Appropriateness of colonoscopy in Europe (EPAGE II). Screening for colorectal cancer.

BACKGROUND AND STUDY AIMS: To summarize the published literature on assessment of appropriateness of colonoscopy for screening for colorectal cancer (CRC) in asymptomatic individuals without personal history of CRC or polyps, and report appropriateness criteria developed by an expert panel, the 2008 European Panel on the Appropriateness of Gastrointestinal Endoscopy, EPAGE II. METHODS: A systematic search of guidelines, systematic reviews, and primary studies regarding colonoscopy for screening for colorectal cancer was performed. The RAND/UCLA Appropriateness Method was applied to develop appropriateness criteria for colonoscopy in these circumstances. RESULTS: Available evidence for CRC screening comes from small case-controlled studies, with heterogeneous results, and from indirect evidence from randomized controlled trials (RCTs) on fecal occult blood test (FOBT) screening and studies on flexible sigmoidoscopy screening. Most guidelines recommend screening colonoscopy every 10 years starting at age 50 in average-risk individuals. In individuals with a higher risk of CRC due to family history, there is a consensus that it is appropriate to offer screening colonoscopy at < 50 years. EPAGE II considered screening colonoscopy appropriate above 50 years in average-risk individuals. Panelists deemed screening colonoscopy appropriate for younger patients, with shorter surveillance intervals, where family or personal risk of colorectal cancer is higher. A positive FOBT or the discovery of adenomas at sigmoidoscopy are considered appropriate indications. CONCLUSIONS: Despite the lack of evidence based on randomized controlled trials (RCTs), colonoscopy is recommended by most published guidelines and EPAGE II criteria available online (http://www.epage.ch), as a screening option for CRC in individuals at average risk of CRC, and undisputedly as the main screening tool for CRC in individuals at moderate and high risk of CRC.

Appropriateness of colonoscopy in Europe (EPAGE II). Surveillance after polypectomy and after resection of colorectal cancer.

BACKGROUND AND STUDY AIMS: To summarize the published literature on assessment of appropriateness of colonoscopy for surveillance after polypectomy and after curative-intent resection of colorectal cancer (CRC), and report appropriateness criteria developed by an expert panel, the 2008 European Panel on the Appropriateness of Gastrointestinal Endoscopy, EPAGE II. METHODS: A systematic search of guidelines, systematic reviews and primary studies regarding the evaluation and management of surveillance colonoscopy after polypectomy and after resection of CRC was performed. The RAND/UCLA Appropriateness Method was applied to develop appropriateness criteria for colonoscopy for these conditions. RESULTS: Most CRCs arise from adenomatous polyps. The characteristics of removed polyps, especially the distinction between low-risk adenomas (1 or 2, small [< 1 cm], tubular, no high-grade dysplasia) vs. high-risk adenomas (large [> or = 1 cm], multiple [> 3], high-grade dysplasia or villous features), have an impact on advanced adenoma recurrence. Most guidelines recommend a 3-year follow-up colonoscopy for high-risk adenomas and a 5-year colonoscopy for low-risk adenomas. Despite the lack of evidence to support or refute any survival benefit for follow-up colonoscopy after curative-intent CRC resection, surveillance colonoscopy is recommended by most guidelines. The timing of the first surveillance colonoscopy differs. The expert panel considered that 56 % of the clinical indications for colonoscopy for surveillance after polypectomy were appropriate. For surveillance after CRC resection, it considered colonoscopy appropriate 1 year after resection. CONCLUSIONS: Colonoscopy is recommended as a first-choice procedure for surveillance after polypectomy by all published guidelines and by the EPAGE II criteria. Despite the limitations of the published studies, colonoscopy is also recommended by most of the guidelines and by EPAGE II criteria for surveillance after curative-intent CRC resection.

Appropriateness of colonoscopy in Europe (EPAGE II). Chronic diarrhea and known inflammatory bowel disease.

