Incidence of adenocarcinoma among patients with Barrett's esophagus.

BACKGROUND: Accurate population-based data are needed on the incidence of esophageal adenocarcinoma and high-grade dysplasia among patients with Barrett's esophagus. METHODS: We conducted a nationwide, population-based, cohort study involving all patients with Barrett's esophagus in Denmark during the period from 1992 through 2009, using data from the Danish Pathology Registry and the Danish Cancer Registry. We determined the incidence rates (numbers of cases per 1000 person-years) of adenocarcinoma and high-grade dysplasia. As a measure of relative risk, standardized incidence ratios were calculated with the use of national cancer rates in Denmark during the study period. RESULTS: We identified 11,028 patients with Barrett's esophagus and analyzed their data for a median of 5.2 years. Within the first year after the index endoscopy, 131 new cases of adenocarcinoma were diagnosed. During subsequent years, 66 new adenocarcinomas were detected, yielding an incidence rate for adenocarcinoma of 1.2 cases per 1000 person-years (95% confidence interval [CI], 0.9 to 1.5). As compared with the risk in the general population, the relative risk of adenocarcinoma among patients with Barrett's esophagus was 11.3 (95% CI, 8.8 to 14.4). The annual risk of esophageal adenocarcinoma was 0.12% (95% CI, 0.09 to 0.15). Detection of low-grade dysplasia on the index endoscopy was associated with an incidence rate for adenocarcinoma of 5.1 cases per 1000 person-years. In contrast, the incidence rate among patients without dysplasia was 1.0 case per 1000 person-years. Risk estimates for patients with high-grade dysplasia were slightly higher. CONCLUSIONS: Barrett's esophagus is a strong risk factor for esophageal adenocarcinoma, but the absolute annual risk, 0.12%, is much lower than the assumed risk of 0.5%, which is the basis for current surveillance guidelines. Data from the current study call into question the rationale for ongoing surveillance in patients who have Barrett's esophagus without dysplasia. (Funded by the Clinical Institute, University of Aarhus, Aarhus, Denmark.).

Short communication: first case of bacteraemia caused by Dielma fastidiosa in a patient hospitalized with diverticulitis.

Dielma fastidiosa is a gram-negative, anaerobic rod belonging to the family Erysipelotrichaceae. D. fastidiosa has previously been isolated in human stool samples as part of the commensal flora; however, prior to this case, it has never been identified as a human pathogen. We present the first case of bacteraemia with D. fastidiosa. Bacterial growth in the blood culture bottle was detected by the automated blood culture system BacT/ALERT 3D. Culturing was performed, and bacterial colonies were identified as D. fastidiosa using MALDI-TOF MS. A subsequent whole-genome sequencing using Illumina NovaSeq was performed, and a phylogenetic tree depicting all available sequences of D. fastidiosa was generated. The reference MALDI-TOF spectrum and species identification was compared with the previously published spectrum. Whole-genome sequencing confirmed the tentative MALDI-TOF species identification. Notably, the maximum-likelihood-based phylogenetic analysis placed the D. fastidiosa isolate from this clinical case within the known variation of the eight publicly available sequences of this species. We identified D. fastidiosa by whole-genome sequencing followed by maximum-likelihood analysis as a possible pathogen in this case of bacteraemia in a patient hospitalized with diverticulitis.

Randomized clinical trial: inhibition of the TRPV1 system in patients with nonerosive gastroesophageal reflux disease and a partial response to PPI treatment is not associated with analgesia to esophageal experimental pain.

OBJECTIVE: Many patients with nonerosive reflux disease (NERD) have insufficient relief on proton pump inhibitors (PPIs). Some patients have a hypersensitive esophagus and may respond to transient receptor potential vanilloid 1 (TRPV1) antagonists. Aim. To investigate the effect of the TRPV1 antagonist AZD1386 on experimental esophageal pain in NERD patients. MATERIAL AND METHODS: Enrolled patients had NERD and a partial PPI response (moderate-to-severe heartburn or regurgitation ≥3 days/week before enrolment despite ≥6 weeks' PPI therapy). Fourteen patients (21-69 years, 9 women) were block-randomized into this placebo-controlled, double-blinded, crossover study examining efficacy of a single dose (95 mg) of AZD1386. On treatment days, each participant's esophagus was stimulated with heat, distension, and electrical current at teaching hospitals in Denmark and Sweden. Heat and pressure pain served as somatic control stimuli. Per protocol results were analyzed. RESULTS: Of 14 randomized patients, 12 were treated with AZD1386. In the esophagus AZD1386 did not significantly change the moderate pain threshold for heat [-3%, 95% confidence interval (CI), -22;20%], distension (-11%, 95% CI, -28;10%), or electrical current (6%, 95% CI, -10;25%). Mean cutaneous heat tolerance increased by 4.9°C (95% CI, 3.7;6.2°C). AZD1386 increased the maximum body temperature by a mean of 0.59°C (95% CI, 0.40-0.79°C), normalizing within 4 h. CONCLUSIONS: AZD1386 had no analgesic effect on experimental esophageal pain in patients with NERD and a partial PPI response, whereas it increased cutaneous heat tolerance. TRPV1 does not play a major role in heat-, mechanically and electrically evoked esophageal pain in these patients. ClinicalTrials.gov identifier: D9127C00002.

Long-term complications to reflux disease in community practice. A 17-year cohort study of 4706 patients.

