Fernando Carballo

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.).

A Nationwide Study of Mortality Associated with Hospital Admission Due to Severe Gastrointestinal Events and Those Associated with Nonsteroidal Antiinflammatory Drug Use

BACKGROUND:The worst outcome of gastrointestinal complications is death. Data regarding those associated with nonsteroidal antiinflammatory drug (NSAID) or aspirin use are scarce.AIM:To determine mortality associated with hospital admission due to major gastrointestinal (GI) events and NSAID/aspirin use.METHODS:The study was based on actual count of deaths from two different data sets from 2001. Study 1 was carried out in 26 general hospitals serving 7,901,198 people. Study 2 used a database from 197 general hospitals, representative of the 269 hospitals in the Spanish National Health System. Information regarding gastrointestinal complications and deaths was obtained throughout the Minimum Basic Data Set (CIE-9-MC) provided by participating hospitals. Deaths attributed to NSAID/aspirin use were estimated on the basis of prospectively collected data from hospitals of study 1.RESULTS:The incidence of hospital admission due to major GI events of the entire (upper and lower) gastrointestinal tract was 121.9 events/100,000 persons/year, but those related to the upper GI tract were six times more frequent. Mortality rate was 5.57% (95% CI = 4.9–6.7), and 5.62% (95% CI = 4.8–6.8) in study 1 and study 2, respectively. Death rate attributed to NSAID/aspirin use was between 21.0 and 24.8 cases/million people, respectively, or 15.3 deaths/100,000 NSAID/aspirin users. Up to one-third of all NSAID/aspirin deaths can be attributed to low-dose aspirin use.CONCLUSION:Mortality rates associated with either major upper or lower GI events are similar but upper GI events were more frequent. Deaths attributed to NSAID/ASA use were high but previous reports may have provided an overestimate and one-third of them can be due to low-dose aspirin use.

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.

Double-balloon enteroscopy: a descriptive study of 50 explorations

AIM To evaluate the utility of double-balloon enteroscopy for small-bowel disease. DESIGN A prospective study of 50 consecutive enteroscopies performed from December 2004 to July 2005 to analyze diagnoses and treatments. PATIENTS 44 patients (33 had undergone a previous capsule endoscopy) with indications for obscure digestive hemorrhage, angiodysplasia, Peutz-Jeghers syndrome, ulcer, suspected Crohns disease, tumors, and refractory celiac disease. RESULTS We carried out enteroscopy studies in 44 patients by the oral route and, in 6 additional patients, by both the oral and anal routes. We reached the ileon with the oral route in all cases but one (jejunal stenosis), and in 4 cases out of 7 with the anal route, with an average duration of 73 minutes. We found angiodysplasia in 19 cases, as well as NSAID-related enteropathy, Crohns disease, diverticulosis, and Waldenströms disease. We performed biopsies in 31% of cases with diagnoses of adenocarcinoma, lymphangiectasia secondary to tumor in celiac disease, and Whipples disease. We treated 19 patients with angiodysplasia (1 to 20 synchronous lesions) with argon, and 4 patients with polyps using polipectomy (sporadic polyps or Peutz-Jeghers syndrome). A retained capsule in one patient with stenosis was removed. CONCLUSIONS Double-balloon enteroscopy is a useful and effective technique in the diagnosis and treatment of small intestine diseases, thus complementing capsule endoscopy. More studies are needed to analyze its impact on the management of this condition.

Risk of Advanced Proximal Neoplasms According to Distal Colorectal Findings: Comparison of Sigmoidoscopy-Based Strategies

BACKGROUND Screening for colorectal cancer with sigmoidoscopy benefits from the fact that distal findings predict the risk of advanced proximal neoplasms (APNs). This study was aimed at comparing the existing strategies of postsigmoidoscopy referral to colonoscopy in terms of accuracy and resources needed. METHODS Asymptomatic individuals aged 50-69 years were eligible for a randomized controlled trial designed to compare colonoscopy and fecal immunochemical test. Sigmoidoscopy yield was estimated from results obtained in the colonoscopy arm according to three sets of criteria of colonoscopy referral (from those proposed in the UK Flexible Sigmoidoscopy, Screening for COlon REctum [SCORE], and Norwegian Colorectal Cancer Prevention [NORCCAP] trials). Advanced neoplasm detection rate, sensitivity, specificity, and number of individuals needed to refer for colonoscopy to detect one APN were calculated. Logistic regression analysis was performed to identify distal findings associated with APN. All statistical tests were two-sided. RESULTS APN was found in 255 of 5059 (5.0%) individuals. Fulfillment of UK (6.2%), SCORE (12.0%), and NORCCAP (17.9%) criteria varied statistically significantly (P < .001). The NORCCAP strategy obtained the highest sensitivity for APN detection (36.9%), and the UK approach reached the highest specificity (94.6%). The number of individuals needed to refer for colonoscopy to detect one APN was 6 (95% confidence interval [CI] = 4 to 7), 8 (95% CI = 6 to 9), and 10 (95% CI = 8 to 12) when the UK, SCORE, and NORCCAP criteria were used, respectively. The logistic regression analysis identified distal adenoma ≥10 mm (odds ratio = 3.77; 95% CI = 2.52 to 5.65) as the strongest independent predictor of APN. CONCLUSIONS Whereas the NORCCAP criteria achieved the highest sensitivity for APN detection, the UK recommendations benefited from the lowest number of individuals needed to refer for colonoscopy.

Prevention or cure in times of crisis: the case of screening for colorectal cancer.

