EST can damage the normal physiology of SO. The choledochoduodenal pressure gradient and SO basal pressure were totally lost 15 to 17 years after EST, following with duodenobiliary reflux. The SO hypoactivity in terms of frequency and amplitude relates to gallstone formation. In managing large CBD stones (> 1cm diameter), generous EST (> 1cm) usually was performed. In order to reduce the long-term risk of recurrent choledocholithiasis, endoscopic papillary balloon dilation (EPBD) or endoscopic papillary large balloon dilation (EPLBD) was an alternative option for large EST, recommended by European Society of Gastrointestinal Endoscopy guideline. However, SO basal pressure was also dramatically reduced after EPBD, from 13.6 mmHg to 6.3 mmHg and 9 mmHg to 3.3 mmHg  independently after 1 week. Even the SO basal pressure could recover to 9.3 mmHg (one month) and 4.2 mmHg (one year) after EPBD, it was significantly lower than those before EPBD. For EPLBD, the SO basal pressure was reduced from 30.4 mmHg to 6.4 mmHg one week after procedure, similar result was observed one year after EPLBD . Compared with EST, EPBD or EPLBD had similar CBD stones recurrent rates [15, 16].
Bile culture and proximal CBD biopsy indicated that bacteria colonization and biliary duct chronic inflammation after SO dysfunction . In Korea，46,181 patients with a history of CBD stones under endoscopic extraction were followed-up for an average 4.2 years, 11.3% (5,228/46,181) had the first CBD stone recurrence, 23.4% and 33.4% for the second and a third recurrence . Although the exact etiology of gallstone formation was still not clear, bacteria probably play an important role in the formation of brown stones, which were usually found as recurrent CBD stones. By scanning electron microscopy and bile culture, Kaufman et. al. indicated that bacteria were only found in brown pigment stones. Furthermore, infected bile was found in 100% of those with recurrent choledocholithiasis. Thus, how to preserve the SO function, reduce bacteria reflux and colonization in bile duct after CBD stone extraction need to be explored.
Inflammation, tissue formation and tissue remodeling were three phases of wound healing. The inflammatory phase involves recruitment of neutrophils, macrophages, inflammatory cells, chemotaxis and endothelial cells. Angiogenesis is a key player in the second proliferative phage, delayed or defective angiogenesis is implicated in healing impairment. Local connective tissue fibroblasts at the wound edge are the major source of myofibroblasts, participated in tissue repair . Compared with the EST control group, EEPP appeared to generate less neutrophils and macrophages infiltration, better angiogenesis and fibroblast proliferation. Based on the histological results, EEPP improved papillary healing after EST. Myofibroblasts is important in maintaining skin homeostasis and orchestrating tissue repair, which is characterized by expression of α-SMA . Thus α-SMA expression is usually used as a marker of fibroblast differentiation, which is critical for tissue formation in the wound healing process. Half year after EEPP, α-SMA was highly expressed in the papilla wound surface, indicated a well healing process and scarring of papilla after EST.
The SO is an important neuromuscular complex that located at the duodenum, and it controlled the volume of bile and pancreatic juice. It is believed that the long-term complications of EST are due to anatomic and physiologic disruption of SO. Up to now, SOM has been the best endoscopic method to identify the function of SO. Guelrud et al. have reported that the normal values for SOM as follows, CBD pressure was 6.8 ±1.7 mm Hg with a range of 4-10 mm Hg, SO basal pressure 14.8±6.3 mm Hg with a range of 4-30 mm Hg, SO amplitude 119.7 ± 32.6 mm Hg with a range of 76-180 mm Hg, SO frequency 5.7 ± 1.2 contractions/min with a range of 3-10 contractions/min. Similar results were obtained in both EST control and EEPP groups before any treatment. After EST, both SO basal pressure and CBD pressure dramatically reduced, but EEPP restored the SO pressure 3 weeks later.
For SO phasic contraction, amplitude, peak and period showed similar pattern with basal and CBD pressure. The decreasing SO myoelectric activity such as amplitude and frequency is related to the formation of gallstone formation. Since EEPP restores SO contraction, EEPP may reduce the risk of recurrent choledocholithiasis. Moreover, SO contraction frequency even further increased in some animals. Whether EEPP can affect recurrent bile duct stone or other complications of EST, need to be further identified. Anatomically, pigs were different with human, with the biliary duct and pancreatic duct open separately at the duodenal bulb. Thus, post-EST pancreatitis was not observed in this study. However, due to small sample size and observation period limitations, whether the long-term complications of EST, especially recurrent choledocholithiasis could be reduced by EEPP need to be further investigated.