Search

Background: Mechanisms for how Helicobacter pylori infection affects risk of gastroesophageal reflux disease (GERD) and Barrett's esophagus are incompletely understood and might differ by sex. Methods: In a case-control study nested in the Melbourne Collaborative Cohort Study with 425 GERD cases and 169 Barrett's esophagus cases (identified at 2007-2010 follow-up), we estimated sex-specific odds ratios for participants who were H. pylori seronegative versus seropositive at baseline (1990-1994). To explore possible mechanisms, we (i) compared patterns of H. pylori-induced gastritis by sex using serum pepsinogen-I and gastrin-17 data and (ii) quantified the effect of H. pylori seronegativity on Barrett's esophagus mediated by GERD using causal mediation analysis. Results: For men, H. pylori seronegativity was associated with 1.69-fold [95% confidence interval (CI), 1.03-2.75] and 2.28-fold (95% CI, 1.27-4.12) higher odds of GERD and Barrett's esophagus, respectively. No association was observed for women. H. pylori-induced atrophic antral gastritis was more common in men (68%) than in women (56%; P = 0.015). For men, 5 of the 15 per 1,000 excess Barrett's esophagus risk from being seronegative were mediated by GERD. Conclusions: Men, but not women, who were H. pylori seronegative had increased risks of GERD and Barrett's esophagus. A possible explanation might be sex differences in patterns of H. pylori-induced atrophic antral gastritis, which could lead to less erosive reflux for men. Evidence of GERD mediating the effect of H. pylori on Barrett's esophagus risk among men supports this proposed mechanism. Impact: The findings highlight the importance of investigating sex differences in the effect of H. pylori on risk of GERD and Barrett's esophagus in future studies. [ABSTRACT FROM AUTHOR]

We examined demographic and lifestyle risk factors for incidence of gastroesophageal reflux disease (GERD) and Barrett's esophagus (BE) in an Australian cohort of 20,975 participants aged 40–63 at recruitment (1990–1994). Information on GERD and BE was collected between 2007 and 2010. GERD symptoms were defined as self-reported heartburn or acid regurgitation. BE was defined as endoscopically confirmed columnar-lined esophagus. Risk factors for developing GERD symptoms, BE diagnosis, age at symptom onset, and age at BE diagnosis were quantified using regression. During a mean follow-up of 15.8 years, risk of GERD symptoms was 7.5% (n  = 1,318) for daily, 7.5% (n  = 1,333) for 2–6 days/week, and 4.3% (n  = 751) for 1 day/week. There were 210 (1.0%) endoscopically diagnosed BE cases, of whom 141 had histologically confirmed esophageal intestinal metaplasia. Female sex, younger age, lower socioeconomic position (SEP) and educational attainment, and former smoking were associated with higher GERD risk. Male sex and smoking were associated with earlier GERD symptom onset. Men, older participants, those with higher SEP, and former smokers were at higher BE risk. There was some evidence higher SEP was associated with earlier BE diagnosis. GERD and BE had different demographic risk factors but shared similar lifestyle factors. Earlier GERD symptom onset for men and smokers might have contributed to higher BE risk. The SEP patterns observed for GERD and BE suggest potential inequity in access to care. These findings would be important in the development of clinical risk prediction models for early detection of BE. [ABSTRACT FROM AUTHOR]

Background: Socio-economic inequalities in colon cancer survival exist in high-income countries, but the reasons are unclear. We assessed the mediating effects of stage at diagnosis, comorbidities, and treatment (surgery and intravenous chemotherapy) on survival from colon cancer. Methods: We identified 2,203 people aged 15 to 79 years with first primary colon cancer diagnosed in Victoria, Australia, between 2008 and 2011. Colon cancer cases were identified through the Victorian Cancer Registry (VCR), and clinical information was obtained from hospital records. Deaths till December 31, 2016 (n = 807), were identified from Victorian and national death registries. Socio-economic disadvantage was based on residential address at diagnosis. For stage III disease, we decomposed its total effect into direct and indirect effects using interventional mediation analysis. Results: Socio-economic inequalities in colon cancer survival were not explained by stage and were greater for men than women. For men with stage III disease, there were 161 [95% confidence interval (CI), 67-256] additional deaths per 1,000 cases in the 5 years following diagnosis for the most disadvantaged compared with the least disadvantaged. The indirect effects through comorbidities and intravenous chemotherapy explained 6 (95% CI, -10-21) and 15 (95% CI, -14-44) per 1,000 of these additional deaths, respectively. Surgery did not explain the observed gap in survival. Conclusions: Disadvantaged men have lower survival from stage III colon cancer that is only modestly explained by having comorbidities or not receiving chemotherapy after surgery. [ABSTRACT FROM AUTHOR]

