The Trajectory of Reflux and its Associating Factors in Patients After Esophagectomy Based on Salivary Pepsin-Testing: A Prospective Longitudinal Study.

Background: Post-esophagectomy reflux remains a significant clinical challenge. This study pioneered the use of salivary pepsin-testing (SPT) as an objective biomarker to explore the reflux, addressing limitations of subjective symptom scoring in esophagectomy outcomes research.

Methods: Consecutive patients (age 18-75 years) with histologically confirmed esophageal carcinoma who underwent esophagectomy were prospectively enrolled to explore the trajectory and associating factors of reflux after surgery. Standardized SPT assessments were performed preoperatively, at 1 week, and thereafter at 1, 3 and 6 months postoperatively. A generalized estimation equation (GEE) was used to analyze both main effects and time-interaction effects of demographic/surgical/behavioral factors on reflux trajectories.

Results: Between 1 March and 1 December 2024, 215 consecutive esophagectomy candidates were recruited. Nine patients (4.2 %) declined enrollment, leaving 206 participants, who were stratified by preoperative SPT, including 111 patients (53.9 %) with elevated baseline levels (≥76.1 ng/ml) in the positive group and 95 patients (46.1 %) in the negative group. During the 6-month follow-up period, both groups demonstrated a similar postoperative reflux trend, which initially increased and then decreased, with the peak occurring 1 month after surgery. The median reflux levels in the pepsin-positive group were higher than those in the pepsin-negative group at all time points, with statistically significant differences (P < 0.05). The GEE main-effect analysis showed that redundancy of conduit was a significant risk factor for postoperative reflux (B = 15.352; 95 % confidence interval [CI], 2.061-6.119). Furthermore, the time-interaction analysis demonstrated that redundancy of conduit remained a risk factor (B = 234.626; 95 % CI, 67.554-401.697). Maintaining a semi-Fowler position (often: B = -63.668 [95 % CI, -195.718 to -68.383]; seldom: B = -55.271 [95 % CI, -178.632 to -108.248]) and pre-sleep fasting ≥2 h (often: B = -35.192 [95 % CI, -178.632 to -108.248]; seldom: B = -11.126 [95 % CI, -124.369 to -26.621]) were protective factors against reflux.

Conclusions: Salivary pepsin-testing objectively quantifies post-esophagectomy reflux trajectories, showing modifiable factors critical for reflux. Semi-Fowler positioning and pre-sleep fasting for at least 2 h were protective factors, whereas redundancy of conduit was the risk factor for reflux within 6 months after esophagectomy. These modifiable factors should be incorporated into enhanced recovery pathways.