Fecal occult blood and calprotectin testing to prioritize primary care patients for colonoscopy referral: The advantage study.

BACKGROUND: Colonoscopy is the gold standard for colorectal cancer (CRC) diagnosis and screening, but endoscopy services are usually overburdened. This study aims to investigate the usefulness of fecal hemoglobin (fHb) and calprotectin (FC) for the identification of patients with high probability of CRC who need urgent referral. METHODS: In a multicenter prospective study, we enrolled symptomatic patients referred from primary care for colonoscopy. Prior to bowel preparation, fHb and FC quantitative tests were performed. The diagnostic performance was estimated for each biomarker/combination. We built a multivariable predictive model based on logistic regression, translated to a nomogram and a risk calculator to assist clinicians in the decision-making process. RESULTS: The study included 1224 patients, of whom 69 (5.6%) had CRC. At the fHb cut-offs of >0 and 10 µg/g, the negative predictive values for CRC were 98.8% (95% confidence interval 97.8%-99.3%) and 98.6% (95%CI 97.7%-99.1%), and the sensitivities were 85.5% (95%CI 75.0%-92.8%) and 79.7% (95%CI 68.3%-88.4%), respectively. When we added the cut-off of 150 µg/g of FC to both fHb thresholds, the sensitivity of fecal tests improved. In the multivariate logistic regression model, the concentration of fHb was an independent predictor for CRC; age and gender were also independently associated with CRC. CONCLUSIONS: fHb and FC are useful as part of a triage tool to identify those symptomatic patients with high probability of CRC. This can be easily applied by physicians to prioritize high-risk patients for urgent colonoscopy.

Importance of endoscopist quality metrics for findings at surveillance colonoscopy: The detection-surveillance paradox.

BACKGROUND: Guidelines recommend surveillance colonoscopies based exclusively on findings at baseline colonoscopy. This recommendation leads to the paradox that the higher the baseline colonoscopy quality, the more surveillance colonoscopies will be indicated according to current guidelines. OBJECTIVE: The aim of this study was to evaluate the effect on follow-up findings of different quality metrics of the endoscopist performing the baseline colonoscopy. METHODS: This retrospective cohort study included individuals with advanced adenomas at baseline colonoscopy. Adenoma detection rate (ADR) and adenomas per colonoscopy rate (APCR) were determined for 44 endoscopists. Surveillance colonoscopies were checked after systematic tracking. RESULTS: A total of 574 individuals were diagnosed with advanced adenomas, of whom 270 received a surveillance colonoscopy. Patients whose baseline colonoscopy endoscopist had an ADR lower than the median of 33.8% had significantly higher rates of advanced neoplasia at follow-up (13.1% vs 4.0%; p = 0.001). On univariate analysis, high-risk advanced adenomas at baseline (HR 0.43; 95% CI 0.19-0.97) and ADR (HR 0.94; 95% CI 0.89-0.99) showed a significant relationship with advanced neoplasia at surveillance. In a multivariate Cox model, the ADR of the endoscopist who performed the baseline colonoscopy was the only independent predictor of risk for developing advanced neoplasia at follow-up (HR 0.94; 95% CI 0.89-0.99). CONCLUSIONS: Our results suggest that the risk of identifying advanced adenomas at follow-up is closely related to the quality metrics of the endoscopist who performs the baseline colonoscopy.

Endoscopist characteristics that influence the quality of colonoscopy.

BACKGROUND AND STUDY AIM: Several factors have been shown to be related to colonoscopy quality; however, little is known about the effects of endoscopist factors. This study analyzed the influence of endoscopist-related characteristics on quality indicators for colonoscopy. PATIENTS AND METHODS: The study included 48 endoscopists who each performed at least 20 colonoscopies in the colonoscopy arm of a randomized controlled trial comparing fecal immunochemical test vs. colonoscopy in colorectal cancer screening. These endoscopists performed a total of 3838 procedures in the trial. The following were calculated for each endoscopist: adenoma detection rate (ADR), advanced ADR, proximal ADR, distal ADR, and adenoma per colonoscopy rate (APCR). The characteristics of endoscopists were assessed with regard to colonoscopy quality using multivariate regression analysis. Endoscopist characteristics included age, sex, exclusive endoscopy practice, years as a physician, years as a specialist, specialty, total (life-long) number of colonoscopies performed, annual colonoscopy volume, number of hours/week dedicated to endoscopy and number of educational activities in the previous year. RESULTS: Factors associated with ADR were age of the endoscopist (odds ratio [OR] 1.11, 95 % confidence interval [CI] 1.01 - 1.21; P = 0.01) and life-long number of colonoscopies (OR 1.06, 95 %CI 1.01 - 1.11; P = 0.01). Only exclusive dedication to endoscopy practice was found to be independently related to proximal ADR (OR 1.71, 95 %CI 1.15 - 2.74; P = 0.001). Life-long number of colonoscopies was independently related to detection of distal adenomas (OR 1.07, 95 %CI 1.01 - 1.13; P = 0.01). None of the analyzed endoscopist characteristics was associated with advanced ADR or APCR. CONCLUSIONS: This study found that the experience of the endoscopist and exclusive dedication to endoscopy practice, but not annual colonoscopy volume, were associated with better colonoscopy quality.

