Colonoscopy examination does not always detect colorectal cancer (CRC)— some patients develop CRC after negative findings from an examination. When this occurs before the next recommended ...examination, it is called interval cancer. From a colonoscopy quality assurance perspective, that term is too restrictive, so the term post-colonoscopy colorectal cancer (PCCRC) was created in 2010. However, PCCRC definitions and methods for calculating rates vary among studies, making it impossible to compare results. We aimed to standardize the terminology, identification, analysis, and reporting of PCCRCs and CRCs detected after other whole-colon imaging evaluations (post-imaging colorectal cancers PICRCs).
A 20-member international team of gastroenterologists, pathologists, and epidemiologists; a radiologist; and a non-medical professional met to formulate a series of recommendations, standardize definitions and categories (to align with interval cancer terminology), develop an algorithm to determine most-plausible etiologies, and develop standardized methodology to calculate rates of PCCRC and PICRC. The team followed the Appraisal of Guidelines for Research and Evaluation II tool. A literature review provided 401 articles to support proposed statements; evidence was rated using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) system. The statements were voted on anonymously by team members, using a modified Delphi approach.
The team produced 21 statements that provide comprehensive guidance on PCCRCs and PICRCs. The statements present standardized definitions and terms, as well as methods for qualitative review, determination of etiology, calculation of PCCRC rates, and non-colonoscopic imaging of the colon.
A 20-member international team has provided standardized methods for analysis of etiologies of PCCRCs and PICRCs and defines its use as a quality indicator. The team provides recommendations for clinicians, organizations, researchers, policy makers, and patients.
Performance characteristics of fecal immunochemical tests (FITs) to screen for colorectal cancer (CRC) have been inconsistent.
To synthesize data about the diagnostic accuracy of FITs for CRC and ...identify factors affecting its performance characteristics.
Online databases, including MEDLINE and EMBASE, and bibliographies of included studies from 1996 to 2013.
All studies evaluating the diagnostic accuracy of FITs for CRC in asymptomatic, average-risk adults.
Two reviewers independently extracted data and critiqued study quality.
Nineteen eligible studies were included and meta-analyzed. The pooled sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio of FITs for CRC were 0.79 (95% CI, 0.69 to 0.86), 0.94 (CI, 0.92 to 0.95), 13.10 (CI, 10.49 to 16.35), 0.23 (CI, 0.15 to 0.33), respectively, with an overall diagnostic accuracy of 95% (CI, 93% to 97%). There was substantial heterogeneity between studies in both the pooled sensitivity and specificity estimates. Stratifying by cutoff value for a positive test result or removal of discontinued FIT brands resulted in homogeneous sensitivity estimates. Sensitivity for CRC improved with lower assay cutoff values for a positive test result (for example, 0.89 CI, 0.80 to 0.95 at a cutoff value less than 20 µg/g vs. 0.70 CI, 0.55 to 0.81 at cutoff values of 20 to 50 µg/g) but with a corresponding decrease in specificity. A single-sample FIT had similar sensitivity and specificity as several samples, independent of FIT brand.
Only English-language articles were included. Lack of data prevented complete subgroup analyses by FIT brand.
Fecal immunochemical tests are moderately sensitive, are highly specific, and have high overall diagnostic accuracy for detecting CRC. Diagnostic performance of FITs depends on the cutoff value for a positive test result.
National Institute of Diabetes and Digestive and Kidney Diseases and National Cancer Institute.
The incidence of esophageal adenocarcinoma has increased markedly in recent decades in many countries. Obesity is a potential risk factor, although the results of individual studies differ. We did a ...systematic review and statistical synthesis of studies that evaluated the association between body mass index (BMI) and the risk of esophageal adenocarcinoma or the adjacent gastric cardia adenocarcinoma.
We identified potential studies using Medline, the Web of Science database, a manual review of the literature and expert bibliographies. Studies were included if they reported (a) a measure of body mass; (b) the occurrence of esophageal or cardia adenocarcinoma diagnosis; and (c) a relative risk or odds ratio (OR) with confidence intervals (CI) or provided sufficient data to permit their calculation.
We identified 14 studies (2 cohort, 12 case-control; 2,488 esophageal and 2,509 cardia adenocarcinomas). A high BMI (>25) was associated with an increased risk of esophageal adenocarcinoma (males, OR, 2.2; 95% CI, 1.7-2.7; females, OR, 2.0; 95% CI, 1.4-2.9). Higher levels of BMI were associated with increased risk (overweight males, OR, 1.8; 95% CI, 1.5-2.2; obese males, OR, 2.4; 95% CI, 1.9-3.2). The overall associations with cardia cancer were heterogeneous, although stratification by study location provided homogeneous results for populations from the United States or Europe. A high BMI was weakly associated with the risk of cardia adenocarcinoma (OR, 1.5; 95% CI, 1.3-1.8; P(heterogeneity) = 0.38).