BACKGROUND AND STUDY AIMS: To summarize the published literature on assessment of appropriateness of colonoscopy for investigation of chronic diarrhea, management of patients with known inflammatory bowel disease (IBD), and for colorectal cancer (CRC) surveillance in such patients, and to report report appropriateness criteria developed by an expert panel, the 2008 European Panel on the Appropriateness of Gastrointestinal Endoscopy, EPAGE II. METHODS: A systematic search of guidelines, systematic reviews, and primary studies regarding the evaluation of chronic diarrhea, the management of IBD, and colorectal cancer surveillance in IBD was performed. The RAND/UCLA Appropriateness Method was applied to develop appropriateness criteria for colonoscopy for these conditions. RESULTS: According to the literature, colonoscopic evaluation may be justified for patients aged > 50 years with recent-onset chronic diarrhea or with alarm symptoms. Surveillance colonoscopy for CRC should be offered to all patients with extensive ulcerative colitis or colonic Crohn's disease of 8 years' duration, and to all patients with less extensive disease of 15 years' duration. Intervals for surveillance colonoscopy depend on duration of evolution, initial diagnosis, and histological findings. The EPAGE II criteria also confirmed the appropriateness of diagnostic colonoscopy for diarrhea of > 4 weeks' duration. They also suggest that, in addition to assessing extent of IBD by colonoscopy, further colonoscopic examination is appropriate in the face of persistent or worsening symptoms. Surveillance colonoscopy in IBD patients was generally appropriate after a lapse of 2 years. In the presence of dysplasia at previous colonoscopy, it was not only appropriate but necessary. CONCLUSIONS: Despite or perhaps because of the limitations of the available published studies, the panel-based EPAGE II (http://www.epage.ch) criteria can help guide appropriate colonoscopy use in the absence of strong evidence from the literature.

Appropriateness of colonoscopy in Europe (EPAGE II). Presentation of methodology, general results, and analysis of complications.

BACKGROUND AND STUDY AIMS: Appropriate use of colonoscopy is a key component of quality management in gastrointestinal endoscopy. In an update of a 1998 publication, the 2008 European Panel on the Appropriateness of Gastrointestinal Endoscopy (EPAGE II) defined appropriateness criteria for various colonoscopy indications. This introductory paper therefore deals with methodology, general appropriateness, and a review of colonoscopy complications. METHODS: The RAND/UCLA Appropriateness Method was used to evaluate the appropriateness of various diagnostic colonoscopy indications, with 14 multidisciplinary experts using a scale from 1 (extremely inappropriate) to 9 (extremely appropriate). Evidence reported in a comprehensive updated literature review was used for these decisions. Consolidation of the ratings into three appropriateness categories (appropriate, uncertain, inappropriate) was based on the median and the heterogeneity of the votes. The experts then met to discuss areas of disagreement in the light of existing evidence, followed by a second rating round, with a subsequent third voting round on necessity criteria, using much more stringent criteria (i. e. colonoscopy is deemed mandatory). RESULTS: Overall, 463 indications were rated, with 55 %, 16 % and 29 % of them being judged appropriate, uncertain and inappropriate, respectively. Perforation and hemorrhage rates, as reported in 39 studies, were in general < 0.1 % and < 0.3 %, respectively CONCLUSIONS: The updated EPAGE II criteria constitute an aid to clinical decision-making but should in no way replace individual judgment. Detailed panel results are freely available on the internet (www.epage.ch) and will thus constitute a reference source of information for clinicians.

Appropriateness of colonoscopy in Europe (EPAGE II). Iron-deficiency anemia and hematochezia.