Rationale, aims, and objectives: Care pathway policies for cancer aim to reduce variation and improve the quality of patient care, and there is increasing evidence that adherence to such pathways is associated with improved survival and lower health care costs. Australia is implementing Optimal Care Pathways (OCPs) for several cancers, including colorectal cancer, but studies evaluating how well care conforms to OCP recommendations are rare. This study examined concordance between OCP recommendations and colorectal cancer care prior to policy rollout and disparities for vulnerable populations. Method: Cross‐sectional survey (2012‐2014) of cancer registry‐identified colorectal cancer patients aged ≥40 approached within 6 months of diagnosis (n = 433), their general practitioner (GP, n = 290), and specialist (n = 144) in Victoria, Australia. We measured concordance with 10 OCP recommendations and variation by geography, socio‐economic, and health insurance status using age‐ and sex‐adjusted logistic regression models. Results: Use of recommended GP investigations varied from 66% for colonoscopy to 13% for digital rectal exam. Recommended waiting times to receive a colonoscopy, see a specialist after referral, and begin adjuvant chemotherapy were exceeded for around a third of patients. Twenty‐eight percent of specialists reported a pretreatment multidisciplinary meeting. Most patients received surgery in a hospital with an intensive care unit (92%) and chemotherapy for high risk disease (84%). In general, care was similar across sociodemographic groups. However, receipt of GP investigations tended to be higher and waiting times longer for rural, low socio‐economic, and non‐privately insured patients. For example, receiving a colonoscopy within 4 weeks was significantly less likely for rural (51%) than urban (78%) patients (odds ratio = 0.30; 95% confidence interval, 0.11‐0.79). Conclusion: Prior to implementation, a significant proportion of colorectal cancer patients received care that did not meet OCP recommendations. Low concordance and inequities for rural and disadvantaged populations highlight components of the pathway to target during policy implementation. [ABSTRACT FROM AUTHOR]

Objective. The molecular and cellular events responsible for regulating development of the oesophageal epithelium are not well understood. At least in part, this is due to the lack of a suitable model system with which to study the process. Here, we report development of a manipulable in vivo transplant model for mouse or human oesophageal epithelium. Material and methods. Epithelial cells were isolated from mouse or human oesophagus and inoculated into de-epithelialized and devitalized rat tracheas. The rat trachea, containing cells, was placed subcutaneously under the dorsal skin of immunodeficient mice. Results. We show that a multilayered stratified squamous epithelium can be generated in 4-6 weeks from as few as 5×104 isolated oesophageal epithelial cells. The reconstituted epithelium recapitulates many of the structural and histological features of the normal oesophageal epithelium, including a basal layer of cuboidal-like cells, suprabasal layers of differentiating squamous cells and, in the case of murine cells, a superficial layer of cornified material. Conclusion. Our model can be used to generate a multilayered normal murine or human epithelium from a single cell suspension of oesophageal epithelial cells. The ability to genetically manipulate the cells prior to growth in the model is a powerful tool with which to study the molecular mechanisms involved in the development of normal oesophagus or in pathogenic processes such as Barrett's metaplasia or tumorigenesis. [ABSTRACT FROM AUTHOR]

The identification and characterization of esophageal stem cells are critical to our understanding of the biology of the esophageal epithelium in health and disease. However, the proliferative compartment within the mouse esophageal epithelium remains poorly characterized. Here, we report that the basal cells of the mouse esophagus can be separated into three phenotypically and functionally distinct subpopulations based on the expression of α6 integrin and transferrin receptor (CD71). Cells that express high levels of α6 integrin and low levels of CD71, termed α6briCD71dim, are a minor subpopulation of small and undifferentiated cells that are enriched for label-retaining cells and thus represent a putative esophageal stem cell population. Conversely, cells expressing high levels of both α6 integrin and CD71 (α6briCD71bri), the majority of basal esophageal cells, are enriched for actively cycling cells and therefore represent a transit-amplifying population. Kinetic analyses revealed that a third cell population, which is α6 integrin-dim and CD71-bright (α6dim), is destined to leave the basal layer and differentiate. [ABSTRACT FROM AUTHOR]