Endoscopic papillectomy enables resection of ampullary lesions but has notable limitations, including piecemeal resection and high recurrence rates. To overcome these limitations, we previously reported the feasibility of endoscopic submucosal dissection including the papilla (ESDIP) as an alternative approach. ESDIP extends conventional ESD to the ampullary region, allowing en bloc resection while dividing the sphincter of Oddi. However, this division increases postoperative exposure to bile and pancreatic juice, making biliary and pancreatic duct drainage essential to prevent complications. In patients with pancreas divisum, anatomical variation often renders endoscopic nasopancreatic drainage (ENPD) unfeasible, resulting in more complex postoperative management. This study aimed to evaluate the feasibility and safety of ESDIP for ampullary tumors in patients with pancreas divisum.

Among 70 patients who underwent ESDIP at our institution between August 2011 and October 2025, two patients with pancreas divisum and ampullary neoplasms were retrospectively analyzed.

ESDIP was performed by creating a distal mucosal incision, forming a mucosal flap from the oral side, conducting submucosal dissection with identification and division of the sphincter of Oddi, and subsequently achieving en bloc resection of the lesion.

According to our standard ESDIP protocol, postoperative management typically involves ERCP-guided biliary and pancreatic drainage to prevent bile and pancreatic juice exposure to the resection defect. However, in the present two cases with pancreas divisum, ENPD was not feasible due to the anatomical configuration of the pancreatic duct.

After resection, endoscopic retrograde biliary drainage (ERBD) was performed. The mucosal defect, excluding the papilla, was partially closed using clips, and continuous duodenal suction was applied using a nasogastric tube placed near the duodenal ESD defect. Octreotide was additionally administered to minimize pancreatic juice exposure.

Primary outcomes included en bloc resection, intraoperative perforation, length of hospital stay, white blood cell count, C-reactive protein, serum amylase level, and post-ERCP pancreatitis.

En bloc resection was achieved in both cases. No intraoperative or delayed perforation, postoperative bleeding, or post-ERCP pancreatitis occurred. One patient experienced mild abdominal pain on postoperative day 1, and computed tomography revealed minor retroperitoneal emphysema, which resolved with conservative treatment. The nasogastric tube was removed on postoperative days 4–5, after which oral intake was resumed. Patients were discharged on postoperative days 10 and 12, respectively, with uneventful clinical courses.

ESDIP for ampullary tumors in patients with pancreas divisum can be safely performed even when ENPD is not feasible. Continuous duodenal suction using a nasogastric tube, combined with partial ulcer closure and octreotide administration, effectively reduced pancreatic juice exposure and enabled safe postoperative management. This strategy may represent a practical therapeutic option for pancreas divisum cases in which pancreatic duct drainage cannot be achieved.