Relationship of colonoscopy-detected serrated polyps with synchronous advanced neoplasia in average-risk individuals.

BACKGROUND: Serrated cancers account for 10% to 20% of all colorectal cancers (CRC) and more than 30% of interval cancers. The presence of proximal serrated polyps and large (≥10 mm) serrated polyps (LSP) has been correlated with colorectal neoplasia. OBJECTIVE: To evaluate the prevalence of serrated polyps and their association with synchronous advanced neoplasia in a cohort of average-risk population and to assess the efficacy of one-time colonoscopy and a biennial fecal immunochemical test for reducing CRC-related mortality. This study focused on the sample of 5059 individuals belonging to the colonoscopy arm. DESIGN: Multicenter, randomized, controlled trial. SETTING: The ColonPrev study, a population-based, multicenter, nationwide, randomized, controlled trial. PATIENTS: A total of 5059 asymptomatic men and women aged 50 to 69 years. INTERVENTION: Colonoscopy. MAIN OUTCOME MEASUREMENTS: Prevalence of serrated polyps and their association with synchronous advanced neoplasia. RESULTS: Advanced neoplasia was detected in 520 individuals (10.3%) (CRC was detected in 27 [0.5%] and advanced adenomas in 493 [9.7%]). Serrated polyps were found in 1054 individuals (20.8%). A total of 329 individuals (6.5%) had proximal serrated polyps, and 90 (1.8%) had LSPs. Proximal serrated polyps or LSPs were associated with male sex (odds ratio [OR] 2.08, 95% confidence interval [CI], 1.76-4.45 and OR 1.65, 95% CI, 1.31-2.07, respectively). Also, LSPs were associated with advanced neoplasia (OR 2.49, 95% CI, 1.47-4.198), regardless of their proximal (OR 4.15, 95% CI, 1.69-10.15) or distal (OR 2.61, 95% CI, 1.48-4.58) locations. When we analyzed subtypes of serrated polyps, proximal hyperplasic polyps were related to advanced neoplasia (OR 1.61, 95% CI, 1.13-2.28), although no correlation with the location of the advanced neoplasia was observed. LIMITATIONS: Pathology criteria for the diagnosis of serrated polyps were not centrally reviewed. The morphology of the hyperplasic polyps (protruded or flat) was not recorded. Finally, because of the characteristics of a population-based study carried out in average-risk patients, the proportion of patients with CRC was relatively small. CONCLUSION: LSPs, but not proximal serrated polyps, are associated with the presence of synchronous advanced neoplasia. Further studies are needed to determine the risk of proximal hyperplastic polyps.

Modifiable endoscopic factors that influence the adenoma detection rate in colorectal cancer screening colonoscopies.