BACKGROUND AND STUDY AIMS: To summarize the published literature on assessment of appropriateness of colonoscopy for the investigation of iron-deficiency anemia (IDA) and hematochezia, and report appropriateness criteria developed by an expert panel, the 2008 European Panel on the Appropriateness of Gastrointestinal Endoscopy, EPAGE II. METHODS: A systematic search of guidelines, systematic reviews and primary studies regarding the evaluation and management of IDA and hematochezia was performed. The RAND/UCLA Appropriateness Method was applied to develop appropriateness criteria for colonoscopy for these conditions. RESULTS: IDA occurs in 2 %-5 % of adult men and postmenopausal women. Examination of both the upper and lower gastrointestinal tract is recommended in patients with iron deficiency. Colonoscopy for IDA yields one colorectal cancer (CRC) in every 9-13 colonoscopies. Hematochezia is a well-recognized alarm symptom and such patients are likely to be referred for colonoscopy. Colonoscopy is unanimously recommended in patients aged > or = 50. Diverticulosis, vascular ectasias, and ischemic colitis are common causes of acute lower gastrointestinal bleeding (LGIB); CRC is found in 0.2 %-11 % of the colonoscopies performed for LGIB. Most patients with scant hematochezia have an anorectal or a distal source of bleeding. The expert panel considered most clinical indications for colonoscopy as appropriate in the presence of IDA (58 %) or hematochezia (83 %). CONCLUSION: Despite the limitations of the published studies, guidelines unanimously recommend colonoscopy for the investigation of IDA and hematochezia in patients aged > or = 50 years. These indications were also considered appropriate by EPAGE II, as were indications in patients at low risk for CRC with no obvious cause of bleeding found during adequate previous investigations.

Appropriateness of colonoscopy in Europe (EPAGE II). Functional bowel disorders: pain, constipation and bloating.

BACKGROUND AND STUDY AIMS: To summarize the published literature on assessment of appropriateness of colonoscopy for the investigation of functional bowel symptoms, and report appropriateness criteria developed by an expert panel, the 2008 European Panel on the Appropriateness of Gastrointestinal Endoscopy, EPAGE II. METHODS: A systematic search of guidelines, systematic reviews and primary studies regarding the evaluation and management of functional bowel symptoms was performed. The RAND/UCLA Appropriateness Method was applied to develop appropriateness criteria for colonoscopy for these conditions. RESULTS: Much of the evidence for use of colonoscopy in evaluation of chronic abdominal pain, and/or constipation and/or abdominal bloating is modest. Major limitations include small numbers of patients and lack of adequate characterization of these patients. Large community-based follow-up studies are needed to enable better definition of the natural history of patients with functional bowel disorders. Guidelines stress that alarm features ("red flags"), such as rectal bleeding, anemia, weight loss, nocturnal symptoms, family history of colon cancer, age of onset > 50 years, and recent onset of symptoms should all lead to careful evaluation before a diagnosis of functional bowel disorder is made. EPAGE II assessed these symptoms by means of 12 clinical scenarios, rating colonoscopy as appropriate, uncertain and inappropriate in 42 % (5/12), 25 % (3/12), and 33 % (4/12) of these, respectively. CONCLUSIONS: Evidence to support the use of colonoscopy in the evaluation of patients with functional bowel disorders and no alarm features is lacking. These patients have no increased risk of colon cancer and thus advice on screening for this is not different from that for the general population. EPAGE II criteria, available online (http://www.epage.ch), consider colonoscopy appropriate in patients of > 50 years with chronic or new-onset bowel disturbances, but not in patients with isolated chronic abdominal pain.

Host- rather than virus-related factors reduce health-related quality of life in hepatitis C virus infection.

BACKGROUND: Hepatitis C virus (HCV) infection is associated with decreased health-related quality of life (HRQOL). Although HCV has been suggested to directly impair neuropsychiatric functions, other factors may also play a role. PATIENTS AND METHODS: In this cross-sectional study, we assessed the impact of various host-, disease- and virus-related factors on HRQOL in a large, unselected population of anti-HCV-positive subjects. All individuals (n = 1736) enrolled in the Swiss Hepatitis C Cohort Study (SCCS) were asked to complete the Short Form 36 (SF-36) and the Hospital Anxiety Depression Scale (HADS). RESULTS: 833 patients (48%) returned the questionnaires. Survey participants had significantly worse scores in both assessment instruments when compared to a general population. By multivariable analysis, reduced HRQOL (mental and physical summary scores of SF-36) was independently associated with income. In addition, a low physical summary score was associated with age and diabetes, whereas a low mental summary score was associated with intravenous drug use. HADS anxiety and depression scores were independently associated with income and intravenous drug use. In addition, HADS depression score was associated with diabetes. None of the SF-36 or HADS scores correlated with either the presence or the level of serum HCV RNA. In particular, SF-36 and HADS scores were comparable in 555 HCV RNA-positive and 262 HCV RNA-negative individuals. CONCLUSIONS: Anti-HCV-positive subjects have decreased HRQOL compared to controls. The magnitude of this decrease was clinically important for the SF-36 vitality score. Host and environmental, rather than viral factors, seem to impact on HRQOL level.

