but still required 2.1 colonoscopies/neoplasm. CONCLUSIONS: In this population, quantified I-FOBT had significantly better specificity than G-FOBT for significant neoplasms, reducing the number of colonoscopies needed/neoplasm detected. Results depend on the number of I-FOBTs performed and the chosen development threshold.

Switching from tacrolimus to sirolimus halts the appearance of new sebaceous neoplasms in Muir-Torre syndrome.

Little is known about the effects of immunosuppression on patients with hereditary nonpolyposis colorectal cancer (HNPCC). We describe a kidney transplant recipient with unrecognized Muir-Torre syndrome in whom the administration of a tacrolimus-based regimen led to the eruption of multiple sebaceous tumors. The patient was later found to harbor an MSH2 mutation. Switching to a sirolimus-based regimen resulted in arrest of the disease. When the patient was switched back to tacrolimus, new facial lesions rapidly appeared. Switching again to sirolimus resulted again in halting the appearance of new lesions. This finding is in line with the known antiangiogenic activity of sirolimus and reports on the regression of cutaneous Kaposi's sarcoma in kidney transplant recipients switched from another immunosuppressive regimen to sirolimus. Further studies on the potential use of sirolimus for the treatment of de novo tumors in immunosuppressed kidney transplant recipients with HNPCC are warranted.

Tacrolimus-Induced Intestinal Angioedema: Diagnosis by Capsule Endoscopy.

Small intestinal angioedema has been reported with angiotensin converting enzyme inhibitors therapy, but not in implanted patients treated with tacrolimus. We present a kidney transplanted patient, hospitalized with severe diarrhea, diagnosed with tacrolimus-induced intestinal angioedema with abdominal computerized tomography and capsule endoscopy. To the best of our knowledge this is the first described case of tacrolimus-induced small bowel angioedema diagnosed with capsule endoscopy.

Can quantification of faecal occult blood predetermine the need for colonoscopy in patients at risk for non-syndromic familial colorectal cancer?

BACKGROUND: Patients at risk for non-syndromic (Lynch or polyposis) familial colorectal neoplasia undergo colonoscopic surveillance at intervals determined by clinically ascertained protocols. The quantitative immunochemical faecal occult blood test for human haemoglobin is specific and sensitive for significant colorectal neoplasia (cancer or advanced adenomatous polyp). AIM: To determine immunochemical faecal occult blood test efficacy for identifying significant neoplasia in at-risk patients undergoing elective colonoscopy. METHODS: We retrospectively identified consecutive at-risk patients who provided three immunochemical faecal occult blood tests before colonoscopy. Quantitative haemoglobin analysis was performed by the OC-MICRO automated instrument using the 100 ng Hb/mL threshold to determine positivity. RESULTS: In 252 at-risk patients undergoing colonoscopy; five had cancer, 14 an advanced adenoma and 46 a non-advanced adenoma. The immunochemical faecal occult blood test was positive in 31 patients (12.3%). Sensitivity, specificity, positive and negative predictive values for cancer were: 100%, 90%, 16% and 100%, and for all significant neoplasia: 74%, 93%, 45% and 98%. With 88% fewer colonoscopies, all colorectal cancers and 74% of all significant neoplasia would have been identified by this one-time immunochemical faecal occult blood test screening. CONCLUSIONS: A sensitive, non-invasive, interval screening test might be useful to predetermine the need for colonoscopy in this at-risk population and minimize unnecessary examinations. This favourable retrospective evaluation will be extended to a prospective study.

A quantitative immunochemical faecal occult blood test is more efficient for detecting significant colorectal neoplasia than a sensitive guaiac test.

BACKGROUND: The sensitive guaiac faecal occult blood test, Haemoccult SENSA (HOS; Beckman Coulter, Fullerton, CA, USA), is our standard screening test for significant colorectal neoplasia. We evaluated an automatically-developed, quantified human haemoglobin immunochemical faecal test, OC-MICRO (Eiken Chemical Co., Tokyo, Japan), to improve test specificity and so reduce the colonoscopy burden. AIM: To compare guaiac faecal occult blood test and immunochemical faecal test diagnostic efficacy and costs for identifying significant neoplasia. METHODS: Colonoscopies were performed on patients who prepared three daily guaiac faecal occult blood tests with or without immunochemical faecal tests. RESULTS: Total colonoscopy was performed on 151 subjects who prepared both guaiac and immunochemical faecal tests (group 1) and the positive predictive values (PPV) were also compared to those of 162 subjects undergoing colonoscopy for positive guaiac faecal occult blood tests (group 2). In group 1, comparative sensitivity, specificity, and PPVs for significant neoplasia with guaiac faecal occult blood test were 75%, 34%, and 12% (PPV, 18% for group 2) and with immunochemical faecal test were 75%, 94% and 60% (P < 0.01 for specificity). The number of colonoscopy examinations needed to detect a significant neoplasm because of positive faecal occult blood tests was six to eight with HOS and two with OC-MICRO at 21-31% the cost of evaluating a positive guaiac faecal occult blood test. CONCLUSION: An immunochemical faecal test maintains the high sensitivity of guaiac faecal occult blood test, but significantly reduces the colonoscopy burden and screening costs.

