Bradley J. Kendall

Leptin and the risk of Barrett’s oesophagus

Background: Obesity is associated with increased risks of Barrett’s oesophagus and oesophageal adenocarcinoma. Alterations in serum leptin and adiponectin, obesity-related cytokines, have been linked with several cancers and have been postulated as potential mediators of obesity-related carcinogenesis; however, the relationship with Barrett’s oesophagus remains unexplored. Methods: Serum leptin and adiponectin concentrations were measured on two subsets of participants within a case–control study conducted in Brisbane, Australia. Cases were people aged 18–79 years with histologically confirmed Barrett’s oesophagus newly diagnosed between 2003 and 2006. Population controls, frequency matched by age and sex to cases, were randomly selected from the electoral roll. Phenotype and medical history data were collected through structured, self-completed questionnaires. Odds ratios (OR) and 95% CI were calculated using multivariable logistic regression analysis. Results: In the pilot analysis (51 cases, 67 controls) risks of Barrett’s oesophagus were highest among those in the highest quartile of serum leptin (OR 4.6, 95% CI 0.6 to 33.4). No association was seen with adiponectin. In the leptin validation study (306 cases, 309 controls), there was a significant threefold increased risk of Barrett’s oesophagus among men in the highest quartile of serum leptin (OR 3.3, 95% CI 1.7 to 6.6) and this persisted after further adjustment for symptoms of gastro-oesophageal reflux (OR 2.4, 95% CI 1.1 to 5.2). In contrast, the risk of Barrett’s oesophagus among women decreased with increasing serum leptin concentrations. Conclusions: High serum leptin is associated with an increased risk of Barrett’s oesophagus among men but not women. This association is not explained simply by higher body mass or gastro-oesophageal reflux among cases. The mechanism remains to be determined.

A Model to Determine Absolute Risk for Esophageal Adenocarcinoma

BACKGROUND & AIMS Esophageal adenocarcinoma (EAC) develops rapidly and has a high mortality rate. We aimed to develop a prediction model to estimate the absolute 5-year risks, based on different profiles of factors, for developing EAC. METHODS We derived a risk model using epidemiologic data from 364 patients with incident EAC and 1580 population controls. Significant risk factors were fitted into an unconditional multiple logistic regression model. The final model was combined with age- and sex-specific EAC incidence data to estimate absolute 5-year risks for EAC. We performed a 10-fold cross-validation of the data to assess the relative performance of the model. RESULTS The final risk model included terms for highest level of education, body mass index, smoking status, frequency of gastroesophageal reflux symptoms and/or use of acid-suppressant medications, and frequency of nonsteroidal anti-inflammatory drug use. The population attributable risk for the model was 0.92. A 10-fold cross-validation produced an area under the receiver operating characteristic curve statistic of 0.75 (95% confidence interval, 0.66-0.84), indicating good discrimination. Adding data on alarm symptoms, frequency of symptoms of dysphagia, and unexplained weight loss to the model significantly improved discrimination (area under the receiver operating characteristic curve, 0.85; 95% confidence interval, 0.78-0.91). CONCLUSIONS Risk models can be used to identify people with a higher than average risk for developing EAC; these individuals might benefit from targeted cancer-prevention strategies.

A Clinical Risk Prediction Model for Barrett Esophagus

Barrett esophagus is the only known precursor to esophageal adenocarcinoma. As definitive diagnosis requires costly endoscopic investigation, we sought to develop a risk prediction model to aid in deciding which patients with gastroesophageal reflux symptoms to refer for endoscopic screening for Barrett esophagus. The study included data from patients with incident nondysplastic Barrett esophagus (n = 285) and endoscopy control patients with esophageal inflammatory changes without Barrett esophagus (“inflammation controls”, n = 313). We used two phases of stepwise backwards logistic regression to identify the important predictors for Barrett esophagus in men and women separately: first, including all significant covariates from univariate analyses and then fitting non-significant covariates from univariate analyses to identify those effects detectable only after adjusting for other factors. The final model pooled these predictors and was externally validated for discrimination and calibration using data from a Barrett esophagus study conducted in western Washington State. The final risk model included terms for age, sex, smoking status, body mass index, highest level of education, and frequency of use of acid suppressant medications (area under the ROC curve, 0.70; 95%CI, 0.66–0.74). The model had moderate discrimination in the external dataset (area under the ROC curve, 0.61; 95%CI, 0.56–0.66). The model was well calibrated (Hosmer–Lemeshow test, P = 0.75), with predicted probability and observed risk highly correlated. The prediction model performed reasonably well and has the potential to be an effective and useful clinical tool in selecting patients with gastroesophageal reflux symptoms to refer for endoscopic screening for Barrett esophagus. Cancer Prev Res; 5(9); 1115–23. ©2012 AACR.