OBJECTIVE: To examine the risk of developing strictures in patients with erosive and non-erosive gastroesophageal reflux disease in a community-based setting, since controlled trials indicate that the use of proton pump inhibitors renders the risk of strictures insignificant. MATERIAL AND METHODS: A 17-year cohort study of 4706 patients referred to endoscopy due to upper GI symptoms, with a population comparison cohort of 47,060 individuals. All patients were followed and treated according to prevailing guidelines by their usual care provider. Main outcomes were relative risks (RR) and 95% confidence intervals (CI) for incident strictures and dilatations. RESULTS: 776 (16.5%) patients were diagnosed with erosive esophagitis, particularly men (61.2%). Over a period of 1-17 years (mean 10.5), 20 patients (2.6%) in the esophagitis group developed a peptic stricture, necessitating one or more dilatations in 16 patients (2.1%). Among the non-esophagitis patients, the incidences for both outcomes were 1.2%. Male gender doubled the risk of developing strictures, and alcohol abuse raised the risk four folds. Erosive patients had a risk of developing strictures eight times (95% CI: 5.0-13.0) higher than controls, whereas non-erosive patients' risk was 4.0 (95% CI: 2.8-5.7). The majority of strictures developed within the first 10 years after a diagnosis of esophagitis. CONCLUSION: Patients with esophagitis had eight times higher risk of strictures than population controls and two times higher than dyspeptic patients without esophagitis. This indicates that long-term outcomes in general practice are poorer than in controlled trials, most likely due to a lack of compliance with medication.

The esophageal multimodal pain model: normal values and degree of sensitization in healthy young male volunteers.

BACKGROUND: Sensory changes are thought to be involved in gastro-esophageal reflux disease (GERD). The esophageal multimodal pain model can be used to investigate sensations in response to distension, heat, electric current and acid. AIMS: The aim of this study was to provide normal values for this model in the normal state and in the acid induced sensitized state. METHODS: Fifty-three healthy men (20-38 years old) underwent esophageal stimulation with distension, heat and electrical current before and after sensitization with 0.1 N HCl acid. Stimulus intensities at painful and non-painful thresholds and referred pain areas were measured. The percentage of individual participants sensitized to each modality was calculated. In 22 subjects the pre-acid tests were repeated on three subsequent visits. RESULTS: To reach moderate pain, subjects tolerated mean distension of 29.1 ± 11 mL, heat stimulation time of 141 ± 33 s, and mean current of 17.6 ± 6.4 mA. After acid exposure, significantly reduced thresholds were observed for mechanical (24%), heat (11%) and electrical (14%) stimulation (P values < 0.05). The percentage of subjects sensitized, defined as reductions in thresholds of ≥10% or ≥20% after acid perfusion, was as follows: for distension 77%/62%, for heat 48%/28%, and for current 58%/44%. The model showed good reliability (intra-class correlations >0.6). CONCLUSIONS: Normal values for healthy young men are now provided for the normal and the sensitized state. The percentage of subjects sensitized after acid stimulation are thoroughly documented, and depends on stimulation type and the cut-off value chosen.

Benign and precursor lesions in the esophagus.

The following, from the 12th OESO World Conference: Cancers of the Esophagus, includes commentaries on the role of salivary stimulation and esophageal secretion of protective factors in prevention of adenocarcinoma sequelae in gastroesophageal reflux disease; the pediatric conditions associated with esophageal cancer; the relationship of achalasia and pseudoachalasia with esophageal cancer; the potential for malignant transformation in eosinophilic esophagitis and overlap syndromes; the role of lymphocytic esophagitis as an overlapping phenotype; the role of Barrett's esophagus as a premalignant condition; the indications and type of treatment of premalignant conditions of the esophagus; and the decision for use of endoscopical procedures in premalignant conditions of the esophagus.

Lifestyle factors among proton pump inhibitor users and nonusers: a cross-sectional study in a population-based setting.

PURPOSE: Lifestyle factors may influence observed associations between proton pump inhibitor (PPI) usage and health outcomes. The aim of the study reported here was to examine characteristics and differences in lifestyle among PPI users and nonusers. METHODS: This cross-sectional study utilized data from a 2006 population-based health survey of 21,637 persons in the Central Danish Region. All persons using prescribed PPIs were identified through linkage to a population-based prescription database. Biometric measures and prevalence of smoking, excessive alcohol consumption, diet, and physical exercise were analyzed, comparing PPI users with nonusers. RESULTS: Among 10,129 (46.8%) male and 11,508 (53.2%) female survey respondents, 1,356 (13.4%) males and 1,691 (14.7%) females reported ever use of PPIs. PPI users were more obese (16.7%) than nonusers (13.1%), with an age- and sex-standardized prevalence ratio (PR) of 1.3 (95% confidence interval [CI]: 1.2-1.4). The prevalence of smokers was also higher in the PPI group (26.2% vs 22.3% [PR =1.2, 95% CI: 1.1-1.3]), as was the prevalence of ex-smokers (41.0% vs 32.0% [PR =1.2, 95% CI: 1.1-1.2]). Unhealthy diet was slightly more common among PPI users than among nonusers (15.4% vs 13.0%), with a PR of 1.2 (95% CI: 1.1-1.3). Physical exercise level and alcohol consumption were similar in the two groups. Hospital-diagnosed comorbidity was observed in 35% of PPI users (a Charlson Comorbidity Index score of 1 or more) compared with only 15% among nonusers. CONCLUSION: PPI users are more obese, smoke more, and have significantly more comorbidities than PPI nonusers. These data are important when evaluating unmeasured confounding in observational studies of PPI effects.