Capsule endoscopy - comparison of two strategies of bowel preparation.

BACKGROUND: Capsule endoscopy can identify lesions of the small bowel that cannot be detected by other techniques. In addition to patient safety, quality of care and cost-efficiency, good preparation is an important factor for good visualization. AIM: To evaluate the efficacy of oral sodium phosphate preparation. METHODS: Forty-six consecutive patients scheduled for capsule endoscopy in two medical centres. The patients treated in Dallas were prepared by 12 h fasting (group A), and those treated in Israel were also asked to drink 45 mL of sodium phosphate with water (group B). An experienced endoscopist, blinded to the method used, graded the quality of preparation according to visual capability, and to relative durations of each grade. RESULTS: The quality of the preparation was poor in 35% of group A compared with 4% of group B (P = 0.023). The mean duration of good preparation with excellent visualization was 122 +/- 110 min in group A and 180 +/- 96 min in group B (P = 0.006). Preparation with sodium phosphate and lower patient weight were significant predictive factors for good visualization. CONCLUSIONS: Bowel preparation offers better visualization than overnight fasting alone and is associated with fewer disturbances by intraluminal turbid fluid.

13C-urea breath test for success of Helicobacter pylori eradication: study of 5885 Israeli patients.

Helicobacter pylori (Hp) infection is highly prevalent in many countries and may cause gastritis, peptic ulcer disease, gastric cancer, and lymphoma. Successful eradication depends on the specific treatment used, patient compliance, and Hp antibiotic resistance. The primary aim was to characterize groups of patients with one or more failures of Hp eradication treatment. The secondary aim was to evaluate the factors that influence eradication failure. Between April 1, 1998, and December 31, 2001, 5885 patients were studied for the success of Hp eradication with the 13C-urea breath test (13C-UBT): 5442 after one course of treatment (Group I), 380 after two courses (Group II), and 63 after three courses (Group III). The 13C-UBT was positive in 27.8%, 37.4%, and 47.6% of patients in Groups I, II, and III, respectively (P(I-II) = 0.000, P(II-III) = 0.126). A combination of omeprazole, amoxicillin, and clarithromycin (OAC) was used in 31.3%, 27.4%, and 7.9% of Groups I, II, and III, respectively, and a combination of omeprazole, amoxicillin, and metronidazole (OAM) in 15.2%, 28.9%, and 28.6%, respectively. Regimens that contained clarithromycin were used in decreasing order in Groups I, II, and III, and regimens containing metronidazole, bismuth, or tetracycline, in increasing order. The only good prognostic factor for successful eradication was Israeli origin, while European-American and Asian-African origin, recurrence of symptoms, a history of duodenal ulcer, and chronic proton pump inhibitor (PPI) use did not favor successful eradication. Our results suggest that origin, history of peptic disease, and chronic PPI use are predictors of eradication failure.

Gallbladder mucin plays a role in gallstone formation.

Mucin is a high-molecular-weight glycoprotein that is synthesized, stored, and secreted by epithelial mucosal cells, especially goblet cells. Mucin proteins are derived from many different genes, termed MUC genes. Several lines of evidence point to a biological role for mucin in cholesterol gallstone formation. Mucin serves as a pronucleating agent in experimental and human gallstone disease, and the hydrophobic binding sites in the polypeptide core of mucin may provide a favorable environment for nucleation of cholesterol monohydrate from supersaturated bile. Mucin hypersecretion is prominent in many animal models of gallstone formation, thus contributing by its pronucleating quality to gallstone formation. According to some research, mucin hypersecretion may also contribute to the formation of brown pigment stones. This may be explained in part by the findings that lipopolysaccharides derived from certain bacteria are effective stimulants of mucin secretion. Aspirin and nonsteroidal anti-inflammatory drugs inhibit gallbladder mucin secretion and prevent gallstone formation in animal models. Expanding our knowledge on mucin research may improve our understanding of the natural history of gallstone formation and enable the development of new treatment strategies.