Factors associated with the technical performance of colonoscopy: An EPAGE Study.

BACKGROUND: Variations in colonoscopy practice exist, which may be related to healthcare quality. AIMS: To determine factors associated with three performance indicators of colonoscopy: complete colonoscopy, adenomatous polyp diagnosis, and duration. PATIENTS: Consecutive patients referred for colonoscopy from 21 centres in 11 countries. METHODS: This prospective observational study used multiple variable regression analyses to identify determinants of the quality indicators. RESULTS: Six thousand and four patients were included in the study. Patients from private, open-access centres (odds ratio: 3.17, 95% confidence interval: 1.87-5.38) were more likely to have a complete colonoscopy than patients from public, gatekeeper centres. Patients from centres where over 50% of the endoscopists were of senior rank were roughly twice as likely to have an adenoma diagnosed, and longer average withdrawal duration (odds ratio: 1.08, 95% confidence interval: 1.07-1.09) was associated with more frequent adenoma diagnoses. Patients who had difficulty during colonoscopy had longer durations to caecum (time ratio: 2.87, 95% confidence interval: 2.72-3.01) and withdrawal durations (time ratio: 1.26, 95% confidence interval: 1.18-1.33) than patients who had no difficulties. CONCLUSIONS: Multiple factors have been identified as being associated with key quality indicators. The non-modifiable factors permit the identification of patients who may be at greater risk of not having quality colonoscopy, while changes to the modifiable factors may help improve the quality of colonoscopy.

[Hepatology]. / Hépatologie.

Therapy by pegylated interferon-alpha (PEG-IFN-alpha), lamivudine and adefovir have significantly improved treatment perspectives for patients with chronic hepatitis B. New nucleos(t)ide analogues should permit the development of more effective combination therapies. In autoimmune hepatitis, if there is no response or an intolerance to therapy with prednisone and imurek, administration of mycophenolate mofetil should be envisaged. Ursodeoxycholic acid (UDCA) therapy, at a dosage of 13-15 mg/ kg/day, remains the treatment of choice for primary biliary cirrhosis and should be administered at an early stage to improve patients' survival. In the treatment of nonalcoholic fatty liver disease, thiazolidinediones show considerable promise, but further clinical studies are required in order to prove their efficacity and safety.

[Effect of pH on the physico-chemical and immunologic properties of rabbit antibodies]. / Influence du pH sur les propriétés physico-chimiques et immunologiques des anticorps de lapin.

The effects of an incubation at low pH (during 20 h at 37 degrees) on the antibody activity and anticomplementary activity of rabbit IgG have been studied. Modifications have also been examined by physicochemical methods. The properties of rabbit anti-sheep red cell IgG are not modified by incubation at pH values between 7.4 and 4.0 during 20 h at 37 degrees. Below pH 4 a decrease of hemolytic activity is apparent concomitant with an important increase of the agglutinating activity. This phenomenon is due to the formation of polymers from native IgG. At pH values below 3.8 the anticomplementary activity of a nonspecific IgG decreases rapidly. One observes an increase of optical rotation, a finding which is compatible with the appearance of heavier compounds with sedimentation coefficients of 9.5 and 11.5 S, probably dimers of native IgG. The increase of optical rotation is partially reversible when the pH is readjusted to 7.4. The use of starch-gel and immunoelectrophoresis has shown the appearance of compounds with higher mobility which are closely related to a peptide (PEP III') which was isolated from a peptic hydrolysate of rabbit IgG. The decrease of anticomplementary activity of nonspecific IgG seems to be closely related to the liberation of PEP III'.