Pooled results from observational studies support a positive association between high BMI and the risk for esophageal and possibly for cardia adenocarcinoma.
The proportion of screening colonoscopic examinations performed by a physician that detect one or more adenomas (the adenoma detection rate) is a recommended quality measure. However, little is known ...about the association between this rate and patients' risks of a subsequent colorectal cancer (interval cancer) and death.
Using data from an integrated health care delivery organization, we evaluated the associations between the adenoma detection rate and the risks of colorectal cancer diagnosed 6 months to 10 years after colonoscopy and of cancer-related death. With the use of Cox regression, our estimates of attributable risk were adjusted for the demographic characteristics of the patients, indications for colonoscopy, and coexisting conditions.
We evaluated 314,872 colonoscopies performed by 136 gastroenterologists; the adenoma detection rates ranged from 7.4 to 52.5%. During the follow-up period, we identified 712 interval colorectal adenocarcinomas, including 255 advanced-stage cancers, and 147 deaths from interval colorectal cancer. The unadjusted risks of interval cancer according to quintiles of adenoma detection rates, from lowest to highest, were 9.8, 8.6, 8.0, 7.0, and 4.8 cases per 10,000 person-years of follow-up, respectively. Among patients of physicians with adenoma detection rates in the highest quintile, as compared with patients of physicians with detection rates in the lowest quintile, the adjusted hazard ratio for any interval cancer was 0.52 (95% confidence interval CI, 0.39 to 0.69), for advanced-stage interval cancer, 0.43 (95% CI, 0.29 to 0.64), and for fatal interval cancer, 0.38 (95% CI, 0.22 to 0.65). Each 1.0% increase in the adenoma detection rate was associated with a 3.0% decrease in the risk of cancer (hazard ratio, 0.97; 95% CI, 0.96 to 0.98).
The adenoma detection rate was inversely associated with the risks of interval colorectal cancer, advanced-stage interval cancer, and fatal interval cancer. (Funded by the Kaiser Permanente Community Benefit program and the National Cancer Institute.).
Gastroesophageal reflux disease (GERD) is a common cause of morbidity and health-care utilization in many countries. Obesity is a potentially modifiable risk factor, but existing studies have ...conflicting results, possibly due to differences in study design, definitions, or populations.
We performed a systematic review and meta-analysis of studies identified using MEDLINE, the Web of Science electronic database, manual literature review, and a review of expert bibliographies. Studies were included if they: (1) evaluated obesity, body mass index (BMI), or another measure of body size; (2) included data on reflux symptoms, esophagitis, or a GERD-related hospitalization; and (3) reported a relative risk or odds ratio (OR) with confidence intervals or provided sufficient data to permit their calculation.
We identified 20 studies that included 18,346 patients with GERD. Studies from the United States demonstrated an association between increasing BMI and the presence of GERD (95% confidence interval CI= 1.36-1.80, overweight, OR = 1.57, P value homogeneity = 0.51, 95% CI = 1.89-2.45, obese, OR = 2.15, P= 0.10). Studies from Europe provided heterogeneous results despite stratification for several factors; individual studies demonstrated both positive associations and no association.
This analysis demonstrates a positive association between increasing BMI and the presence of GERD within the United States; this relationship became apparent only after stratification by country and level of BMI. These results support the evaluation of weight reduction as a potential therapy for GERD. Further studies are needed to evaluate potential mechanisms and any differences in this relationship among different study populations.
Screening colonoscopy's effectiveness in reducing colorectal cancer mortality risk in community populations is unclear, particularly for right-colon cancers, leading to recommendations against its ...use for screening in some countries. This study aimed to determine whether, among average-risk people, receipt of screening colonoscopy reduces the risk of dying from both right-colon and left-colon/rectal cancers.
We conducted a nested case-control study with incidence-density matching in screening-eligible Kaiser Permanente members. Patients who were 55-90 years old on their colorectal cancer death date during 2006-2012 were matched on diagnosis (reference) date to controls on age, sex, health plan enrolment duration and geographical region. We excluded patients at increased colorectal cancer risk, or with prior colorectal cancer diagnosis or colectomy. The association between screening colonoscopy receipt in the 10-year period before the reference date and colorectal cancer death risk was evaluated while accounting for other screening exposures.
