“Quality time” for patients with Barrett’s esophagus

Since the 1970s, the term “quality time” has been increasingly used to refer to time spent with loved ones (family, partners, or friends) that is especially rewarding, productive, or profitable, or to time engaged in some favored activity, such as a hobby [1]. Such quality time is inherently linked to “quality of life”, meaning an individual’s emotional, social, and physical wellbeing, including their ability to function in the ordinary tasks of living. Simply put, quality time (QT) equals quality of life (QoL) times time, or QT = QoL × t. The higher the quality of life and the longer the time the one lives, the better …

For patients with Barrett’s esophagus, the opportunity to experience quality time, or the actual time available that can be enjoyed, is often limited. It is well known that the diagnosis of Barrett’s esophagus with intestinal metaplasia is associated with a decrease in QoL on generic and organ system-specific measures, along with increased health care costs and increased health care utilization. These patients not only live with symptoms of gastroesophageal reflux disease (GERD), such as heartburn and regurgitation, but they have to submit to regular endoscopic surveillance and take acid-suppressive medications, or undergo endoscopic and surgical interventions with various levels of risk, costs, absence from work, and stressful life events. More importantly, patients with this disease live with anxiety about the unpredictable development of dysplasia and cancer of the esophagus with their notorious implications for morbidity and mortality [2].

The incidence of cancer in patients with Barrett’s esophagus and intestinal metaplasia, if untreated, is 0.5 % to 0.9 % per year [3]. The current guideline-based recommendation for Barrett’s patients with intestinal metaplasia without dysplasia is endoscopic surveillance with periodic multiple biopsies from the entire surface affected by the disease. Surveillance has limitations, including errors in biopsy sampling, lack of compliance with surveillance, cost, and failure to avert adenocarcinoma. This passive surveillance approach is not in any way changing quality time for Barrett’s patients. Ablation or resection strategies are implemented only if high grade dysplasia is found, while in some instances esophagectomy is performed [4].

In this issue of Endoscopy, two important studies open a horizon of hope for patients with Barrett’s, with a promise of quality time. In the first study, Fleischer and colleagues, present 5-year data on the durability of radiofrequency energy ablation (RFA) of Barrett’s esophagus, using the HALO³⁶⁰ and HALO⁹⁰ systems [5]. In this prospective, multicenter US trial, patients with nondysplastic Barrett’s esophagus (NDBE) of up to 6 cm in length, who had previously received endoscopic RFA and had demonstrated complete resolution of intestinal metaplasia (CR-IM) at 2.5 years, were followed up to 5 years. At that point, the investigators obtained four-quadrant biopsies from every 1 cm of the original extent of the disease and all specimens were reviewed by one expert gastrointestinal pathologist. Patients with NDBE at 5 years underwent focal RFA (HALO⁹⁰) and repeat biopsy. The primary outcomes were: (i) proportion of patients with persisting CR-IM at the 5-year biopsy, and (ii) proportion of patients with CR-IM at the 5-year biopsy or after single-session focal RFA.

Of their 60 eligible patients, 50 signed informed consent and 1473 esophageal specimens were obtained at 5 years (mean number of specimens per patient 30, standard deviation [SD] 13), with 85 % of specimens containing lamina propria or deeper layers. CR-IM was demonstrated in 92 % (46/50) of patients, while 8 % (4/50) had focal NDBE. Focal RFA converted all treatment failures to CR-IM. There were no buried glands, dysplasia, strictures, or serious adverse events. Kaplan-Meier CR-IM survival analysis showed that the probability of maintaining CR-IM for at least 4 years after the first durable CR-IM was 0.91 (95 % confidence interval 0.77 – 0.97) and the mean duration of CR-IM was 4.22 years (standard error [SE] 0.12 years). The authors concluded that in patients with NDBE treated with RFA, CR-IM was found to be durable in the majority of patients (92 %) at 5 year follow-up, biopsy depth was adequate for detecting recurrence, and all failures (4/4, 100 %) were converted to CR-IM with focal RFA.