[When and how to treat hepatitis B and C?]. / Quand et comment traiter les hépatites B et C?

The introduction of pegylated interferon-alpha (PEG-IFN-alpha) as well as lamivudine and adefovir has greatly improved the perspectives for patients with chronic hepatitis B. In addition, new nucleos(t)ide analogues are currently being evaluated and may allow the development of effective combination therapy regimens in the future. In the absence of resistance development, lamivudine reduces the risk of decompensation and hepatocellular carcinoma in patients with cirrhosis. Current standard therapy of chronic hepatitis C, PEG-IFN-alpha combined with ribavirin, results in a sustained virologic response in 20-80% of patients, depending on the viral genotype and additional factors, such as ethnicity, fibrosis stage, body mass index, viral load, alcohol consumption, and coinfections. Novel antiviral strategies are currently being explored.

[Auto-immune liver diseases and their treatment]. / Les hépatopathies auto-immunes et leurs traitements.

There are three main types of auto-immune liver disease, auto-immune hepatitis, primary biliary cirrhosis and primary sclerosing cholangitis. In the case of auto-immune hepatitis, prednisone therapy, with or without azathioprine, can improve quality of life and halt progression to cirrhosis. If there is no response or if the therapy is poorly tolerated, mycophenolate mofetil or cyclosporin should be considered. Ursodeoxycholic acid (UDCA), at a dosage of 13 to 15 mg/kg/day slows the progression of fibrosis in patients with primary biliary cirrhosis. Pruritus may be treated with cholestyramine, rifampicin or opiate antagonists. Ursodeoxycholic acid at a dosage of 20 to 30 mg/kg/day will slow the evolution of fibrosis.

[Complications of liver cirrhosis: oesophageal varices, ascites and hepato-cellular carcinoma]. / Les complications de la cirrhose hépatique: varices oesophagiennes, ascite et carcinome hépato-cellulaire.

The principal treatment for bleeding oesophageal varices is endoscopic ligation. Non-cardioselective beta-blockers are the gold-standard of primary prophylaxis. The principal treatment for ascites is a salt-free diet and diuretics, mainly spironolactone, if necessary associated with a loop diuretic. In refractory ascites, paracentesis or installation of a transjugular intrahepatic portosystemic shunt (TIPS) are two possible treatment options. Cirrhosis patients are at higher risk of developing hepato-cellular carcinoma. Surgery is only possible in a small number of cases. Percutaneous destruction techniques have nearly the same survival rate as that obtained by surgery and should be proposed to patients where surgery is not an option.

The histological patterns of chronic active hepatitis--excluding cirrhosis--and their prognostic significance.

In a retrospective clinico-pathological analysis of 30 cases of chronic active hepatitis, no significant correlation could be demonstrated between any histological feature and the end result of the evolution. The so-called "bridging" lesion, in particular, has no prognostic value. A possible effect of the therapy (cortico-steroids or not) on the final outcome could not be established. There is however a clearcut difference in the rate of development, be it favorable or not, between the slow progress of chronic aggressive hepatitis, and the rapidly changing subacute hepatitis. We therefore feel that such a distinction should be maintained, and question the nomenclature proposed by the International Association for Study of the Liver.

Gastric ulcer: a double blind comparison of 800 mcg misoprostol versus 300 mg ranitidine.

Seventy-nine patients with endoscopically confirmed gastric ulcers received either ranitidine (37 patients) or misoprostol (42 patients) in a randomized double-blind manner. Fifty-six percent of the patients treated with ranitidine, and 38% of those treated with misoprostol presented with endoscopically healed ulcers after four weeks of treatment. After eight weeks complete healing had occurred in 86% of the patients receiving ranitidine, and 74% of those on misoprostol. These differences were not statistically significant. In smokers, ranitidine was superior to misoprostol, leading to a higher healing rate at four weeks (73% versus 20%). Thus there was no evidence that in patients with gastric ulcer misoprostol overcomes the negative effect of cigarette smoking.