We analysed 1747 patients who died from colorectal cancer and 3460 colorectal cancer-free controls. Compared with no endoscopic screening, receipt of a screening colonoscopy was associated with a 67% reduction in the risk of death from any colorectal cancer (adjusted OR (aOR)=0.33, 95% CI 0.21 to 0.52). By cancer location, screening colonoscopy was associated with a 65% reduction in risk of death for right-colon cancers (aOR=0.35, CI 0.18 to 0.65) and a 75% reduction for left-colon/rectal cancers (aOR=0.25, CI 0.12 to 0.53).
Screening colonoscopy was associated with a substantial and comparably decreased mortality risk for both right-sided and left-sided cancers within a large community-based population.
Background & Aims Although patients with Barrett’s esophagus commonly undergo endoscopic surveillance, its effectiveness in reducing mortality from esophageal/gastroesophageal junction ...adenocarcinomas has not been evaluated rigorously. Methods We performed a case-control study in a community-based setting. Among 8272 members with Barrett’s esophagus, we identified 351 esophageal adenocarcinoma: 70 in persons who had a prior diagnosis of Barrett’s esophagus (who were eligible for surveillance); 51 of these patients died, 38 as a result of the cancers (cases). Surveillance histories were contrasted with a sample of 101 living persons with Barrett’s esophagus (controls), matched for age, sex, and duration of follow-up evaluation. Results Surveillance within 3 years was not associated with a decreased risk of death from esophageal adenocarcinoma (adjusted odds ratio, 0.99; 95% confidence interval, 0.36–2.75). Fatal cases were nearly as likely to have received surveillance (55.3%) as were controls (60.4%). A Barrett’s esophagus length longer than 3 cm and prior dysplasia each were associated with subsequent mortality, but adjustment for these did not change the main findings. Although all patients should be included in evaluations of effectiveness, excluding deaths related to cancer treatment and patients who failed to complete treatment, changed the magnitude, but not the significance, of the association (odds ratio, 0.46; 95% confidence interval, 0.13–1.64). Conclusions Endoscopic surveillance of patients with Barrett’s esophagus was not associated with a substantially decreased risk of death from esophageal adenocarcinoma. The results do not exclude a small to moderate benefit. However, if such a benefit exists, our findings indicate that it is substantially smaller than currently estimated. The effectiveness of surveillance was influenced partially by the acceptability of existing treatments and the occurrence of treatment-associated mortality.
Proton pump inhibitors (PPIs) and histamine 2 receptor antagonists (H2RAs) suppress the production of gastric acid and thus may lead to malabsorption of vitamin B12. However, few data exist regarding ...the associations between long-term exposure to these medications and vitamin B12 deficiency in large population-based studies.
To study the association between use of PPIs and H2RAs and vitamin B12 deficiency in a community-based setting in the United States.
We evaluated the association between vitamin B12 deficiency and prior use of acid-suppressing medication using a case-control study within the Kaiser Permanente Northern California population. We compared 25,956 patients having incident diagnoses of vitamin B12 deficiency between January 1997 and June 2011 with 184,199 patients without B12 deficiency. Exposures and outcomes were ascertained via electronic pharmacy, laboratory, and diagnostic databases.
Risk of vitamin B12 deficiency was estimated using odds ratios (ORs) from conditional logistic regression.
Among patients with incident diagnoses of vitamin B12 deficiency, 3120 (12.0%) were dispensed a 2 or more years' supply of PPIs, 1087 (4.2%) were dispensed a 2 or more years' supply of H2RAs (without any PPI use), and 21,749 (83.8%) had not received prescriptions for either PPIs or H2RAs. Among patients without vitamin B12 deficiency, 13,210 (7.2%) were dispensed a 2 or more years' supply of PPIs, 5897 (3.2%) were dispensed a 2 or more years' supply of H2RAs (without any PPI use), and 165,092 (89.6%) had not received prescriptions for either PPIs or H2RAs. Both a 2 or more years' supply of PPIs (OR, 1.65 95% CI, 1.58-1.73) and a 2 or more years' supply of H2RAs (OR, 1.25 95% CI, 1.17-1.34) were associated with an increased risk for vitamin B12 deficiency. Doses more than 1.5 PPI pills/d were more strongly associated with vitamin B12 deficiency (OR, 1.95 95% CI, 1.77-2.15) than were doses less than 0.75 pills/d (OR, 1.63 95% CI, 1.48-1.78; P = .007 for interaction).
Previous and current gastric acid inhibitor use was significantly associated with the presence of vitamin B12 deficiency. These findings should be considered when balancing the risks and benefits of using these medications.
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