Introduction

Most upper GI (UGI) cancers develop in the context of premalignant conditions, such as Barrett’s oesophagus (BO), squamous dysplasia and gastric atrophy (GA) or gastric intestinal metaplasia (GIM). Endoscopic recognition of these premalignant conditions offers an opportunity for surveillance to prevent advanced UGI cancer. However, their prevalence is poorly defined and as such, there are no diagnostic key performance indicators (KPIs) in UGI endoscopy.

Aims & Methods

The primary aim of this study was to define the prevalence of premalignant UGI conditions in a standard endoscopy referral population. Secondary aims included identifying factors associated with the presence and missed diagnosis of these conditions. PROSPERO is a prospective, multicentre study with 11 participating Trusts in the UK, recruiting at least 1,000 symptomatic patients newly referred on any diagnostic pathway, without known premalignant conditions or an UGI endoscopy performed within the last 3 years. All patients underwent standardised photodocumentation and biopsy protocol including a minimum of 4 gastric biopsies (antrum & body) and 4 oesophageal biopsies. The prevalence of premalignant conditions in the prospective cohort was compared to an equal-sized historic cohort. Demographic, lifestyle and medical data were obtained from patient-filled questionnaires and assessed for their predictive value with regards to diagnosis of UGI premalignant/malignant pathology. Endoscopic data were evaluated for impact on missed detection of these pathologies. Multivariable logistic regression models were used to identify factors associated with premalignant/malignant UGI pathology.

Results

To date, 847 patients have been recruited, of which 745 (mean age 58yrs, 40.3% male and 55.3% referred as 2ww or urgent) have histological data. Premalignant UGI pathologies were diagnosed in 101 patients (13.6%), including 44 cases of BO (5.9%) and 56 cases (7.5%) of GA/GIM. Five BO cases harboured dysplasia (ID/LGD/HGD) and three cases harboured intramucosal cancer. Only 26% of cases of GA/GIM were suspected endoscopically. For actionable GA/GIM, requiring future surveillance, only 34% of cases were suspected endoscopically. There were 11 cases of UGI cancer (1.5%). The rate of histological diagnoses of GA/GIM in the historic cohort was significantly lower (1.2% vs 7.5%; p<0.0001). Premalignant stomach was significantly more likely to be detected when gastric narrow band imaging (NBI) was used (p=0.0002) and when the procedure was performed by gastroenterologists as opposed to other endoscopists (p=0.03). Duration of endoscopy and endoscopist experience did not influence rate of diagnosis. Multivariable analysis revealed that male sex (Odds Ratio (OR) 1.72; 95% Confidence Interval (CI) 1.01-2.93; p=0.01), age (OR 1.03; CI 1.01-1.05; p=0.001) lack of vegetable/fruit consumption (OR 8.67; CI 2.13-37.49; p=0.002) and black (OR 29.45; CI 4.32-247.65; p=0.0006) or mixed ethnicity (OR 62.05; CI 6.25-1453.28; p=0.0009) significantly increased the risk of any premalignant/malignant UGI pathology.

Conclusion

This prospective study quantified, for the first time, the prevalence of premalignant UGI conditions (13.6%) in a symptomatic patient population referred for UGI endoscopy. Premalignant stomach pathology was found to missed in the majority of cases and its detection was enhanced when NBI was used. We identified pre-test risk factors associated with the presence of UGI pathology. This data can be utilised for future development of diagnostic KPIs and training tools in UGI endoscopy.

Introduction

Treatment response in patients with severe erosive gastroesophageal reflux disease (eGERD) is often inadequate using regular doses of proton pump inhibitors (PPIs), thus necessitating escalation of dosing. High-dose PPIs improve compliance in such patients, leading to better outcomes. However, comparative data on effectiveness of high-dose PPIs is limited.

Aims & Methods

This interim analysis assessed symptomatic improvement of regurgitation in an ongoing, prospective, real-world, observational study to compare the effectiveness of rabeprazole 40mg to pantoprazole 80mg and omeprazole 40mg/esomeprazole 80mg. Adult patients with endoscopically confirmed severe eGERD were enrolled. Patients shifted from low-dose PPIs or started on high-dose PPIs were included; those with complications of GERD were excluded.

Results

A total of 260 patients (rabeprazole, 130; omeprazole/esomeprazole, 65; pantoprazole, 65) from 37 sites in India were analyzed. Although symptomatic improvement of diurnal and nocturnal regurgitation based on patient-reported severity scores was observed among the three arms after 4±1 weeks of treatment, the complete-resolution rate of diurnal regurgitation was significantly higher with rabeprazole (17.97%) compared to omeprazole/esomeprazole (5.08%; p=0.018) and higher than pantoprazole (8.20%; p=0.077). Similarly, complete resolution of nocturnal regurgitation was significantly higher with rabeprazole (14.06%) compared to omeprazole/esomeprazole (1.59%; p=0.007) and higher than pantoprazole (7.94%; p=0.221). Among patients with associated work-related stress (n=132), one-fifth in the rabeprazole arm experienced complete resolution of diurnal regurgitation compared to none in the omeprazole/esomeprazole (p=0.013) or pantoprazole (p=0.030) arms. Patients with lack of regular physical exercise (83.08%) exhibited higher rate of complete resolution of nocturnal regurgitation with rabeprazole (13.73%) compared to the other PPIs. Overall, elderly patients >60 years of age (mean±SD, 68.82±6.54 years) treated with rabeprazole showed significantly higher complete-resolution rates of diurnal regurgitation compared to pantoprazole (36.67% vs. 0%; p=0.003). For complete resolution of nocturnal regurgitation, rabeprazole proved to be significantly better when compared to omeprazole/esomeprazole (31.25% vs. 0%; p=0.015) in elderly patients (Table 1).

Conclusion

The interim results showed that rabeprazole led to significantly higher complete-resolution rates of diurnal and nocturnal regurgitation at 4±1 weeks of treatment than omeprazole/esomeprazole in adults with severe eGERD. In elderly patients, rabeprazole showed significant resolution over pantoprazole.

Disclosure

Study funded by: Dr. Reddy's Laboratories Ltd., Hyderabad, Telangana, India