Effect of different drinks on fluid and electrolyte losses from a jejunostomy.

The effectiveness of 5 different solutions on the absorption of fluid and electrolytes was tested in 7 patients with a proximal intestinal stoma and large fluid losses, all of whom previously needed intravenous infusions to maintain balance. In 4 patients it proved possible to replace the intravenous infusions with an enteral supplement. The WHO glucose/electrolyte solution without added potassium (NaCl 3.5 g, NaHCO3 2.5 g, glucose 20 g/l) gave satisfactory results, though was slightly less effective than a solution containing more sodium in which maltose was substituted for glucose. Neither sucrose nor an oligosaccharide (Caloreen) gave an advantage over glucose in the formulations used. In 3 patients losses were so great, and absorption of sodium from oral solutions so small, that intravenous supplements had to be continued. These 3 patients could be distinguished from the other 4 by the fact that more than 250 ml emerged from the stoma during the 3 hours after a drink of 500 ml of glucose/electrolyte solution. In all patients a drink of water or tea led to a loss of sodium from the stoma; water should be restricted in such patients and replaced by a glucose/electrolyte solution.

[Early diagnosis of colorectal cancer: technical problems and acceptability]. / Diagnostic précoce du cancer colo-rectal: problèmes techniques et acceptabilité.

There has been little change in the survival rate of colorectal cancer over the last 20 years. Earlier diagnosis probably offers the best hope for improving this survival. At the present time, the only practical method of population screening is by the detection of occult blood in the faeces. Almost all published screening trials are uncontrolled. Although cancer detected by occult blood screening tends to be at a relatively early stage, only controlled trials can answer the critical question of whether screening decreases mortality from bowel cancer. High risk patients (prior adenoma or colorectal cancer, extensive colitis of more than 10 years duration, family history of polyposis) should have colonoscopy at regular intervals.

[Is the measurement of carcinoembryonic antigen still indicated in digestive cancers?]. / Le dosage de l'antigène carcino-embryonnaire est-il encore indiqué dans les cancers digestifs?

Carcinoembryonic antigen (CEA) is not useful for detecting asymptomatic cancer. Its sensitivity and specificity are not high. For some cancers, antigen levels at the time of diagnosis provide more precise prognosis than staging alone. Regular determination of CEA is useful as a method of surveillance after surgery for cancer in the colon and in the rectum. Unfortunately the clinical gain of detecting postoperative relapses is low since curative surgical treatment is usually impossible.

[Screening for colorectal tumors using fecal occult blood studies]. / Dépistage des tumeurs colorectales par la recherche de sang occulte dans les selles.

Guaiac tests such as Hemoccult are widely used but are affected by several factors. Occult blood testing does uncover subclinical colorectal cancer often at early stage, but a favorable effect on survival remains to be proven. The sensitivity for the detection of malignancies is from moderate to good, but it is poor for benign polyps. Predictive value of a positive test for cancer ist about 8-12%. Thus, most of the individuals with a positive test would not need colonic investigations. Recommendations relating to the testing for of occult blood could change rapidly with the new immunologic techniques or with new data on mortality coming from controlled clinical trial now being conducted.

Treatment and relapse prophylaxis of duodenal ulcer with pirenzepine and cimetidine.

The effect of pirenzepine and cimetidine on healing, symptoms and relapse rate of duodenal ulcer was studied in a placebo-controlled double-blind trial. Cimetidine (1 g daily) was superior at the beginning of therapy to a low dose of pirenzepine (75 mg daily) and placebo with regard to symptoms. No significant differences in ulcer healing were found between the 3 groups of treatment. The relapse rate after treatment with pirenzepine was lower than after treatment with cimetidine.