Colorectal cancer is a serious health problem in which screening is capable of reducing both the mortality and the incidence of the disorder. Colonoscopy, the mainstay of this type of screening, allows to establish an early diagnosis and also to eliminate malignant pre cursor lesions. The screening test which is performed in Spanish programs is the determination of fecal occult blood using the immunochemical method which gives around 70% of positive values for colonoscopy for any type of neoplasia. As a result, in 2009 the National Health System set as an objective that these programs cover 50% of the population by 2015. It is well known that colon screening is highly cost effective with a ratio of around 2500 € per QALY, much lower than ratios of other programs. Only the direct costs of colon and rectal cancer in Spain can be estimated at more than one thousand million euros per year. Early diagnosis and the cancers avoided thanks to screening can reduce these costs by 40%. The impact that the introduction of this screening has on health ser vices can be lessened if the indications for colonoscopy are followed adequately. In conclusion, there is no justification for not acting to prevent CRC and this is especially so in times of crisis as there is no better social cost invested than that which saves suffering, deaths and even money.

Effect of Aspirin and Antiplatelet Drugs on the Outcome of the Fecal Immunochemical Test

OBJECTIVE To evaluate the effect of aspirin and nonaspirin antiplatelet agents (NAAAs) on the performance of the fecal immunochemical test (FIT). PARTICIPANTS AND METHODS We performed a post hoc analysis of results from a clinical trial that involved 28,696 asymptomatic average-risk men and women aged 50 to 69 years invited to participate in a colorectal cancer screening program with FIT between November 1, 2008, and June 31, 2011. RESULTS The test was returned by 6390 individuals (22.3%), of whom 5821 (91.1%) reported not using antiplatelet drugs (nonusers group) and 569 (8.9%) reported using these drugs at the time of testing (users group). The FIT result was positive in 48 of 569 users (8.4%) and 365 of 5821 nonusers (6.3%) (P=.05). A positive FIT result was found in 7.3% (28/384) of aspirin users, 7.1% (10/140) of NAAA users, and 22.2% (10/45) of those undergoing dual antiplatelet therapy (DAPT) (aspirin plus an NAAA). The DAPT subgroup had a significantly higher positive FIT rate than the nonuser group (odds ratio, 3.5; 95% CI, 1.7-7.3; P<.05). The positive predictive value (PPV) for advanced neoplasia (AN) in nonusers was 50.4% vs 50.0% in users (P = .40). The PPV for AN was 57.0% in aspirin users, 30.0% in NAAA users, and 50.0% in DAPT users, without statistically significant differences between the user and nonuser groups. CONCLUSION The use of DAPT increased the rate of positive FIT results. Use of aspirin, NAAAs, or both did not modify the PPV for AN in this population-based colorectal screening program.

Economic evaluation of colorectal cancer (CRC) screening.

Because of its incidence and mortality colorectal cancer represents a serious public health issue in industrial countries. In order to reduce its social impact a number of screening strategies have been implemented, which allow an early diagnosis and treatment. These basically include faecal tests and studies that directly explore the colon and rectum. No strategy, whether alone or combined, has proven definitively more effective than the rest, but any such strategy is better than no screening at all. Selecting the most efficient strategy for inclusion in a population-wide program is an uncertain choice. Here we review the evidence available on the various economic evaluations, and conclude that no single method has been clearly identified as most cost-effective; further research in this setting is needed once common economic evaluation standards are established in order to alleviate the methodological heterogeneity prevailing in study results.

Effect of double-balloon enteroscopy on pancreas: An experimental porcine model

AIM To evaluate the effect of double-balloon enteroscopy (DBE) on pancreas histology and levels of pancreatic enzymes. METHODS Conventional upper gastrointestinal endoscopy was performed on five control pigs. Oral DBE was performed with an EN-450T5 enteroscope on 20 pigs. Two experimental groups (10 pigs each) were defined according to DBE duration: 90 min for Group 1 and 140 min for group 2. During oral insertion, the balloons were not inflated in the descending part of the duodenum to avoid the minor duodenal papilla. Serum amylase, lipase and C-reactive protein (CRP) levels were monitored before the procedure and repeated every 30 min until the exploration was finished, as well as 24 h and 7 d after. After the procedure and for a total of 7 d, the pigs were observed twice a day for signs of decreased activity, irritability, vomiting or anorexia. Gross and microscopic examination of the pancreas was performed on day 7. RESULTS All animals tolerated DBE without clinical manifestations of acute pancreatitis. Experimental groups had higher levels of enzymes than the control group at 24 h. Throughout the exploration, the amylase levels increased significantly above the baseline 24 h after DBE, although the increase was not statistically significant and did not reach 20% of the baseline. An increase in lipase and CRP was observed at 24 h after the procedure, although by day 7, all enzymatic levels had returned to baseline. No differences between groups 1 and 2 were found for any enzyme and sampling site during and after the procedure. Similarly, no correlation between insertion depth and enzyme levels was observed. Direct in situ and post-removal inspection of the pancreas did not show any evidence of fluid collection, abscesses or hemorrhage. Histological examination of the pancreas from groups 1 and 2 revealed the existence of focal areas (0.14-0.26 mm2) of ischemic necrosis in 47.4% of the animals. In the pigs with damaged pancreas, the left lobe (tail) was always affected. However, this only happened in 83.3% of the samples from the right lobe (head) and in 33.3% of the samples from the body of the pancreas. Significant differences were found between the left lobe (tail) and the body for the percentage of affected pancreas. Both the size of the lesions and the percentage of affected pancreas were higher in the left pancreatic lobe (tail). The presence of the lesions was not related to the exploration length. CONCLUSION The increase in pancreatic enzymes after DBE could be related to focal points of pancreatic ischemic necrosis due to mechanical stress.

Carbon dioxide insufflation safety in double-balloon enteroscopy: an experimental animal study.

The aim of the present study was to assess the safety and efficacy of CO2 during double‐balloon enteroscopy (DBE) in an experimental animal model study. In this study, insufflation with room air and with CO2 was compared.