Temporal Changes in the Endoscopic Frequency of New Cases of Barrett's Esophagus in an Australian Health Region

OBJECTIVES:The number of patients diagnosed with Barretts esophagus (BE) has increased in recent decades, although data from populations outside Europe and North America are scarce. This increase has significant implications for health resource utilization and costs. We sought to determine changes in the endoscopic frequency of new cases of BE in an Australian population during the period 1990–2002.METHODS:We identified all persons newly diagnosed with BE in an Australian health region in 1990, 1998, and 2002. BE cases were categorized as short segment (SSBE) (<3 cm), long segment (≥3 cm), or undefined length. We compared the total number of esophagogastroduodenoscopies (EGD) and the number of new cases of BE for the three time periods.RESULTS:Between 1990 and 2002, the endoscopic frequency of new cases of BE increased from 2.9 to 18.9 per 1,000 endoscopies (p < 0.001). The greatest increase was for SSBE, increasing from no new cases in 1990 to 6.2 new cases per 1,000 EGD in 2002. In contrast there was a 17% decrease (2.3–1.9 new cases per 1,000 EGD) for long segment BE during the same period. There were 3,090 EGDs undertaken in 1990, 3,518 in 1998, and 2,593 in 2002, an increase of 14% over the first 8-yr interval (p < 0.001), and a decline of 26% over the subsequent 4 yr (p < 0.001).CONCLUSIONS:In an Australian population undergoing EGD, the endoscopic frequency and absolute number of new cases of BE, particularly SSBE disease, has increased significantly between 1990 and 2002. This increased frequency of patients diagnosed with BE has broad future economic and clinical implications.

The risk of Barrett's esophagus associated with abdominal obesity in males and females.

Esophageal adenocarcinoma arises from Barretts esophagus (BE). Both occur predominantly in males. The role of abdominal obesity in this sex distribution is uncertain. Our study aimed to determine whether there is an association between abdominal obesity and risk of BE and if present was it modified by sex. A structured interview and anthropometric measures were conducted within a population‐based case–control study. We recruited 237 BE cases (70% male) and 247 population controls, frequency matched by age and sex. Odds ratios (OR) and 95% confidence intervals (CI) were calculated using multivariable logistic regression analysis. In the overall group and males, all measures of abdominal obesity [waist circumference (WC), waist–hip ratio (WHR), sagittal abdominal diameter (SAD) and waist–height ratio (WHtR)] were strongly associated with risk of BE (Overall: WC OR 2.2 95% CI 1.4–3.5, WHR 1.8 95% CI 1.2–2.9, SAD 2.3 95% CI 1.4–3.7, WHtR 1.9 95% CI 1.2–3.0, males WC 2.5 95% CI 1.4–4.3, WHR 2.4 95% CI 1.3–4.2, SAD 2.5 95% CI 1.4–4.3, WHtR 1.9 95% CI 1.1–3.4). These associations were minimally attenuated by adjusting for ever‐symptoms of gastroesophageal reflux (GER). These findings suggest in males, non‐GER factors related to abdominal obesity may be important in the development of BE. In females, there was modest association between measures of abdominal obesity and risk of BE but these were all abolished after adjusting for ever‐symptoms of GER. The power to detect differences between sexes in the risk of BE associated with abdominal obesity was limited by the number of females in the study.

Cancers in Australia in 2010 attributable to modifiable factors: summary and conclusions.

Objective: To estimate the numbers and proportions of cancers occurring in Australia in 2010 attributable to modifiable causal factors.

Australian clinical practice guidelines for the diagnosis and management of Barrett's esophagus and early esophageal adenocarcinoma

Barretts esophagus (BE), a common condition, is the only known precursor to esophageal adenocarcinoma (EAC). There is uncertainty about the best way to manage BE as most people with BE never develop EAC and most patients diagnosed with EAC have no preceding diagnosis of BE. Moreover, there have been recent advances in knowledge and practice about the management of BE and early EAC. To aid clinical decision making in this rapidly moving field, Cancer Council Australia convened an expert working party to identify pertinent clinical questions. The questions covered a wide range of topics including endoscopic and histological definitions of BE and early EAC; prevalence, incidence, natural history, and risk factors for BE; and methods for managing BE and early EAC. The latter considered modification of lifestyle factors; screening and surveillance strategies; and medical, endoscopic, and surgical interventions. To answer each question, the working party systematically reviewed the literature and developed a set of recommendations through consensus. Evidence underpinning each recommendation was rated according to quality and applicability.

Cancers in Australia in 2010 attributable to overweight and obesity

Objectives: To estimate the proportion and number of cancers occurring in Australia in 2010 attributable to overweight/obesity.

Cancers in Australia in 2010 attributable to insufficient physical activity

Objectives: To estimate the proportion and numbers of cancers occurring in Australia in 2010 attributable to insufficient levels of physical activity.

Cancers in Australia in 2010 attributable to infectious agents

Objectives: To estimate the proportion and numbers of cancers in Australia in 2010 attributable to infectious agents.