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Prevalence and associated factors of worry for cancer in patients with a Barrett’s esophagus – Scientific Reports


This was a cross sectional, exploratory, self-administered questionnaire study assessing worry for cancer in patients with a BE and refractory reflux symptoms. Patients were included from a single, tertiary referral centre for surveillance and endoscopic treatment of BE, the Catharina Hospital Eindhoven, the Netherlands. Participants completed the questionnaire before their endoscopy appointment from April 2018 until March 2022. Due to the COVID-19 pandemic, inclusion was interrupted between January 2021 and July 2021.

Dysplastic Barrett’s esophagus (DBE) group

This first group of patients had a history or presence of confirmed low grade dysplasia, high grade dysplasia or EAC (defined as R0 endoscopic resection of a pT1a or pT1b adenocarcinoma) in histology prevalent BE and treated with at least one endoscopic procedure, e.g. endoscopic submucosal dissection (ESD), endoscopic mucosal resection (EMR) or radio frequency ablation (RFA). Patients were excluded when treated with a surgical esophageal resection, R1 endoscopic resection, and patients who underwent neoadjuvant/adjuvant chemotherapy or radiation as part of treatment of EAC.

Non Dysplastic Barrett’s esophagus (NDBE) group

The patients in this second group were recruited from an endoscopic surveillance program for BE. All patients had proven macroscopic (metaplastic columnar epithelium above the gastro-esophageal (≥ 1 cm) junction, which was clearly visible endoscopically) and histologic (presence of intestinal metaplasia confirmed from esophageal biopsy) NDBE. Patients were excluded if there was presence of low-or high-grade dysplasia or EAC in BE histology.

Refractory reflux group

The group contained of patients with reflux symptoms referred for an upper endoscopy. In these patients symptoms of heartburn, regurgitation, and/or chest pain were present for at least three months and three times a week15. Patients used a standard-dose of Proton-Pump inhibitors (PPI) therapy for at least three months with a minimum of three times a week. Patients with pre-existing esophageal disorders or BE were excluded.

At the time of completing the questionnaire, all participants were above 18 years of age. Furthermore, patients were able to read, understand and complete the Dutch informed consent form and the study questionnaires. Patients were invited to participate with a postal invitation and received a one-time postal reminder when they did not respond after four weeks.

Questionnaires

The questionnaire asked participants to complete baseline items on age, gender, employment status, educational level, and comorbidity (diabetes, arthritis, mental illnesses, cancer, and diseases of hart, neurology, kidney, lung, and skin). In addition, data on the previous performed ET (date of procedure, histology and length of BE) were obtained from the medical record of the DBE patients.

Worry for cancer was assessed using the Cancer Worry Scale (CWS). The CWS is used in research to assess concerns about developing cancer or cancer recurrence and the impact of these concerns on daily functioning16. The CWS was translated in Dutch by Douma and colleagues17. The six items of the CWS are rated on a 4-point Likert scale ranging from “never” to “almost always”. Scores range from 6 to 32, with a higher score indicating more fear of cancer. Based on a previous Dutch validation study, patients were divided into three categories: no cancer worry (score < 6), low level of cancer worry (score 7–9), and high level of cancer worry (score ≥ 10)16.

The presence of reflux symptoms was measured using the Reflux Disease Questionnaire (RDQ). Extensive research has found this questionnaire to be reliable, valid, responsive and above all practical18. Furthermore, the RDQ outcome seems to correlate well with quality of life19. A Dutch validation study showed the RDQ is a valid and reliable questionnaire with excellent construct validity and a good relationship to quality of life20. RDQ includes 12 items assessing the frequency and severity of heartburn, acid regurgitation and dyspeptic complaints, which are scored on a 5-point Likert scale. The mean of all three dimensions gives a total score ranging from 0 to 5. Where a score of 0 represent nil symptoms, a score of 1–2 mild symptoms, and 3–5 severe symptoms of reflux21.

Analyses

Continuous sociodemographic data, are presented with means and standard deviation (SD). Categorical variables are summarized with frequency and percentages(%). The DBE patients were allocated according to the time from the last ET (respectively 0–5, 6–11, 12–35, and > 36 months), the worst pathology found (LGD, HGD, EAC and high risk EAC). A high risk EAC was defined as EAC with at least SM1 invasion or vascular invasion. NDBE patients were distributed according the length of their BE (< 10 cm and > 10 cm).

To answer the first research question, which was: what is the proportion of BE patients with high levels of worry for cancer? The scores of the CWS were divided into three categories: no cancer worry (score < 6), low level of cancer worry (score 7–9), and high level of cancer worry (score ≥ 10).

The second research question was to investigate what the differences are on cancer worry and reflux symptoms between patients endoscopically treated for BE neoplasia (DBE), non-dysplastic BE patients (NDBE) and a non- BE control group of patients with reflux symptoms. Therefore, a one-way ANOVA was first was used to determine differences between the three patient groups (DBE, NDBE, refractory reflux). Then a post-hoc test was performed to identify differences on outcomes between the BE groups DBE and NDBE. Finally, a student t-test or Mann Whitney U (depending on normality), and the Chi-Square test for categorical variables were used to identify differences between all BE patients (DBE and NDBE) and the reflux control group.

For the final research question on exploring which factors were associated with worry for cancer, Spearman’s rho or Pearson ‘r (depending on continuous or categorical variables) were used. The outcome variable was total CWS score and the dependent variables: gender, age, marital status, employment status, total comorbidities, positive history of cancer, positive family history with cancer, months after ET, worst pathology and BE duration. Statistical analyses were performed using IBM Statistical Package for Social Sciences (SPSS) software (version 25). In this explorative study, significance levels were set at the 0.05 level (two-sided).

Ethics approval and consent to participate

All subjects gave written informed consent in accordance with the Declaration of Helsinki. The protocol was approved by the Medical Ethical Committee United (MEC-U) with reference W19.068.



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