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Background <p>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.</p> Methods <p>Consecutive patients (age 18–75&#xa0;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&#xa0;week, and thereafter at 1, 3 and 6&#xa0;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.</p> Results <p>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 (<i>P</i> &lt; 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.</p> Conclusions <p>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.</p>

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

  • 期刊论文

  • 发表日期：

    2025年8月27日

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  • Yuan Yu,
  • Fengxia Yu,
  • Rui Liang,
  • Ran Kang,
  • Xinzhe Liu,
  • Xiaofei Chu,
  • Fengyu Lu,
  • Jie Sun,
  • Jia Gao,
  • Lin Ding,
  • Jianxin Liu,
  • Yue Zhou,
  • Ping Fan,
  • Yu Zang,
  • Yujie Yang,
  • Yin Li

摘要

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.