RDX5791, a First-in-Class Minimally Systemic NHE3 Inhibitor in Clinical Development for CIC and IBS-C, Increases Intestinal Sodium Leading to Enhanced Intestinal Fluid Volume and Transit

5,619,926.58 person years in our analysis. During a median of 3 years, ~ 10% of our cohort of first cancer patients (n: 135,725/1,391,490) developed a second primary cancer. Of them, 2,214 (1.6%) had a second esophageal cancer. Cancer patients had a 1.7 higher risk of developing any esophageal cancer (SIR: 1.7 (95% CI: 1.6-1.7)) and a 2.2 higher risk of developing ESCC (SIR: 2.2 (95% CI: 2.1-2.4)) as compared to the general population. The SIR for a second ESCC after lung cancer was 3.70 (95% CI: 3.0-4.5). There was a remarkably high risk for developing a second ESCC in patients diagnosed with head-and-neck cancer with a SIR of 22.4 (95% CI: 20.0-25.0). In male patients the SIR for head-and-neck cancer was 19.3 (95% CI: 16.9-22.0) and 36.9 (95% CI: 29.8-45.4) for female patients. Of the 9,584 female patients with a first head-and-neck cancer 92 developed a second ESCC with a Number Needed to Screen of 96. Conclusions This first nationwide, population-based study in the Western world on the incidence of ESCC in head-and-neck cancer survivors shows that these patients have a 22 times higher risk of developing ESCC. This observation is even more pronounced in female patients. These data suggest that that head-and-neck cancer survivors may benefit from periodical screening for ESCC.