Background: NOTES (Natural Orifice Translumenal Endoscopic Surgery) continues to present the surgical community with new challenges as we move further into a clinical setting. Of the 45 clinical NOTES cases we have performed, we have only encountered problems with removal of a specimen in the transgastric route: while attempting to remove the gallbladder, we were unable to extract the specimen due to large gallstones in two patients. The gallbladders were removed through the umbilicus for patient safety. In order to understand this problem, we developed a cadaveric human model for measuring the maximum size of specimen removal through the esophagus.Methods: After the stomach was identified, a gastrotomy was made and the stomach irrigated to ensure a clear view. An upper endoscope was passed into the stomach and an endocatch bag containing different sized spheres was grasped with an endoscopic grasper. Under direct visualization a simulated gallbladder removal through the mouth was attempted. The force needed to pass the GE junction and the cricopharyngeal junction was noted using a spring loaded scale. Lastly, the stomach and distal esophagus was explanted and examined.Results: Three different sized spheres were used to simulate large gallstones. These ranged in diameter from 2.5 to 4 cm in diameter. We found that the largest was unable to cross the GE junction with a reasonable amount of force. The medium sized ball, 3 cm, crossed the GE junction with 39.2 N force and 7.45 N to transverse the cricopharyngeal junction. The smallest ball 2.5 cm crossed the GE junction with 7.84 N of force and crossed the cricopharyngeal junction with 83.35 N of force. Upon inspection of the explanted stomach small tears in the mucosa were noted at the GE junction.Conclusions: New challenges recurrently surface as we move from the animate lab to a clinical setting. Those patients where a large gallstone is noted on preoperative ultrasound may not be a candidate for transgastric removal until a solution has been found. The gastrointestinal literature has extensively noted the maximum diameter of an object that can be safely removed per oral. This experiment confirmed a safe size is under 2 cm. The tensile strength of the esophagus is 25-27 N thus the forces we applied in this experiment far surpass the safe level in a clinical setting. We propose that intragastric lithotripsy may be an effective alternative, however further work will need to be done before introducing this to the clinical arena.