BACKGROUND: Adenoma detection rate (ADR) has become the most important quality indicator for colonoscopy. OBJECTIVE: The aim of this study was to investigate which modifiable factors, directly related to the endoscopic procedure, influenced the ADR in screening colonoscopies. DESIGN: Observational, nested study. SETTING: Multicenter, randomized, controlled trials. PATIENTS: Asymptomatic people aged 50 to 69 years were eligible for a multicenter, randomized, controlled trial designed to compare colonoscopy and fecal immunochemical testing in colorectal cancer screening. A total of 4539 individuals undergoing a direct screening colonoscopy were included in this study. INTERVENTION: Colonoscopy. MAIN OUTCOME MEASUREMENTS: Bowel cleansing, sedation, withdrawal time in normal colonoscopies, and cecal intubation were analyzed as possible predictors of adenoma detection by using logistic regression analysis, adjusted for age and sex. RESULTS: In multivariate analysis, after adjustment for age and sex, factors independently related to the ADR were a mean withdrawal time longer than 8 minutes (odds ratio [OR] 1.51; 95% CI, 1.17-1.96) in normal colonoscopies and split preparation (OR 1.26; 95% CI, 1.01-1.57). For advanced adenomas, only withdrawal time maintained statistical significance in the multivariate analysis. For proximal adenomas, withdrawal time and cecal intubation maintained independent statistical significance, whereas only withdrawal time longer than 8 minutes and a <10-hour period between the end of preparation and colonoscopy showed independent associations for distal adenomas. LIMITATIONS: Only endoscopic variables have been analyzed. CONCLUSION: Withdrawal time was the only modifiable factor related to the ADR in colorectal cancer screening colonoscopies associated with an increased detection rate of overall, advanced, proximal, and distal adenomas.

Colonoscopy versus fecal immunochemical testing in colorectal-cancer screening.

BACKGROUND: Colonoscopy and fecal immunochemical testing (FIT) are accepted strategies for colorectal-cancer screening in the average-risk population. METHODS: In this randomized, controlled trial involving asymptomatic adults 50 to 69 years of age, we compared one-time colonoscopy in 26,703 subjects with FIT every 2 years in 26,599 subjects. The primary outcome was the rate of death from colorectal cancer at 10 years. This interim report describes rates of participation, diagnostic findings, and occurrence of major complications at completion of the baseline screening. Study outcomes were analyzed in both intention-to-screen and as-screened populations. RESULTS: The rate of participation was higher in the FIT group than in the colonoscopy group (34.2% vs. 24.6%, P<0.001). Colorectal cancer was found in 30 subjects (0.1%) in the colonoscopy group and 33 subjects (0.1%) in the FIT group (odds ratio, 0.99; 95% confidence interval [CI], 0.61 to 1.64; P=0.99). Advanced adenomas were detected in 514 subjects (1.9%) in the colonoscopy group and 231 subjects (0.9%) in the FIT group (odds ratio, 2.30; 95% CI, 1.97 to 2.69; P<0.001), and nonadvanced adenomas were detected in 1109 subjects (4.2%) in the colonoscopy group and 119 subjects (0.4%) in the FIT group (odds ratio, 9.80; 95% CI, 8.10 to 11.85; P<0.001). CONCLUSIONS: Subjects in the FIT group were more likely to participate in screening than were those in the colonoscopy group. On the baseline screening examination, the numbers of subjects in whom colorectal cancer was detected were similar in the two study groups, but more adenomas were identified in the colonoscopy group. (Funded by Instituto de Salud Carlos III and others; ClinicalTrials.gov number, NCT00906997.).

Double-guidewire technique for difficult bile duct cannulation: a multicenter randomized, controlled trial.

BACKGROUND: ERCP can be associated with serious complications. Difficulty in common bile duct (CBD) cannulation is one of the main risk factors for post-ERCP pancreatitis. The double-guidewire technique (DGT) has been considered a promising alternative approach in difficult cannulation situations. OBJECTIVE: To compare the performance of DGT with the standard cannulation technique (SCT) in patients in whom CBD cannulation is difficult to perform. DESIGN: Multicenter randomized, controlled trial. SETTING: Six tertiary referral centers. PATIENTS: A total of 188 patients with difficult CBD cannulation defined by completion of 5 unsuccessful cannulation attempts were enrolled. INTERVENTIONS: Ninety-seven patients were assigned to the DGT group and 91 to the SCT group. Both techniques were compared for an extra 10 cannulation attempts. MAIN OUTCOME MEASUREMENTS: CBD cannulation rate, number of attempts required to cannulate, and ERCP-related complications. RESULTS: Successful CBD cannulation was achieved in 46 of 97 (47%) patients in the DGT group compared with 51 of 91 (56%) in the SCT group (OR 0.85; 95% CI, 0.64-1.12). The median number of attempts required for each group was 9 and 7, respectively (P = .128). The incidence of post-ERCP pancreatitis was 17% in the DGT group and 8% in the SCT group (OR 2.13; 95% CI, 0.89-5.05). LIMITATIONS: Reduced number of enrolled subjects and a lack of detailed information regarding the number and extent of pancreatic duct contrast injections. CONCLUSIONS: In patients with difficult CBD cannulation, DGT was not superior to SCT in achieving CBD cannulation. DGT might be associated with a higher risk of post-ERCP pancreatitis.