Although their study had some limitations, such as patient attrition and lack of a control group, its strengths were that it was a prospective multicenter trial with 5-year follow-up and a histologic outcome, not merely an endoscopic one, with extensive biopsies. Importantly, subepithelial biopsies revealed no evidence of “buried” glands or dysplasia. Unfortunately their study did not address quality of life issues in the cohort; it would have been great if the authors could have linked complete eradication of NDBE to less anxiety about dysplasia and cancer.

In the second study in this issue of Endoscopy, Shaheen and colleagues assessed the impact of dysplastic Barrett’s esophagus on quality of life, and determined whether quality of life gets better after endoscopic treatment of dysplastic Barrett’s with RFA [6]. They analyzed changes in QoL in the AIM Dysplasia Trial, a multicenter study of patients with dysplastic disease who were randomized to RFA therapy or a sham intervention. As part of this study, the participants completed a 10-item Barrett’s esophagus QoL questionnaire at baseline and at 12 months. A total of 127 patients were randomized to RFA (n = 84) or the sham intervention (n = 43). At baseline, the majority of patients reported fear of esophageal cancer (71 % RFA, 85 % sham) and worry about the possibility of an esophagectomy (61 % RFA, 68 % sham). They reported depression, general worry, impaired QoL, stress, and dissatisfaction with their medical condition. Importantly, women were negatively affected by the condition to a disproportionate extent. Out of those randomized, 117 participants completed the study to the 12-month end point. Compared with the sham intervention group, RFA-treated patients who achieved CR-IM had significantly reduced fear about esophageal cancer (P < 0.003) and worry about esophagectomy (P < 0.009). Furthermore, they had significantly reduced depression (P < 0.02), general worry (P < 0.001), impact on daily QoL (P < 0.009), stress (P < 0.03), dissatisfaction with the condition of their esophagus (P < 0.01), and impact on work and family life (P < 0.02). The authors concluded that dysplastic Barrett’s esophagus substantially impairs QoL and that its complete eradication by endoscopic RFA significantly improves QoL of patients at 12 months, compared with those undergoing a sham procedure.

For anyone who practices patient-centered medicine, this study is of major importance. Not only does this new endoscopic therapy improve important endoscopic and histologic outcomes, it also significantly improves QoL parameters. As such, it brings patients with dysplastic Barrett’s closer to an optimal QT. Even when the outcome was not perfect and there was not complete elimination of metaplasia, downgrading from dysplasia to metaplasia had a favorable effect (dose response). Most of the RFA-treated patients who did not achieve complete eradication of intestinal metaplasia had downgrading of their disease, with eradication of dysplasia. Because NDBE presumably has a lower risk of progression to cancer, it is not surprising that these patients also reported a significant decrease in worry about the development of cancer and exhibited better QoL compared with those who underwent the sham procedure.

To date, as the authors discuss, no validated QoL measure for Barrett’s esophagus has been described and generic instruments may be insensitive to clinically significant changes specific to this disease, which is, after all, an endoscopic/histologic entity symptomatically expressed as GERD. Because of this, the authors created a disease-targeted measure to assess certain reality-based aspects of QoL in Barrett’s esophagus, based on previous interviews aimed at identifying areas of greatest concern for such patients. Although this questionnaire may have some limitations, it nevertheless provides a practical tool for starters. More work is needed on this aspect of management of Barrett’s esophagus, since ultimately quality of life is what really matters. It would have been ideal if Shaheen et al. had provided us with longer-term (5-year) data and demonstrated that the QoL gains were sustainable over time, improving QT. But I am sure that this study is already underway …

In their own way, both studies commend RFA therapy, demonstrating benefits in both endoscopic and clinical outcomes. Although they involved two theoretically distinct groups of patients, with nondysplastic and dysplastic Barrett’s esophagus, the specific gains are clear and applicable to all. Increasingly, the distinction between these two groups is becoming obsolete since the disease is biologically one entity [7], and – at least in this author’s view – management and eradication of Barrett’s esophagus at the time of recognition is imperative, before the inadequacies of our current approaches can take their toll on its victims.

Competing interests: None

References

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