Circulating endogenous cannabinoid anandamide and portal, systemic and renal hemodynamics in cirrhosis.

BACKGROUND: Endocannabinoids may participate in the homeostasis of arterial pressure. Recently, anandamide, the most extensively studied endocannabinoid, has been proposed as a key mediator in the peripheral arterial vasodilation of cirrhosis. OBJECTIVES: To determine if circulating levels of anandamide are related to the extent of the peripheral arterial vasodilation, the severity of portal hypertension and the degree of liver and renal dysfunction of patients with cirrhosis. METHODS: Plasma levels of anandamide and several systemic, portal and renal hemodynamic parameters were determined in 18 patients with cirrhosis and eight healthy subjects (control group). RESULTS: Plasma levels of anandamide were elevated in patients compared to the control group (P<0.05), nevertheless, no differences between patients with ascites and well-compensated patients were found. There was no correlation between anandamide concentration and arterial pressure, cardiac output and systemic vascular resistance, Child-Pugh's score, portal pressure, renal vascular resistance, plasma renin activity or plasma aldosterone concentration. CONCLUSIONS: Circulating levels of anandamide are increased in cirrhotic patients. However, this elevation was unrelated to the extent of arterial vasodilation, the severity of portal hypertension or the degree of hepatic and renal dysfunction. Although a local hormonal action cannot be excluded, our results do not support a relevant contribution of this system in the hemodynamic disturbance of cirrhosis.

Factors influencing the rate of fibrosis progression in chronic hepatitis C.

Alcohol consumption, age at infection, and male gender have been identified as risk factors for faster fibrosis progression in patients with chronic hepatitis C (CHC). Yet the influence of liver steatosis, light to moderate alcohol consumption, or iron overload on this progression remains controversial. To analyze the effect of individual risk factors and their interaction on fibrosis progression in a group of patients with CHC and a definite date of infection, we studied 133 consecutive untreated patients. Covariates included were age, body mass index (BMI), gender, age at infection, alcohol intake, serum lipids, glycemia, serum ALT, AST, GGT, iron, and ferritin, grade and stage (METAVIR and Scheuer), and hepatic stainable iron (Perl's stain). The rate of fibrosis progression was inferred from the METAVIR score. By logistic regression analysis, hepatic steatosis (odds ratio [OR], 3.035; 95% confidence interval [CI], 1.16-7.93), serum ferritin levels higher than 290 ng/ml (OR, 5.5; 1.6-18.65), and light to moderate ethanol intake (1-50 g/day) (OR, 5.22; 1.5-17.67) were independently associated with faster fibrosis progression. There was no effect of interaction between these variables on the rate of fibrosis progression. Liver steatosis, serum ferritin levels, and light to moderate alcohol intake are associated with faster fibrosis progression in chronic hepatitis C. Combination of these factors did not further accelerate this progression. The impact of modification of these factors on progression should be tested in longitudinal studies.

Relationship between response to interferon-alpha and function of peripheral blood mononuclear cells in chronic hepatitis C patients.

The factors responsible for the low response of chronic hepatitis C patients to interferon-a treatment are not fully understood, although it is known that interferon requires an efficient host immune response to achieve viral clearance. This study was designed to test the hypothesis that hepatitis C virus infection is associated with functional impairment of peripheral blood mononuclear cells, which influence the response to interferon. The proliferative and apoptotic responses of peripheral blood mononuclear cells and purified T cells stimulated with polyclonal mitogenic signals were assessed in 35 chronic hepatitis C patients and 30 healthy controls. Patients were divided into responders and nonresponders according to their sustained response to a course of alpha-interferon-a (3 MU three times weekly for 12 months). The proliferative response to polyclonal mitogens (PHA, TPA) was significantly decreased in nonresponders compared to responders and controls. The defective response was partially normalized by the exogenous addition of interleukin-2 or interleukin-4, and cannot be ascribed to increased apoptosis. Interestingly, the proliferative response of enriched T cells to the same signals was normal. In conclusion, the clinical response to interferon-a defines two different patterns of proliferation by mononuclear cells in chronic hepatitis C patients. This suggests that an alteration of the immune system in these patients may underlie their inadequate response to antiviral therapy.